cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5124064.v1
title: Supplementary Material for: Virtual Ligand-Based Screening Reveals Purmorphamine Analogs with the Capacity to Induce the Osteogenic Differentiation of Human Mesenchymal Stem Cells

description: Human mesenchymal stem cells (hMSCs) have extensive proliferative capacity, are able to self-renew and have the potential to differentiate into cells of the connective tissue lineages. These properties make them a putative cell type for tissue engineering applications, as well as a possible in vivo target for the pharmaceutical modulation of the differentiation processes.<b> </b>The aim of this study was to find one or more small-molecule substances that would enhance the osteogenic differentiation of hMSCs in vitro. The strategy used here was ligand-based virtual screening for substances similar to the previously suggested osteoinductive purmorphamine followed by an in vitro screening of the selected analogs in hMSCs isolated from bone marrow. We investigated the osteoinductive capacity of several purmorphamine analogs by determining the protein and gene expression of markers for osteogenic differentiation as well as the extracellular matrix (ECM) mineralization of these cells. Treatment with two candidate substances or purmorphamine resulted in increased levels of alkaline phosphatase (ALP) activity compared to the control. Other purmorphamine analogs demonstrated higher calcium deposition in the ECM after 5 weeks of osteogenic differentiation, compared to both purmorphamine and the control condition. The resulting substances, which had positive effects on the osteogenic differentiation, are promising as possible modes of treatment for bone-related diseases or defects that target and enhance the osteogenic differentiation of MSCs<i>,</i> in vitro or in vivo. Furthermore, the concept of combining the virtual ligand-based screening method with in vitro screening, using human adult stem cells as a possible strategy for drug discovery, is demonstrated.
DOI: 10.6084/m9.figshare.5124031
title: Supplementary Material for: A Systematic Literature Review of Complementary and Alternative Medicine Prevalence in EU

description: <b><i>Background: </i></b>Studies suggest that complementary and alternative medicine (CAM) is widely used in the European Union (EU). We systematically reviewed data, reporting research quality and the prevalence of CAM use by citizens in Europe; what it is used for, and why. <b><i>Methods: </i></b>We searched for general population surveys of CAM use by using Ovid MEDLINE (1948 to September 2010), Cochrane Library (1989 to September 2010), CINAHL (1989 to September 2010), EMBASE (1980 to September 2010), PsychINFO including PsychARTICLES (1989 to September 2010), Web of Science (1989 to September 2010), AMED (1985 to September 2010), and CISCOM (1989 to September 2010). Additional studies were identified through experts and grey literature. Cross-sectional, population-based or cohort studies reporting CAM use in any EU language were included. Data were extracted and reviewed by 2 authors using a pre-designed extraction protocol with quality assessment instrument. <b><i>Results: </i></b>87 studies were included. Inter-rater reliability was good (kappa = 0.8). Study methodology and quality of reporting were poor. The prevalence of CAM use varied widely within and across EU countries (0.3–86%). Prevalence data demonstrated substantial heterogeneity unrelated to report quality; therefore, we were unable to pool data for meta-analysis; our report is narrative and based on descriptive statistics. Herbal medicine was most commonly reported. CAM users were mainly women. The most common reason for use was dissatisfaction with conventional care; CAM was widely used for musculoskeletal problems. <b><i>Conclusion: </i></b>CAM prevalence across the EU is problematic to estimate because studies are generally poor and heterogeneous. A consistent definition of CAM, a core set of CAMs with country-specific variations and a standardised reporting strategy to enhance the accuracy of data pooling would improve reporting quality.
DOI: 10.6084/m9.figshare.5124034
title: Supplementary Material for: Virtual Reality Exposure Therapy Does Not Provide Any Additional Value in Agoraphobic Patients: A Randomized Controlled Trial

description: <b><i>Background:</i></b> A number of studies have demonstrated the efficacy of virtual reality exposure therapy (VRET) in specific phobias, but research in seriously impaired patients with agoraphobia is lacking. In this randomized controlled trial with patients with agoraphobia and panic disorder, VRET and exposure in vivo were compared in terms of outcome and processes involved. <b><i>Methods:</i></b> Patients with panic disorder with agoraphobia (n = 55) were randomly assigned to receive 4 sessions of cognitive behavioral therapy (CBT) followed by either 6 sessions of VRET or 6 sessions of exposure in vivo or to a waiting list control condition. <b><i>Results:</i></b> Analyses showed that both active treatment packages were significantly more effective than no treatment and that no differences between VRET and exposure in vivo were found in three out of four outcome measures. On the panic disorder severity scale, however, CBT plus exposure in vivo was more effective than CBT plus VRET. The results show clear synchrony of temporal processes involved in VRET and exposure in vivo on weekly avoidance measures and cognitive measures. Further, it was shown that initial changes in agoraphobic cognitions during the CBT phase predicted later changes in agoraphobic avoidance behavior. <b><i>Conclusion:</i></b> These data support the notion that therapeutic processes involved might be the same in VRET and exposure in vivo. However, given the slight superiority of exposure in vivo above VRET, the costs involved in the implementation of VRET and the lack of long-term follow-up, VRET cannot yet be recommended for patients with agoraphobia.
DOI: 10.6084/m9.figshare.5124037
title: Supplementary Material for: Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

description: The sex hormone estradiol (E<sub>2</sub>) appears to mediate both anti-atherogenic and pro-inflammatory effects in premenopausal women, suggesting a complex immunomodulatory role. Tumor necrosis factor (TNF) is a key pro-inflammatory cytokine involved in the pathogenesis of atherosclerosis and other inflammatory diseases. Alterations at the TNF receptors (TNFRs) and their downstream signaling/transcriptional pathways can affect inflammatory responses. Given this background, we hypothesized that chronic E<sub>2</sub> exposure would alter endothelial inflammatory response involving modulation at the levels of TNFRs and signaling pathways. HUVECs were used as the model system. Pre-treatment with E<sub>2</sub> did not significantly alter TNF-induced upregulation of pro-inflammatory molecules ICAM-1 (3–6 times) and VCAM-1 (5–7 times). However, pharmacological inhibition of transcriptional pathways suggested a partial shift from NF-ĸB (from 97 to 64%) towards the JNK/AP-1 pathway in ICAM-1 upregulation on E<sub>2</sub> treatment. In contrast, VCAM-1 expression remained NF-ĸB dependent in both control (∼96%) and E<sub>2</sub> treated (∼85%) cells. The pro-inflammatory TNF effects were mediated by TNFR1. Interestingly, E<sub>2</sub> pre-treatment increased TNFR2 levels in these cells. Concomitant TNFR2 activation (but not TNFR1 activation alone) led to the shift towards JNK/AP-1-mediated ICAM-1 upregulation in E<sub>2</sub>-treated cells, suggesting the effects of chronic E<sub>2</sub> to be dependent on TNFR2 signaling.
DOI: 10.6084/m9.figshare.5124040
title: Supplementary Material for: GH-Releasing Hormone Receptor Gene: A Novel Splice-Disrupting Mutation and Study of Founder Effects

description: <b><i>Background:</i></b> Mutations in GH-releasing hormone receptor gene <i>(GHRHR)</i> are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD). <b><i>Objective:</i></b> To search for <i>GHRHR</i> mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations. <b><i>Methods:</i></b> The coding region of <i>GHRHR</i> was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking <i>GHRHR</i> were analyzed in patients with c.57+1G&gt;A (IVS1+1G&gt;A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G&gt;A (p.E382E) mutation. <b><i>Results:</i></b> A novel homozygous intronic <i>GHRHR</i> c.752-1G&gt;A (IVS7-1G&gt;A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G&gt;A];[1146G&gt;A] and a heterozygous c.527C&gt;T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G&gt;A mutation and independent recurrence for the c.1146G&gt;A mutation. <b><i>Conclusion:</i></b> We report a novel splice-disrupting mutation in <i>GHRHR</i> in 2 siblings and provide evidence that all c.57+1G&gt;A (IVS1+1G&gt;A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.
DOI: 10.6084/m9.figshare.5124028
title: Supplementary Material for: Using Ecological Niche Modelling to Predict Spatial and Temporal Distribution Patterns in Chinese Gibbons: Lessons from the Present and the Past

description: Ecological niche modelling (ENM) is used to predict species’ tolerance to changing environmental conditions. Understanding changes in the spatial distribution of species across time is essential in order to develop effective conservation strategies. Here we map the past and present distribution of gibbons across China, a country experiencing extensive anthropogenic habitat destruction and ongoing biodiversity loss. The distribution of gibbons across three time intervals is described based on fossil, historical and modern-day data, and ENM, implemented using DIVA-GIS, is used to predict how modern-day gibbon distributions might respond to future climate change. Predictions based on modern-day data alone fail to reveal patterns of environmental tolerance and geographical distribution shown by gibbons in the relatively recent historical period, emphasizing the need to incorporate past as well as present data in conservation analyses.
DOI: 10.6084/m9.figshare.5124037.v1
title: Supplementary Material for: Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

description: The sex hormone estradiol (E<sub>2</sub>) appears to mediate both anti-atherogenic and pro-inflammatory effects in premenopausal women, suggesting a complex immunomodulatory role. Tumor necrosis factor (TNF) is a key pro-inflammatory cytokine involved in the pathogenesis of atherosclerosis and other inflammatory diseases. Alterations at the TNF receptors (TNFRs) and their downstream signaling/transcriptional pathways can affect inflammatory responses. Given this background, we hypothesized that chronic E<sub>2</sub> exposure would alter endothelial inflammatory response involving modulation at the levels of TNFRs and signaling pathways. HUVECs were used as the model system. Pre-treatment with E<sub>2</sub> did not significantly alter TNF-induced upregulation of pro-inflammatory molecules ICAM-1 (3–6 times) and VCAM-1 (5–7 times). However, pharmacological inhibition of transcriptional pathways suggested a partial shift from NF-ĸB (from 97 to 64%) towards the JNK/AP-1 pathway in ICAM-1 upregulation on E<sub>2</sub> treatment. In contrast, VCAM-1 expression remained NF-ĸB dependent in both control (∼96%) and E<sub>2</sub> treated (∼85%) cells. The pro-inflammatory TNF effects were mediated by TNFR1. Interestingly, E<sub>2</sub> pre-treatment increased TNFR2 levels in these cells. Concomitant TNFR2 activation (but not TNFR1 activation alone) led to the shift towards JNK/AP-1-mediated ICAM-1 upregulation in E<sub>2</sub>-treated cells, suggesting the effects of chronic E<sub>2</sub> to be dependent on TNFR2 signaling.
DOI: 10.6084/m9.figshare.5124025
title: Supplementary Material for: Correlated Evolution of Gonadotropin-Releasing Hormone and Gonadotropin-Inhibitory Hormone and Their Receptors in Mammals

description: <b><i>Background:</i></b> Evolutionary rate variation in genes (proteins) is manifested both within the species (genome) and between the species (genomes). However, the interdependent components of a biological system in form of a gene or a protein are expected to evolve in a correlated manner under a common functional constraint. <b><i>Methods:</i></b> The phylogenetic analysis and correlation analysis of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) and their receptors (GnRHR and GnIHR) was conducted along with other control neuropeptides. <b><i>Results:</i></b> Both neuropeptides and their receptors regulating the reproductive neuroendocrine axis in vertebrates exhibited a correlated evolution under a common physiological constraint to regulate the release of gonadotropin. This result supports a coordinated substitution of amino acids in the GnRH and the GnIH neuropeptides along with their receptors in terms of similar evolutionary rates and distances with similar nucleotide composition of genes. <b><i>Conclusion:</i></b> This is the first demonstration of the correlated evolution of two components of an endocrine system regulating the release of gonadotropin which are acting in concert for successful reproduction.
DOI: 10.6084/m9.figshare.5124031.v1
title: Supplementary Material for: A Systematic Literature Review of Complementary and Alternative Medicine Prevalence in EU

description: <b><i>Background: </i></b>Studies suggest that complementary and alternative medicine (CAM) is widely used in the European Union (EU). We systematically reviewed data, reporting research quality and the prevalence of CAM use by citizens in Europe; what it is used for, and why. <b><i>Methods: </i></b>We searched for general population surveys of CAM use by using Ovid MEDLINE (1948 to September 2010), Cochrane Library (1989 to September 2010), CINAHL (1989 to September 2010), EMBASE (1980 to September 2010), PsychINFO including PsychARTICLES (1989 to September 2010), Web of Science (1989 to September 2010), AMED (1985 to September 2010), and CISCOM (1989 to September 2010). Additional studies were identified through experts and grey literature. Cross-sectional, population-based or cohort studies reporting CAM use in any EU language were included. Data were extracted and reviewed by 2 authors using a pre-designed extraction protocol with quality assessment instrument. <b><i>Results: </i></b>87 studies were included. Inter-rater reliability was good (kappa = 0.8). Study methodology and quality of reporting were poor. The prevalence of CAM use varied widely within and across EU countries (0.3–86%). Prevalence data demonstrated substantial heterogeneity unrelated to report quality; therefore, we were unable to pool data for meta-analysis; our report is narrative and based on descriptive statistics. Herbal medicine was most commonly reported. CAM users were mainly women. The most common reason for use was dissatisfaction with conventional care; CAM was widely used for musculoskeletal problems. <b><i>Conclusion: </i></b>CAM prevalence across the EU is problematic to estimate because studies are generally poor and heterogeneous. A consistent definition of CAM, a core set of CAMs with country-specific variations and a standardised reporting strategy to enhance the accuracy of data pooling would improve reporting quality.
DOI: 10.6084/m9.figshare.5124034.v1
title: Supplementary Material for: Virtual Reality Exposure Therapy Does Not Provide Any Additional Value in Agoraphobic Patients: A Randomized Controlled Trial

description: <b><i>Background:</i></b> A number of studies have demonstrated the efficacy of virtual reality exposure therapy (VRET) in specific phobias, but research in seriously impaired patients with agoraphobia is lacking. In this randomized controlled trial with patients with agoraphobia and panic disorder, VRET and exposure in vivo were compared in terms of outcome and processes involved. <b><i>Methods:</i></b> Patients with panic disorder with agoraphobia (n = 55) were randomly assigned to receive 4 sessions of cognitive behavioral therapy (CBT) followed by either 6 sessions of VRET or 6 sessions of exposure in vivo or to a waiting list control condition. <b><i>Results:</i></b> Analyses showed that both active treatment packages were significantly more effective than no treatment and that no differences between VRET and exposure in vivo were found in three out of four outcome measures. On the panic disorder severity scale, however, CBT plus exposure in vivo was more effective than CBT plus VRET. The results show clear synchrony of temporal processes involved in VRET and exposure in vivo on weekly avoidance measures and cognitive measures. Further, it was shown that initial changes in agoraphobic cognitions during the CBT phase predicted later changes in agoraphobic avoidance behavior. <b><i>Conclusion:</i></b> These data support the notion that therapeutic processes involved might be the same in VRET and exposure in vivo. However, given the slight superiority of exposure in vivo above VRET, the costs involved in the implementation of VRET and the lack of long-term follow-up, VRET cannot yet be recommended for patients with agoraphobia.
DOI: 10.6084/m9.figshare.5124040.v1
title: Supplementary Material for: GH-Releasing Hormone Receptor Gene: A Novel Splice-Disrupting Mutation and Study of Founder Effects

description: <b><i>Background:</i></b> Mutations in GH-releasing hormone receptor gene <i>(GHRHR)</i> are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD). <b><i>Objective:</i></b> To search for <i>GHRHR</i> mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations. <b><i>Methods:</i></b> The coding region of <i>GHRHR</i> was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking <i>GHRHR</i> were analyzed in patients with c.57+1G&gt;A (IVS1+1G&gt;A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G&gt;A (p.E382E) mutation. <b><i>Results:</i></b> A novel homozygous intronic <i>GHRHR</i> c.752-1G&gt;A (IVS7-1G&gt;A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G&gt;A];[1146G&gt;A] and a heterozygous c.527C&gt;T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G&gt;A mutation and independent recurrence for the c.1146G&gt;A mutation. <b><i>Conclusion:</i></b> We report a novel splice-disrupting mutation in <i>GHRHR</i> in 2 siblings and provide evidence that all c.57+1G&gt;A (IVS1+1G&gt;A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.
DOI: 10.6084/m9.figshare.5124010
title: Supplementary Material for: Stroke and Transient Ischemic Attack Incidence Rate in Spain: The IBERICTUS Study

description: <b><i>Background:</i></b> In Spain, stroke is a major public health concern, but large population-based studies are scarce and date from the 1990s. We estimated the incidence and in-hospital mortality of stroke through a multicentered population-based stroke register in 5 geographical areas of Spain, i.e. Lugo, Almería, Segovia, Talavera de la Reina and Mallorca, representing north, south, central (×2) and Mediterranean areas of Spain, respectively, the aim and novelty being that all methodologies were standardized, and diagnoses were verified by a neurologist using neuroimaging techniques. <b><i>Methods:</i></b> The register identified subjects &gt;17 years of age who suffered a first-ever stroke or transient ischemic attack (TIA) between 1 January and 31 December 2006. Stroke and TIA were defined according to the WHO criteria. The Lausanne Stroke Registry definitions were used to classify ischemic stroke subtypes, as follows: (1) large-artery atherosclerosis (LAA); (2) cardioembolism (CE); (3) lacunar stroke or small-artery occlusion (SAO); (4) stroke of other infrequent cause (SIC), and (5) stroke of undetermined cause (UND). We used several complementary data sources such as hospital discharge registers, emergency room registers and primary care surveillance systems. <b><i>Results:</i></b> In the 1-year study period, we identified 2,700 first-ever cerebrovascular episodes (53% men; 2,257 strokes + 443 TIA episodes). Brain CT in the acute stage was performed in 99% of cases. Of a total of 2,257 stroke patients, 1,817 (81%) had cerebral infarction, 350 (16%) had intracerebral hemorrhage, 59 (3%) had subarachnoid hemorrhage (SAH) and 31 (1%) had unclassifiable stroke. The overall unadjusted annual incidence for all cerebrovascular events was 187 per 100,000 [95% confidence interval (CI) 180–194; incidence for men: 202, 95% CI 189–210; incidence for women: 187, 95% CI 180–194]. The subtype of ischemic stroke could be determined in 1,779 patients and was classified as LAA in 624 (35%), CE in 352 (20%), SAO in 316 (18%), SIC in 56 (3%) and UND in 431 (24%). The incidence rates per 100,000 (95% CI) standardized to the 2006 European population were as follows: all cerebrovascular events, 176 (169–182); all stroke (non-TIA), 147 (140–153); TIA, 29 (26–32); ischemic stroke, 118 (112–123); intracerebral hemorrhage, 23 (21–26), and SAH, 4.2 (3.1–5.2). Incidence rates clearly increased with age in both genders, with a peak at or above 85 years of age. The in-hospital mortality was 14%. <b><i>Conclusions:</i></b> Our results show that the incidence of stroke and TIA in Spain is moderate compared to other Western and European countries. However, it is expected that these figures will change due to progressively aging populations.