cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123194
title: Supplementary Material for: Mortality Associated with Dose Response of Erythropoiesis-Stimulating Agents in Hemodialysis versus Peritoneal Dialysis Patients

description: <i>Background:</i> Several studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients. <i>Methods:</i> We compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models. <i>Results:</i> Poisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5–3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000–5,999, 6,000–8,999 and ≧9,000 U/week (reference &lt;3,000 U/week) were 0.97 (0.87–1.07), 0.85 (0.76–0.95) and 1.08 (0.98–1.18), respectively; whereas in HD patients across commensurate ESA dose increments of 10,000–19,999, 20,000–29,999 and ≧30,000 U/week (reference &lt;10,000 U/week) were 1.14 (1.11–1.17), 1.54 (1.50–1.58) and 2.15 (2.10–2.21), respectively. In PD and HD patients, the adjusted death HR of the 4th to 1st quartile of ESA responsiveness index were 1.14 (1.04–1.26) and 2.37 (2.31–2.43), respectively. <i>Conclusions:</i> Between 2001 and 2006, most PD patients received substantially lower ESA dose for same achieved hemoglobin levels, and low ESA responsiveness was associated with higher mortality in both HD and PD patients.
DOI: 10.6084/m9.figshare.5123200
title: Supplementary Material for: Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro

description: The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
DOI: 10.6084/m9.figshare.5123191
title: Supplementary Material for: Co-Occurrence of Addictive Behaviours: Personality Factors Related to Substance Use, Gambling and Computer Gaming

description: <i>Aim:</i> To investigate co-occurrence and shared personality characteristics of problematic computer gaming, problematic gambling and substance use. <i>Methods:</i> Cross-sectional survey data were collected from 2,553 German students aged 12–25 years. Self-report measures of substance use (alcohol, tobacco and cannabis), problematic gambling (South Oaks Gambling Screen – Revised for Adolescents, SOGS-RA), problematic computer gaming (Video Game Dependency Scale, KFN-CSAS-II), and of twelve different personality characteristics were obtained. <i>Results:</i> Analyses revealed positive correlations between tobacco, alcohol and cannabis use and a smaller positive correlation between problematic gambling and problematic computer gaming. Problematic computer gaming co-occurred only with cannabis use, whereas problematic gambling was associated with all three types of substance use. Multivariate multilevel analyses showed differential patterns of personality characteristics. High impulsivity was the only personality characteristic associated with all five addictive behaviours. Depression and extraversion were specific to substance users. Four personality characteristics were specifically associated with problematic computer gaming: irritability/aggression, social anxiety, ADHD, and low self-esteem. <i>Conclusions:</i> Problematic gamblers seem to be more similar to substance users than problematic computer gamers. From a personality perspective, results correspond to the inclusion of gambling in the same DSM-V category as substance use and question a one-to-one proceeding for computer gaming.
DOI: 10.6084/m9.figshare.5123200.v1
title: Supplementary Material for: Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro

description: The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
DOI: 10.6084/m9.figshare.5123203.v1
title: Supplementary Material for: Five-Year Follow-Up of 10 Patients Treated with Globus Pallidus Internus Deep Brain Stimulation for Segmental or Multisegmental Dystonia

description: <i>Introduction:</i> Globus pallidus internus (GPi) deep brain stimulation (DBS) represents a validated, effective, and safe treatment for patients affected by generalized dystonia resistant to conservative treatment. Segmental and multisegmental dystonia have more recently been proposed as further indications for GPi DBS despite the lack of long-term homogenous follow-up. Here we present an original and detailed long-term follow-up (5 years) of a homogeneous population of 11 patients affected by segmental or multisegmental dystonia. <i>Materials and Methods:</i> Ten patients underwent bilateral GPi DBS electrode implantations under a Leksell stereotactic guide, with intraoperative neurophysiological monitoring. The follow-ups at 1, 3 and 5 years were collected using video-BFMDRS for motor and disability scores. The statistical analysis of the results is provided. <i>Results:</i> We reported a statistically significant improvement in motor and disability overall scores until 5 years after treatment. At the last follow-up, even the single motor subitems were statistically improved. <i>Discussion:</i> We observed a continuous and statistically significant improvement in all of the motor subitems and in the overall disability score until the 3-year follow-up. These results did not improve any further but they appeared steady at the last follow-up. We also report a significant improvement in the cranial-cervical subitems. <i>Conclusions:</i> GPi DBS should definitely be considered a safe and effective treatment also for segmental and multisegmental dystonia even in cases of relevant or prevalent cranial-cervical involvement.
DOI: 10.6084/m9.figshare.5123185
title: Supplementary Material for: Aloe Emodin Induces G2/M Cell Cycle Arrest and Apoptosis via Activation of Caspase-6 in Human Colon Cancer Cells

description: Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study, we analyzed the molecular mechanisms involved in the growth-inhibitory activity of this hydroxyanthraquinone in colon cancer cell, WiDr. In our observation AE inhibited cell proliferation by arresting the cell cycle at the G2/M phase and inhibiting cyclin B1. AE appreciably induced cell death specifically through the induction of apoptosis and by activating caspases 9/6. Apoptotic execution was found to be solely dependent on caspase-6 rather than caspase-3 or caspase-7. This is the first study indicating that the AE induces apoptosis specifically through the activation of caspase-6.
DOI: 10.6084/m9.figshare.5123188.v1
title: Supplementary Material for: Evaluation of Antidepressant-Like Activity of Novel Water-Soluble Curcumin Formulations and St. John's Wort in Behavioral Paradigms of Despair

description: <i>Background:</i> Curcumin is the active principle of <i>Curcuma longa</i>, one of the widely used components in the traditional system of medicine in India. Despite its efficacy in experimental studies aiming at neuronal disorders like depression, curcu-min's poor water solubility challenges the production of therapeutic formulations. This study investigates the antidepressant-like activity of novel water-soluble curcumin formulations, dispensed in three different concentrations. Further, the study comparatively evaluates St. John's wort (SJW), another herbal preparation. <i>Methods:</i> These compounds were evaluated in the forced swimming test in mice, and the corresponding changes in the neurotransmitter levels were measured. <i>Results:</i> Three water-soluble curcumin formulations, C-5, C-20 and C-50 (50-200 mg/kg p.o.) decreased the immobility period, and increased serotonin and dopamine levels in the brain tissues. A subeffective dose (50 mg/kg) of these formulations enhanced the antidepressant-like effect of classical antidepressants with varied mechanisms of action. In addition, an SJW dose of 25 mg/kg showed a significant antidepressant-like effect in all the behavioral studies and also significantly increased brain neurotransmitter levels, especially that of serotonin. The effects produced by C-5 were comparable with those of SJW and fluoxetine, respectively. <i>Conclusion:</i> In all these observations, the water-soluble formulations showed a significant antidepressant-like effect, including enhancement of neurotransmitter levels as compared to the similar dose of a conventional curcumin preparation. Thus, these formulations may be used as a novel treatment option in the management of mental depression.
DOI: 10.6084/m9.figshare.5123179
title: Supplementary Material for: From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes <b><i>(IGHG)</i></b> to Phenotypes in Childhood Asthma

description: <b><i>Background:</i></b> IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes <i>(IGHG)</i> on chromosome 14q32.3. Investigation of the alternative GM allotypes of γ3, γ1 and γ2 chains has disclosed new structural and functional IgG subclasses and B-cell variants, with possible effects on childhood asthma. <b><i>Objective:</i></b> To investigate different <i>IGHG</i> (GM) gene complexes in a childhood asthma population for allergy parameters. <b><i>Methods:</i></b><i>IGHG</i> alleles and correlated allotypic (allelic) IgG subclass levels were analyzed with a sensitive indirect competitive ELISA in 10-year-old children with bronchial asthma. Individual <i>IGHG</i> diplotype-, genotype- and haplotype-related B cells were compared for allelic IgG subclass levels, IgE sensitization, IgE, IgA and IgM levels, and numbers of peripheral blood eosinophils and lymphocytes. <b><i>Results:</i></b> The group with homozygous <i>IGHG</i>*<i>bfn/</i>*<i>bfn</i> (B1/B1 cells) demonstrated low IgG1*f levels (p &lt; 0.001) but increased IgG2*n levels (p &lt; 0.001) together with increasd IgE and <i>IGHG2</i>*<i>n </i>gene dose-dependent IgE sensitization (atopic phenotype). The <i>IGHG</i>*<i>bf–n</i>/*<i>bf–n</i> (B2/B2 cells) demonstrated low IgG1*f (p &lt; 0.05) and IgG2*–n (p &lt; 0.001) and the <i>IGHG</i>*<i>ga–n/</i>*<i>ga–n</i> (B4/B4 cells) low IgG1*a (p &lt; 0.001) and IgG2*–n (p &lt; 0.02) together with low IgE sensitization (non-atopic phenotype). B*<sup>bfn</sup> (B1) and B*<sup>bf–n</sup> (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*<sup>gan</sup> (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. <b><i>Conclusion:</i></b><i>IGHG</i> diplotypes present different phenotypes in childhood asthma. The <i>IGHG2</i>*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite <i>IGHG2</i>*<i>–n</i> presents non-IgE-mediated asthma and IgG subclass deficiencies.
DOI: 10.6084/m9.figshare.5123182
title: Supplementary Material for: High Indoor Microbial Levels Are Associated with Reduced Th1 Cytokine Secretion Capacity in Infancy

description: <b><i>Background:</i></b> Exposure to microbes and their components may affect the maturation of the immune system.<b> </b>We examined the association of house dust microbial content with cytokine-producing capacity at birth and at the age of 1 year. <b><i>Methods:</i></b> Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 at birth (n = 228) and at the age of 1 year (n = 200) following 24- and 48-hour whole-blood stimulation with staphylococcal enterotoxin B (SEB), lipopolysaccharide and the combination of phorbol ester and ionomycin was measured. Concentrations of ergosterol (marker for fungal biomass), muramic acid (marker for Gram-positive bacteria) and 3-hydroxy fatty acids with a carbon chain length from 10 to 14 (marker for Gram-negative bacteria) in living room floor dust were analyzed using gas chromatography-tandem mass spectrometry. Five single microbial species or groups were determined using a quantitative polymerase chain reaction method. <b><i>Results:</i></b> A high total level of the studied Gram-positive bacteria in general or <i>Mycobacterium </i>spp. in house dust was associated with decreased SEB-stimulated IFN-γ production, especially at the age of 1 year. The total level of indoor fungi analyzed <i>(Penicillium</i> spp<i>., Aspergillus </i>spp<i>. </i>and<i> Paecilomyces variotii</i> group, <i>Trichoderma viride/atroviride/koningii,</i><i>Wallemia sebi)</i> was also inversely associated with IFN-γ production at the age of 1 year, but this association did not remain significant after adjustment for potential confounders. A few associations were found between microbial exposures and other measured cytokines. <b><i>Conclusions:</i></b> High indoor microbial exposures may affect immune development in early life by reducing T helper type 1 cytokine secretion capacity. The observed hyporesponsiveness may reflect the adaptation of the immune system to environmental antigens. In future, more attention should be paid especially to the immunomodulatory role of exposures to Gram-positive bacteria.
DOI: 10.6084/m9.figshare.5123185.v1
title: Supplementary Material for: Aloe Emodin Induces G2/M Cell Cycle Arrest and Apoptosis via Activation of Caspase-6 in Human Colon Cancer Cells

description: Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study, we analyzed the molecular mechanisms involved in the growth-inhibitory activity of this hydroxyanthraquinone in colon cancer cell, WiDr. In our observation AE inhibited cell proliferation by arresting the cell cycle at the G2/M phase and inhibiting cyclin B1. AE appreciably induced cell death specifically through the induction of apoptosis and by activating caspases 9/6. Apoptotic execution was found to be solely dependent on caspase-6 rather than caspase-3 or caspase-7. This is the first study indicating that the AE induces apoptosis specifically through the activation of caspase-6.
DOI: 10.6084/m9.figshare.5123173
title: Supplementary Material for: Lack of Any Cardiac Involvement in a Patient with Andersen-Tawil Syndrome Associated with the c.574A→G Mutation in <i>KCNJ2</i>

description: The Andersen-Tawil syndrome (ATS) is characterized by hypo-normokaliemic muscle periodic paralysis, dysmorphic features and ventricular arrhythmias. Most cases are caused by mutations in <i>KCNJ2,</i> encoding for the potassium inwardly rectifying channel, Kir2.1 (ATS1). Although <i>KCNJ2</i> mutations show no obvious genotype-phenotype correlations and incomplete penetrance, signs of cardiac involvement are usually present in most ATS1 cases. In contrast, here we describe an Italian ATS1 patient, carrying a c.574A→G mutation in <i>KCNJ2,</i> who had both facial dysmorphisms and muscle periodic paralysis but who did not manifest any cardiac involvement, although the same mutation was originally described in a Japanese kindred, in which all affected individuals manifested a severe cardiac phenotype.
DOI: 10.6084/m9.figshare.5123170
title: Supplementary Material for: Prenatal Stress Produces Sexually Dimorphic and Regionally Specific Changes in Gene Expression in Hippocampus and Frontal Cortex of Developing Rat Offspring

description: Prenatal stress has been known to induce structural changes in the brain and lead to negative psychological well-being. To further understanding of the mechanisms that underlie these effects, whole genome microarray analysis was used to analyze gene expression changes in the developing brain. Epigenetic changes in the hippocampus and frontal cortex of offspring exposed to stress during gestation were investigated. Biological process ontology and pathway analysis was used to increase understanding of the changes produced in response to prenatal stress. The study identified over 700 genes in the frontal cortex and hippocampus that are differentially expressed following prenatal stress. The epigenetic changes demonstrate sex-dependent and region-specific profiles, exhibiting very little overlap between sexes and brain area. Frontal cortex changes were largely related to neurotransmitter function, whereas hippocampal changes were more prominent in females and concentrated around growth factors. These findings have important implications for generalized intervention strategies using a single methodology for all individuals.
DOI: 10.6084/m9.figshare.5123176
title: Supplementary Material for: First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome

description: Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the <i>TCOF1</i> gene and follows autosomal dominant inheritance. Recently, mutations in the <i>POLR1D </i>and<i> POLR1C</i> genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout <i>TCOF1</i>. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within <i>TCOF1</i> lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in <i>TCOF1</i>, <i>POLR1D</i> and <i>POLR1C</i>. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within <i>TCOF1</i>. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by <i>TCOF1.</i>
DOI: 10.6084/m9.figshare.5123167
title: Supplementary Material for: Comparative Analysis of a Putative Tuberculosis-Susceptibility Gene, <i>MC3R</i>, and Pseudogene Sequences in Cattle, African Buffalo, Hyena, Rhinoceros and Other African Bovids and Ruminants

description: Studies in humans have suggested the possible involvement of melanocortin-3-receptor (MC3R) and other components of the central melanocortin system in host defense against mycobacteria. We report a genomic DNA nucleotide sequence highly homologous to human <i>MC3R</i> in several bovids and non-bovid African wildlife species. Nucleotide sequence analysis indicates that the orthologous genes of cattle and buffalo are highly homologous (89.4 and 90%, respectively) to the human <i>MC3R</i> gene. Sequence results also identified a typical non-functional, duplicated pseudogene, <i>MC3RP</i>, in 7 species from the family Bovidae. No pseudogene was found in animals outside Bovidae. The presence of the pseudogene in tuberculosis-susceptible species could have possible immunomodulatory effects on susceptibility to bovine tuberculosis infection, as well as a considerable influence on energy metabolism and food conversion efficiency.
DOI: 10.6084/m9.figshare.5123170.v1
title: Supplementary Material for: Prenatal Stress Produces Sexually Dimorphic and Regionally Specific Changes in Gene Expression in Hippocampus and Frontal Cortex of Developing Rat Offspring

description: Prenatal stress has been known to induce structural changes in the brain and lead to negative psychological well-being. To further understanding of the mechanisms that underlie these effects, whole genome microarray analysis was used to analyze gene expression changes in the developing brain. Epigenetic changes in the hippocampus and frontal cortex of offspring exposed to stress during gestation were investigated. Biological process ontology and pathway analysis was used to increase understanding of the changes produced in response to prenatal stress. The study identified over 700 genes in the frontal cortex and hippocampus that are differentially expressed following prenatal stress. The epigenetic changes demonstrate sex-dependent and region-specific profiles, exhibiting very little overlap between sexes and brain area. Frontal cortex changes were largely related to neurotransmitter function, whereas hippocampal changes were more prominent in females and concentrated around growth factors. These findings have important implications for generalized intervention strategies using a single methodology for all individuals.