cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127505
title: Supplementary Material for: Time Trends in Incidence of Pathological and Etiological Stroke Subtypes during 16 Years: The Erlangen Stroke Project

description: <b><i>Background:</i></b> Population-based data, which continuously monitors<b> </b>time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. <b><i>Methods:</i></b> Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. <b><i>Results:</i></b> Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95% CI 1.39-3.90). <b><i>Conclusions:</i></b> Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.
DOI: 10.6084/m9.figshare.5127508.v1
title: Supplementary Material for: <b><i>MAN1B1</i></b> Mutation Leads to a Recognizable Phenotype: A Case Report and Future Prospects

description: Intellectual disability (ID) is one of the most common reasons for referral to genetic counseling. Nevertheless, in over 50% of the cases no diagnosis can be made. Here, we present how exome sequencing in combination with medical genetics evaluation led to the identification of a known pathogenic homozygous mutation in <i>MAN1B1 </i>in a consanguineous Turkish family. The phenotype comprised mild ID, truncal obesity and facial dysmorphism, comparable to that of the patients in the 3 recent publications on mutations in this gene. Clinically, the majority of patients in the literature showed congenital disorder of glycosylation syndrome type 2. In this study, we summarize the current knowledge about <i>MAN1B1</i> mutations from the literature as well as databases and suggest that exome sequencing should be implemented in a larger scale in routine diagnostics, since autosomal recessive ID has proven to be extremely heterogeneous. Even syndromic patterns may only become recognizable retrospectively.
DOI: 10.6084/m9.figshare.5127496
title: Supplementary Material for: Stage-Specific Effects of Fibroblast Growth Factor 2 on the Differentiation of Dental Pulp Cells

description: Dentinogenesis is a complex and multistep process, which is regulated by various growth factors, including members of the fibroblast growth factor (FGF) family. Both positive and negative effects of FGFs on dentinogenesis have been reported, but the underlying mechanisms of these conflicting results are still unclear. To gain a better insight into the role of FGF2 in dentinogenesis, we used dental pulp cells from various transgenic mice, in which fluorescent protein expression identifies cells at different stages of odontoblast differentiation. Our results showed that the continuous exposure of pulp cells to FGF2 inhibited mineralization and revealed both the stimulatory and inhibitory effects of FGF2 on the expression of markers of dentinogenesis and various transgenes. During the proliferation phase of in vitro growth, FGF2 increased the expression of markers of dentinogenesis and the percentages of dentin matrix protein 1/green fluorescent protein (DMP1-GFP)-positive functional odontoblasts and dentin sialophosphoprotein (DSPP)-Cerulean-positive odontoblasts. Additional exposure to FGF2 during the differentiation/mineralization phase of in vitro growth decreased the extent of mineralization and the expression of markers of dentinogenesis and of the DMP1-GFP and DSPP-Cerulean transgenes. Recovery experiments showed that the inhibitory effects of FGF2 on dentinogenesis were related to the blocking of the differentiation of cells into mature odontoblasts. These observations together showed the stage-specific effects of FGF2 on dentinogenesis by dental pulp cells, and they provide critical information for the development of improved treatments for vital pulp therapy and dentin regeneration.
DOI: 10.6084/m9.figshare.5127499
title: Supplementary Material for: Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

description: <b><i>Background:</i></b> Vitamin D seems to influence the evolution of atopic dermatitis (AD) in children. <b><i>Methods:</i></b> We tested the vitamin D serum levels of 39 children with AD (AD group t₀) and of 20 nonallergic healthy controls (C group). AD severity was evaluated using the AD scoring system (SCORAD index). Cytokine serum levels (IL-2, IL-4, IL-6, IFN-γ, TNF-α) and atopy biomarkers were also measured. The patients were then treated with vitamin D oral supplementation of 1,000 IU/day (25 mg/day) for 3 months. We then reevaluated the vitamin D serum levels, AD severity and cytokine serum levels in all of the treated children (AD group t<sub>1</sub>). <b><i>Results:</i></b> The cross-sectional analysis on patients affected by AD (AD group t₀) showed that the initial levels of all the tested cytokines except for TNF-α were higher than those of the healthy control group (C group), falling outside the normal range. After 3 months of supplementation the patients had significantly increased vitamin D levels (from 22.97 ± 8.03 to 29.41 ± 10.73 ng/ml; p = 0.01). A concomitant significant reduction of both the SCORAD index (46.13 ± 15.68 at the first visit vs. 22.57 ± 15.28 at the second visit; p &lt; 0.001) and of all the altered cytokines (IL-2, IL-4, IL-6, IFN-γ) was also found. <b><i>Conclusions:</i></b> This study showed vitamin D supplementation to be an effective treatment in reducing AD severity in children through normalization of the Th1 and Th2 interleukin serum pattern.
DOI: 10.6084/m9.figshare.5127502.v1
title: Supplementary Material for: Innate IgG Molecules and Innate B Cells Expressed by Immunoglobulin Constant Heavy G Chain (Fcγ) Genetic Marker Genes Are Involved in the ‘Allergic March' of IgE Sensitization in Children

description: <b><i>Background:</i></b> Interindividual variations of immunoglobulin constant heavy G chain <i>(IGHG)</i> genes on chromosome 14q32.3 are identified by alternative genetic markers (GM) of IgG3, IgG1 and IgG2, respectively. They express structurally and functionally innate IgG molecules and B cells, associated with allergic disease, replicated in several studies. <b><i>Materials and Methods:</i></b> 1-year-old and 10-year-old, IgE-sensitized and non-sensitized children from the German Multicenter Allergy Study birth cohort were assessed by new serological methods for the mendelian<i> IGHG</i> (Fcγ) (GM) genes, as innate IgG molecules and innate B cells. <b><i>Results:</i></b> Food allergy sensitization in thirty-five 1-year-old children (124 not sensitized) was associated with the <i>IGHG</i>*<i>bfn</i> haplotype and B*<sup>bfn</sup> cells (OR 1.9, 95% CI 1.2-3.1; p = 0.010). Aeroallergen sensitization in ninety-nine 10-year-old children (95 not sensitized) was associated with the same genes (OR 1.4, 95% CI 1.02-1.9; p = 0.034). The IgE sensitization was most prominent in the restrictive homozygous <i>IGHG</i>*<i>bfn/</i>*<i>bfn </i>diplotype, 34% at age 1, increasing to 60% at age 10, rating the highest numbers of positive IgE tests, expressing increased levels of IgE and innate IgG2*n. <b><i>Conclusions:</i></b> The <i>IGHG</i>*<i>bfn </i>haplotype (B*<sup>bfn</sup> cells) and increased innate IgG2*n levels are predictive factors for IgE sensitization in childhood. <i>IGHG</i> genes can be assessed for prognostic and preventive purposes in clinical care.
DOI: 10.6084/m9.figshare.5127493
title: Supplementary Material for: Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review

description: <b><i>Background:</i></b> Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. <b><i>Methods:</i></b> The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms' OR ‘withdrawal syndrome' OR ‘discontinuation syndrome' OR ‘discontinuation symptoms', AND ‘SSRI' OR ‘serotonin' OR ‘antidepressant' OR ‘paroxetine' OR ‘fluoxetine' OR ‘sertraline' OR ‘fluvoxamine' OR ‘citalopram' OR ‘escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. <b><i>Results:</i></b> There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. <b><i>Conclusions:</i></b> Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome'.
DOI: 10.6084/m9.figshare.5127490
title: Supplementary Material for: A Comprehensive Whole-Genome Integrated Cytogenetic Map for the Alpaca<b><i> (Lama pacos)</i></b>

description: Genome analysis of the alpaca (<i>Lama pacos</i>, LPA) has progressed slowly compared to other domestic species. Here, we report the development of the first comprehensive whole-genome integrated cytogenetic map for the alpaca using fluorescence in situ hybridization (FISH) and CHORI-246 BAC library clones. The map is comprised of 230 linearly ordered markers distributed among all 36 alpaca autosomes and the sex chromosomes. For the first time, markers were assigned to LPA14, 21, 22, 28, and 36. Additionally, 86 genes from 15 alpaca chromosomes were mapped in the dromedary camel (<i>Camelus dromedarius</i>, CDR), demonstrating exceptional synteny and linkage conservation between the 2 camelid genomes. Cytogenetic mapping of 191 protein-coding genes improved and refined the known Zoo-FISH homologies between camelids and humans: we discovered new homologous synteny blocks (HSBs) corresponding to HSA1-LPA/CDR11, HSA4-LPA/CDR31 and HSA7-LPA/CDR36, and revised the location of breakpoints for others. Overall, gene mapping was in good agreement with the Zoo-FISH and revealed remarkable evolutionary conservation of gene order within many human-camelid HSBs. Most importantly, 91 FISH-mapped markers effectively integrated the alpaca whole-genome sequence and the radiation hybrid maps with physical chromosomes, thus facilitating the improvement of the sequence assembly and the discovery of genes of biological importance.
DOI: 10.6084/m9.figshare.5127493.v1
title: Supplementary Material for: Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review

description: <b><i>Background:</i></b> Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. <b><i>Methods:</i></b> The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms' OR ‘withdrawal syndrome' OR ‘discontinuation syndrome' OR ‘discontinuation symptoms', AND ‘SSRI' OR ‘serotonin' OR ‘antidepressant' OR ‘paroxetine' OR ‘fluoxetine' OR ‘sertraline' OR ‘fluvoxamine' OR ‘citalopram' OR ‘escitalopram'. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. <b><i>Results:</i></b> There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. <b><i>Conclusions:</i></b> Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome' that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome'.
DOI: 10.6084/m9.figshare.5127505.v1
title: Supplementary Material for: Time Trends in Incidence of Pathological and Etiological Stroke Subtypes during 16 Years: The Erlangen Stroke Project

description: <b><i>Background:</i></b> Population-based data, which continuously monitors<b> </b>time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. <b><i>Methods:</i></b> Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. <b><i>Results:</i></b> Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95% CI 1.39-3.90). <b><i>Conclusions:</i></b> Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.
DOI: 10.6084/m9.figshare.5127478
title: Supplementary Material for: Monitoring of Hematopoietic Chimerism by Real-Time Quantitative PCR of Micro Insertions/Deletions in Samples with Low DNA Quantities

description: <b><i>Background:</i></b> Sensitive and accurate methods to detect hematopoietic chimerism after hematopoietic stem cell transplantation (HSCT) are essential to evaluate engraftment and to monitor response to therapeutic procedures such as donor lymphocyte infusion. Continuous long-term follow up, however, requires large amounts of pre-HSCT samples limiting the application of many widely used techniques for sensitive chimerism monitoring. <b><i>Methods: </i></b>DNAs from 42 normal healthy donors and 16 HSCT donor/recipient pairs were employed to validate the use of allele-specific insertion/deletion (indel) quantitative real-time polymerase chain reaction (qPCR) to quantify chimerism in samples with low amounts of DNA. Consequently, indel-qPCR analyses of samples from 16 HSCT patients were compared to short-tandem repeat (STR) specific PCR analyses. <b><i>Results</i></b>: Typing with reduced amounts of input DNA (15 vs. 60 ng) allowed for the reliable distinction of positive (mean threshold cycle (ct) 28.05) and negative (ct &gt;36) signals. The high informativity of primer/probe sets, with 12 out of 19 markers exceeding 20% informativity, was confirmed in our cohort (n = 74). Importantly, a fourfold reduction of input DNA compared to published protocols did not alter PCR efficiencies and allowed for a more sensitive detection of chimerism in 7 of 16 HSCT patients compared to results obtained by STR-PCR. <b><i>Conclusions</i></b>: Our data suggest that indel-qPCR is a more sensitive technique for the detection of hematopoietic chimerism compared to STR-PCR and works efficiently for samples with low amounts of DNA.
DOI: 10.6084/m9.figshare.5127481
title: Supplementary Material for: Prenatal Diagnosis of a Female Fetus with Ring Chromosome 9, 46,XX,r(9)(p24q34), and a de novo Interstitial 9p Deletion

description: Ring chromosomes are circular structures formed as a result of breaks in the chromosome arms and the fusion of the proximal broken ends with a loss of distal material, or by fusion of dysfunctional telomeres without any loss. The mechanism underlying this process has not yet been sufficiently explained. Commonly, rings occur as acquired genetic abnormalities; however, sometimes they are found as constitutional aberrations with a prevalence of around 1:50,000 live births. Here, we present a new case of r(9) in a female fetus with intrauterine growth retardation and slight craniofacial dysmorphisms. Both parents had a normal phenotype. Amniotic fluid karyotype showed r(9)(p24q34). An array CGH revealed 3 deletion segments: a ring chromosome with a 2.57-Mb deletion at 9pterp24.2 (chr9:163,131-2,729,722), a 2.60-Mb deletion at 9q34.3qter (chr9:138,523,302-141,122,055), and also a 0.15-Mb interstitial deletion at 9p24.1 (chr9:5,090,443-5,235,765). These deletions overlap with proposed regions for the 9p24.3 deletion and Kleefstra syndrome. Segregation analysis revealed a maternal origin of the rearranged chromosome. We conclude that both the ring chromosome and the interstitial deletion occurred de novo<i>. </i>This last deletion has not been reported before. Prenatal array CGH, combined with fine mapping of breakpoints contributes to the assessment of genotype-phenotype correlations.
DOI: 10.6084/m9.figshare.5127484
title: Supplementary Material for: Neuroendocrine Merkel Cell Carcinoma Is Associated with Mutations in Key DNA Repair, Epigenetic and Apoptosis Pathways: A Case-Based Study Using Targeted Massively Parallel Sequencing

description: <b><i>Introduction:</i></b> Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma with a poorly understood molecular etiology. We implemented a comprehensive deep sequencing approach to identify mutations in the tumor DNA from a cohort of patients treated at our institution over the past 15 years. Our results indicate mutations that may constitute therapeutic targets in MCC. <b><i>Methods:</i></b> Five patients were treated for MCC within the study interval. Patients with adequate tissue (n = 4), positive neuroendocrine differentiation (chromogranin, synaptophysin, and cytokeratin 20), and histopathological confirmation of MCC were included in the study. DNA was extracted from archival tumor tissue samples and analyzed by massively parallel sequencing using a targeted, multiplex PCR approach followed by semiconductor sequencing. <b><i>Results:</i></b> We demonstrate high-penetrance nonsense mutations in PDE4DIP (n = 4) as well as various missense mutations in the DNA damage response (PRKDC, AURKB, ERCC5, ATR, and ATRX) and epigenetic modulating enzymes (MLL3). <b><i>Conclusion:</i></b> We describe several mutations in potential disease-relevant genes and pathways. These targets should be evaluated in a larger cohort to determine their role in the molecular pathogenesis of MCC.
DOI: 10.6084/m9.figshare.5127487
title: Supplementary Material for: SRS06, a New Semisynthetic Andrographolide Derivative with Improved Anticancer Potency and Selectivity, Inhibits Nuclear Factor-κB Nuclear Binding in the A549 Non-Small Cell Lung Cancer Cell Line

description: <b><i>Background:</i></b> Andrographolide has been reported with anticancer and anti-inflammatory properties through the inhibition of the activity of signaling molecules such as v-Src, nuclear factor-κB (NF-κB), STAT3, and PI3K. NF-κB has been proven to promote cancer cell survival, and targeting this pathway will halt the growth of cancer cells. Efforts have been made to produce semisynthetic derivatives of andrographolide with improved anticancer potency and selectivity. Subsequently, the effect of a selected derivative, 3,14,19-tripropionylandrographolide (SRS06), was tested for its action against NF-κB. <b><i>Methods:</i></b> Screening against 60 US National Cancer Institute (NCI) human cancer cell lines representing leukemia and non-small cell lung (NSCL), colon, CNS, melanoma, ovarian, renal, prostate, and breast cancers was performed to determine the tumor type selectivity and potency of SRS06. Microculture tetrazolium, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and sulforhodamine B assays were used to determine the in vitro anticancer activity, while Western blot studies were performed to ascertain the inhibitory effect of SRS06 on the NF-κB signaling cascade. The TransAM™ p65 assay kit was used to determine NF-κB p65 DNA binding activity in the NSCL cancer cell line A549. <b><i>Results:</i></b> From the NCI screening, SRS06 was found to exhibit potent growth-inhibitory effects on multiple cancer cell lines with 10-fold lower 50% growth inhibition (GI<sub>50</sub>) compared with andrographolide. It was also discerned that the compound preferentially targeted melanoma, CNS, renal, colon, ovarian, prostate, and NSCL cancer cell lines. The DNA fragmentation assay indicated that the main mode of cell death of SRS06-treated A549 cells was via apoptosis. At 5 µmol/l the compound decreased NF-κB protein expression and caused a significant reduction in the nuclear p65 DNA binding activity. <b><i>Conclusion:</i></b> SRS06 displayed improved anticancer selectivity and potency when compared with andrographolide. We alluded its anticancer activity to its effect of inhibiting NF-κB nuclear binding.