cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122996.v1
title: Supplementary Material for: Performance of Genotype Imputations Using Data from the 1000 Genomes Project

description: Genotype imputations based on 1000 Genomes (1KG) Project data have the advantage of imputing many more SNPs than imputations based on HapMap data. It also provides an opportunity to discover associations with relatively rare variants. Recent investigations are increasingly using 1KG data for genotype imputations, but only limited evaluations of the performance of this approach are available. In this paper, we empirically evaluated imputation performance using 1KG data by comparing imputation results to those using the HapMap Phase II data that have been widely used. We used three reference panels: the CEU panel consisting of 120 haplotypes from HapMap II and 1KG data (June 2010 release) and the EUR panel consisting of 566 haplotypes also from 1KG data (August 2010 release). We used Illumina 324,607 autosomal SNPs genotyped in 501 individuals of European ancestry. Our most important finding was that both 1KG reference panels provided much higher imputation yield than the HapMap II panel. There were more than twice as many successfully imputed SNPs as there were using the HapMap II panel (6.7 million vs. 2.5 million). Our second most important finding was that accuracy using both 1KG panels was high and almost identical to accuracy using the HapMap II panel. Furthermore, after removing SNPs with MACH Rsq &lt;0.3, accuracy for both rare and low frequency SNPs was very high and almost identical to accuracy for common SNPs. We found that imputation using the 1KG-EUR panel had advantages in successfully imputing rare, low frequency and common variants. Our findings suggest that 1KG-based imputation can increase the opportunity to discover significant associations for SNPs across the allele frequency spectrum. Because the 1KG Project is still underway, we expect that later versions will provide even better imputation performance.
DOI: 10.6084/m9.figshare.5122984
title: Supplementary Material for: The Role of Vascular Endothelial Growth Factors and Fibroblast Growth Factors in Angiogenesis during Otitis Media

description: The middle ear response to otitis media includes transformation and hyperplasia of the mucosal epithelium and subepithelial connective tissue. Significant neovascularization is also noted, which occurs both to support the hypertrophied mucosa and to mediate the increased trafficking of leukocytes. We investigated the role of two known potent angiogenic growth factor families, the fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), in middle ear mucosal angiogenesis. DNA microarrays were used to evaluate the expression of FGFs and VEGFs, as well as their receptors and unique signaling proteins, in the middle ears of mice undergoing a complete course of acute bacterial otitis media. In addition, a member of each family was introduced to the middle ear submucosal compartment of the normal middle ears of guinea pigs, by a continuous-release osmotic minipump system over 1 week. During the course of bacterial otitis media, a significant regulation of a number of genes important for angiogenesis was identified. Histologic evaluation of middle ear mucosa following micropump infusion of both FGF1 and VEGF-A showed significant angiogenesis at the site of infusion in comparison to control saline infusion. These results support a role for FGFs and VEGFs in the neovascularization of the middle ear mucosa during otitis media, and offer a potential avenue for therapeutic intervention.
DOI: 10.6084/m9.figshare.5122993.v1
title: Supplementary Material for: Vocal Parameters That Indicate Threat Level Correlate with FOS Immunolabeling in Social and Vocal Control Brain Regions

description: Transmitting information via communicative signals is integral to interacting with conspecifics, and some species achieve this task by varying vocalizations to reflect context. Although signal variation is critical to social interactions, the underlying neural control has not been studied. In response to a predator, black-capped chickadees <i>(Poecile atricapilla)</i> produce mobbing calls (<i>chick-a-dee </i>calls) with various parameters, some of which convey information about the threat stimulus. We predicted that vocal parameters indicative of threat would be associated with distinct patterns of neuronal activity within brain areas involved in social behavior and those involved in the sensorimotor control of vocal production. To test this prediction, we measured the syntax and structural aspects of <i>chick-a-dee</i> call production in response to a hawk model and assessed the protein product of the immediate early gene FOS in brain regions implicated in context-specific vocal and social behavior. These regions include the medial preoptic area (POM) and lateral septum (LS), as well as regions involved in vocal motor control, including the dorsomedial nucleus of the intercollicular complex and the HVC. We found correlations linking call rate (previously demonstrated to reflect threat) to labeling in the POM and LS. Labeling in the HVC correlated with the number of D notes per call, which may also signal threat level. Labeling in the call control region dorsomedial nucleus was associated with the structure of D notes and the overall number of notes, but not call rate or type of notes produced. These results suggest that the POM and LS may influence attributes of vocalizations produced in response to predators and that the brain region implicated in song control, the HVC, also influences call production. Because variation in <i>chick-a-dee</i> call rate indicates predator threat, we speculate that these areas could integrate with motor control regions to imbue mobbing signals with additional information about threat level.
DOI: 10.6084/m9.figshare.5122972
title: Supplementary Material for: Polymorphisms and Noncardioembolic Stroke in Three Case-Control Studies

description: <i>Background:</i> Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES). <i>Methods:</i> We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls). <i>Results:</i> Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in <i>HTT</i> (OR 1.39, 90% CI 1.12–1.71), rs2924914 near <i>CSMD1</i> (OR 1.22, 90% CI 1.04–1.43), rs1264352 near <i>DDR1</i> (OR 1.20, 90% CI 1.02–1.41), rs544115 in <i>NEU3</i> (OR 1.63, 90% CI 1.02–2.62), rs12481805 in <i>UMODL1</i> (OR 1.31, 90% CI 1.01–1.81), and rs2857595 near <i>NCR3</i> (OR 1.15, 90% CI 1.00–1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69. <i>Conclusions:</i> Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations.
DOI: 10.6084/m9.figshare.5122975
title: Supplementary Material for: T Cell Epitopes of the Timothy Grass Pollen Allergen Phl p 5 of Mice and Men and the Detection of Allergen-Specific T Cells Using Class II Ultimers

description: <i>Background:</i> Knowledge of allergen-specific T cell epitopes is a prerequisite not only for therapeutic approaches but also for elucidating immunological mechanisms of type I allergy. Ex vivo detection of allergen-specific T cells using class II tetramer technology has become an important tool for investigating immune responses in atopic and healthy individuals. <i>Methods:</i> Using <sup>3</sup>H-thymidine incorporation assays, T cell epitopes specific for the major timothy grass pollen allergen Phl p 5.0101 were mapped in 11 allergic donors and two different mouse strains. Different protocols for expansion/restimulation of T cells from the blood of allergic donors and detection of allergen-specific T cells by Class II Ultimer staining were evaluated. <i>Results:</i> We identified several new Phl p 5.0101 class II T cell epitopes in allergic patients and confirmed previously published ones. Additionally, we discovered the major T cell epitopes in BALB/c and C57BL/6 mice. Using a novel Class II Ultimer, we detected epitope-specific T cells expanded from the blood of an allergic donor. <i>Conclusions:</i> Epitope mapping of Phl p 5.0101 revealed an immunodominant epitope in BALB/c and C57BL/6 mice and an immunodominant region in humans (amino acids 259–282), which was recognized by 8 out of 11 allergic donors. Detection of Phl p 5-specific T cells was demonstrated using a Class II Ultimer specific for epitope 196–210. Successful detection of ultimer-positive T cells was strongly dependent on a resting phase after in vitro expansion.
DOI: 10.6084/m9.figshare.5122978
title: Supplementary Material for: Adrenarche and Puberty in Children with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

description: There have been only a few studies on adrenarche in girls with classic congenital adrenal hyperplasia (CAH) showing that dehydroepiandrosterone sulfate (DHEAS) levels did not rise at the physiological age of adrenarche. <i>Objective:</i> Longitudinal analysis of serum DHEAS levels and Tanner stages in CAH children. <i>Design:</i> We studied 98 CAH patients (52 females), aged between 1 month and 18.0 years. All patients had genetically proven classic CAH and received steroid substitution therapy. <i>Results:</i> Serum DHEAS levels did not differ between CAH children and healthy children from the age of 1 year until 5–6 years. Beginning at the age of 7–8 years, there was a continuous but blunted increase in DHEAS levels in CAH boys and girls compared to healthy children. There was no correlation of DHEAS levels with the genotype, glucocorticoid dosage, auxological data, or quality of metabolic control. Pubarche (PH2) as well as gonadarche (G2) and thelarche (B2) occurred significantly earlier in CAH boys and girls than in the reference group, but timing of menarche was normal. <i>Conclusions:</i> Pubarche and adrenarche are dissociated in classic CAH: earlier pubarche, gonadarche and thelarche, respectively, in both sexes contrast with the absence of typical adrenarche.
DOI: 10.6084/m9.figshare.5122981
title: Supplementary Material for: Should I Stay or Should I Go? Ephs and Ephrins in Neuronal Migration

description: In neuroscience, Ephs and ephrins are perhaps best known for their role in axon guidance. It was first shown in the visual system that graded expression of these proteins is instrumental in providing molecular coordinates that define topographic maps, particularly in the visual system, but also in the auditory, vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum and other structures. Perhaps unsurprisingly, the role of these proteins in regulating cell-cell interactions also has an impact on cell mobility, with evidence that Eph-ephrin interactions segregate cell populations based on contact-mediated attraction or repulsion. Consistent with these studies, evidence has accumulated that Ephs and ephrins play important roles in the migration of specific cell populations in the developing and adult brain. This review focusses on two examples of neuronal migration that require Eph/ephrin signalling – radial and tangential migration of neurons in cortical development and the migration of newly generated neurons along the rostral migratory stream to the olfactory bulb in the adult brain. We discuss the challenge involved in understanding how cells determine whether they respond to signals by migration or axon guidance.
DOI: 10.6084/m9.figshare.5122984.v1
title: Supplementary Material for: The Role of Vascular Endothelial Growth Factors and Fibroblast Growth Factors in Angiogenesis during Otitis Media

description: The middle ear response to otitis media includes transformation and hyperplasia of the mucosal epithelium and subepithelial connective tissue. Significant neovascularization is also noted, which occurs both to support the hypertrophied mucosa and to mediate the increased trafficking of leukocytes. We investigated the role of two known potent angiogenic growth factor families, the fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs), in middle ear mucosal angiogenesis. DNA microarrays were used to evaluate the expression of FGFs and VEGFs, as well as their receptors and unique signaling proteins, in the middle ears of mice undergoing a complete course of acute bacterial otitis media. In addition, a member of each family was introduced to the middle ear submucosal compartment of the normal middle ears of guinea pigs, by a continuous-release osmotic minipump system over 1 week. During the course of bacterial otitis media, a significant regulation of a number of genes important for angiogenesis was identified. Histologic evaluation of middle ear mucosa following micropump infusion of both FGF1 and VEGF-A showed significant angiogenesis at the site of infusion in comparison to control saline infusion. These results support a role for FGFs and VEGFs in the neovascularization of the middle ear mucosa during otitis media, and offer a potential avenue for therapeutic intervention.
DOI: 10.6084/m9.figshare.5122969
title: Supplementary Material for: Der inferenzbasierte Ansatz bei Zwangsstörungen

description: Obwohl die kognitive Verhaltenstherapie, häufig in der Form der Exposition und Reaktionsverhinderung, das in der Behandlung der Zwangsstörung am weitesten verbreitete Behandlungsverfahren darstellt, profitieren Betroffene mit bestimmten Subtypen der Zwangserkrankung (z.B. überwertigen Ideen oder ich-syntonen Zwangs-gedanken) davon nur unzureichend oder gar nicht. Aufgrund der begrenzten Erfolge von auf verhaltenstherapeutischen oder kognitiv-verhaltenstherapeutischen Modellen basierenden Verfahren hat sich die Forschung vermehrt ausschließlich kognitiven Theorien und Behandlungsmodellen zugewandt. Der inferenzbasierte Ansatz zur Behandlung der Zwangsstörung geht davon aus, dass zwangstypische Kognitionen und Bewertungen von vorausgehenden Zweifeln und Inferenzen herrühren. Dieser Ansatz konzentriert sich auf die fehlerhaften Denkprozesse, die dem zwanghaften Zweifeln zugrunde liegen, welches Zwangsverhalten auslöst. Die vorliegende Arbeit fasst den gegenwärtigen Stand des inferenzbasierten Modells und die es stützenden empirischen Befunde zusammen.
DOI: 10.6084/m9.figshare.5122972.v1
title: Supplementary Material for: Polymorphisms and Noncardioembolic Stroke in Three Case-Control Studies

description: <i>Background:</i> Gene variants associated with disease could reveal novel mechanisms. We searched for single nucleotide polymorphisms (SNPs) associated with noncardioembolic stroke (nonCES). <i>Methods:</i> We tested 24,926 SNPs in or near genes for association with nonCES in the Vienna Study (551 cases, 815 controls) and then evaluated the associated SNPs in the UCSF-CC Study (570 cases, 1,604 controls) first in pooled DNA samples and then in individual DNA samples. We then asked whether the risk alleles of the SNPs associated with increased risk in both studies were also associated with increased risk of nonCES in the German Study (728 cases, 1,041 controls). <i>Results:</i> Six of the 46 SNPs that were associated with nonCES in both the Vienna and the UCSF-CC Studies were also associated with nonCES in the German Study: rs362277 in <i>HTT</i> (OR 1.39, 90% CI 1.12–1.71), rs2924914 near <i>CSMD1</i> (OR 1.22, 90% CI 1.04–1.43), rs1264352 near <i>DDR1</i> (OR 1.20, 90% CI 1.02–1.41), rs544115 in <i>NEU3</i> (OR 1.63, 90% CI 1.02–2.62), rs12481805 in <i>UMODL1</i> (OR 1.31, 90% CI 1.01–1.81), and rs2857595 near <i>NCR3</i> (OR 1.15, 90% CI 1.00–1.32). Accounting for multiple testing of 46 SNPs, these 6 SNPs had a false discovery rate of 0.69. <i>Conclusions:</i> Some of the 6 SNPs may be associated with nonCES but most may be false positives. These 6 SNPs merit investigation in additional nonCES study populations.
DOI: 10.6084/m9.figshare.5122981.v1
title: Supplementary Material for: Should I Stay or Should I Go? Ephs and Ephrins in Neuronal Migration

description: In neuroscience, Ephs and ephrins are perhaps best known for their role in axon guidance. It was first shown in the visual system that graded expression of these proteins is instrumental in providing molecular coordinates that define topographic maps, particularly in the visual system, but also in the auditory, vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum and other structures. Perhaps unsurprisingly, the role of these proteins in regulating cell-cell interactions also has an impact on cell mobility, with evidence that Eph-ephrin interactions segregate cell populations based on contact-mediated attraction or repulsion. Consistent with these studies, evidence has accumulated that Ephs and ephrins play important roles in the migration of specific cell populations in the developing and adult brain. This review focusses on two examples of neuronal migration that require Eph/ephrin signalling – radial and tangential migration of neurons in cortical development and the migration of newly generated neurons along the rostral migratory stream to the olfactory bulb in the adult brain. We discuss the challenge involved in understanding how cells determine whether they respond to signals by migration or axon guidance.
DOI: 10.6084/m9.figshare.5122966
title: Supplementary Material for: Arbeitszeitrestriktion als Methode der Behandlung von Prokrastination

description: Prokrastination (pathologisches Aufschieben) ist eine klinisch bedeutsame Störung der Selbststeuerung, bei der die Betroffenen persönlich wichtige Arbeiten nicht oder nicht rechtzeitig und nur unter großem Druck erledigen. In üblichen Behandlungsansätzen werden vielfältige psychoedukative und kognitiv-behaviorale Methoden verwendet. Alternativ dazu stellen wir hier die Arbeitszeitrestriktion als Methode zur Behandlung von Prokrastination vor: Patienten dürfen <i>nur zu bestimmten Zeiten und nur für eine begrenzte Dauer</i> arbeiten. Erst nach einer Erhöhung ihrer Arbeitseffizienz, d.h. durch eine möglichst gute Ausnutzung der zuvor geplanten Arbeitszeiten, können sie sich zusätzliche Arbeitszeit verdienen. Die Verknappung der Arbeitszeit bewirkt einen Perspektivwechsel von «Ich <i>muss</i> (eigentlich dauernd) lernen» zu «Ich <i>darf</i> (nur jetzt) lernen». Die kurze Intervention im Umfang von nur 5 Sitzungen ist sowohl im Gruppensetting als auch im Einzelsetting durchführbar; wir beschreiben hier die Anwendung im Gruppenformat. Die Evaluation der Arbeitszeitbegrenzung im Gruppensetting erbrachte überzeugende Effektstärken in den Selbstbeurteilungsinstrumenten und im täglich in einem Online-Arbeitstagebuch protokollierten Lern- und Arbeitsverhalten.
DOI: 10.6084/m9.figshare.5122978.v1
title: Supplementary Material for: Adrenarche and Puberty in Children with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

description: There have been only a few studies on adrenarche in girls with classic congenital adrenal hyperplasia (CAH) showing that dehydroepiandrosterone sulfate (DHEAS) levels did not rise at the physiological age of adrenarche. <i>Objective:</i> Longitudinal analysis of serum DHEAS levels and Tanner stages in CAH children. <i>Design:</i> We studied 98 CAH patients (52 females), aged between 1 month and 18.0 years. All patients had genetically proven classic CAH and received steroid substitution therapy. <i>Results:</i> Serum DHEAS levels did not differ between CAH children and healthy children from the age of 1 year until 5–6 years. Beginning at the age of 7–8 years, there was a continuous but blunted increase in DHEAS levels in CAH boys and girls compared to healthy children. There was no correlation of DHEAS levels with the genotype, glucocorticoid dosage, auxological data, or quality of metabolic control. Pubarche (PH2) as well as gonadarche (G2) and thelarche (B2) occurred significantly earlier in CAH boys and girls than in the reference group, but timing of menarche was normal. <i>Conclusions:</i> Pubarche and adrenarche are dissociated in classic CAH: earlier pubarche, gonadarche and thelarche, respectively, in both sexes contrast with the absence of typical adrenarche.
DOI: 10.6084/m9.figshare.5122960
title: Supplementary Material for: Growth Kinetics in Von Hippel-Lindau-Associated Renal Cell Carcinoma

description: <i>Objective:</i> To evaluate the growth kinetics of renal cell carcinoma (RCC) in von Hippel-Lindau (VHL) disease in a large trial by CT/MRI scan. VHL disease is a multisystemic disorder predisposing to renal cysts and cancer. There is a general assumption that VHL-associated RCC presents slower growth rates than sporadic RCC. <i>Patients and Methods:</i> We describe growth kinetics of 96 renal tumours in 64 VHL patients with analysed germline mutation (54/64 treated, 10/64 active surveillance) over a mean follow-up of 54.9 months. We calculated tumour volume, growth rate, multiplication of tumour volume per year and overall, as well as tumour volume doubling time. <i>Results:</i> The mean growth rate of 96 tumours was 4.4 mm/year (SD 3.2, median 4.1 mm/year), mean volume doubling time was 25.7 months (SD 20.2, median 22.2 months). We saw a median 1.4-fold increase in tumour volume per year. At treatment time point, VHL kidneys comprised 39% tumour and 15.7% cyst volume fraction. We saw no correlation between tumour size and growth parameters. <i>Conclusion:</i> VHL-associated RCC show large variances in tumour growth behaviour. Compared to the literature, in our study the growth rates (mm/year) of RCC in VHL disease did not differ from those of sporadic RCC. Fast tumour growth increases the risk for metastases.
DOI: 10.6084/m9.figshare.5122975.v1
title: Supplementary Material for: T Cell Epitopes of the Timothy Grass Pollen Allergen Phl p 5 of Mice and Men and the Detection of Allergen-Specific T Cells Using Class II Ultimers

description: <i>Background:</i> Knowledge of allergen-specific T cell epitopes is a prerequisite not only for therapeutic approaches but also for elucidating immunological mechanisms of type I allergy. Ex vivo detection of allergen-specific T cells using class II tetramer technology has become an important tool for investigating immune responses in atopic and healthy individuals. <i>Methods:</i> Using <sup>3</sup>H-thymidine incorporation assays, T cell epitopes specific for the major timothy grass pollen allergen Phl p 5.0101 were mapped in 11 allergic donors and two different mouse strains. Different protocols for expansion/restimulation of T cells from the blood of allergic donors and detection of allergen-specific T cells by Class II Ultimer staining were evaluated. <i>Results:</i> We identified several new Phl p 5.0101 class II T cell epitopes in allergic patients and confirmed previously published ones. Additionally, we discovered the major T cell epitopes in BALB/c and C57BL/6 mice. Using a novel Class II Ultimer, we detected epitope-specific T cells expanded from the blood of an allergic donor. <i>Conclusions:</i> Epitope mapping of Phl p 5.0101 revealed an immunodominant epitope in BALB/c and C57BL/6 mice and an immunodominant region in humans (amino acids 259–282), which was recognized by 8 out of 11 allergic donors. Detection of Phl p 5-specific T cells was demonstrated using a Class II Ultimer specific for epitope 196–210. Successful detection of ultimer-positive T cells was strongly dependent on a resting phase after in vitro expansion.