cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125639
title: Supplementary Material for: Association Analysis of Ten Candidate Genes in a Large Multinational Cohort of Small for Gestational Age Children and Children with Idiopathic Short Stature (NESTEGG study)

description: <b><i>Background:</i></b> Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. <b><i>Patients and Methods:</i></b> We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (<i>GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ </i>and<i> INS</i>) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. <b><i>Results:</i></b> We found several clinical associations for <i>GH1, GHR, IGF1, IGF1R, PPARγ </i>and <i>MAPK1.</i> One SNP remained significant after Bonferroni's correction: <i>IGF1R</i> SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. <b><i>Conclusion:</i></b><i>IGF1R</i> SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.
DOI: 10.6084/m9.figshare.5125642
title: Supplementary Material for: The Sitting Height/Height Ratio for Age in Healthy and Short Individuals and Its Potential Role in Selecting Short Children for <b><i>SHOX</i></b> Analysis

description: <b><i>Aims:</i></b> To determine the presence of abnormal body proportion, assessed by sitting height/height ratio for age and sex (SH/H SDS) in healthy and short individuals, and to estimate its role in selecting short children for <i>SHOX</i> analysis. <b><i>Methods:</i></b> Height, sitting height and weight were evaluated in 1,771 healthy children, 128 children with idiopathic short stature (ISS), 58 individuals with <i>SHOX</i> defects (SHOX-D) and 193 females with Turner syndrome (TS). <b><i>Results:</i></b> The frequency of abnormal body proportion, defined as SH/H SDS &gt;2, in ISS children was 16.4% (95% CI 10-22%), which was higher than in controls (1.4%, 95% CI 0.8-1.9%, p &lt; 0.001). The <i>SHOX</i> gene was evaluated in all disproportionate ISS children and defects in this gene were observed in 19%. Among patients with SHOX-D, 88% of children (95% CI 75-100%) and 96% of adults had body disproportion. In contrast, SH/H SDS &gt;2 were less common in children (48%, 95% CI 37-59%) and in adults (28%, 95% CI 20-36%) with TS. <b><i>Conclusion:</i></b> Abnormal body proportions were observed in almost all individuals with SHOX-D, 50% of females with TS and 16% of children considered ISS. Defects in <i>SHOX</i> gene were identified in 19% of ISS children with SH/H SDS &gt;2, suggesting that SH/H SDS is a useful tool to select children for undergoing <i>SHOX</i> molecular studies.
DOI: 10.6084/m9.figshare.5125645.v1
title: Supplementary Material for: Branchio-Otic Syndrome Caused by a Genomic Rearrangement: Clinical Findings and Molecular Cytogenetic Studies in a Patient with a Pericentric Inversion of Chromosome 8

description: Branchio-oto-renal (BOR) syndrome is an autosomal dominantly inherited developmental disorder, which is characterized by anomalies of the ears, the branchial arches and the kidneys. It is caused by mutations in the genes <i>EYA1,</i><i>SIX1</i> and <i>SIX5</i>. Genomic rearrangements of chromosome 8 affecting the <i>EYA1</i> gene have also been described. Owing to this fact, methods for the identification of abnormal copy numbers such as multiplex ligation-dependent probe amplification (MLPA) have been introduced as routine laboratory techniques for molecular diagnostics of BOR syndrome. The advantages of these techniques are clear compared to standard cytogenetic and array approaches as well as Southern blot. MLPA detects deletions or duplications of a part or the entire gene of interest, but not balanced structural aberrations such as inversions and translocations. Consequently, disruption of a gene by a genomic rearrangement may escape detection by a molecular genetic analysis, although this gene interruption results in haploinsufficiency and, therefore, causes the disease. In a patient with clinical features of BOR syndrome, such as hearing loss, preauricular fistulas and facial dysmorphisms, but no renal anomalies, neither sequencing of the 3 genes linked to BOR syndrome nor array comparative genomic hybridization and MLPA were able to uncover a causative mutation. By routine cytogenetic analysis, we finally identified a pericentric inversion of chromosome 8 in the affected female. High-resolution multicolor banding confirmed the chromosome 8 inversion and narrowed down the karyotype to 46,XX,inv(8)(p22q13). By applying fluorescence in situ hybridization, we narrowed down both breakpoints on chromosome 8 and found the <i>EYA1 </i>gene in q13.3 to be directly disrupted. We conclude that standard karyotyping should not be neglected in the genetic diagnostics of BOR syndrome or other Mendelian disorders, particularly when molecular testing failed to detect any causative alteration in patients with a convincing phenotype.
DOI: 10.6084/m9.figshare.5125633
title: Supplementary Material for: Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way

description: <b><i>Objective:</i></b> Considering a causal role of androgens in thymic involution, age-related remodeling of peripheral T-cell compartments in the absence of testicular hormones was evaluated. <b><i>Methods:</i></b> Rats were orchidectomized (ORX) at the age of 1 month, and T-peripheral blood lymphocytes (PBLs) and splenocytes from young (75-day-old) and aged (24-month-old) rats were examined for differentiation/activation and immunoregulatory marker expression. <b><i>Results:</i></b> In ORX rats, following the initial rise, the counts of CD4+ and CD8+ PBLs diminished with aging. This reflected the decline in thymic export as shown by recent thymic emigrant (RTE) enumeration. Orchidectomy increased the count of both of the major T-splenocyte subsets in young rats, and they (differently from controls) remained stable with aging. The CD4+:CD8+ T-splenocyte ratio in ORX rats shifted towards CD4+ cells compared to age-matched controls. Although in the major T-cell subsets in the blood and spleen from aged ORX rats the numbers of RTEs were comparable to the corresponding values in age-matched controls, the numbers of mature naïve and memory/activated cells substantially differed. Compared with age-matched controls, in aged ORX rats the numbers of CD4+ mature naïve PBLs and splenocytes were reduced, whereas those of CD4+ memory/activated cells (predictive of early mortality) were increased. Additionally, in spleens from aged ORX rats, despite unaltered thymic export, CD4+CD25+FoxP3+ and natural killer T cell counts were greater than in age-matched controls. <b><i>Conclusion:</i></b> (i) Age-related decline in thymopoietic efficacy is not dependent on androgen presence, and (ii) androgens are involved in the maintenance of peripheral T-cell (particularly CD4+ cell) homeostasis during aging.
DOI: 10.6084/m9.figshare.5125636
title: Supplementary Material for: Health Economic Analysis on a Psychosocial Intervention for Family Caregivers of Persons with Dementia

description: <b><i>Background/Aims:</i></b> Psychosocial intervention has shown positive effects on the caregivers' burden and satisfaction. The aims of this study were to describe the cost and cost-effectiveness of such an intervention. <b><i>Methods:</i></b> We analyzed resource use and costs of formal care for 308 persons with dementia and their caregivers' health-related quality of life (HRQoL). <b><i>Results:</i></b> The costs of home help services were lower in the subgroup of spouse caregivers in the intervention group and the cost of nursing home placement was lower in the intervention group. While the person with dementia lived at home, caregivers in the intervention group reported a higher HRQoL (p &lt; 0.01). After the person with dementia had moved to a nursing home, spouses in the control group had a lower HRQoL (p &lt; 0.001). <b><i>Conclusion:</i></b> The result can be interpreted as a positive effect of the intervention focusing on the identified specific needs of the family caregivers.
DOI: 10.6084/m9.figshare.5125654.v1
title: lengths_hap

description: number of SNPs for each chromosome
DOI: 10.6084/m9.figshare.5125636.v1
title: Supplementary Material for: Health Economic Analysis on a Psychosocial Intervention for Family Caregivers of Persons with Dementia

description: <b><i>Background/Aims:</i></b> Psychosocial intervention has shown positive effects on the caregivers' burden and satisfaction. The aims of this study were to describe the cost and cost-effectiveness of such an intervention. <b><i>Methods:</i></b> We analyzed resource use and costs of formal care for 308 persons with dementia and their caregivers' health-related quality of life (HRQoL). <b><i>Results:</i></b> The costs of home help services were lower in the subgroup of spouse caregivers in the intervention group and the cost of nursing home placement was lower in the intervention group. While the person with dementia lived at home, caregivers in the intervention group reported a higher HRQoL (p &lt; 0.01). After the person with dementia had moved to a nursing home, spouses in the control group had a lower HRQoL (p &lt; 0.001). <b><i>Conclusion:</i></b> The result can be interpreted as a positive effect of the intervention focusing on the identified specific needs of the family caregivers.
DOI: 10.6084/m9.figshare.5125639.v1
title: Supplementary Material for: Association Analysis of Ten Candidate Genes in a Large Multinational Cohort of Small for Gestational Age Children and Children with Idiopathic Short Stature (NESTEGG study)

description: <b><i>Background:</i></b> Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. <b><i>Patients and Methods:</i></b> We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (<i>GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ </i>and<i> INS</i>) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. <b><i>Results:</i></b> We found several clinical associations for <i>GH1, GHR, IGF1, IGF1R, PPARγ </i>and <i>MAPK1.</i> One SNP remained significant after Bonferroni's correction: <i>IGF1R</i> SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. <b><i>Conclusion:</i></b><i>IGF1R</i> SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.
DOI: 10.6084/m9.figshare.5125630
title: Supplementary Material for: Environmental and Occupational Risk Factors for Amyotrophic Lateral Sclerosis: A Case-Control Study

description: <b><i>Background/Aims:</i></b> Environmental and occupational exposures are implicated as risk factors for amyotrophic lateral sclerosis (ALS), the etiology of which is largely unknown, although no causal relationships have been established. <b><i>Objective:</i></b> The aim of the study was to evaluate the associations of personal risk factors and self-reported environmental and occupational exposures with risk of ALS. <b><i>Methods:</i></b> The cases involved ALS patients (n = 66) identified from major neurological centers in Pittsburgh and Philadelphia, Pa., USA, from 2008 to 2010. The age-, race- and sex-matched controls included outpatient hospital and population-based controls (n = 66). A detailed questionnaire obtaining data on occupation, vocational and avocational exposure as well as personal lifestyle factors was administered. <b><i>Results:</i></b> Occupational exposure to metals (odds ratio, OR = 3.65; 95% CI: 1.15, 11.60) and pesticides (OR = 6.50; 95% CI: 1.78, 23.77) was related to increased risk of ALS after controlling for smoking and education. No associations were found for occupational exposure to organic or aromatic solvents. <b><i>Conclusion:</i></b> Workers exposed to metals and pesticides may be at greater risk of ALS. Future research should involve more accurate exposure assessment through the use of job exposure matrices, confirmation of occupation and biomarkers.
DOI: 10.6084/m9.figshare.5125654.v3
title: input for PolyGEE

description: 1.) number of SNPs for each chromosome in lengths_hap2.) file paths to haplotype files in files_hap<br><br>3.) haplotype data for all 22 chromosomes from 1000 Genomes phase 3 ( http://www.internationalgenome.org/ )
DOI: 10.6084/m9.figshare.5125627
title: Supplementary Material for: Headache from the Doctors' Perspective

description: <b><i>Background:</i></b> General practitioners (GPs) and neurologists are involved in treating headache patients in Portugal. Having migraine themselves might influence the way they perceive and treat migraine patients. <b><i>Objective:</i></b> To identify clinicians' perceptions about migraine, their own headache status and management of their own migraine. <b><i>Methods:</i></b> An observational cross-sectional survey of GPs and neurologists using anonymous questionnaires including demographic data, headache and migraine status and migraine perception questions. <b><i>Results:</i></b> Of 348 respondent physicians, 20% were neurologists and 53% were females with an average age of 48 years. The majority had an interest in migraine and considered it disabling (93%), although 65-85% reported management difficulties, GPs more often than neurologists. Satisfaction with current treatment options was high (69-79%). 63 physicians suffered from migraine and 81% felt it influenced their perception of the disease. Portuguese physicians preferentially treat their own migraines with NSAIDs (33%), analgesics (29%) and triptans (20%). <b><i>Conclusion:</i></b> Portuguese physicians treating migraine patients have realistic perceptions about the disease and those with migraine feel their perception is influenced by their experience. Although reporting management difficulties, the majority of physicians are satisfied with current treatment options for migraine.
DOI: 10.6084/m9.figshare.5125630.v1
title: Supplementary Material for: Environmental and Occupational Risk Factors for Amyotrophic Lateral Sclerosis: A Case-Control Study

description: <b><i>Background/Aims:</i></b> Environmental and occupational exposures are implicated as risk factors for amyotrophic lateral sclerosis (ALS), the etiology of which is largely unknown, although no causal relationships have been established. <b><i>Objective:</i></b> The aim of the study was to evaluate the associations of personal risk factors and self-reported environmental and occupational exposures with risk of ALS. <b><i>Methods:</i></b> The cases involved ALS patients (n = 66) identified from major neurological centers in Pittsburgh and Philadelphia, Pa., USA, from 2008 to 2010. The age-, race- and sex-matched controls included outpatient hospital and population-based controls (n = 66). A detailed questionnaire obtaining data on occupation, vocational and avocational exposure as well as personal lifestyle factors was administered. <b><i>Results:</i></b> Occupational exposure to metals (odds ratio, OR = 3.65; 95% CI: 1.15, 11.60) and pesticides (OR = 6.50; 95% CI: 1.78, 23.77) was related to increased risk of ALS after controlling for smoking and education. No associations were found for occupational exposure to organic or aromatic solvents. <b><i>Conclusion:</i></b> Workers exposed to metals and pesticides may be at greater risk of ALS. Future research should involve more accurate exposure assessment through the use of job exposure matrices, confirmation of occupation and biomarkers.
DOI: 10.6084/m9.figshare.5125633.v1
title: Supplementary Material for: Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way

description: <b><i>Objective:</i></b> Considering a causal role of androgens in thymic involution, age-related remodeling of peripheral T-cell compartments in the absence of testicular hormones was evaluated. <b><i>Methods:</i></b> Rats were orchidectomized (ORX) at the age of 1 month, and T-peripheral blood lymphocytes (PBLs) and splenocytes from young (75-day-old) and aged (24-month-old) rats were examined for differentiation/activation and immunoregulatory marker expression. <b><i>Results:</i></b> In ORX rats, following the initial rise, the counts of CD4+ and CD8+ PBLs diminished with aging. This reflected the decline in thymic export as shown by recent thymic emigrant (RTE) enumeration. Orchidectomy increased the count of both of the major T-splenocyte subsets in young rats, and they (differently from controls) remained stable with aging. The CD4+:CD8+ T-splenocyte ratio in ORX rats shifted towards CD4+ cells compared to age-matched controls. Although in the major T-cell subsets in the blood and spleen from aged ORX rats the numbers of RTEs were comparable to the corresponding values in age-matched controls, the numbers of mature naïve and memory/activated cells substantially differed. Compared with age-matched controls, in aged ORX rats the numbers of CD4+ mature naïve PBLs and splenocytes were reduced, whereas those of CD4+ memory/activated cells (predictive of early mortality) were increased. Additionally, in spleens from aged ORX rats, despite unaltered thymic export, CD4+CD25+FoxP3+ and natural killer T cell counts were greater than in age-matched controls. <b><i>Conclusion:</i></b> (i) Age-related decline in thymopoietic efficacy is not dependent on androgen presence, and (ii) androgens are involved in the maintenance of peripheral T-cell (particularly CD4+ cell) homeostasis during aging.
DOI: 10.6084/m9.figshare.5125624
title: Supplementary Material for: Vasopressin-Induced Constriction of the Isolated Rat Occipital Artery is Segment Dependent

description: <b><i>Background:</i></b> Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have been shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. <b><i>Methods:</i></b> OA were isolated and bisected into proximal and distal segments relative to the external carotid artery. <b><i>Results:</i></b> Bisection highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V<sub>1</sub> receptor agonist were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-hydroxytryptamine (5-HT) and the 5-HT<sub>2</sub> receptor agonist than proximal segments. Angiotensin II (AT)<sub>2</sub>, V<sub>2</sub> and 5-HT<sub>1B/1D</sub> receptor agonists did not elicit vascular responses. Additionally, AT<sub>1</sub> receptor agonists elicited mild, yet not significantly different maximal responses between segments. <b><i>Conclusion:</i></b> The results of this study are consistent with contractile properties of rat OA being mediated via AT<sub>1</sub>, V<sub>1</sub> and 5-HT<sub>2</sub> receptors and dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration-response curve, retained this unique segmental difference. We hypothesize that these segmental differences may be important in the regulation of blood flow through the OA in health and disease.
DOI: 10.6084/m9.figshare.5125654.v2
title: input for PolyGEE

description: number of SNPs for each chromosome in lengths_hapfile paths to haplotype files in files_hap<br><br>
DOI: 10.6084/m9.figshare.5125618
title: Supplementary Material for: NO-Dependent Endothelial Dysfunction in Type II Diabetes Is Aggravated by Dyslipidemia and Hypertension, but Can Be Restored by Angiotensin-Converting Enzyme Inhibition and Weight Loss

description: <b><i>Aims:</i></b> Insulin resistance, dyslipidemia and hypertension are independent mediators of endothelial dysfunction. It is incompletely defined whether dyslipidemia and hypertension in addition to diabetes mellitus type II (DMII), as seen in the metabolic syndrome (MS), worsen diabetes-induced endothelial dysfunction. Furthermore, it is unclear whether treatment influences endothelial dysfunction similarly in MS and DMII. Therefore, we studied vascular reactivity and the effect of in vivo treatment with angiotensin-converting enzyme inhibition (ACE-I) or hypocaloric diet in LDL receptor- and leptin-deficient (ob/ob), double knockout mice (DKO), featuring MS and in ob/ob mice with DMII. <b><i>Methods and Results:</i></b> Vascular reactivity was studied in isolated aortic ring segments. Maximum vasorelaxant response to acetylcholine (Ach) was more depressed in DKO than in ob/ob mice, whereas response to bradykinin (BK) was equally attenuated in both genotypes (52 ± 3 and 23 ± 9% reversal of preconstriction induced by 10<sup>-7</sup>M phenylephrine in DKO vs. 76 ± 3 and 23 ± 8% reversal of preconstriction in ob/ob mice, respectively). ACE-I and hypocaloric diet improved ACh-induced vasorelaxation significantly (89 ± 2 and 59 ± 2% reversal of preconstriction in DKO vs. 80 ± 3 and 84 ± 4% in ob/ob mice, respectively), but not the response to BK. <b><i>Conclusion:</i></b> These results indicate a differential impact of DMII and MS on endothelial function. ACE-I and hypocaloric diet improved ACh-, but not BK-induced vasorelaxation in these mouse models of DMII and MS.