cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5125681
title: Supplementary Material for: Low Frontal Assessment Battery Score as a Risk Factor for Falling in Patients with Hoehn-Yahr Stage III Parkinson's Disease: A 2-Year Prospective Study

description: <b><i>Background:</i></b> Recently, we evaluated factors responsible for falling, including walking speed evaluated with the use of originally designed, suddenly narrowed paths, in patients with Hoehn-Yahr stage III PD. We prospectively studied the same cohort of patients with PD who were followed up for 2 years, to determine predictors of future falls. <b><i>Methods:</i></b> We performed clinical assessments and evaluated balance in 26 patients. A total of 19 variables including PD-related independent variables, balance investigation-related independent variables and gait independent-related variables were evaluated. <b><i>Results:</i></b> The Frontal Assessment Battery (FAB) score (p = 0.002), Tinetti balance (p = 0.009), and gait velocity (p = 0.001) were higher in fallers than in non-fallers. On multiple logistic regression analysis, the FAB score was related to falling (odds ratio = 3.328, p = 0.033, 95% confidence interval = 1.104-10.03). On the FAB, the scores of ‘inhibitory control' and ‘sensitivity to interference' were significantly lower in fallers than in non-fallers. <b><i>Conclusions:</i></b> The use of the originally designed, suddenly narrowed path was the primary reason for demonstrating for the first time that a low FAB score is a risk factor for future falls. Calculation of the FAB score may be useful for predicting the risk of future falls.
DOI: 10.6084/m9.figshare.5125675
title: Supplementary Material for: Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

description: <b><i>Background:</i></b> A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. <b><i>Methods:</i></b> We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. <b><i>Results:</i></b> Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA<sub>1c</sub> levels or daily insulin doses of the girls treated with metformin compared with the placebo group. <b><i>Conclusion:</i></b> Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.
DOI: 10.6084/m9.figshare.5125681.v1
title: Supplementary Material for: Low Frontal Assessment Battery Score as a Risk Factor for Falling in Patients with Hoehn-Yahr Stage III Parkinson's Disease: A 2-Year Prospective Study

description: <b><i>Background:</i></b> Recently, we evaluated factors responsible for falling, including walking speed evaluated with the use of originally designed, suddenly narrowed paths, in patients with Hoehn-Yahr stage III PD. We prospectively studied the same cohort of patients with PD who were followed up for 2 years, to determine predictors of future falls. <b><i>Methods:</i></b> We performed clinical assessments and evaluated balance in 26 patients. A total of 19 variables including PD-related independent variables, balance investigation-related independent variables and gait independent-related variables were evaluated. <b><i>Results:</i></b> The Frontal Assessment Battery (FAB) score (p = 0.002), Tinetti balance (p = 0.009), and gait velocity (p = 0.001) were higher in fallers than in non-fallers. On multiple logistic regression analysis, the FAB score was related to falling (odds ratio = 3.328, p = 0.033, 95% confidence interval = 1.104-10.03). On the FAB, the scores of ‘inhibitory control' and ‘sensitivity to interference' were significantly lower in fallers than in non-fallers. <b><i>Conclusions:</i></b> The use of the originally designed, suddenly narrowed path was the primary reason for demonstrating for the first time that a low FAB score is a risk factor for future falls. Calculation of the FAB score may be useful for predicting the risk of future falls.
DOI: 10.6084/m9.figshare.5125672
title: Supplementary Material for: Invertebrate Models in Addiction Research

description: While drug addiction is a uniquely human problem, most research examining the biological mechanisms of the transition from substance use to addiction is conducted with vertebrate animal models. Many other fields of neuroscience have greatly benefitted from contributions from simple and manipulable invertebrate model systems. However, the potential of invertebrate research has yet to be fully capitalised on in the field of addiction neuroscience. This may be because of the complexity of addiction and the clinical imperative of addiction research. We argue that the homocentric diagnostic criteria of addiction are no more a hindrance to the use of invertebrate models than they are to vertebrate models. We highlight the strengths of the diversity of different invertebrate model systems in terms of neuroanatomy and molecular machinery, and stress that working with a range of different models will aid in understanding addiction and not be a disadvantage. Finally, we discuss the specific advantages of utilising invertebrate animals for addiction research and highlight key areas in which invertebrates are suited for making unique and meaningful contributions to this field.
DOI: 10.6084/m9.figshare.5125666
title: Supplementary Material for: Impact of Different Operational Definitions on Mild Cognitive Impairment Rate and MMSE and MoCA Performance in Transient Ischaemic Attack and Stroke

description: <b><i>Background:</i></b> Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences <i>within</i> established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke. <b><i>Methods:</i></b> Consecutive patients underwent the MMSE, MoCA and neuropsychological battery ≥1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (&gt;1, &gt;1.5 and &gt;2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment. <b><i>Results:</i></b> 91 non-demented subjects completed neuropsychological testing (mean age ± SD 69.7 ± 11.6 years, 54 male, 49 stroke) at a mean of 3.1 ± 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at &gt;2 SD cut-off to 61/91 (67%) MCI-modified at &gt;1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut-off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original. <b><i>Conclusion:</i></b> Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies.
DOI: 10.6084/m9.figshare.5125669
title: Supplementary Material for: MRI Follow-Up after 24 h Is an Accurate Surrogate Parameter for Treatment Success after Thrombolysis

description: Medicine
DOI: 10.6084/m9.figshare.5125675.v1
title: Supplementary Material for: Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

description: <b><i>Background:</i></b> A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. <b><i>Methods:</i></b> We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. <b><i>Results:</i></b> Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA<sub>1c</sub> levels or daily insulin doses of the girls treated with metformin compared with the placebo group. <b><i>Conclusion:</i></b> Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.
DOI: 10.6084/m9.figshare.5125663
title: Supplementary Material for: Parenchyma, Pipes, Perfusion and Penumbra Imaging: The Multimodal CT in Wake-Up Stroke Basilar Thrombosis

description: Medicine
DOI: 10.6084/m9.figshare.5125657
title: Supplementary Material for: Familial Coaggregation of Alzheimer's Disease and Parkinson's Disease: Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families. <b><i>Methods:</i></b> The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively. <b><i>Results:</i></b> We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias. <b><i>Conclusions:</i></b> There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD.
DOI: 10.6084/m9.figshare.5125660
title: Supplementary Material for: Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

description: <b><i>Background:</i></b> Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. <b><i>Methods:</i></b> A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. <b><i>Results:</i></b> Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone methylation levels of MET resembled MIBC. We observed furthermore a correlation of histone methylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9me2, H3K9me3, H3K27me1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. <b><i>Conclusions:</i></b> Global histone H3K9 and H3K27 methylation levels are altered in BCa.
DOI: 10.6084/m9.figshare.5125666.v1
title: Supplementary Material for: Impact of Different Operational Definitions on Mild Cognitive Impairment Rate and MMSE and MoCA Performance in Transient Ischaemic Attack and Stroke

description: <b><i>Background:</i></b> Mild cognitive impairment (MCI) is at least as prevalent as dementia after transient ischaemic attack (TIA)/stroke and is increasingly recognised as an important outcome in observational studies and randomised trials. However, there is no consensus on how impairment should be defined, and numerous different criteria exist. Previous studies have shown that different criteria for cognitive impairment impact on prevalence rates in epidemiological studies. However, there are few data on how operational differences <i>within</i> established criteria (e.g. Petersen-MCI) affect measured impairment rates and the performance of short cognitive tests such as the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), particularly in cerebrovascular disease. We therefore evaluated the effect of different operational definitions on measured rates of Petersen-MCI and on reliability of short cognitive tests in patients with TIA and stroke. <b><i>Methods:</i></b> Consecutive patients underwent the MMSE, MoCA and neuropsychological battery ≥1 year after TIA or stroke in a population-based study. MCI was defined using the Petersen method and subclassified as single or multiple domain, both with (original) and without (modified) subjective memory impairment. Different cut-offs (&gt;1, &gt;1.5 and &gt;2 standard deviations, SD) on a given test relative to published norms were compared together with use of single versus multiple tests to define domain impairment. <b><i>Results:</i></b> 91 non-demented subjects completed neuropsychological testing (mean age ± SD 69.7 ± 11.6 years, 54 male, 49 stroke) at a mean of 3.1 ± 1.9 years after the index event. Rates of cognitive impairment ranged from 14/91 (15%) for MCI-original at &gt;2 SD cut-off to 61/91 (67%) MCI-modified at &gt;1 SD cut-off, and the proportion of MCI that was multiple domain varied, e.g. 24/46 (52%) versus only 5/27 (20%) at 1 versus 2 SD cut-off for MCI-modified. Requirement for subjective memory complaint approximately halved estimates [e.g. 17 (19%) vs. 39 (43%) for MCI at 1.5 SD cut-off, single test definition], whereas use of multiple tests versus a single test to define a cognitive domain had less impact. In general, diagnostic accuracy was higher, and optimal cut-offs lower, on MMSE and MoCA for multiple-domain versus single-domain MCI, but the MoCA appeared superior for detecting MCI-modified, whereas the MMSE performed well in detecting MCI-original. <b><i>Conclusion:</i></b> Even within established criteria for MCI, differences in operational methodology result in 4-fold variation in MCI estimates. Optimal MMSE and MoCA cut-offs are lower, and reliability more similar, when criteria for MCI are more stringent. Our findings have implications for sample size and adjusted relative risk calculations in randomised trials and for comparisons between studies.
DOI: 10.6084/m9.figshare.5125657.v1
title: Supplementary Material for: Familial Coaggregation of Alzheimer's Disease and Parkinson's Disease: Systematic Review and Meta-Analysis

description: <b><i>Background:</i></b> Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families. <b><i>Methods:</i></b> The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively. <b><i>Results:</i></b> We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias. <b><i>Conclusions:</i></b> There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD.
DOI: 10.6084/m9.figshare.5125648
title: Supplementary Material for: Disruption of the ATE1 and SLC12A1 Genes by Balanced Translocation in a Boy with Non-Syndromic Hearing Loss

description: We report on a boy with non-syndromic hearing loss and an apparently balanced translocation t(10;15)(q26.13;q21.1). The same translocation was found in the normally hearing brother, father and paternal grandfather; however, this does not exclude its involvement in disease pathogenesis, for example, by unmasking a second mutation. Breakpoint analysis via FISH with BAC clones and long-range PCR products revealed a disruption of the arginyltransferase 1 <i>(ATE1)</i> gene on translocation chromosome 10 and the solute carrier family 12, member 1 gene <i>(SLC12A1)</i> on translocation chromosome 15. SNP array analysis revealed neither loss nor gain of chromosomal regions in the affected child, and a targeted gene enrichment panel consisting of 130 known deafness genes was negative for pathogenic mutations. The expression patterns in zebrafish and humans did not provide evidence for ear-specific functions of the<i> ATE1</i> and <i>SLC12A1</i> genes. Sanger sequencing of the 2 genes in the boy and 180 <i>GJB2</i> mutation-negative hearing-impaired individuals did not detect homozygous or compound heterozygous pathogenic mutations. Our study demonstrates the many difficulties in unraveling the molecular causes of a heterogeneous phenotype. We cannot directly implicate disruption of <i>ATE1</i> and/or <i>SLC12A1</i> to the abnormal hearing phenotype; however, mutations in these genes may have a role in polygenic or multifactorial forms of hearing impairment. On the other hand, it is conceivable that our patient carries a disease-causing mutation in a so far unidentified deafness gene. Evidently, disruption of <i>ATE1 </i>and/or <i>SLC12A1</i> gene function alone does not have adverse effects.
DOI: 10.6084/m9.figshare.5125654
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.5125645
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.