cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121076.v1
title: Supplementary Material for: Induction of GNE in Myofibers after Muscle Injury

description: <i>Objective:</i> The aim of the present study was to clarify the expression of uridine diphospho-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) protein and mRNA in damaged or regenerating myofibers. <i>Methods:</i> We investigated the muscle expression pattern of GNE protein by immunohistochemistry using a murine model involving intramuscular injection of cardiotoxin (CTX), and the expression level of GNE mRNA by quantitative real-time polymerase chain reaction analysis of damaged or regenerating myofibers that had been collected directly from tissue sections using laser-capture microdissection. <i>Results:</i> The expression of GNE protein was increased in severely damaged myofibers as well as in regenerating myofibers with central nuclei, both of which also showed an increase in the expression of GNE mRNA. In regenerating myofibers, immunoreactivity for GNE protein in nuclei relative to that in the cytoplasm was higher at 7 days than at 4 days after CTX injection. <i>Conclusion:</i> Our findings suggest that GNE expression is induced when myofibers are damaged or regenerating, and that GNE plays a role in muscle regeneration.
DOI: 10.6084/m9.figshare.5121064.v1
title: Supplementary Material for: An Extensive Comparison of Quantitative Trait Loci Mapping Methods

description: <i>Background:</i> The choices of study design and statistical approach for mapping a quantitative trait (QT) are of great importance. Larger sibships and a study design based upon phenotypically extreme siblings can be expected to have a greater statistical power. On the other hand, selected samples and/or deviation from normality can influence the robustness and power. Unfortunately, the effects of violation of multivariate normality assumptions and/or selected samples are only known for a limited number of methods. Some recommendations are available in the literature, but an extensive comparison of robustness and power under several different conditions is lacking. <i>Methods:</i> We compared eight freely available and commonly applied QT mapping methods in a Monte-Carlo simulation study under 36 different models and study designs (three genetic models, three selection schemes, two family structures and the possible effect of deviation from normality). <i>Results:</i> Empirical type I error fractions and empirical power are presented and explained as a whole and for each method separately, followed by a thorough discussion. <i>Conclusions:</i> The results from this extensive comparison could serve as a valuable source for the choice of the study design and the statistical approach for mapping a QT.
DOI: 10.6084/m9.figshare.5121073.v1
title: Supplementary Material for: Molecular Cytogenetic Analysis of Cervical Squamous Cell Carcinoma Cells Demonstrates Discordant Levels of Numerical and Structural Chromosomal Instability and Identifies ‘Selected’ Chromosome Rearrangements

description: The processes underlying the karyotype complexity and heterogeneity characteristic of cervical squamous cell carcinoma (SCC) cells are not well understood, nor is it known which chromosome abnormalities provide a selective advantage. We used molecular cytogenetics to quantify for the first time the prevalence of all chromosomal abnormalities detectable in 8 cervical SCC cell lines. Of 225 rearrangements identified, 118 occurred frequently (≧70% metaphases) in one or more lines, indicating selection. Most of these selected rearrangements (107; 48% of the total) were included in published lists of abnormalities detected in independent cell stocks (although their significance was not previously recognised), indicating that they arose early in the establishment of the lines and were therefore most likely to have been present in the original tumours. The 8 cell lines showed 4.7- and 11.0-fold variation in levels of numerical and structural chromosomal instability (N-CIN and S-CIN) respectively, as determined by quantifying non-clonal abnormalities. We observed discordance between N-CIN and S-CIN (p = 0.148), with modal chromosome number showing a strong association with N-CIN (p = 0.007) but not with S-CIN (p = 0.602). These data imply that different mechanisms underlie N-CIN and S-CIN in cervical SCC. Despite ongoing S-CIN, newly arisen in vitro rearrangements were infrequently selected, supporting the view that selection is an important determinant of somatic evolution in malignancy. There was a positive association between numbers of non-clonal and clonal rearrangements (p = 0.002 for non-clonal vs. selected rearrangements), suggesting that factors affecting S-CIN determine the total numbers of rearrangements present in established cervical SCC cells.
DOI: 10.6084/m9.figshare.5121058
title: Supplementary Material for: Influence of Recanalization on Uric Acid Patterns in Acute Ischemic Stroke

description: <i>Background:</i> Most epidemiological studies have reported a significant association between elevated serum levels of uric acid (UA) and increased cardiovascular disease. On the other hand, UA is the most abundant antioxidant in the human body. We hypothesized that UA levels would change noticeably in association with the degree of oxidative stress in acute ischemic stroke. <i>Methods:</i> We analyzed consecutive patients with acute ischemic stroke in the anterior circulation system within 24 h of symptom onset, confirmed by diffusion-weighted imaging (DWI), and with a modified NIH Stroke Scale (mNIHSS) score of 5 or greater. Baseline demographics, serial clinical scores, serial UA and allantoin (a nonenzymatic metabolite of UA) levels, UA change (baseline UA – UA at 48 h), and DWI lesion volumes were compared between 45 patients with recanalized vessels (RV) and 43 patients with nonrecanalized vessels (NV) in follow-up imaging. <i>Results:</i> The RV (vs. NV) patients were more likely to receive thrombolytic treatment (p = 0.005), achieve a reduction in day-14-mNIHSS scores (p = 0.001), and greater changes in UA (p = 0.024) and allantoin levels (p = 0.003). The UA levels dropped at 48 h and gradually increased in a U-shaped pattern. UA change (r = 0.360; p = 0.001) rather than baseline UA (r = 0.044; p = 0.681) was significantly correlated with infarct volume. In the RV (vs. NV) patients, there was a stronger association between infarct volume and UA change (r = 0.483; p = 0.001) or allantoin levels (r = 0.466; p = 0.017). <i>Conclusion:</i> Our results suggest that UA might be a consumptive and reproducible antioxidant in acute ischemic stroke, and this pattern appears to be influenced by recanalization success and infarct volume size.
DOI: 10.6084/m9.figshare.5121061
title: Supplementary Material for: Genetic Susceptibility to Type 2 Diabetes Is Associated with Reduced Prostate Cancer Risk

description: <i>Objective:</i> To examine the collective effects of type 1 (T1D) and type 2 diabetes (T2D) risk alleles on prostate cancer (PCa) risk.<i> Methods:</i> Using data on 14 and 18 single nucleotide polymorphisms (SNPs) that effect T1D and T2D risk, respectively, we generated risk scores (a ‘risk allele count’ and a ‘genetic relative risk’) for both T1D and T2D for 1,171 non-Hispanic white, PSA-screened PCa cases and 1,101 matched controls from the Cancer Genetic Markers of Susceptibility study. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between the diabetes risk scores and PCa risk. <i>Results:</i> Both T2D risk scores, but neither T1D score, showed an inverse association with PCa (p &lt; 0.01). These associations remained significant after excluding HNF1B SNP rs4430796 (a known PCa risk factor) from the analysis. The highest quartile of the T2D allele count (&gt;20 risk alleles) was associated with reduced PCa risk (OR = 0.77; CI: 0.60–0.99) compared to the lowest category (&lt;17 risk alleles). <i>Conclusions:</i> These results suggest that individuals with increased genetic susceptibility to T2D have decreased risk for PCa. This association is consistent with the observation that individuals with T2D are at decreased risk for PCa; however, data on T2D status was not available for this analysis.
DOI: 10.6084/m9.figshare.5121067.v1
title: Supplementary Material for: Using Both Cases and Controls for Testing Hardy-Weinberg Proportions in a Genetic Association Study

description: <i>Objectives:</i> Assessment of the Hardy-Weinberg proportion (HWP) in controls has been widely used as a quality control measure in case-control association studies. However, when the disease being studied is common, controls might not represent the general population, which could result in inaccurate HWP test results. Such results could lead investigators to discard important single-nucleotide polymorphisms (SNPs) that could potentially be causal. In this paper, we showed the inappropriateness of the HWP test in controls and proposed a mixture HWP (mHWP) exact test using a mixture sample that mimics the general population. <i>Methods:</i> The mHWP exact test estimates HWP in a mixture sample that is a combination of both cases and controls proportional to the prevalence of disease. We implemented a re-sampling procedure to construct mixture samples and then obtained the empirical p value of HWP in the general population. Simulation studies were performed to investigate the performance of the proposed mHWP exact test. The method was also applied to a genetic association study of obesity. <i>Results:</i> The results showed that the mHWP exact test is more likely than either the traditional HWP method in controls or the likelihood-based approach to keep causal SNPs for further analysis when the disease is more common. <i>Conclusion:</i> The mHWP exact test using a mixture sample is a better HWP test for case-control genetic association studies than the traditional HWP in controls or the likelihood-based approach, and it will improve our ability to keep causal SNPs in the case-control genetic association studies.
DOI: 10.6084/m9.figshare.5121055
title: Supplementary Material for: Quantification of Population Structure Using Correlated SNPs by Shrinkage Principal Components

description: <i>Background/Aims:</i> Association studies using unrelated individuals have become the most popular design for mapping complex traits. One of the major challenges of association mapping is avoiding spurious association due to population stratification. Principal component analysis (PCA) on genome-wide marker genotypes is one of the most popular population stratification control methods. It implicitly assumes that the markers are in linkage equilibrium, a condition that is rarely satisfied and that we plan to relax. <i>Methods:</i> We carefully examined the impact of linkage disequilibrium (LD) on PCA, and proposed a simple modification of the standard PCA to automatically adjust for the correlations among markers. <i>Results:</i> We demonstrated that LD patterns in genome-wide association datasets can distort the techniques for stratification control, showing ‘subpopulations’ reflecting localized LD phenomena rather than plausible population structure. We showed that the proposed method effectively removes the artifactual effect of LD patterns, and successfully recovers underlying population structure that is not apparent from standard PCA. <i>Conclusion:</i> PCA is highly influenced by sets of SNPs with high LD, obscuring the true population substructure. Our shrinkage PCA applies to all available markers, regardless of the LD patterns. The proposed method is easier to implement than most existing LD adjusted PCA methods.
DOI: 10.6084/m9.figshare.5121049
title: Supplementary Material for: Metakognitive und andere kognitiv-verhaltenstherapeutische Verfahren bei posttraumatischer Belastungsstörung

description: In dieser Arbeit sollen Grundannahmen und Interventionen der Metakognitiven Therapie (MKT) zur Behandlung von posttraumatischen BelastungsstÖrungen (PTBS) mit denen der Kognitiven Verhaltenstherapie (KVT) verglichen werden. In der KVT gelten Vermeidung und dysfunktionale GedÄchtnisprozesse («TraumagedÄchtnis») sowie problematische Kognitionen als ursÄchlich fÜr die Ausbildung einer PTBS. Als wichtigste Intervention gelten daher Expositionsbehandlung und kognitive Umstrukturierung. In der MKT gelten dysfunktionale kognitive und Aufmerksamkeitsprozesse (GrÜbeln, Sorgen, Vermeidung, GedankenunterdrÜckung, selektive Aufmerksamkeit fÜr Gefahrenquellen) als Ursachen der PTBS. Exposition oder Diskussionen von Gedankeninhalten werden nicht als notwendig erachtet, vielmehr werden die Patienten angeleitet, Traumaerinnerungen aus innerer Distanz achtsam wahrzunehmen («losgelÖste Achtsamkeit») und scheinbar unkontrollierbare perseverierende Denkprozesse (GrÜbeln und Sorgen) zu kontrollieren. Erste empirische Wirksamkeitsnachweise fÜr Erwachsene und eigene Erfahrungen in der Arbeit mit Kindern und Jugendlichen sind vielversprechend.
DOI: 10.6084/m9.figshare.5121052
title: Supplementary Material for: Hemifacial Spasms Provoked by Ipsilateral Gaze

description: Medicine
DOI: 10.6084/m9.figshare.5121055.v1
title: Supplementary Material for: Quantification of Population Structure Using Correlated SNPs by Shrinkage Principal Components

description: <i>Background/Aims:</i> Association studies using unrelated individuals have become the most popular design for mapping complex traits. One of the major challenges of association mapping is avoiding spurious association due to population stratification. Principal component analysis (PCA) on genome-wide marker genotypes is one of the most popular population stratification control methods. It implicitly assumes that the markers are in linkage equilibrium, a condition that is rarely satisfied and that we plan to relax. <i>Methods:</i> We carefully examined the impact of linkage disequilibrium (LD) on PCA, and proposed a simple modification of the standard PCA to automatically adjust for the correlations among markers. <i>Results:</i> We demonstrated that LD patterns in genome-wide association datasets can distort the techniques for stratification control, showing ‘subpopulations’ reflecting localized LD phenomena rather than plausible population structure. We showed that the proposed method effectively removes the artifactual effect of LD patterns, and successfully recovers underlying population structure that is not apparent from standard PCA. <i>Conclusion:</i> PCA is highly influenced by sets of SNPs with high LD, obscuring the true population substructure. Our shrinkage PCA applies to all available markers, regardless of the LD patterns. The proposed method is easier to implement than most existing LD adjusted PCA methods.
DOI: 10.6084/m9.figshare.5121061.v1
title: Supplementary Material for: Genetic Susceptibility to Type 2 Diabetes Is Associated with Reduced Prostate Cancer Risk

description: <i>Objective:</i> To examine the collective effects of type 1 (T1D) and type 2 diabetes (T2D) risk alleles on prostate cancer (PCa) risk.<i> Methods:</i> Using data on 14 and 18 single nucleotide polymorphisms (SNPs) that effect T1D and T2D risk, respectively, we generated risk scores (a ‘risk allele count’ and a ‘genetic relative risk’) for both T1D and T2D for 1,171 non-Hispanic white, PSA-screened PCa cases and 1,101 matched controls from the Cancer Genetic Markers of Susceptibility study. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between the diabetes risk scores and PCa risk. <i>Results:</i> Both T2D risk scores, but neither T1D score, showed an inverse association with PCa (p &lt; 0.01). These associations remained significant after excluding HNF1B SNP rs4430796 (a known PCa risk factor) from the analysis. The highest quartile of the T2D allele count (&gt;20 risk alleles) was associated with reduced PCa risk (OR = 0.77; CI: 0.60–0.99) compared to the lowest category (&lt;17 risk alleles). <i>Conclusions:</i> These results suggest that individuals with increased genetic susceptibility to T2D have decreased risk for PCa. This association is consistent with the observation that individuals with T2D are at decreased risk for PCa; however, data on T2D status was not available for this analysis.
DOI: 10.6084/m9.figshare.5121043
title: Supplementary Material for: Bone Marrow-Sparing Intensity-Modulated Radiotherapy (IMRT) for Neo-Adjuvant Therapy of Inoperable Cervical Cancer in a Patient with Severe Thrombocytopenia

description: <i>Background:</i> Therapy possibilities are limited in patients with cervix carcinoma and thrombocytopenia. <i>Case Report:</i> We describe a 50-year-old woman with inoperable cervical carcinoma and chronic lymphatic B cell leukemia (B-CLL). Due to thrombocytopenia, a combined radiochemotherapy could not be performed. Intensitymodulated radiotherapy (IMRT) aiming at maximal bone sparing was planned. After a total dose of 45 Gy, a laparoscopic omentum plastic was performed to enable radiotherapy (RT) to full dose. 3 days later, an external beam boost was restarted to a cumulative dose of 50.4 Gy. Regular blood analysis showed low but stable blood counts. 4 weeks after RT, magnetic resonance imaging (MRI) showed a 30% regression of the tumor volume and, after transfusion of fresh-frozen plasma, a hysterectomy could be performed. 6 months after therapy, no recurrence or late toxicities had occurred. <i>Conclusion:</i> The clinical implementation of IMRT may potentially improve the therapeutic outcome of patients with cervix cancer, allowing dose escalation without increasing normal-tissue toxicity.
DOI: 10.6084/m9.figshare.5121046
title: Supplementary Material for: Associations of Clinical Stroke Misclassification (‘Clinical-Imaging Dissociation’) in Acute Ischemic Stroke

description: <i>Background:</i> Up to 20% of lacunar infarcts are clinically misdiagnosed as cortical infarcts and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this ‘clinical-imaging dissociation’ (C-ID). <i>Methods:</i> Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts and proximity to cortex for small subcortical infarcts. We examined factors associated with C-ID. <i>Results:</i> 137 patients with a mild cortical or lacunar syndrome had an acute ischemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61–130.1), left hemisphere location (OR 8.95, 95% CI 1.23–64.99) and diabetes (OR 17.1, 95% CI 1.49–196.16) predicted C-ID. On multivariate analysis of all 137 patients, C-ID was associated with diabetes (OR 7.12, 95% CI 1.86–27.2). <i>Conclusions:</i> C-ID occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimized in research by verification with high-sensitivity imaging.
DOI: 10.6084/m9.figshare.5121040
title: Supplementary Material for: Novel Adenovirus Vectors ‘Capsid-Displaying’ a Human Complement Inhibitor

description: Adenovirus (Ad) vectors are currently the most commonly utilized gene transfer vectors in humans worldwide. Unfortunately, upon contact with the circulatory system, Ads induce several, innate, complement-dependent toxicities that limit the full potential for Ad-based gene transfer applications. Therefore, we have constructed several novel Ad5-based vectors, ‘capsid-displaying’ as fiber or pIX fusion proteins, a complement-regulatory peptide (COMPinh). These novel Ads dramatically minimize Ad-dependent activation of the human and non-human primate complement systems, as determined by several assays. In summary, our work has shown that a novel COMPinh-displaying Ad5 has the potential for broadening the safe use of Ad vectors in future human applications.
DOI: 10.6084/m9.figshare.5121043.v1
title: Supplementary Material for: Bone Marrow-Sparing Intensity-Modulated Radiotherapy (IMRT) for Neo-Adjuvant Therapy of Inoperable Cervical Cancer in a Patient with Severe Thrombocytopenia

description: <i>Background:</i> Therapy possibilities are limited in patients with cervix carcinoma and thrombocytopenia. <i>Case Report:</i> We describe a 50-year-old woman with inoperable cervical carcinoma and chronic lymphatic B cell leukemia (B-CLL). Due to thrombocytopenia, a combined radiochemotherapy could not be performed. Intensitymodulated radiotherapy (IMRT) aiming at maximal bone sparing was planned. After a total dose of 45 Gy, a laparoscopic omentum plastic was performed to enable radiotherapy (RT) to full dose. 3 days later, an external beam boost was restarted to a cumulative dose of 50.4 Gy. Regular blood analysis showed low but stable blood counts. 4 weeks after RT, magnetic resonance imaging (MRI) showed a 30% regression of the tumor volume and, after transfusion of fresh-frozen plasma, a hysterectomy could be performed. 6 months after therapy, no recurrence or late toxicities had occurred. <i>Conclusion:</i> The clinical implementation of IMRT may potentially improve the therapeutic outcome of patients with cervix cancer, allowing dose escalation without increasing normal-tissue toxicity.
DOI: 10.6084/m9.figshare.5121046.v1
title: Supplementary Material for: Associations of Clinical Stroke Misclassification (‘Clinical-Imaging Dissociation’) in Acute Ischemic Stroke

description: <i>Background:</i> Up to 20% of lacunar infarcts are clinically misdiagnosed as cortical infarcts and vice versa. The reasons for this discrepancy are unclear. We assessed clinical and imaging features which might explain this ‘clinical-imaging dissociation’ (C-ID). <i>Methods:</i> Patients with an acute stroke syndrome (cortical or lacunar) underwent magnetic resonance imaging including diffusion-weighted imaging (DWI). We recorded DWI-positive infarcts and proximity to cortex for small subcortical infarcts. We examined factors associated with C-ID. <i>Results:</i> 137 patients with a mild cortical or lacunar syndrome had an acute ischemic lesion on DWI. Of these, 21/93 (23%) with a cortical syndrome had an acute lacunar infarct and 7/44 (16%) with a lacunar syndrome had an acute cortical infarct. From 72 patients with an acute lacunar infarct on DWI, lesion proximity to cortex (odds ratio (OR) 14.5, 95% confidence interval (CI) 1.61–130.1), left hemisphere location (OR 8.95, 95% CI 1.23–64.99) and diabetes (OR 17.1, 95% CI 1.49–196.16) predicted C-ID. On multivariate analysis of all 137 patients, C-ID was associated with diabetes (OR 7.12, 95% CI 1.86–27.2). <i>Conclusions:</i> C-ID occurs in a fifth of patients with mild stroke. Lacunar infarcts lying close to cortex are more likely to cause cortical symptoms. Diabetes is associated with any clinical-imaging mismatch. Stroke misclassification which can arise with clinical classification alone should be minimized in research by verification with high-sensitivity imaging.