cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122870
title: Supplementary Material for: Frequent Early Cardiac Complications Contribute to Worse Stroke Outcome in Atrial Fibrillation

description: <i>Background:</i> Atrial fibrillation (AF) is associated with worse outcomes following ischemic stroke and more frequent cardiac complications in the general population. We aimed to establish whether early cardiac complications contribute to the poorer ischemic stroke outcomes in patients with AF, independent of baseline differences in age, stroke severity and cardiovascular risk factors. This might have important implications for acute stroke management in patients with AF. <i>Methods:</i> We searched VISTA-Acute, an academic database containing standardized data for 28,131 patients from 30 randomized-controlled acute stroke trials and 1 stroke registry, for imaging-confirmed placebo-treated patients with complete documentation of baseline demographics, cardiovascular risk factors, presence or absence of AF, neurologic impairment [National Institutes of Health Stroke Scale (NIHSS)], cardiac complications and 3-month outcome (modified Rankin Scale). A total of 2,865 patients from 6 randomized-controlled trials met the selection criteria, of whom 819 had AF. Binary logistic regression modeling was used to determine the independent effect of AF on stroke outcome and serious cardiac adverse events (SCAE), a composite end point including acute coronary syndrome, symptomatic heart failure, cardiopulmonary arrest, ventricular tachycardia, ventricular fibrillation and cardiac mortality. <i>Results:</i> All patients were enrolled into the source trials within 24 h of stroke onset. At baseline, patients with AF were older (mean 75 vs. 67 years, p &lt; 0.001) and had greater neurologic impairment (median NIHSS 15 vs. 13, p &lt; 0.001). The median time to first cardiac adverse event was 3 days [median difference 0, 95% confidence interval (CI) 0–1, p = 0.06] for both patients with and without AF. SCAE occurred more frequently [14.2 vs. 6%, odds ratio (OR) = 2.58, 95% CI 1.97–3.37] in patients with AF, particularly cardiac mortality (4.9 vs. 2.6%, OR = 1.89, 95% CI 1.25–2.88), symptomatic heart failure (6.5 vs. 2.2%, OR = 3.01, 95% CI 2.01–4.50), and ventricular tachycardia and/or fibrillation (2.4 vs. 0.8%, OR = 3.18, 95% CI 1.64–6.16). At 3 months, AF was independently associated with SCAE (OR = 2.14, 95% CI 1.61–2.86) and early mortality (OR = 1.44, 95% CI 1.14–1.81) after adjusting for all baseline imbalances. <i>Conclusion:</i> Early SCAE are common after stroke and are independently associated with the presence of AF. Given that many cardiac complications are potentially remediable, these results highlight the need for more rigorous surveillance for cardiac complications in acute ischemic stroke patients with AF.
DOI: 10.6084/m9.figshare.5122876.v1
title: Supplementary Material for: Small Cell Carcinoma Arising from the Bulbar Urethra: A Case Report and Literature Review

description: Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm.
DOI: 10.6084/m9.figshare.5122882.v1
title: Supplementary Material for: Rectal Carcinoma Metastatic to the Male Breast after 7 Years: Case Report

description: <i>Background:</i> Colorectal cancer metastasis to a mammary location is very rare. <i>Case Report:</i> A 38-year-old male, who had undergone anterior resection of an advanced rectal carcinoma 7 years earlier, presented with a right mammary mass. Core needle biopsy of the mass indicated cytology consistent with breast adenocarcinoma. After neoadjuvant chemotherapy and modified radical mastectomy, pathology identified the mass as rectal carcinoma. <i>Conclusion:</i> The authors highlight the difficulty of making an accurate diagnosis of rectal cancer metastasis to the breast of a male.
DOI: 10.6084/m9.figshare.5122861
title: Supplementary Material for: Human BRCA1-Associated Breast Cancer: No Increase in Numerical Chromosomal Instability Compared to Sporadic Tumors

description: BRCA1 is a major gatekeeper of genomic stability. Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a <i>BRCA1 </i>germline mutation compared to 62 unselected breast cancers. We applied fluorescence in situ hybridization (FISH) with centromere-specific probes for the chromosomes 1, 7, 8, 10, 17, and X and locus-specific probes for 3q27 <i>(BCL6)</i>, 5p15.2 (D5S23), 5q31 <i>(EGR1)</i>, 10q23.3 <i>(PTEN)</i>, and 14q32 (<i>IGH</i><i>@</i>) on formalin-fixed paraffin-embedded tissue microarray sections. Our hypothesis of an increased level of CIN in <i>BRCA1</i>-associated breast cancer could not be confirmed by this approach. Surprisingly, we detected no significant difference in the extent of CIN in <i>BRCA1</i>-mutated versus sporadic tumors. The only exception was the CIN value for chromosome 1. Here, the extent of CIN was slightly higher in the group of sporadic tumors.
DOI: 10.6084/m9.figshare.5122864
title: Supplementary Material for: Comparison of Six Statistics of Genetic Association Regarding Their Ability to Discriminate between Causal Variants and Genetically Linked Markers

description: <i>Objectives:</i> Genome-wide association (GWA) studies still rely on the common-disease common-variant hypothesis since the assumption is associated with increased power. In GWA studies, polymorphisms are genotyped and their association with disease is investigated. Most of the identified associations are indirect and reflect a shared inheritance of the genotyped markers and genetically linked causal variants. We have compared six statistics of genetic association regarding their ability to discriminate between markers and causal susceptibility variants, including a probability value (Pval) and a Bayes Factor (BF) based on logistic regression, and the attributable familial relative risk (FRR). <i>Methods:</i> We carried out a simulation-based sensitivity analysis to explore several conceivable scenarios. Theoretical results were illustrated by established causal associations with age-related macular degeneration and by using imputed data based on HapMap for a case-control study of breast cancer. <i>Results:</i> Our data indicate that a representation of genetic association by FRRs and BFs generally facilitates the distinction of causal variants. The FRR showed the best discriminative power under most investigated scenarios, but no single statistic outperformed the others in all situations. For example, rare moderate- to low-penetrance variants (allele frequency: 1%, dominant odds ratio: ≤2.0) seem to be best discriminated by BFs. <i>Conclusions:</i> Present results may help to fully utilize the data generated in association studies that take advantage of next generation sequencing and/or multiple imputation based on the 1000 Genomes Project.
DOI: 10.6084/m9.figshare.5122867
title: Supplementary Material for: The First Report of a Patient with Probable Variant Creutzfeldt-Jakob Disease in Turkey

description: Variant Creutzfeldt-Jakob disease (vCJD) was first reported in the UK in 1996. Here, we report the first Turkish case of vCJD. A 47-year-old man, who has never lived outside of Turkey and had had no transfusion, was admitted to the University Hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. The immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. Brain magnetic resonance imaging revealed high-signal lesions involving the bilateral caudate and lentiform nucleus on T<sub>2</sub>- and diffusion-weighted imaging. The patient developed akinetic mutism 10 months after disease onset. The clinical presentation and neuroimaging findings were compatible with the vCJD cases reported since 1996 and met the World Health Organization’s case definition for probable vCJD.
DOI: 10.6084/m9.figshare.5122858
title: Supplementary Material for: A New Image-Based Stroke Registry Containing Quantitative Magnetic Resonance Imaging Data

description: <i>Background:</i> Conventional stroke registries contain alphanumeric text-based data on the clinical status of stroke patients, but this format captures imaging data in a very limited form. There is a need for a new type of stroke registry to capture both text- and image-based data. <i>Methods and Results:</i> We designed a next-generation stroke registry containing quantitative magnetic resonance imaging (MRI) data, ‘DUIH_SRegI’, developed a supporting software package, ‘Image_QNA’, and performed experiments to assess the feasibility and utility of the system. Image_QNA enabled the mapping of stroke-related lesions on MR onto a standard brain template and the storage of this extracted imaging data in a visual database. Interuser and intrauser variability of the lesion mapping procedure was low. We compared the results from the semi automatic lesion registration using Image_QNA with automatic lesion registration using SPM5 (Statistical Parametric Mapping version 5), a well-regarded standard neuroscience software package, in terms of lesion location, size and shape, and found Image_QNA to be superior. We assessed the clinical usefulness of an image-based registry by studying 47 consecutive patients with first-ever lacunar infarcts in the corona radiata. We used the enriched dataset comprised of both image-based and alphanumeric databases to show that diffusion MR lesions overlapped in a more posterolateral brain location for patients with high NIH Stroke Scale scores (≧4) than for patients with low scores (≤3). In April 2009, we launched the first prospective image-based acute (≤1 week) stroke registry at our institution. The registered data include high signal intensity ischemic lesions on diffusion, T<sub>2</sub>-weighted, or fluid attenuation inversion recovery MRIs, and low signal intensity hemorrhagic lesions on gradient-echo MRIs. An interim analysis at 6 months showed that the time requirement for the lesion registration (183 consecutive patients, 3,226 MR slices with visible stroke-related lesions) was acceptable at about 1 h of labor per patient by a trained assistant with physician oversight. <i>Conclusions:</i> We have developed a novel image-based stroke registry, with database functions that allow the formulation and testing of intuitive, image-based hypotheses in a manner not easily achievable with conventional alphanumeric stroke registries.
DOI: 10.6084/m9.figshare.5122867.v1
title: Supplementary Material for: The First Report of a Patient with Probable Variant Creutzfeldt-Jakob Disease in Turkey

description: Variant Creutzfeldt-Jakob disease (vCJD) was first reported in the UK in 1996. Here, we report the first Turkish case of vCJD. A 47-year-old man, who has never lived outside of Turkey and had had no transfusion, was admitted to the University Hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. The immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. Brain magnetic resonance imaging revealed high-signal lesions involving the bilateral caudate and lentiform nucleus on T<sub>2</sub>- and diffusion-weighted imaging. The patient developed akinetic mutism 10 months after disease onset. The clinical presentation and neuroimaging findings were compatible with the vCJD cases reported since 1996 and met the World Health Organization’s case definition for probable vCJD.
DOI: 10.6084/m9.figshare.5122855
title: Supplementary Material for: Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

description: <i>Background:</i> Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the <i>CST3</i> gene and the development of cerebral white matter lesions. <i>Methods:</i> In a total of 2,676 participants, 3<i> CST3</i> genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. <i>Results:</i> A significant association was found between one <i>CST3</i> gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. <i>Conclusions:</i> Our study shows that polymorphisms in the <i>CST3</i> gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the<i> CST3</i> gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.
DOI: 10.6084/m9.figshare.5122858.v1
title: Supplementary Material for: A New Image-Based Stroke Registry Containing Quantitative Magnetic Resonance Imaging Data

description: <i>Background:</i> Conventional stroke registries contain alphanumeric text-based data on the clinical status of stroke patients, but this format captures imaging data in a very limited form. There is a need for a new type of stroke registry to capture both text- and image-based data. <i>Methods and Results:</i> We designed a next-generation stroke registry containing quantitative magnetic resonance imaging (MRI) data, ‘DUIH_SRegI’, developed a supporting software package, ‘Image_QNA’, and performed experiments to assess the feasibility and utility of the system. Image_QNA enabled the mapping of stroke-related lesions on MR onto a standard brain template and the storage of this extracted imaging data in a visual database. Interuser and intrauser variability of the lesion mapping procedure was low. We compared the results from the semi automatic lesion registration using Image_QNA with automatic lesion registration using SPM5 (Statistical Parametric Mapping version 5), a well-regarded standard neuroscience software package, in terms of lesion location, size and shape, and found Image_QNA to be superior. We assessed the clinical usefulness of an image-based registry by studying 47 consecutive patients with first-ever lacunar infarcts in the corona radiata. We used the enriched dataset comprised of both image-based and alphanumeric databases to show that diffusion MR lesions overlapped in a more posterolateral brain location for patients with high NIH Stroke Scale scores (≧4) than for patients with low scores (≤3). In April 2009, we launched the first prospective image-based acute (≤1 week) stroke registry at our institution. The registered data include high signal intensity ischemic lesions on diffusion, T<sub>2</sub>-weighted, or fluid attenuation inversion recovery MRIs, and low signal intensity hemorrhagic lesions on gradient-echo MRIs. An interim analysis at 6 months showed that the time requirement for the lesion registration (183 consecutive patients, 3,226 MR slices with visible stroke-related lesions) was acceptable at about 1 h of labor per patient by a trained assistant with physician oversight. <i>Conclusions:</i> We have developed a novel image-based stroke registry, with database functions that allow the formulation and testing of intuitive, image-based hypotheses in a manner not easily achievable with conventional alphanumeric stroke registries.
DOI: 10.6084/m9.figshare.5122861.v1
title: Supplementary Material for: Human BRCA1-Associated Breast Cancer: No Increase in Numerical Chromosomal Instability Compared to Sporadic Tumors

description: BRCA1 is a major gatekeeper of genomic stability. Acting in multiple central processes like double-strand break repair, centrosome replication, and checkpoint control, BRCA1 participates in maintaining genomic integrity and protects the cell against genomic instability. Chromosomal instability (CIN) as part of genomic instability is an inherent characteristic of most solid tumors and is also involved in breast cancer development. In this study, we determined the extent of CIN in 32 breast cancer tumors of women with a <i>BRCA1 </i>germline mutation compared to 62 unselected breast cancers. We applied fluorescence in situ hybridization (FISH) with centromere-specific probes for the chromosomes 1, 7, 8, 10, 17, and X and locus-specific probes for 3q27 <i>(BCL6)</i>, 5p15.2 (D5S23), 5q31 <i>(EGR1)</i>, 10q23.3 <i>(PTEN)</i>, and 14q32 (<i>IGH</i><i>@</i>) on formalin-fixed paraffin-embedded tissue microarray sections. Our hypothesis of an increased level of CIN in <i>BRCA1</i>-associated breast cancer could not be confirmed by this approach. Surprisingly, we detected no significant difference in the extent of CIN in <i>BRCA1</i>-mutated versus sporadic tumors. The only exception was the CIN value for chromosome 1. Here, the extent of CIN was slightly higher in the group of sporadic tumors.
DOI: 10.6084/m9.figshare.5122864.v1
title: Supplementary Material for: Comparison of Six Statistics of Genetic Association Regarding Their Ability to Discriminate between Causal Variants and Genetically Linked Markers

description: <i>Objectives:</i> Genome-wide association (GWA) studies still rely on the common-disease common-variant hypothesis since the assumption is associated with increased power. In GWA studies, polymorphisms are genotyped and their association with disease is investigated. Most of the identified associations are indirect and reflect a shared inheritance of the genotyped markers and genetically linked causal variants. We have compared six statistics of genetic association regarding their ability to discriminate between markers and causal susceptibility variants, including a probability value (Pval) and a Bayes Factor (BF) based on logistic regression, and the attributable familial relative risk (FRR). <i>Methods:</i> We carried out a simulation-based sensitivity analysis to explore several conceivable scenarios. Theoretical results were illustrated by established causal associations with age-related macular degeneration and by using imputed data based on HapMap for a case-control study of breast cancer. <i>Results:</i> Our data indicate that a representation of genetic association by FRRs and BFs generally facilitates the distinction of causal variants. The FRR showed the best discriminative power under most investigated scenarios, but no single statistic outperformed the others in all situations. For example, rare moderate- to low-penetrance variants (allele frequency: 1%, dominant odds ratio: ≤2.0) seem to be best discriminated by BFs. <i>Conclusions:</i> Present results may help to fully utilize the data generated in association studies that take advantage of next generation sequencing and/or multiple imputation based on the 1000 Genomes Project.
DOI: 10.6084/m9.figshare.5122846
title: Supplementary Material for: Klinische Forschung zur Anthroposophischen Medizin – Update eines «Health Technology Assessment»-Berichts und Status Quo

description: <i>Hintergrund und Fragestellung:</i> 2005 wurde ein «Health Technology Assessment»(HTA)-Bericht zu Wirksamkeit, Sicherheit, Wirtschaftlichkeit und Bedarf der Anthroposophischen Medizin (AM) erstellt. Im Kontext des «Schweizer Volksvotums pro Komplementärmedizin» (Mai 2009) erfolgte ein Update des HTA-Berichts. <i>Design:</i> Update des HTA-Berichts durch eine systematische Übersichtsarbeit. <i>Methoden:</i> Das Update wurde in Anlehnung an den bereits vorhandenen HTA-Bericht sowie entsprechend den Vorgaben des Schweizer Bundesamtes für Gesundheit durchgeführt. Nach klinischen Studien wurde systematisch in vier Datenbanken, in einer spezialisierten Zeitschrift und mit Hilfe umfassender Expertenkontakte gesucht. Studien wurden nach vorab definierten Kriterien ausgewählt, die Daten extrahiert und die Qualität individuell überprüft. <i>Ergebnisse:</i> 70 neue klinische Studien zur Wirksamkeit wurden gefunden. Damit liegen derzeit insgesamt 265 klinische Studien zur AM vor: 38 randomisierte Studien, 36 prospektive und 49 retrospektive, nichtrandomisierte, vergleichende Studien sowie 90 prospektive und 52 retrospektive Studien ohne Kontrollgruppe. Die Studien untersuchten ein weites Spektrum an AM-Therapien bei einer Vielzahl von Erkrankungen; das Gesamtsystem der AM untersuchten 38 Studien, in 10 Studien ging es um nichtpharmakologische Therapien, 133 befassten sich mit Misteltherapie bei Krebs und 84 untersuchten sonstige AM-Arzneitherapien. Die Studien zeigten in der Mehrzahl ein positives Ergebnis für AM. Die methodische Qualität der Studien variierte sehr; einige wiesen erhebliche Schwächen auf, andere waren sorgfältig durchgeführt. Die Praxisrelevanz war überwiegend hoch. Bei Beschränkung auf die qualitativ besseren Studien ergab sich ein positives Ergebnis für die AM. Nebenwirkungen und Risiken waren selten und im Schweregrad meist mild oder mäßig. Studien zur Sicherheit zeigten eine insgesamt gute Verträglichkeit. <i>Schlussfolgerung:</i> Studien unterschiedlichen Designs und unterschiedlicher Qualität beschreiben bei einer Vielzahl von Erkrankungen ein für die AM medizinisch gutes und für die Patienten zufriedenstellendes, sicheres und vermutlich auch kostengünstiges Behandlungsergebnis. Weiterführende qualitativ hochwertige Evaluationen sind wünschenswert.