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141.
Georg Hahn Sharon M. Lutz Julian Hecker Dmitry Prokopenko Michael H. Cho Edwin K. Silverman Scott T. Weiss Christoph Lange 《Genetic epidemiology》2021,45(1):82-98
locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing. 相似文献
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Dr. Christoph Brochhausen Christoph B. Wiedenroth Dr. Maryam Ghalibafian Prof. Dr. Andreas Schwarting Dr. Jürgen Bohl Prof. C. James Kirkpatrick MD PhD DSc FRCPath FBSE 《Intensivmedizin und Notfallmedizin》2008,45(1):31-36
Heat stroke is a lifethreatening disease with high mortality, characterized by a body temperature of over 40°C and clinical symptoms of central nervous system dysfunction. However, the pathophysiological mechanisms are not fully understood. A new interesting explanation for the clinical symptoms could be a systemic inflammatory response due to barrier dysfunction in the intestine leading to endothelial damage and a syndrome of multiorgan dysfunction. We describe a 37-year-old male patient who collapsed while working in a vineyard in an environmental temperature of 32°C with a body temperature of 42.5°C. Despite intensive care treatment, he died with symptoms of shock and multiorgan dysfunction. Autopsy was performed followed by the histological evaluation of paraffin-embedded tissue. As correlates for clinical shock symptoms, shock kidneys and shock liver could be demonstrated. Furthermore, multiple microthrombi were found, together with clinically undetectable fibrinogen values. Finally, the patient died due to massive diffuse gastrointestinal bleeding and bleeding in pleural and pericardial cavities. No signs of severe edema of the central nervous system were detectable. This case supports the hypothesis that in heat stroke endothelial damage occurs with consecutive cascade of inflammatory and coagulatory reactions, which may play a critical pathophysiological role. 相似文献
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Csepregi A Röcken C Hoffmann J Gu P Saliger S Müller O Schneider-Stock R Kutzner N Roessner A Malfertheiner P Ebert MP 《Journal of cancer research and clinical oncology》2008,134(5):579-589
Purpose We investigated the impact of promoter methylation on APC protein expression in patients with hepatocellular carcinoma (HCC).
Materials and methods 50 patients [HCC (n=19), liver metastasis (n=19), cholangiocellular cancer (n=7), and benign liver tumors (n=5)] were studied
for methylation using Methylight analysis. APC mutation was investigated by protein truncation test and direct sequencing
of genomic DNA. The protein expression was evaluated by immunohistochemistry and Western blot analysis.
Results The APC promoter was hypermethylated in 81.8% of non-cancerous liver tissue samples. All HCC samples and ten patients with
liver metastasis (52.6%) exhibited APC promoter methylation. The degree of methylation was significantly higher in samples
from HCC compared to the non-cancerous liver tissue samples (63.1% vs. 24.98%; p=0.001). The level of APC protein expression
was significantly reduced in HCC samples compared to that of the corresponding non-tumor liver tissue (p<0.05).
Conclusions Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression
in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological
function remains unresolved. 相似文献
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