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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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Angela Zagatina Nadezhda Zhuravskaya Maxim Kamenskikh Dmitry Shmatov Sergey Sayganov Fausto Rigo 《Ultrasound in medicine & biology》2018,44(7):1402-1410
There is a lack of information on the prognostic value of local high velocity in coronary arteries during echocardiography. The aim of the study described here was to define the prognostic value of local velocity >70?cm/s in the left main, anterior or circumflex artery during echocardiography. There were 412 patients in the prospective study. Death, non-fatal myocardial infarction, acute pulmonary edema, acute coronary syndrome and revascularization were defined as major adverse cardiac events (MACEs). Over 10.5?mo, there were 207 patients with MACEs. Seventeen patients died, 10 had non-fatal acute cardiac events and 184 underwent revascularization. Deaths occurred in patients with high local velocity (6.4% vs. 0%, p?<0.009). Acute cardiac events occurred in 10% versus 0% (p?<0.003). MACEs were observed in 62% versus 0% (p?<0.0000001). Only maximal velocity was an independent prognostic predictor of death (odds ratio?=?1.02, 95% confidence interval: 1.01–1.03, p?<0.02) and MACEs (odds ratio?=?1.04, 95% confidence interval: 1.02–1.05, p?<0.0001). The success rate of coronary artery visualization for at least one segment was 91%. 相似文献
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Dmitry Popkov 《Strategies in trauma and limb reconstruction (Online)》2018,13(3):191-197
Telescopic rodding has been developed in order to obtain long-lasting osteosynthesis in the growing long bones of children with osteogenesis imperfecta (OI). The major and still unsolved drawback of any telescopic rod or nail design is a lack of rotational stability and, currently, no telescopic system allows immediate weight-bearing. When these problems are associated with insufficient longitudinal bone stability and diminished healing capacity, the result can be unfavourable causing secondary bone fragment displacement, delayed or non-union. This article presents a case report of operative treatment in a 9-year-old girl affected with OI type VIII complicated with postoperative defect and pseudarthrosis of the femur causing functional impairment with loss of walking ability. A combination of intramedullary flexible nailing and minimal external fixation was applied for treatment of femoral defect-pseudarthrosis in a girl of 9 years with OI type VIII. Intramedullary and extramedullary nails with wrapping of titanium nickel mesh subperiosteally provided osteosynthesis and deformity correction of the tibia of a small intramedullary canal diameter. Upright standing and walking with progressive weight-bearing was started 4 days after surgery. There were no septic or vascular complications nor complications related to Ilizarov fixator. Radiographs demonstrated bone union in the femur 46 days after surgery. At the follow-up visit 9 months after fixator removal, clinical alignment remained excellent without any relapse of deformity. Bone remodelling with restitution of medullary canal was noted on lower limb radiographs. The patient was able to stand and walk without pain with an aide or walker. At the follow-up visit 17 months after fixator removal, there was no decrease in achieved functional abilities and the treatment outcome remained satisfactory. Use of an external fixator with intramedullary nailing for treatment of postoperative pseudarthrosis in patient with severe OI (recessive form of OI, type VIII) provides longitudinal, rotational and angular stability. Furthermore, this approach ensured early functional activity and walking with full weight-bearing, both favourable conditions for bone tissue regeneration. The external fixator was applied for a short period and only for additional stability and not for progressive deformity correction or other manipulation. In addition, the combination of intramedullary and extramedullary nailing and subperiosteal titanium nickel mesh seems to be promising for osteosynthesis in the deformity correction of bones with small diameter in children with OI. 相似文献
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The coexistence of an acute coronary syndrome (ACS) and non-cardiac surgery (NCS) in an individual patient can be summarized in two challenging clinical scenarios for the treating physician: 1) Post-operative patients who develop ACS and 2) Patients with ACS who subsequently require NCS. Both settings are characterized by a struggle on the part of treating physicians attempting to optimize antithrombotic therapies for ACS while minimizing post-surgical bleeding risk. In this review we address specific clinical issues related to patients with coexistent NCS and ACS, discussing possible management strategies balancing ischemic and bleeding risk in these complex patient scenarios. 相似文献
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Oleg V. Grinchuk Efthymios Motakis Surya Pavan Yenamandra Ghim Siong Ow Piroon Jenjaroenpun Zhiqun Tang Aliaksandr A. Yarmishyn Anna V. Ivshina Vladimir A. Kuznetsov 《Oncotarget》2015,6(39):42197-42221
More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers. 相似文献