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Breast Cancer in East Africa: Prevalence and Spectrum of Germline SNV/Indel and CNVs in BRCA1 and BRCA2 Genes Among Breast Cancer Patients in Tanzania
No full textBackground: Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. Methods: One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results: Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). Conclusions: Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies. © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd
The minnesota manual dexterity test as a bimanual performance measure in people with multiple sclerosis
No full textBackground: Increasing knowledge about unilateral or bilateral upper limb (UL) involvement in multiple sclerosis (MS) has revealed the need for an objective assessment tool. Objective: The aims of our study were to evaluate manual dexterity using Minnesota Manual Dexterity Test (MMDT) in people with MS (pwMS), to investigate the validity and feasibility of MMDT, and to examine its relationship with other variables. Methods: Eighty pwMS and forty healthy controls were enrolled. Demographic and clinical characteristics of pwMS were recorded, and manual dexterity, activity performance of the UL, hand grip and pinch strength, and fatigue levels were evaluated. Validity was performed using the Nine Hole Peg Test (NHPT). Feasibility was evaluated with questions directed to pwMS. The relationship between MMDT and strength, ABILHAND, fatigue, Expanded Disability Status Scale (EDSS) and disease duration was examined and multiple regression analysis was established. Results: For the MMDT of pwMS were mean placing-dominant 82.73 s, mean placing-nondominant 88.6 s, and mean two-hand turning and placing 61.75 s. All results were statistically significantly different compared to healthy controls. There was moderate to high correlation between the subtests of the MMDT and the NHPT. 85–90% positive feedback was received for the feasibility of MMDT. A significant interaction was found between all subtests of MMDT and EDSS, ABILHAND and disease duration in predicting manual dexterity scores. Conclusions: MMDT is a valid and feasible tool for assessing manual dexterity and it can be used as an appropriate outcome measure in researches aiming to evaluate bilateral UL function in pwMS. © 202
In Silico Analysis of SARS-CoV-2 Spike Protein N501Y and N501T Mutation Effects on Human ACE2 Binding
No full textThe SARS-CoV-2 is an RNA-based virus and the most vital step of its survival is the attachment to hACE2 through its spike protein. Although SARS-CoV-2 has the ability to maintain high accurate replication and it can be accepted as a low mutation risked virus, it already showed more than nine thousand mutations in spike protein, of which 44 mutations are located within a 3.2 Å interacting distance from the hACE2 receptor. Mutations on spike protein, N501Y and N501T raised serious concerns for higher transmissibility and resistance towards current vaccines. In the current study, the mutational outcomes of N501Y and N501T on the hACE2-SARS CoV-2 spike protein complexation were analyzed by employing all-atom classic molecular dynamics (MD) simulations. These simulations revealed that both N501Y and N501T mutations increased the binding strength of spike protein to the host hACE2, predicted by binding free energy analysis via MM/GBSA rescoring scheme. This study highlights the importance of energy-based analysis for identifying mutational outcomes and will shed light on handling long-term and effective treatment strategies including repurposing anti-viral drugs, anti-SARS-CoV-2 antibodies, vaccines, and antisense based-therapie
Comparison of Weight-Based Versus Standard Dosing of Tranexamic Acid for Blood Loss and Transfusion Amount in Knee Arthroplasty Without Tourniquet
No full textThe aim of the study is to compare weight-based versus standard dosing of intravenous (IV) tranexamic acid (TXA) for blood loss and transfusion amount in total knee arthroplasty (TKA) without a tourniquet. A total of 99 patients were divided into two groups: Group 1 (standard): 1 g of IV TXA 30 min before skin incision, and 1 g at postoperative 30 min and 3 h. Group 2 (weight-based): 10 mg/kg IV TXA 30 min before the skin incision, and 10 mg/kg at postoperative 30 min, and 3 h. Hemoglobin levels, before, and 1, and 2 days after the operation, postoperative amount of decrease in hemoglobin levels, and amount of erythrocyte transfusion were recorded. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society Score (KSS) were applied in the evaluation of TKA results preoperatively, and at 1., 3., 6., and 12. months, postoperatively. In both study groups, hemoglobin levels in male patients dropped significantly more deeply than female patients. Also, in both study groups, hemoglobin levels were significantly lower in patients with comorbid illnesses. A statistically significant difference was not detected between both groups in terms of pre-and postoperative WOMAC scores, KSS knee scores, and KSS function scores. Our study showed that standard and weight-based dosing of IV TXA treatments were similar in efficacy and safety. Both treatments reduce blood loss and the need for transfusion. Also, there was no significant difference in terms of reliability between two groups
Effect of Breast Cancer and Brast Cancer Treatment on the Blood Serum Concentrations of Trace Elements and Selenoproteins
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Trace elements (TEs) playing critical roles in chemical events that occur at the cellular level in the body are necessary for biological processes in human health. The role of TEs and seleno-proteins and their relationship with breast cancer (BC) have not been studied thoroughly and therefore remain relatively unknown. Our study aimed to investigate possible changes in the serum selenoproteins (Glutathione Peroxidase 1 (GPX1), Glutathione Peroxidase 6 (GPX6), Selenoprotein F (Sel-F), Selenoprotein H (Sel-H), Selenoprotein S (Sel-S), Selenopro-tein V (Sel-V), Selenoprotein M (Sel-M)), and TEs (Se, Zn, Mn, Cu, and Fe) levels, and TEs ratios (Fe/Se, Fe/Zn, Fe/Mn, Cu/Se, Cu/Zn, and Cu/Mn) in patients with BC before and after treatment (surgery, radiotherapy, and chemotherapy), and to evaluate the results in the patient groups with healthy controls. A total of 35 patients with BC and 25 healthy subjects were included in the study. Blood samples were collected from the patient group on the day prior to treatment, and on the day treatment was completed. Serum GPX1, GPX6, Sel-F, Sel-H, and Sel-S levels were decreased in both before and after treatment groups compared to the control. The treatment of BC resulted in increasing the concentration of Sel-V compared to before treatment levels. The treatment of BC resulted in lowering serum Se, Zn, and Fe concentrations compared to before treatment levels. Also, serum Se, Zn, and Fe levels were decreased in both before and after treatment groups compared to the control. The ratios of Cu/Se, Cu/Zn, and Cu/Mn were increased after treatment compared to the values before treatment. Cu/Se and Cu/Zn ratios were increased, but Fe/Mn ratios were decreased after treatment compared to healthy control. This study indicates that changes in serum levels of TEs such as Zn, Mn, Cu, and Se, as well as their ratios and selenoproteins, may be related to the treatments of BC. Further studies are required to clarify the exact specific mechanisms involved in the status of TEs and selenoproteins in therapeutic strategies of BC. © 2022, Polish Society Magnesium Research. All rights reserved
Research on the Role of Self-Efficacy in the Effect of Workplace Envy on Intention to Quit
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The aim of this study is to examine the mediating role of self-efficacy (SE) on the relationship between workplace envy and intention to quit. We expect that feelings of envy will be among the factors affecting the intention to quit that are frequently discussed in Organizational Behavior (OB) literature. In addition, to the best of our knowledge, the effects of SE on the relationship between envy and intention to leave have not been examined in the literature. In this study, we aim to fill the gap in the literature by revealing the possible effects of SE from a behavioral perspective.We conducted a survey of the academics of ten universities, randomly selected from five different geographical regions of Turkey. A total of 237 academics working at both state and foundation universities participated in the study. The SmartPLS package program, which is a multi-level structural equation modeling (SEM) application, was used in the analysis of the data. As a result of the analyses, we find that self-efficacy partially mediates the relationship between workplace envy and intention to quit. We expect that the results of the study will help researchers and managers who are interested in the subject to understand and manage the effects of workplace envy
Measurement of integrated luminosities at BESIII for data samples at center-of-mass energies between 4.0 and 4.6 GeV*
No full textThe integrated luminosities of data samples collected in the BESIII experiment in 2016-2017 at center-of-mass energies between 4.19 and 4.28 GeV are measured with a precision better than 1% by analyzing large-angle Bhabha scattering events. The integrated luminosities of old datasets collected in 2010-2014 are updated by considering corrections related to detector performance, offsetting the effect of newly discovered readout errors in the electromagnetic calorimeter, which can haphazardly occur
Multi-Functional Solution Model for Spectrum Compatible Ground Motion Record Selection Using Stochastic Harmony Search Algorithm
No full textSelection of appropriate ground motion (GM) records for nonlinear dynamic analysis (NDA) of structures plays a crucial role to estimate structural responses reasonably. In this study, a multi-functional solution model utilizing stochastic harmony search (HS) algorithm is proposed to obtain scaled or unscaled real GM component sets for uni-directional analysis of two-dimensional structural models and GM component pair sets for bi-directional analysis of three-dimensional structural models. The solution model allows to consider compatibility between target spectrum and both mean spectrum and individual spectra besides desired spectral variability. Uniform hazard spectrum, conditional mean spectrum or scenario-based spectrum can be selected as target spectrum. Combined response spectra of selected component pairs such as SRSS, geometric mean and maximum directional can also be handled by the solution model. To demonstrate the efficiency of the solution model, various examples were presented. In addition, a sensitivity analysis was performed to evaluate the effect of HS parameters on the solution accuracy. Results show that the proposed solution model can be regarded as efficient to obtain appropriate GM record sets to be used for NDAs within a probabilistic seismic design and/or performance assessment framework. © 2022, The Author(s), under exclusive licence to Springer Nature B.V
Observation of the doubly Cabibbo-suppressed decays D + → K + π 0 π 0 and D + → K + π 0 η
No full textBy analyzing e+e− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy of 3.773 GeV with the BESIII detector, we report the first observations of the doubly Cabibbo-suppressed decays D+→ K+π0π0 and D+→ K+π0η. The branching fractions of D+→ K+π0π0 and D+→ K+π0η are measured to be (2.1 ± 0.4stat ± 0.1syst) × 10−4 and (2.1 ± 0.5stat ± 0.1syst) × 10−4 with statistical significances of 8.8σ and 5.5σ, respectively. In addition, we search for the subprocesses D+→ K*(892)+π0 and D+→ K*(892)+η with K*(892)+→ K+π0. The branching fraction of D+→ K*(892)+η is determined to be (4.4−1.5stat+1.8± 0.2syst) × 10−4, with a statistical significance of 3.2σ. No significant signal for D+→ K*(892)+π0 is found and we set an upper limit on the branching fraction of this decay at the 90% confidence level to be 5.4 × 10−4. [Figure not available: see fulltext.] © 2022, The Author(s)
Path dependency in aesthetic control management within Turkish planning history
No full textThis article examines the effects of socio-economic and political events on the control and management of aesthetics by analysing Turkey’s urban planning process using Istanbul as the case study. The external events were analysed in Istanbul by exploring the historical patterns of Turkey’s urban planning and development history. The urban aesthetics concept, characterized by different periods from the late Ottoman era until today, includes the involvement, development, and continuity of different concepts of aesthetics in the planning process. In this study, the path dependence concept has been used as a methodology, which reveals that critical junctures or major changes have happened by changing economic and political conditions at the national and international levels. Five critical junctures were identified. The findings indicate that path dependence and trajectories revealed different institutional structures without any integrity for aesthetic control under planning regulations. © 2022 Informa UK Limited, trading as Taylor & Francis Group