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Approximately three percent of the human genome is occupied by microsatellites a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Selleckchem BMS303141 Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.
Neurotrauma is an important but preventable cause of death and disability worldwide, with the majority being associated with road traffic collisions (RTCs). The greatest burden is seen in low -and middle- income countries (LMICs) where variations in the environment, infrastructure, population and habits can challenge the success of conventional preventative approaches. It is therefore necessary to understand local perspectives to allow for the development and implementation of context-specific strategies which are effective and sustainable.
This study took place in Colombia where qualitative data collection was carried out with ten key informants between October and November 2019. Semi-structured interviews were conducted and explored perceptions on RTCs and neurotrauma, preventative strategies and interventions, and the role of research in prevention. Interview transcripts were analysed by thematic analysis using a framework approach.
Participants' confirmed that RTCs are a significant problem in Colomnd research by illustrating different solutions to the challenges surrounding prevention and by highlighting areas for further research.
RTCs are a major problem in Colombia despite the current preventative strategies and interventions. Findings from this study have a potential to influence policy, practice and research by illustrating different solutions to the challenges surrounding prevention and by highlighting areas for further research.Improving the effectiveness of route planning, especially in road transport deliveries is a challenge we need to face in the context of advancing climate change and the sustainable development goals. The main aim of the paper is to demonstrate the above average and utilitarian significance of the multiple probabilistic traveling salesman problem (MPTSP) in the coordination and modeling of sustainable product transportation, which is a novelty at the theoretical, conceptual, methodological and empirical level. We propose a new, hybrid algorithm of solving MPTSP instances (it connects harmony search, k-means and 2-opt), which can be successfully used in economic practice for coordination and modeling of Industry 4.0. The effectiveness of proposed approach is tested using a case study of drugs distribution services and datasets obtained from the transportation enterprise located in Poland. The study focuses on the issue of planning routes, with particular emphasis on the changing demand of customers. It should be stressed that this work may be of interest to researchers but also to management practitioners. The value added of this research lies in the innovative modeling the coordination of sustainable drug transportation as an instance of MPTSP and proposing an effective method to solve it. The main research results confirm that proposed method contributes to overall sustainability of studied supply chain.[This corrects the article DOI 10.1371/journal.pone.0231147.].
We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping.
Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model.
46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11-14) vs 12 (10-14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003).
Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov NCT03394404.
Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov NCT03394404.
HIV risk screening tool validation studies have not typically included process evaluations to understand tool implementation. The study aim was to assess the fidelity to which an HIV risk screening tool was administered by lay workers and acceptability of delivering home-based screening coupled with HIV testing to beneficiaries in an orphans and vulnerable children (OVC) program.
This cross-sectional study was conducted March-April 2019 in two regions of Tanzania. Community case workers (CCW) were observed conducting screenings with OVC 2-19 years and participated in focus group discussions. Research staff used structured observation checklists to capture if screening questions were asked or reworded by CCW. In-depth interviews were conducted with older adolescents and caregivers in their homes following screening and testing. A composite score was developed for the checklist. Qualitative data were thematically analyzed to address screening and testing perceptions and experiences.
CCW (n = 32) participad in an OVC program. Improvements to questions and their delivery and ongoing mentorship could strengthen tool performance and HIV case finding using a targeted testing approach. Overall, home-based HIV risk screening and testing were acceptable to beneficiaries and CCW, could improve testing uptake, and serve as a platform to promote healthy behaviors for those with limited health system interactions.
We found sub-optimal fidelity to the administration of the screening tool by CCW in home environments to children and adolescents enrolled in an OVC program. Improvements to questions and their delivery and ongoing mentorship could strengthen tool performance and HIV case finding using a targeted testing approach. Overall, home-based HIV risk screening and testing were acceptable to beneficiaries and CCW, could improve testing uptake, and serve as a platform to promote healthy behaviors for those with limited health system interactions.[This corrects the article DOI 10.1371/journal.pone.0243141.].Prostate cancer differently affects different regions of the world, displaying higher rates in more developed areas. After the implementation of prostate-specific antigen (PSA) testing, several studies described rising rates globally, but it is possible that indolent lesions are being detected given the lack of changes in mortality data. The Brazilian government recommends against PSA screening in the male population regardless of age, but the Urology Society issued a report recommending that screening should start at 50 years old for certain men and for those aged ≥75 years with a life expectancy exceeding 10 years. In this study, we examined the incidence and mortality rates of invasive prostate cancer over time in the Sergipe state of Brazil. The databases of the Aracaju Cancer Registry and Mortality Information System were used to calculate age-standardized rates for all prostate tumors (International Classification of Diseases 10th edition C61 and D07.5) in the following age ranges 20-44, 45-54, and ≥65 years. We identified 3595 cases of cancer, 30 glandular intraepithelial high-grade lesions, and 3269 deaths. Using the Joinpoint Regression Program, we found that the incidence of prostate cancer dramatically increased over time until the mid-2000s for all age groups, after which the rates declined. Prostate cancer mortality rates increased until 2005, followed by a non-significant annual percent change of 22.0 in 2001-2005 and a stable rate thereafter. We noticed that the increases and decreases of the incidence rates of prostate cancer were associated with the screening recommendations. Meanwhile, the increased mortality rates did not appear to be associated with decreased PSA testing; instead, they were linked to the effects of age and improvements in identification of the cause of death. Thus, we do not believe a PSA screening program would benefit the population of this study.
Tests are scarce resources, especially in low and middle-income countries, and the optimization of testing programs during a pandemic is critical for the effectiveness of the disease control. Hence, we aim to use the combination of symptoms to build a predictive model as a screening tool to identify people and areas with a higher risk of SARS-CoV-2 infection to be prioritized for testing.
We performed a retrospective analysis of individuals registered in "Dados do Bem," a Brazilian app-based symptom tracker. We applied machine learning techniques and provided a SARS-CoV-2 infection risk map of Rio de Janeiro city.
From April 28 to July 16, 2020, 337,435 individuals registered their symptoms through the app. Of these, 49,721 participants were tested for SARS-CoV-2 infection, being 5,888 (11.8%) positive. Among self-reported symptoms, loss of smell (OR[95%CI] 4.6 [4.4-4.9]), fever (2.6 [2.5-2.8]), and shortness of breath (2.1 [1.6-2.7]) were independently associated with SARS-CoV-2 infection. Our final model obtained a competitive performance, with only 7% of false-negative users predicted as negatives (NPV = 0.
Here's my website: https://www.selleckchem.com/products/bms303141.html
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