Examining Acute Coronary Syndrome Across Ethnicity,Sex, and Age

Acute coronary syndrome (ACS) remains one of the leading causes of death in the United States. With its heightened prevalence, considerable variabilities in the disease process exist across ethnicities, sex, and age. This creates substantial disparities in the recognition and management of ACS, which consequently contributes to poor outcomes. It is of utmost importance that nurse practitioners remain vigilant, cognizant, and maintain a high index of suspicion to accurately identify ACS presentations and thus efficaciously intervene to successfully manage the disease process.     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

Adopting global tools for the advancement of pharmacy practice and workforce in Saudi Arabia

BackgroundThe continuing expansion of the pharmacist’s role necessitates continuous evaluation of current practice to identify strategies for improvements. The International Pharmaceutical Federation (FIP) has developed tools to support stakeholders in identifying development needs and planning advancement strategies. The aim of this research was to utilise the FIP Global Competency Framework, version 2 (GbCF v2), and FIP Development Goals (DGs) to evaluate competencies related to pharmacy practice in Saudi Arabia, and to understand the strategies needed to develop and improve the current practice.MethodsThe study involved four phases. Phase 1 involved translation of the FIP GbCF v2 into the Arabic language. Phase 2 was a consensus panel validation to establish the initial relevance of the competencies to current practice. Phase 3 included a national survey distributed to all registered pharmacists in Saudi Arabia. The final phase was conducted through mapping ‘not relevant’ competencies to FIP DGs to identify priorities.ResultsThe translation phase yielded a bilingual framework that could be utilized by pharmacists in Saudi Arabia. The initial validation phase identified 61 behavioral statements (from 124 in the GbCF v2) as ‘highly relevant’ or ‘relevant’ to pharmacy practice. Findings from the national survey identified a list of ‘not relevant’ competencies that could highlight gaps in current practice. The final mapping phase generated a list of three FIP DG priorities: DG5 (competency development), DG8 (working with others) and DG11 (impact and outcomes).ConclusionThe study indicated that competencies in the GbCF v2 were relevant to pharmacists practicing in the country. However, some competencies were perceived as ‘not relevant’ to current practice and these highlighted gaps in the current practice that need attention. Mapping ‘not relevant’ competencies to FIP DGs should be used as a starting point towards developing strategies, systems, and protocols to advance pharmacy practice in Saudi Arabia.     

Communicating regulatory high-throughput sequencing data using BioCompute Objects

This project demonstrates the use of the IEEE 2791–2020 Standard (BioCompute Objects [BCO]) to enable the complete and concise communication of results from next generation sequencing (NGS) analysis. One arm of a clinical trial was replicated using synthetically generated data made to resemble real biological data and then two independent analyses were performed. The first simulated a pharmaceutical regulatory submission to the US Food and Drug Administration (FDA) including analysis of results and a BCO. The second simulated an FDA review that included an independent analysis of the submitted data. Of the 118 simulated patient samples generated, 117 (99.15%) were in agreement in the two analyses. This process exemplifies how a template BCO (tBCO), including a verification kit, facilitates transparency and reproducibility, thereby reinforcing confidence in the regulatory submission process.     

High Order Finite Difference Hermite WENO Fixed-Point Fast Sweeping Method for Static Hamilton-Jacobi Equations

In this paper, we combine the nonlinear HWENO reconstruction in [43] and the fixed-point iteration with Gauss-Seidel fast sweeping strategy, to solve the static Hamilton-Jacobi equations in a novel HWENO framework recently developed in [22]. The proposed HWENO frameworks enjoys several advantages. First, compared with the traditional HWENO framework, the proposed methods do not need to introduce additional auxiliary equations to update the derivatives of the unknown function $\phi$. They are now computed from the current value of $\phi$ and the previous spatial derivatives of $\phi$. This approach saves the computational storage and CPU time, which greatly improves the computational efficiency of the traditional HWENO scheme. In addition, compared with the traditional WENO method, reconstruction stencil of the HWENO methods becomes more compact, their boundary treatment is simpler, and the numerical errors are smaller on the same mesh. Second, the fixed-point fast sweeping method is used to update the numerical approximation. It is an explicit method and does not involve the inverse operation of nonlinear Hamiltonian, therefore any Hamilton-Jacobi equations with complex Hamiltonian can be solved easily. It also resolves some known issues, including that the iterative number is very sensitive to the parameter $ε$ used in the nonlinear weights, as observed in previous studies. Finally, to further reduce the computational cost, a hybrid strategy is also presented. Extensive numerical experiments are performed on two-dimensional problems, which demonstrate the good performance of the proposed fixed-point fast sweeping HWENO methods.     

Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past,present and future

The primary cilium is a highly specialized and evolutionary conserved organelle in eukaryotes that plays a significant role in cell signaling and trafficking. Over the past few decades tremendous progress has been made in understanding the physiology of cilia and the underlying pathomechanisms of various ciliopathies. Syndromic ciliopathies consist of a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis. These disorders have multiorgan involvement in addition to retinal degeneration underscoring the ubiquitous distribution of primary cilia in different cell types. Genotype-phenotype correlation is often challenging due to the allelic heterogeneity and pleiotropy of these disorders. In this review, we discuss the clinical and genetic features of syndromic ciliopathies with a focus on Bardet-Biedl syndrome (BBS) as a representative disorder. We discuss the structure and function of primary cilia and their role in retinal photoreceptors. We describe the progress made thus far in understanding the functional and genetic characterization including expression quantitative trait locus (eQTL) analysis of BBS genes. In the future directions section, we discuss the emerging technologies, such as gene therapy, as well as anticipated challenges and their implications in therapeutic development for ciliopathies.