Gene-Environment Interaction Analysis Incorporating Sex, Cardiometabolic Diseases, and Multiple Deprivation Index Reveals Novel Genetic Associations With COVID-19 Severity

Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors [obesity and type 2 diabetes (T2D), tested jointly], and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the placental growth factor (PGF) gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.

Alpha2-antiplasmin deficiency affects depression and anxiety-like behavior and apoptosis induced by stress in mice

Objectives Depression is a psychiatric disorder that affects about 10% of the world’s population and is accompanied by anxiety. Depression and anxiety are often caused by various stresses. However, the etiology of depression and anxiety remains unknown. It has been reported that alpha2-antiplasmin (α2AP) not only inhibits plasmin but also has various functions such as cytokine production and cell growth. This study aimed to determine the roles of α2AP on the stress-induced depression and anxiety. Methods We investigated the mild repeated restraint stress-induced depressive and anxiety-like behavior in the α2AP+/+ and α2AP−/− mice using the social interaction test (SIT), sucrose preference test (SPT), and elevated plus maze (EPM). Results The stresses such as the mild repeated restraint stress suppressed α2AP expression in the hippocampus of mice, and the treatment of fluoxetine (selective serotonin reuptake inhibitor [SSRI]) recovered the stress-caused α2AP suppression. We also showed that α2AP deficiency promoted the mild restraint stress-stimulated depression-like behavior such as social withdrawal and apathy and apoptosis in mice. In contrast, α2AP deficiency attenuated the mild restraint stress induced the anxiety-like behavior in mice. Conclusions α2AP affects the pathogenesis of depression and anxiety induced by stress.

PENGARUH PERUBAHAN TARIF, METODE PENGHITUNGAN DAN MODERNISASI SISTEM PAJAK TERHADAP KEPATUHAN WAJIB PAJAK UMKM DENGAN KEADILAN PAJAK SEBAGAI VARIABEL MODERASI

This research was conducted to determine and test the effect of changes in tax rates (X1), tax calculation methods (X2) and modernization of the tax system (X3) on MSME taxpayer compliance with tax justice as a moderating variable (M). As for the population in this study, the UMKM taxpayers in the food and beverage sector are registered at the Surabaya City Trade Office. Data collection uses purposive sampling method, provided that the taxpayer has a NPWP and has a gross turnover (turnover) in one tax year not to exceed Rp4.8 billion. The samples used in this study were 80 respondents. Data analysis in this study used multiple linear regression and interaction regression with the help of SPPS version 17. The results of the study using multiple linear regression analysis showed that partially changes in tax rates did not have a positive effect and insignificant on taxpayer compliance, while the tax calculation method and tax system modernization partially have a positive and significant effect on taxpayer compliance. Multiple regression analysis with the interaction test for variable changes in tax rates to taxpayer compliance with tax justice as a moderating variable, the method of calculating taxes against taxpayer compliance with tax justice as a moderating variable and modernization of the tax system towards taxpayer compliance with tax fairness as a moderating variable partial positive and significant effect which means that tax justice is able to moderate all the variables used in this study.

Subgroup Analysis in Pulmonary Hypertension-specific Therapy Trials: a Systematic Review

Background. Pulmonary hypertension (PH) treatment decisions are driven by randomized controlled trials (RCTs) results. Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient’s characteristics. As subgroup claims may mislead clinician treatment decisions, there is a need for standards of such analyses.Objective. To evaluate the appropriateness and interpretation of subgroup analysis performed in pulmonary hypertension-specific therapy RCTs.Methods. A systematic review of the literature for pulmonary hypertension-specific therapy RCTs published between January 2000 and December 2020 was conducted. Claims of subgroup effects were evaluated with Sun X et al., 2012 criteria.Results. 30 RCTs were included. Evaluated subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and interaction test. The trial protocol was not available for most RCTs; significant differences were found in those articles which published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting 4 or fewer Sun criteria. Conclusion. Subgroup analyses in pulmonary hypertension-specific therapies are of poor quality. The lack of published protocols limited our capability to assess whether the published results correspond to the initially predefined analyses. Most claims of subgroup effect did not meet critical criteria.

Gene-environment interaction analysis incorporating sex, cardiometabolic diseases, and multiple deprivation index reveals novel genetic associations with COVID-19 severity

Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors (obesity and type 2 diabetes [T2D], tested jointly), and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the PGF gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.

The Role of Macroeconomic Factors as Moderating the Global Sharia Stock Index to the Indonesian Sharia Stock Index

This study examined the influence of the global sharia stock index on the Indonesian sharia stock index considering macroeconomic factors and their moderating role. The Global sharia Stock Index in this study used the Dow Jones sharia Market Index and the FTSE Global sharia Index Series. The role of moderation is proxied by inflation rate and exchange rate. The research data analysis method used multiple regression analysis and interaction test or moderating regression analysis. The results of the study showed that there was an influence of the Global Sharia Stock Index on the Indonesian Sharia Stock Index. In the moderation equation 1 (inflation) and moderation 2 (exchange rate) that interact with the Dow Jones sharia Market Index has a positive influence on each moderation equation. This showed that a moderating interaction with the Dow Jones sharia Market Index will strengthen its influence on the Indonesian Sharia Stock Index. The FTSE Global sharia Index Series that interacted with inflation in moderating equation 1 and the exchange rate in moderating equation 2 showed a negative effect. This showed that the interaction of the FTSE Global sharia Index Series with the two macroeconomic variables in each equation weakens its influence on the Indonesian Sharia Stock Index.

Chip formation and the interaction of mesoscopic geometric features of cutter

Most of the researches on the properties of micro-textured tools are based on an orthogonal test, while the interaction between micro-textured parameters is ignored. Therefore, this thesis is based on an interaction test to study the cutting performance of cutting tools. According to the chip morphology obtained from the interactive test, the micro texture diameter of 60 μm is obtained when the cutting is stable. It was also found that the synergistic effect of multiple mesoscopic geometric features had a significant influence on cutting performance. By analysis, we found the optimized parameters for the milling tool were D = 60 μm, l = 100 μm, l1 = 150 μm, r = 60 μm. Furthermore, prediction models of the cutting performance were established by univariate linear regression and the validity of these models was verified. Thus, this thesis provides a reference for improving the performance of cutting tools and for achieving efficient and high-quality machining of titanium alloys.

Pengaruh Rasio Keuangan Terhadap Harga Saham Syariah Dengan Earning Per Share Sebagai Variabel Moderating

This research is using secondary data obtained from the official website of IDX and Investing. Total population in this study are all JII members companies from 2016-2018 and the number of samples in this study are 18 companies that are members of the Indonesia Stock Exchange, especially in the Jakarta Islamic Index from 2016-2018. Data analysis techniques used in this study are the classic assumption test and the Moderated Regression Analysis (MRA) analysis test or commonly called the interaction test. Based on the results of the research conducted obtained the results of variables that have partial significant effect are DER, DPR, ROA, PBV while other variables such as PER, CR, NPM and DYR has no effect on sharia stock prices. Then for the moderation variable (Earning Per Share) proved able to moderate each independent variable and this moderating variable can strengthen the relationship between the independent variable (X) to the dependent (Y).

Spiritual Intelligence Moderates the Relationship Between Psychological Well-Being, Role Stress and Auditor Performance

The purpose of this study is to investigate the impact of psychological well-being and role stress on auditor performance, with spiritual intelligence serving as a moderating variable. The data collection for this study was obtained from a questionnaire and was collected at the Bali Province Public Accountant Office. The sample was determined using a purposive sampling method with 54 auditors from the Bali Province Public Accountants as respondents. In this study, the interaction test MRA was used to analyze data. According to the findings of the study, psychological well-being has a positive effect on auditor performance. This research also shows that role stress can impair auditor performance. Auditors' spiritual intelligence has the potential to strengthen the relationship between psychological well-being and auditor performance. On the other hand, spiritual intelligence mitigates the impact of role stress on auditor performance. Keywords: Psychological Well-Being; Stress; Auditor Performance; Spiritual Intelligence.