Cochran's Q-test Research Articles

Long Non-Coding RNAs as Diagnostic Biomarkers for Ischemic Stroke: A Systematic Review and Meta-Analysis

Ischemic stroke is a serious cerebrovascular disease, highlighting the urgent need for reliable biomarkers for early diagnosis. Recent reports suggest that long non-coding RNAs (lncRNAs) can be potential biomarkers for ischemic stroke. Therefore, our study seeks to investigate the potential diagnostic value of lncRNAs for ischemic stroke by analyzing existing research. A comprehensive literature search was conducted across the PubMed, ScienceDirect, Wiley Online Library, and Web of Science databases for articles published up to July 10, 2024. Statistical analyses were performed using Stata 17.0 software to calculate pooled sensitivity, specificity, positive likelihood ratio (PLR), diagnostic odds ratio (DOR), negative likelihood ratio (NLR), and area under the curve (AUC). Heterogeneity was explored with the Cochran-Q test and the I2 statistical test, and publication bias was assessed with Deeks’ funnel plot. A total of 44 articles were included, involving 4302 ischemic stroke patients and 3725 healthy controls. Results demonstrated that lncRNAs H19, GAS5, PVT1, TUG1, and MALAT1 exhibited consistent trends across multiple studies. The pooled sensitivity of lncRNAs in the diagnosis of ischemic stroke was 79% (95% CI: 73–84%), specificity was 88% (95% CI: 77–94%), PLR was 6.63 (95% CI: 3.11–14.15), NLR was 0.23 (95% CI: 0.16–0.33), DOR was 28.5 (95% CI: 9.88–82.21), and AUC was 0.88 (95% CI: 0.85–0.90). Furthermore, the results of subgroup analysis indicated that lncRNA H19 had superior diagnostic performance. LncRNAs demonstrated strong diagnostic accuracy in distinguishing ischemic stroke patients from healthy controls, underscoring their potential as reliable biomarkers. Because most of the articles included in this study originate from China, large-scale, high-quality, multi-country prospective studies are required to further validate the reliability of lncRNAs as biomarkers for ischemic stroke.

Impact of ambient air pollution on physical activity engagement among university students.

PM2.5 poses significant health risks with prolonged exposure, potentially reducing physical activity levels. This study aims to investigate the impact of ambient PM2.5 levels on physical activity engagement among individuals. The retrospective cross-sectional study involved 423 students from Chiang Mai University residing there between January and August 2023. We used the validated Thai version of the International Physical Activity Questionnaire to assess physical activity intensity during high and low pollution periods. Individuals who engage in at least 150 min of moderate-intensity or 75 min of high-intensity physical activity per week meet the recommended physical activity guidelines. Multiple logistic regression analyzed air pollution's relation to physical activity intensity, and Cochran's Q-test compared activity levels across pollution periods. Recommended physical activity prevalence was 76.36% during high PM2.5 and 71.63% during low PM2.5 periods, it showed higher physical activity during polluted periods (p = 0.049). Individuals' behavior showed a preference for indoor exercise (p < 0.001), consistent PM2.5 level checks (p < 0.001) during high PM2.5 periods. Internal motivation significantly associated with recommended physical activity in both low and high PM2.5 periods (aOR = 2.46, 95% CI = 1.14 - 5.27 and aOR = 4.00, 95% CI = 1.84 - 8.70, respectively). The outdoor exercise significantly associated with the recommended physical activity only during the low PM2.5 period (aOR = 1.72, 95% CI = 1.03 - 2.87). University students showed increased physical activity intensity during high PM2.5 periods, favoring indoor exercise in polluted environments. This behavioral shift highlights environmental pollution's influence on lifestyle choices and cornering on health outcomes. Government and university support is crucial for implementing measures to mitigate PM2.5 pollution, including promoting safe indoor exercise, enhancing pollution control measures, and developing air quality monitoring and warning systems.

Recurrent aphthous stomatitis and neoplasms of the mouth and pharynx: a two-sample Mendelian randomization study

BackgroundThe association between recurrent aphthous stomatitis (RAS) and neoplasms of the mouth and pharynx (NOMAP) has been reported in some previous observational studies. However, causality is still confused. Our research aims to explore the relationship between RAS and NOMAP through a Mendelian randomization (MR) analysis and to explore whether RAS can serve as a risk factor for NOMAP to provide a reference for the clinical strategy.MethodsAn exposure dataset for RAS were collected from a published study based on the UK Biobank (UKB). Outcome datasets included Genome-wide association studies (GWAS) summary statistics of NOMAP from the FinnGen datasets. The core method was inverse variance weighting (IVW). The Bonferroni correction, MR-Egger, weighted median, weighted mode, Cochcan’s Q test, MR-PRESSO, and leave-one-out methods served as complementary methods.ResultsWe found no significant evidence of causal relationships between RAS and NOMAP. After applying the Bonferroni correction, the corrected P was equal to 0.00625 (0.05/1/8). The IVW method provided the sole evidence for RAS on Benign neoplasm of floor of mouth (BNFM) (OR = 2.509, 95% CI: 1.296–4.857, P = 0.006), but the subsequent MR-Egger regression method showed that this result may be due to horizontal pleiotropy (P = 0.035). The Cochran Q-test, MR-Egger regression, and MR-PRESSO did not reveal any heterogeneity or directional pleiotropy for the other outcomes.ConclusionsIn conclusion, this is the first MR analysis to investigate the relationship between RAS and NOMAP. Our research confirmed at the genetic level that no causal association has been identified between RAS and NOMAP, therefore facilitating a logical therapeutic perspective and the development of clinical therapies for them.

Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization.

Age-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze this potential association using Mendelian randomization (MR). In this study, AMD was classified into two types: exudative AMD and atrophic AMD. Inverse-variance weighting (IVW) was used as the main analysis method. The association between nine cathepsins and the two classifications of AMD were analyzed using multivariable Mendelian randomization (MVMR). Sensitivity analysis included Cochran's Q-test and the MR-Egger intercept test. Two-sample MR analysis showed that higher levels of cathepsin L2 were associated with a delay in the development of atrophic AMD (IVW: p = 0.017; OR = 0.885; 95% CI = 0.799-0.979). Reverse MR analysis indicated that cathepsin E levels were increased in individuals with atrophic (IVW: p = 0.023; OR = 1.058; 95% CI = 1.007-1.111) and exudative AMD (IVW: p = 0.018; OR = 1.061; 95% CI 1 = 1.010-1.115). MVMR analysis indicated a causal relationship between cathepsin G (IVW: p = 0.025; OR = 1.124; 95% CI = 1.014-1.245), cathepsin O (IVW: p = 0.043, OR = 1.158, 95% CI = 1.004-1.336), and exudative AMD after coordinating for other types of cathepsin. This study demonstrated a potential link between the cathepsin family and the onset of AMD. Elevated serum concentrations of cathepsin L2 may serve as a protective factor for atrophic AMD, while increased levels of serum cathepsin G and O concentrations may promote the development of exudative AMD. Besides, the development of AMD may be associated with elevated serum concentrations of cathepsin E.

Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis.

Globally, the prevalence of chronic kidney disease (CKD) is increasing among young people living with HIV (YPLHIV), with inconsistent estimates. Aggregated data on the prevalence of CKD are needed in sub-Saharan Africa (SSA) to inform strategies for early diagnosis and management. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of CKD among YPLHIV in SSA. We searched Medline/PubMed, EMBASE, African Index Medicus, and African Journals Online for articles reporting the prevalence of CKD among YPLHIV in SSA using predefined search strategies up to 15th January 2024. The reference lists of identified articles were checked for additional eligible studies. The eligibility criteria were studies among YPLHIV aged 10-24 years reporting CKD prevalence defined by either glomerular filtration rate (GFR), albumin-to-creatinine ratio (ACR) or proteinuria. We used a narrative synthesis to report differences between the included studies. The DerSimonian-Laird random effects model was used to pool the CKD prevalence, and heterogeneity was assessed using the Cochrane Q-test and I-squared values. We assessed the risk of bias in each article using the Joanna Briggs Institute checklist and publication bias in a funnel plot and Egger's test. Of 802 retrieved articles, 15 fulfilled the eligibility criteria and were included in the meta-analysis. Of these, 12 (80%) were cross-sectional studies that used estimated GFR to diagnose CKD. Only one study followed the standard definition of CKD. The pooled CKD prevalence from 15 studies was 12% (95% CI 6.0-19.5%), ranging from 0.8% to 53.1% according to the definition used, with a high degree of heterogeneity (I2 = 97.7%, p<0.001). The included studies were of moderate quality, with no evidence of publication bias. Sensitivity analysis showed that the findings were robust to the methodological and analytic approach. CKD prevalence among YPLHIV is moderately high and highly heterogeneous across SSA. The standard definition of CKD should be used to enable estimation of CKD prevalence in different studies and settings. HIV programs enrolling YPLHIV should routinely screen for CKD to ensure early diagnosis and management. PROSPERO registration number: CRD42022347588.

Association between human blood metabolome and risk of myocarditis: a mendelian randomization study

Myocarditis is a common disease of the cardiovascular and immune systems, but the relationship between relevant blood metabolites and the risk of myocarditis has not been well-established. To identify potential biometabolic markers associated with myocarditis, we conducted a two-sample Mendelian randomization (MR) study. We performed preliminary MR analysis using the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods to adjust for false discovery rate (FDR). Confounders were screened using the GWAS Catalog website. Sensitivity analyses included Cochrane Q-test, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), scatterplots, funnel plots, and forest plots. For genetic and directional analysis, we employed co-localization analysis and the Steiger test. MR analysis was performed using the FinnGen database and meta-analysis was performed using the IEU database. MR analysis identified significant correlations for five metabolic biomarkers after FDR correction. These included four known metabolites: kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, and 5-acetylamino-6-formylamino-3-methyluracil, as well as one unknown metabolite, X-25,422. Among these, kynurenine (OR = 1.441, 95%CI = 1.089–1.906, p-value = 0.018) and 1-stearoyl-GPE (18:0) (OR = 1.263, 95%CI = 1.029–1.550, p-value = 0.029) were identified as risk factors for myocarditis, while deoxycarnitine (OR = 0.813, 95%CI = 0.676–0.979, p-value = 0.029), 5-acetylamino-6-formylamino-3-methyluracil (OR = 0.864, 95% CI = 0.775–0.962, p-value = 0.018), and X-25,422 (OR = 0.721, 95%CI = 0.587–0.886, p-value = 0.009) were found to be protective factors. No evidence of heterogeneity, horizontal pleiotropy, or sensitivity issues was observed, and no shared genetic factors between exposure and outcome were detected. The causality was in the correct direction. Meta-analysis further confirmed the causal relationship between the five metabolites and myocarditis. This study identifies a causal relationship between five circulating metabolites and myocarditis. Kynurenine, 1-stearoyl-GPE (18:0), deoxycarnitine, X-25,422, and 5-acetylamino-6-formylamino-3-methyluracil may serve as potential drug targets for myocarditis, providing a theoretical basis for the prevention, diagnosis, and treatment of the condition.

Novel insights of phenylalanine in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) and cardiovascular complications

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to cardiovascular risk, necessitating an exploration of potential metabolic contributors, such as amino acids. While amino acids are implicated in metabolic disorders, their specific relationship with MASLD and subsequent cardiovascular complications is not well-defined. We aimed to delineate the association between circulating amino acids and MASLD, identifying amino acids that could potentially link MASLD to cardiovascular issues. Methods Utilizing UK Biobank data, we tested the association of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Afterwards, we performed Mendelian Randomization (MR) using genome-wide association study (GWAS) data from 8,434 MASLD cases and 770,180 controls, and GWAS of amino acids including 115,052 participants from UK Biobank. Multiple MR methods, including MR-Egger, Cochran's Q-test, and MR-PRESSO, were applied to assess pleiotropy and heterogeneity. Survival analysis in MASLD patients assessed the link between significant amino acid and incident severe cardiovascular outcomes, including stroke, heart failure, myocardial infarction, and mortality, using three different covariate combinations: Model 1 included age, sex, and fasting time; Model 2 included in addition smoking, alcohol use, education, physical activity, and Model 3 included body mass index (BMI) in addition to model 2. Results Nine out of the ten amino acids were statistically significantly associated with MASLD across all three models (p&amp;lt;6.25×10^-3). Among them valine, leucine, isoleucine, total branched-chain amino acids, tyrosine, alanine, and phenylalanine were positively associated with MASLD, while glutamine and glycine were negatively associated with MASLD. The genetic predisposition of MASLD was significantly associated with increased phenylalanine (beta=0.05, p=4.0×10^-4) and tyrosine (beta=0.15, p=2.0×10^-3), suggesting that alterations in these amino acids may result from the progression of MASLD. We also detected heterogeneity (Cochran’s Q-test: p=8.4×10^-9) and pleiotropy (MR-Egger: p=0.02) for tyrosine, but not for phenylalanine. Furthermore, phenylalanine levels in MASLD patients were significantly (p&amp;lt;6.25×10^-3) associated with the incidence of heart failure, stroke, and mortality, but not with myocardial infarction across all three models. We did not identify a significant association between baseline tyrosine levels and any cardiovascular complications or mortality across the three models (Figure 1). Conclusion Our findings indicate a strong association between certain amino acids and MASLD, with phenylalanine, in particular, emerging as a potential mediator of cardiovascular risk in MASLD patients. The absence of heterogeneity and pleiotropy for phenylalanine strengthens its candidacy as a biomarker for future cardiovascular complications in MASLD.

Association of diuretics with falls and wrist fractures: a Mendelian randomization study.

The association between diuretics and falls in older adult has been reported in previous studies, but discrepancy remains between the different types of diuretics. The association of diuretics with the risk of wrist fractures due to diuretics is also unclear. Therefore, in this study, we determined the association of diuretics with falls and wrist fractures by Mendelian randomization. We used a two-sample Mendelian randomization (MR) approach to evaluate the effects of the loop diuretics\potassium-sparing diuretics\thiazide diuretics (LDs\PSDs\TDs) on the risk of falls and wrist fracture using the three diuretic-associated genetically-predicted single nucleotide polymorphisms (SNPs) as genetic tools. The inverse variance weighting (IVW) method was used as the main evaluation method, with odds ratio (OR) as the evaluation criterion. Additionally, weighted median (WME), MR-Egger, weighted mode (WM) and simple mode (SM) methods were used together for the MR analysis, and sensitivity analyses were performed to assess the robustness of the main results. A total of 35 SNPs were included in this study as instrumental variables to replace LDs, PSDs, and TDs, which were 24, 7, and 4. Genetic substitutions for diuretics associated with increased risk of falls were LDs (OR = 1.012043, 95%CI: 1.001607-1.022588, p = 0.022337), PSDs (OR = 1.023794, 95%CI: 1.005605-1.042312, p = 0.010138). Genetically proxied TDs showed no association with falls, but the use of TDs showed a negative correlation with the incidence of wrist fracture (OR = 0.833, 95%CI: 0.767-0.905, p < 0.001). The Cochran Q-test showed no heterogeneity and MR-PRESSO method excluded data pleiotropy. Our findings suggest that the use of loop diuretics (LDs) or potassium-sparing diuretics (PSDs) increases the incidence of falls, but there is no causal relationship between thiazide diuretics (TDs) and falls, and TDs may actually reduce the risk of wrist fractures. Clinical use of diuretics necessitates vigilance and appropriate preventive measures to minimize fall-related events.

Meta-analysis on the Diagnostic Value of SDC2 Methylation in Colorectal Cancer Screening Among Chinese

To systematically evaluate the diagnostic value of syndecan-2 (SDC2) gene methylation status in the detection of Colorectal cancer (CRC) and advanced adenomas (AA) through meta-analysis. Databases including PubMed, Web of Science were searched from 2020 to June 14, 2024. Relevant studies were selected based on predefined inclusion and exclusion criteria. The true positive (TP), false positive (FP), false negative (FN), and true negative (TN) results were calculated for each study. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A bivariate meta-analysis model was used to pool the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR), and a summary receiver operating characteristic (SROC) curve was constructed. Spearman’s correlation coefficient, Cochran-Q test, and I² test were used to evaluate heterogeneity. Sensitivity analysis was performed to explore the potential sources of heterogeneity. 24 literatures were included for meta-analysis. The pooled sensitivity was 0.77 for CRC and 0.52 for AA, and the pooled specificity was 0.93 for CRC and 0.91 for AA. The pooled PLR was 10.63 for CRC and 5.57 for AA, and the pooled NLR was 0.25 for CRC and 0.53 for AA. The DOR was 43.21 for CRC and 10.47 for AA. The SROC AUC was 0.91 for CRC and 0.83 for AA. The methylation level of the SDC2 gene in stool samples has significant diagnostic value for colorectal cancer and is considered an ideal biomarker for the early detection of this disease.

Causal relationship between immunophenotypes and mitral valve prolapse: a bidirectional Mendelian randomization study.

Emerging evidence indicates a significant link between various immune cell types and the development of heart valve disorders. Mitral valve prolapse (MVP) is a common condition that can lead to heart failure, arrhythmias, and even sudden death. Currently, the role of immune cells in MVP is not well understood. Thus, this study aimed to explore the causal relationship between immunophenotypes and the risk of MVP. This study conducted a two-sample Mendelian randomization (MR) analysis to examine the link between 731 immunophenotypes and MVP. Publicly available data from genome-wide association studies were used for both the exposures and outcomes. The primary method for assessing the causal relationship between mitral valve prolapse and the 731 immunophenotypes was the inverse variance weighted method. Additionally, to ensure the MR results were reliable and valid, sensitivity analyses, including leave-one-out analysis, the Cochran Q-test, and the Egger intercept test, were conducted. The findings indicated that multiple immune cell phenotypes potentially cause changes in the risk of developing MVP. After adjusting for the false discovery rate, nine immune phenotypes were found to increase the risk of MVP, while nine others appeared to decrease it. In addition, reverse MR analysis found no causal relationship between MVP and these eighteen immunophenotypes. Through genetic analyses, this research demonstrated a significant causal relationship between certain immune cells and MVP, providing new insights for future basic and clinical research.

Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study.

Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis. In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. 91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01-1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00-1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78-0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88-0.98), STAM-binding protein (OR 0.83, 95% CI 0.69-0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger's intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05. Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD.

Causal association between common rheumatic diseases and arrhythmia: a Mendelian randomization study.

Observational studies have suggested a link between rheumatic diseases and arrhythmias. However, these studies have been limited by confounding factors and reverse causality, leaving the causal relationship between rheumatic diseases and arrhythmias uncertain. This study addresses this inquiry using genetic evidence. Selected single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data were employed as instrumental variables. Inverse variance weighting (IVW), MR-Egger regression, and the weighted median method were utilized in the two-sample Mendelian randomization analysis. Horizontal pleiotropy was identified and rectified through the MR-PRESSO test and MR-Egger regression. The stability and reliability of the Mendelian randomization results were appraised using the remain-one method, Cochran Q-test, and funnel plot. Odds ratios (OR) were utilized to assess the causal relationship between six rheumatic diseases and five types of arrhythmias. The Inverse Variance Weighted (IVW) method indicated a significant association between rheumatoid arthritis (RA) and an elevated risk of right bundle branch block (RBBB) (OR: 1.10, 95% CI: 1.02-1.18, p = 0.009). Additionally, gout was significantly correlated with an augmented risk of RBBB (OR: 1.28, 95% CI: 1.09-1.51, p = 0.003). Conversely, dermatomyositis (DM) exhibited a negative association with the risk of atrioventricular block (AVB) (OR: 0.94, 95% CI: 0.90-0.99, p = 0.020). No significant associations were observed between other rheumatic diseases and arrhythmias. A two-sample Mendelian Randomization (MR) study provides data indicating that in European populations, a genetically predicted gout or rheumatoid arthritis (RA) may increase the incidence of right bundle branch block (RBBB). To clarify and investigate the processes behind these causal links, more research is necessary. Because racial genetic variability exists, care should be used when interpreting our findings.

Estrogen receptor beta (ERβ) in esophageal cancer - a systematic review and meta-analysis.

Esophageal cancer is the eighth most common cause of cancer-related deaths worldwide. There are two main histological subtypes of esophageal cancer: adenocarcinoma and squamous cell carcinoma. Among the factors associated with the development of esophageal cancer, estrogen receptor beta (ERβ) has been found to have a clinical significance. To investigate the relationship between ERβ expression and esophageal cancer. English Medical literature searches were conducted for ERβ expression in patients with esophageal cancer versus healthy controls. Searches were performed up to August 31, 2023, using MEDLINE, PubMed, Embase and Google Scholar. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 4, Biostat Inc., Englewood, NJ, USA). Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated using Cochrane Q-test, and it was considered present if the Q-test P value was less than 0.10. I2 statistic was used to measure the proportion of inconsistency in individual studies, with I2 > 50% representing heterogeneity. We also calculated a potential publication bias. Ten studies representing 11 substudies were selected according to the inclusion criteria. The odds ratio of ERβ expression in fixed effect analysis was 0.448, 95% CI: 0.237 to 0.846, 55.2% lower in esophageal cancer than in normal mucosa. Heterogeneity and inconsistency were low, and no publication bias was demonstrated. This meta-analysis showed that ERβ expression is lower in esophageal cancer biopsy specimens than in healthy controls, this finding may have a significant effect on survival and can lead to new therapeutic avenues.

The Causal Effect of Urate Level on Female Infertility: A Mendelian Randomization Study.

This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis. To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a "leave-one-out" sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study. The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06-1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran's Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A "leave-one-out" sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings. In the European population, the urate level is significantly and causally associated with an increased risk of female infertility.

Obstetric care provider’s knowledge about the use of low dose aspirin for preeclampsia prevention in low and middle income countries: a systematic review and meta-analysis

Introduction: Preeclampsia can elevate the likelihood of unfavorable consequences for a mother, such as severe morbidity and mortality. World Health Organization recommends low dose acetylsalicylic acid (aspirin, 75 mg per day) for the prevention of preeclampsia in women at moderate or high risk of developing the condition. The use of low dose aspirin is dependent on the knowledge of health care providers working in the antenatal care units. We found inconsistent figures regarding the knowledge level of health care providers on low dose aspirin for preeclampsia prevention around different low and middle income countries in the world. Thus, determining the pooled knowledge level of health care providers is very important.MethodsThis systematic review and meta-analysis (SRMA) was conducted on the knowledge level of among obstetric care providers towards preeclampsia prevention in low and middle income countries. We identified relevant literature in the English language only. A comprehensive search was conducted on databases such as PubMed, Google Scholar, HINARI, and Scopus. Subsequently, all datasets were exported to Mendeley reference manager and transferred to a Microsoft Excel spreadsheet to eliminate duplicate data during the review process. The extracted Microsoft Excel spreadsheet format data was imported to STATA software version 17 (STATA corporation, Texas, USA) for analysis. Then random effect model was used to estimate the pooled level of knowledge of health care providers on low dose aspirin for preeclampsia prevention in low income countries. Cochrane Q-test and I2 statistics were computed to assess heterogeneity among all the studies included in this SRMA.ResultA total of 1231 articles were identified through our search strategies, including Google Scholar, PubMed, Hinari and Scopus. Ultimately, six articles met the eligibility criteria for inclusion in the final SRMA. The pooled knowledge level of healthcare providers regarding the use of low-dose aspirin for preeclampsia prevention in low-income countries was found to be 16.38% (95% CI: 4.36–28.40). The Cochrane heterogeneity index, with a substantial I2 value of 98.89% and a significant P-value of 0.01, indicated significant heterogeneity among the primary studies included.Conclusionthe knowledge level of obstetric care providers in low and middle income countries is found very low and all the governmental and non-governmental organizations should strive to enhance the knowledge of obstetric care providers on the use of low dose aspirin for preeclampsia prevention in low and middle income countries.

Wasting and its associated factors among under-two years children in Ethiopia: a systematic review and meta-analysis

IntroductionGlobally, about 45 million under-five children have suffered from wasting where Asian and African countries have the major share of these wasted children. Despite wasting is affected all types of populations, the long and short term effect is more severe and sensitive in under-two aged children. Hence, this review was intended to assess pooled prevalence and associated factors of wasting among under-two children in Ethiopia.MethodsThe search was done using electronic data bases (Hinari, PubMed, Google scholar, Scopus) and research repositories from June 19–22/2023. The review included articles published between January 2013 and December 2023.The study included Cross-sectional/case control studies which report the prevalence and associated factors of wasting in under-two aged children. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) quality assessment checklists for observational studies. The presence of heterogeneity between included studies was evaluated using Cochrane Q-test and the I2 statistics. Publication bias was checked through graphical and statistical test. Associated factors were estimated by random effect model using DerSimonian-Laird model weight.ResultsThe pooled prevalence of wasting among under-two children was 10.91% (95% CI: 8.97–12.85; I2 = 86.36%). Absence of maternal antenatal follow up (OR; 3.23: 95%CI: 1.20–5.26), no exclusive breast feeding until six months (OR; 5.30; 95%CI: 1.17–9.43), current illness of the child (OR; 2.58: 95%CI: 1.78–3.37), large family size (OR; 12.38; 95%CI: 1.37–26.13) and low wealth status of the households (OR; 3.91; 95%CI: 1. 54-8.36) were significant factors of wasting among under-two children.ConclusionsThis study disclosed that the pooled prevalence of wasting among under- two children were high in Ethiopia. Absence of maternal antenatal follow up, no exclusive breast feeding, low wealth status of the households, large family size and current illness of the child were significant factors of wasting. Strictly adherence of maternal antenatal follow up, counsel the parents to feed only breast milk until six months, limit the number of family size to the level of the household income and early treatment of the sick child were recommended. Furthermore, scale up the wealth status and living standard of the family can address the agenda of reducing and eradicating all forms of malnutrition. This review registered at PROSPERO with registration number CRD42023414914 (https://www.crd.york.ac.uk/prospero/#myprospero).

Health care providers`attitude and associated factors to safe abortion in Ethiopia, 2023: A systematic review and meta-analysis.

In sub-Saharan Africa, the number of maternal deaths due to unsafe abortions has been gradually rising. In Ethiopia, unplanned pregnancies contribute to 25% of births, accounting for 6%-9% of the maternal deaths resulting from unsafe abortions. Despite several disjointed cross-sectional studies that have been carried out in the past, there is no comprehensive data on the attitudes of healthcare practitioners and other related aspects regarding safe abortion in Ethiopia. This study attempted to measure pooled health care providers' attitudes and determinants of safe abortion in Ethiopia. African Journals Online, Medline/PubMed, EMBASE, Science Direct, Hinari, and Google Scholar were the databases that were accessed. The studies were evaluated critically by using the Joanna Briggs Critical Appraisal methods. The study followed the recommendations set forth by Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Data were extracted in an Excel spreadsheet and imported to STATA versions 17 software for meta-analysis. The random- effects model was used to pooled the health care providers' attitudes toward safe abortion. Heterogeneity between studies was evaluated using the Cochrane Q-test and I2 statistics (I squared statistics). To evaluate publication bias, egger's tests and funnel plots were employed. Forest plot was used to present the odds ratio (OR) with a 95% confidence interval. In this review and meta-analysis, a total of eight papers with a 2,826 sample size were considered. Overall, 65.49% of Ethiopian health care professionals had a positive attitude towards safe abortion (95%CI: 49.64, 81.34; I2 = 99.20%, P = 0.000). Knowledge of the abortion law (OR = 2.25, 95% CI: 1.06, 3.43), being a male provider (OR = 1.89, 95% CI: 1.23, 2.54), receiving training on abortion (OR = 2.91, 95% CI: 1.17, 4.65), working as a midwife (OR = 3.029, 95% CI: 1.605, 4.453) and practicing abortion procedures (OR = 2.55, 95% CI: 1.32, 3.78) were positively associated with the attitudes of the providers regarding safe abortion in Ethiopia. In Ethiopia, there was a low pooled prevalence of positive attitude towards safe abortion. Safe abortion services in Ethiopia are more likely to be viewed favorably by health care professionals who have received abortion service training and are familiar with abortion laws. As a result, it is imperative that all healthcare facilities and other relevant parties ensure that health professionals receive training on safe abortion services and are aware of Ethiopia's abortion laws.

Exploring the therapeutic potential of interleukin-6 receptor blockade in cardiovascular disease treatment through Mendelian randomization

Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10–9) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research.

Causal association between B cell count and psoriasis using two-sample Mendelian randomization.

To investigate the causality between B cell count and psoriasis by Mendelian randomization (MR). Collected B cell count and psoriasis data from IEU Open GWAS Project. Employed inverse variance weighting (IVW), MR-Egger, WM, weighted mode for analysis, ensuring result robustness. Assessed horizontal pleiotropy with MR-Egger, detected outliers using MR-PRESSO and examined instrumental variables heterogeneity with Cochran's Q-test. The IVW method suggested an association between a genetically predicted memory B cell count and the risk of psoriasis vulgaris. IVW results also showed no causality between other exposure factors and the corresponding outcomes. Also, the global test of MR-PRESSO analysis showed a significant association between a genetically predicted transitional absolute B cell count and the lower risk of psoriasis vulgaris. MR-Egger regression showed that horizontal pleiotropy did not influence the analysis results. We found that memory B cell absolute counts are associated with a lower risk of psoriasis. These data further elucidate the role of memory B cells in psoriasis and provide new options for psoriasis treatment.

Risk of Parkinson's disease and depression severity in different populations: A two-sample Mendelian randomization analysis.

Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression. Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS database）and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9. In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR]=0.990; 95% CI, 0.984-0.996; p=.002), but no causal relationship was observed between PD and MDD (IVW method, OR=0.974; 95% CI, 0.942-1.009; p=.141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR=1.001; 95% CI, 0.829-1.209; p=.990) and between PD and MDD (IVW method, OR=1.017; 95% CI, 0.982-1.052; p=.342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable. The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.