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Skin Research and Technology : Official... Jun 2024An increasing amount of research demonstrates that metabolic disorders are related to rosacea. However, the correlations and causal relationships among them remain...
BACKGROUND
An increasing amount of research demonstrates that metabolic disorders are related to rosacea. However, the correlations and causal relationships among them remain unknown.
METHODS
We conducted not only forward 2-sample MR (Mendelian randomization) analyses but also reverse MR analyses which showed positive results in the forward MR analysis. In the forward MR analyses, inverse-variance weighted (IVW) and MR-Egger were performed as MR analyses. Cochran's Q test and the MR-Egger Intercept were used for sensitivity analyses. Concerning reverse MR analyses, IVW, MR-Egger, weighted median, simple mode, and weighted mode were applied. Cochran's Q test, MR-Egger Intercept, and MR pleiotropy residual sum and outlier (MR-PRESSO) outlier test were applied as sensitivity analyses.
RESULTS
A total of 24 metabolites and 1 metabolite ratio were shown to have a causal effect on rosacea. N-lactoyl phenylalanine (N-Lac-Phe) was estimated as statistically significant by Bonferroni correction. Interestingly, we found three metabolites that were negatively associated with rosacea, especially caffeine, which are in line with the results of a large cohort study of females. For reverse MR analysis, we revealed that rosacea could potentially decrease the generation of two metabolites: octadecenedioate (C18:1-DC) and methyl vanillate sulfate.
CONCLUSION
This study identified blood metabolites that may be associated with the development of rosacea. However, the exact mechanism by which these positive metabolites influence rosacea remains uncertain due to the paucity of experimental investigations. The combination of genetics and metabolomics offers novel viewpoints on the research of underlying mechanisms of rosacea and has significant value in screening and prevention of rosacea.
Topics: Rosacea; Humans; Mendelian Randomization Analysis; Female; Causality
PubMed: 38895784
DOI: 10.1111/srt.13796 -
SAGE Open Medicine 2024Irregular menstrual cycle has negative health and psychosocial repercussions for women of reproductive age worldwide. However, there is no national data for policymakers... (Review)
Review
INTRODUCTION
Irregular menstrual cycle has negative health and psychosocial repercussions for women of reproductive age worldwide. However, there is no national data for policymakers and health planners in Ethiopia. Therefore, this review aimed to determine the overall burden of irregular menstrual cycle and predictors among reproductive-age women in Ethiopia.
METHODS
International databases (SCOPUS, CINAHL, CAB Abstract, EMBASE, PubMed, Web of Science, Google, and Google Scholar) and lists of references were employed to search literature in Ethiopia. The random-effects model was used to calculate the odds ratios of the outcome variable using STATA version 18. The heterogeneity of the studies was measured by computing and -values. In addition, sensitivity analysis and funnel plots were performed to test the stability of pooled data in the presence of outliers and publication bias.
RESULTS
The review includes 21 studies and 9109 populations. The overall burden of irregular menstrual cycles among reproductive-age women was 35% (95% CI: 30-41) with = 96.96%. Sleeping for <5 h a day (AOR: 2.49; 95% CI: 1.49-3.49) and a stressful life (AOR: 3.15; 95% CI: 1.44-4.85) were predictors of irregular menstrual cycles.
CONCLUSION
More than one in every three reproductive-age women in Ethiopia experience irregular menstrual cycles. Sleeping for <5 h a day and stress increase the likelihood of an irregular menstrual cycle, which can be modified by improving sleeping hours and decreasing stress stimulators through psychotherapy.
PubMed: 38895544
DOI: 10.1177/20503121241259623 -
BioRxiv : the Preprint Server For... Jun 2024Quality control (QC) is a crucial step to ensure the reliability and accuracy of the data obtained from RNA sequencing experiments, including spatially-resolved...
Quality control (QC) is a crucial step to ensure the reliability and accuracy of the data obtained from RNA sequencing experiments, including spatially-resolved transcriptomics (SRT). Existing QC approaches for SRT that have been adopted from single-nucleus RNA sequencing (snRNA-seq) methods are confounded by spatial biology and are inappropriate for SRT data. In addition, no methods currently exist for identifying histological tissue artifacts unique to SRT. Here, we introduce SpotSweeper, spatially-aware QC methods for identifying local outliers and regional artifacts in SRT. SpotSweeper evaluates the quality of individual spots relative to their local neighborhood, thus minimizing bias due to biological heterogeneity, and uses multiscale methods to detect regional artifacts. Using SpotSweeper on publicly available data, we identified a consistent set of Visium barcodes/spots as systematically low quality and demonstrate that SpotSweeper accurately identifies two distinct types of regional artifacts, resulting in improved downstream clustering and marker gene detection for spatial domains.
PubMed: 38895212
DOI: 10.1101/2024.06.06.597765 -
Frontiers in Immunology 2024Investigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease's etiology and developing effective...
BACKGROUND
Investigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease's etiology and developing effective interventions. Our study adopts a novel approach to examine the potential causal connections between these factors.
METHODS
Utilizing a two-sample Mendelian Randomization (MR) framework, we incorporated a multi-variable MR (MVMR) strategy to assess the mediatory mechanisms involved. This approach involved analyzing data from the MiBioGen consortium for gut microbiota and the FinnGen for RVD, among other sources. Instrumental variables (IVs) were carefully selected based on rigorous MR principles, and statistical analysis was conducted using bidirectional two-sample MR, such as inverse variance-weighted (IVW), weighted median, MR-Egger regression and MR Steiger Test methods. The MR-PRESSO strategy was employed for outlier detection, and MVMR was used to untangle the complex relationships between multiple microbiota and RVD.
RESULTS
Our analysis highlighted several gut microbiota classes and families with potential protective effects against RVD, including , and . In contrast, certain genera, such as and , were identified as potential risk factors. The MVMR analysis revealed significant mediation effects of various immune cell traits and biomarkers, such as CD4CD8 T cells, CD3 on Terminally Differentiated CD8+ T cell and Pentraxin-related protein PTX, elucidating the complex pathways linking gut microbiota to RVD.
CONCLUSION
This study underscores the intricate and potentially causal relationship between gut microbiota and RVD, mediated through a range of immune and hormonal factors. The use of MVMR in our methodological approach provides a more comprehensive understanding of these interactions, highlighting the gut microbiota's potential as therapeutic targets in RVD management. Our findings pave the way for further research to explore these complex relationships and develop targeted interventions for RVD.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Rheumatic Heart Disease; Mediation Analysis
PubMed: 38895120
DOI: 10.3389/fimmu.2024.1362753 -
Frontiers in Microbiology 2024Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal...
BACKGROUND
Previous studies have highlighted a robust correlation between gut microbiota/immune cells and ischemic stroke (IS). However, the precise nature of their causal relationship remains uncertain. To address this gap, our study aims to meticulously investigate the causal association between gut microbiota/immune cells and the likelihood of developing IS, employing a two-sample Mendelian randomization (MR) analysis.
METHODS
Our comprehensive analysis utilized summary statistics from genome-wide association studies (GWAS) on gut microbiota, immune cells, and IS. The primary MR method employed was the inverse variance-weighted (IVW) approach. To address potential pleiotropy and identify outlier genetic variants, we incorporated the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) technique, along with MR-Egger regression. Heterogeneity was assessed using Cochran's Q-test. Additionally, leave-one-out analysis was conducted to pinpoint any individual genetic variant influencing the observed causal associations. Finally, a reverse MR analysis was performed to explore the potential of reverse causation.
RESULTS
Our investigation revealed four gut microbial taxa and 16 immune cells with a significant causal relationship with IS ( < 0.05). Notably, two bacterial features and five immunophenotypes were strongly associated with a lower IS risk: genus. (OR: 0.907, 95% CI: 0.836-0.983, = 0.018), genus. (OR: 0.918, 95% CI: 0.853-0.983, = 0.988), Activated & resting Treg % CD4++ (OR: 0.977, 95% CI: 0.956-0.998, = 0.028). Additionally, significant associations between IS risk and two bacterial features along with eleven immunophenotypes were observed: genus. (OR: 1.106, 95% CI: 1.043-1.172, < 0.001), genus. (OR: 1.119, 95% CI: 1.034-1.210, = 0.005), CD127 on granulocyte (OR: 1.039, 95% CI: 1.009-1.070, = 0.011). Our analyses did not reveal heterogeneity based on the Cochrane's Q-test ( > 0.05) nor indicate instances of horizontal pleiotropy according to MR-Egger and MR-PRESSO analyses ( > 0.05). Furthermore, the robustness of our MR results was confirmed through leave-one-out analysis.
CONCLUSION
Our study provides further evidence supporting the potential association between gut microbiota and immune cells in relation to IS, shedding light on the underlying mechanisms that may contribute to this condition. These findings lay a solid foundation for future investigations into targeted prevention strategies.
PubMed: 38894965
DOI: 10.3389/fmicb.2024.1402718 -
Iranian Journal of Public Health Feb 2024Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic...
BACKGROUND
Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic stroke. However, higher LDL-C levels were closely related to IS. Based on two antagonistic viewpoints, a Mendelian randomization (MR) study was designed to evaluate the causal effects of LDL-C levels on IS.
METHODS
Datasets of LDL-C levels and ischemic stroke were acquired from genome-wide association studies (GWAS). Weighted median method was conducted for main analysis, and MR-Egger and inverse-variance weighted (IVW) methods were performed for auxiliary analyses. Heterogeneity and pleiotropic tests were utilized to confirm the reliability of this study.
RESULTS
A total of 359 single nucleotide polymorphisms (SNPs) were associated with LDL-C levels ( < 5 × 10) and 337 SNPs were available in ischemic stroke with eliminating outliers. LDL-C levels were significantly associated with ischemic stroke (OR = 1.104, 95%CI = 1.019 - 1.195, = 1.52 × 10). MR-Egger and IVW showed directionally similar estimates (MR-Egger: OR = 1.120, 95%CI = 1.040 - 1.207, = 3.12 × 10; IVW: OR = 1.120, 95%CI = 1.064 - 1.178, = 1.17 × 10).
CONCLUSION
LDL-C levels had causal effects on IS, providing insights into the design of future interventions to reduce the burden of ischemic stroke.
PubMed: 38894840
DOI: 10.18502/ijph.v53i2.14924 -
Journal of Clinical Medicine May 2024: To determine whether a sitting position with the femoral heads centered into the acetabulum is more effective than the usual sitting position in preventing migration...
UNLABELLED
: To determine whether a sitting position with the femoral heads centered into the acetabulum is more effective than the usual sitting position in preventing migration percentage progression in non-ambulatory children with bilateral cerebral palsy. : This was a multicenter, randomized controlled trial.
INCLUSION CRITERIA
spastic or dyskinetic cerebral palsy, Gross Motor Function Classification System level IV-V, age 1-6 years, migration percentage <41%, and informed consent.
EXCLUSION CRITERIA
contractures affecting the hip, anterior luxation, previous hip surgery, and lumbar scoliosis. The treatment group sat with their hips significantly abducted to reduce the head into the acetabulum in a customized system for at least five hours/day for two years. Controls sat with the pelvis and lower limbs aligned but the hips less abducted in an adaptive seating system. The primary outcome was migration percentage (MP) progression. Health-related quality of life and family satisfaction were among the secondary outcomes. The study was approved by the local ethics board and conducted in accordance with CONSORT reporting guidelines.
CLINICALTRIALS
gov ID: NCT04603625.
RESULTS
Overall median MP progression was 1.6 after the first year and 2.5 after the second year. No significant differences were observed between the groups. MP exceeded 40% and 50% in 1.8% and 0% of the experimental group and 5.4% and 3.6% of controls in years 1 and 2, respectively. Both groups expressed satisfaction with the postural system and stable health-related quality of life. : MP remained stable over the two-year period in both groups. Considering outliers which progressed over 50%, a more protective trend of the hip-centering sitting approach emerged, but this needs to be confirmed in a final, larger dataset.
PubMed: 38892841
DOI: 10.3390/jcm13113129 -
European Journal of Medical Research Jun 2024Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study...
OBJECTIVE
Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study conducted a two-way MR study to clarify the causal effect and related influencing factors between them.
METHODS
All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR-Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers.
RESULTS
MR analysis revealed no significant causal relationship between estradiol and vaginitis risk. There was a negative correlation between estradiol and age at menarche (IVW, OR: 0.9996, 95% CI: 0.9992-1.0000, P = 0.0295; WM, OR: 0.9995, 95% CI: 0.9993-0.9998, P = 0.0003), and there was a positive correlation between age at menarche and vaginitis (IVW, OR: 1.5108, 95% CI: 1.1474-2.0930, P = 0.0043; MR-Egger, OR: 2.5575, 95% CI: 1.7664-9.6580, P = 0.0013). Estradiol was negatively correlated with age at menopause (IVW, OR: 0.9872, 95% CI: 0.9786-0.9959, P = 0.0041). However, there was no causal relationship between age at menopause and vaginitis (P > 0.05). In addition, HPV E7 Type 16, HPV E7 Type 18, and Lactobacillus had no direct causal effects on estradiol and vaginitis (P > 0.05). Sensitivity analyses revealed no heterogeneity and horizontal pleiotropy.
CONCLUSION
When estrogen levels drop, it will lead to a later age of menarche, and a later age of menarche may increase the risk of vaginitis, highlighting that the longer the female reproductive tract receives estrogen stimulation, the stronger the defense ability is formed, and the prevalence of vaginitis is reduced. In conclusion, this study indirectly supports an association between reduced level of estrogen or short time of estrogen stimulation and increased risk of vaginitis.
Topics: Humans; Female; Mendelian Randomization Analysis; Estradiol; Vaginitis; Menarche; Inflammation
PubMed: 38890725
DOI: 10.1186/s40001-024-01914-4 -
Diabetology & Metabolic Syndrome Jun 2024The aim of this study was to investigate whether a causal relationship exists between serum uric acid (SUA) and diabetic microvascular complications using a two-sample...
BACKGROUND
The aim of this study was to investigate whether a causal relationship exists between serum uric acid (SUA) and diabetic microvascular complications using a two-sample Mendelian randomization (MR) method.
METHODS
We used the MR approach, utilizing genome-wide association study (GWAS) summary statistics, to estimate the causal effect of SUA on diabetic microvascular complications in European individuals. The summary statistical data of SUA were obtained from the open database (IEU OPEN GWAS PROJECT) (p < 5 × 10), and data on diabetic microvascular complications (diabetic nephropathy, diabetic neuropathy, diabetic retinopathy) were obtained from the FinnGen consortium. F-statistics were calculated to assess the correlation between instrumental variables (IVs) and SUA, and single nucleotide polymorphisms (SNPs) associated with confounders or outcomes were excluded by consulting the PhenoScanner database. Inverse variance weighting (IVW) was used for primary estimation, and MR‒Egger, weighted median (WM), and Mendelian randomization pleiotropy residuals sum and outliers (MR-PRESSO) were used for additional assessment. Heterogeneity was assessed using the Cochran's Q test, and polytropy was assessed using the MR‒Egger intercept.
RESULTS
MR analysis revealed a causal relationship between a genetically predicted increase in SUA and diabetic nephropathy [OR = 1.32, 95%(CI) = 1.07-1.63, p = 0.008]. The results were consistent with those after MR-PRESSO [OR = 1.30, 95%(CI) = 1.07-1.58, p = 0.008]. There was a causal relationship between type 2 diabetes mellitus (T2DM) and renal complication IVW [OR = 1.27, 95%(CI) = 1.00-1.62, p = 0.049]. These results were consistent with those after MR-PRESSO [OR = 1.27, 95%(CI) = 1.00-1.62, p = 0.050]. There was no significant causal relationship between the genetically predicted increase in SUA and diabetic retinopathy [OR 1.09, 95%(CI) = 0.94-1.26, p = 0.249] or diabetic neuropathy [OR = 1.08, 95%(CI) = 0.84-1.40, p = 0.549].
CONCLUSIONS
This MR analysis suggests a causal relationship between genetically predicted uric acid increases and diabetic microvascular complications. A significant causal relationship exists between SUA and diabetic nephropathy but not between SUA and diabetic retinopathy or diabetic neuropathy.
PubMed: 38890685
DOI: 10.1186/s13098-024-01377-x -
Frontiers in Cardiovascular Medicine 2024The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal...
BACKGROUND
The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal significance of this association is still unclear. This study sought to assess GERD's role as a potential contributing factor in AF.
METHODS
With the use of a two-sample Mendelian randomization (MR) technique, we assessed the causal relationship between GERD and AF. The association of genetic variants with GERD was examined using data from a recent genome-wide association study (GWAS) that included 602,604 people. Data on the association between genetic variations and AF was obtained from a second GWAS with 1,030,836 participants. The effect sizes were examined based on the inverse-variance weighted method. Additional statistical techniques, including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, outlier, and weighted median were used in the sensitivity analysis.
RESULTS
MR analyses in inverse-variance weighted models, using 76 single nucleotide polymorphisms (SNPs) as markers, revealed a relationship between genetically predicted GERD and a greater AF incidence [odds ratio (OR): 1.165, 95% CI 1.102-1.231; = 7.637 × 10]. According to MR-Egger, there was no evidence of gene pleiotropy that could be found (intercept = 0.003, = 0.581). The findings of the sensitivity study, which used several MR methods, were found to be reliable.
CONCLUSION
The MR analysis revealed a correlation between GERD and increased AF incidence, supporting the idea that treating patients with GERD as early as possible might reduce their chance of developing AF.
PubMed: 38887451
DOI: 10.3389/fcvm.2024.1393383