Summary Of Data Research Articles

Genetic Determinants of Telomere Length and Risk of Aneurysmal Subarachnoid Hemorrhage: A Bidirectional Two-Sample Mendelian Randomization Study

Background Our objective is to investigate the potential causal relationship between telomere length (TL) and aneurysmal subarachnoid hemorrhage (aSAH) and intracranial aneurysms (IAs) by conducting a bidirectional two-sample Mendelian Randomization (MR) study. Methods We utilized publicly available summary data from genome-wide association studies (GWAS) for comprehensive analysis. Telomere length-associated data were sourced from the Epidemiology Unit (IEU) GWAS database (n = 472,174), while data pertaining to intracranial aneurysms were derived from a GWAS meta-analysis conducted by Bakker et al, encompassing aneurysmal subtypes including aSAH (n = 77,074), IAs (n = 79,429), and unruptured intracranial aneurysms (uIA) (n = 74,004), all sampled from European populations. The primary method for MR analysis employed was the Inverse Variance Weighted (IVW) method. Additionally, we conducted various sensitivity analyses to assess the heterogeneity and pleiotropy of study findings. Reverse MR analysis was employed to explore potential reverse causality. Results In the forward MR analysis, the IVW method indicated a negative association between TL and aSAH (OR = 0.636, 95% CI: 0.459–0.883, p = 0.006) as well as IAs (OR = 0.670, 95% CI: 0.499–0.900, p = 0.0079). There was no evidence of heterogeneity or horizontal pleiotropy in the forward MR analysis. Reverse MR analysis did not reveal any causal relationship between aSAH, IAs, uIA and TL. Conclusions In European populations, there exists a causal relationship between longer TL and reduced risks of aSAH and IAs Further research is warranted to elucidate the underlying mechanisms and the potential of TL as an intervention target for lowering the incidence of aSAH and IAs.

Shifting Rhythms: A Systematic Review Exploring the Multifaceted Effects of Shift Work and Circadian Disruption on Employee Cardiovascular Health.

Shift work has long been studied as a contributing risk factor for cardiovascular disease. This study aims to provide a comprehensive summary of data regarding shiftwork and its impact on the cardiovascular system from the last decade. It explores the association of shift schedules with multiple aspects of cardiovascular disease and the physiological processesthat lead up to it. It also identifies gaps in current knowledge regarding the topic. Two hundred and sixty-eight articles were gathered from PubMed, Google Scholar, and Science Direct using relevant medical subject headings (MeSH) strategy and advanced search using keywords including 'Shift work,' 'Night shift,' 'Occupational health,' 'Circadian rhythm,' 'Cardiovascular disease,' 'Cardiovascular health.'The search was conducted in April and completed in May 2023. Systemic reviews, meta-analysis, cohort and cross-sectional studies from the last 10 years were included, and assessment of multiple systematic reviews (AMSTAR), Newcastle Ottawa, and Joanna Briggs Institute (JBI) tools were used, respectively, for quality assessment. A total of 14 articles were included in our review, including five systematic reviews and meta-analyses, six prospective cohort studies, and three cross-sectional studies. Each study reported a significant association between shift work with some aspect of cardiovascular disease.An increase in the risk of myocardial infarction, coronary heart disease, hypertension, atherosclerosis, and metabolic syndrome is reported. Circadian disruption, unhealthy diet, and emotional and physiological stress contribute to these effects. Oxidative damage and inflammatory biomarkers appear to play a role in this process, but more research is warranted for a deeper understanding of these changes. Despite an abundance of evidence pointing towards the short-term and long-term harm to shift workers' cardiovascular health, there is limited research regarding the policies that are needed to better monitor cardiovascular damage in employees. The focus needs to shift toward prevention-based policies and their efficacy in workplace settings.

Intravenous Direct Thrombin Inhibitors for Acute Venous Thromboembolism or Heparin-Induced Thrombocytopenia with Thrombosis in Children: A Systematic Review of the Literature.

Intravenous direct thrombin inhibitors (DTIs) are used for thromboembolic disorders. This systematic review aims to characterize intravenous DTI agents, dosing, monitoring strategies (or use), bleeding, and mortality, in pediatric patients with acute venous thromboembolism (VTE) or heparin-induced thrombocytopenia with thrombosis (HITT). MEDLINE, Embase, and Cochrane's CENTRAL were searched from inception through July 2023. Case series, retrospective studies, and prospective studies providing per-patient or summary data for patients < 18 years of age with VTE or HITT treated with an intravenous DTI were included. Selection and data extraction were conducted independently by two reviewers. Sixteen studies (7 case reports, 1 case series, 5 retrospective studies, 3 prospective studies) with 85 patients were included. Target conditions included acute VTE in 54 (64%) and HITT in 31 (36%) patients. Bivalirudin, argatroban, and lepirudin were used in 52 (61%), 27 (32%), and 6 (7%) patients, respectively. Fifty-two (61%) patients received a bolus dose, and weighted mean infusion rates for bivalirudin, argatroban, and lepirudin were 0.2 mg/kg/hr, 1.2 mcg/kg/min, and 0.15 mg/kg/hr, respectively. The activated partial thromboplastin time was utilized for monitoring in 82 (96%) patients. Complete or partial thrombus resolution was reported in 53 (62%) patients, mortality in 6 (7%) patients, and bleeding complications in 14 (16%) patients. In this systematic review involving 85 pediatric patients treated with an intravenous DTI for acute VTE or HITT, bivalirudin was the most commonly utilized agent, with a rate of resolution over 60% despite a high acuity in the population studied. Prospective collaborative studies are warranted to establish optimal dosing and further characterize VTE and bleeding outcomes.

Fine-Mapping the Results From Genome-Wide Association Studies of Primary Biliary Cholangitis Using Susie and h2-D2.

The main goal of fine-mapping is the identification of relevant genetic variants that have a causal effect on some trait of interest, such as the presence of a disease. From a statistical point of view, fine mapping can be seen as a variable selection problem. Fine-mapping methods are often challenging to apply because of the presence of linkage disequilibrium (LD), that is, regions of the genome where the variants interrogated have high correlation. Several methods have been proposed to address this issue. Here we explore the 'Sum of Single Effects' (SuSiE) method, applied to real data (summary statistics) from a genome-wide meta-analysis of the autoimmune liver disease primary biliary cholangitis (PBC). Fine-mapping in this data set was previously performed using the FINEMAP program; we compare these previous results with those obtained from SuSiE, which provides an arguably more convenient and principled way of generating 'credible sets', that is set of predictors that are correlated with the response variable. This allows us to appropriately acknowledge the uncertainty when selecting the causal effects for the trait. We focus on the results from SuSiE-RSS, which fits the SuSiE model to summary statistics, such as z-scores, along with a correlation matrix. We also compare the SuSiE results to those obtained using a more recently developed method, h2-D2, which uses the same inputs. Overall, we find the results from SuSiE-RSS and, to a lesser extent, h2-D2, to be quite concordant with those previously obtained using FINEMAP. The resulting genes and biological pathways implicated are therefore also similar to those previously obtained, providing valuable confirmation of these previously reported results. Detailed examination of the credible sets identified suggests that, although for the majority of the loci (33 out of 56) the results from SuSiE-RSS seem most plausible, there are some loci (5 out of 56 loci) where the results from h2-D2 seem more compelling. Computer simulations suggest that, overall, SuSiE-RSS generally has slightly higher power, better precision, and better ability to identify the true number of causal variants in a region than h2-D2, although there are some scenarios where the power of h2-D2 is higher. Thus, in real data analysis, the use of complementary approaches such as both SuSiE and h2-D2 is potentially warranted.

Artificial Sweetener and the Risk of Adverse Pregnancy Outcomes: A Mendelian Randomization Study.

The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118-2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145-0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019-0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042-2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration.

Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.

Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis. Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC. Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk. This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.

Association between lipid-lowering agents with intervertebral disc degeneration, sciatica and low back pain: a drug-targeted mendelian randomized study and cross-sectional observation

BackgroundAbnormal lipid metabolism is linked to intervertebral disc degeneration (IVDD), sciatica, and low back pain (LBP), but it remains unclear whether targeted interventions can prevent these issues. This study investigated the causal effects of lipid-lowering drug use on IVDD, sciatica, and LBP development.MethodsSingle-nucleotide polymorphisms (SNPs) linked to total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C) were obtained from the Global Lipids Genetics Consortium’s genome-wide association study (GWAS). Genes near HMGCR, PCSK9, and NPC1L1 were selected to represent therapeutic inhibition targets. Using Mendelian randomization (MR) focusing on these drug targets, we identified causal effects of PCSK9, HMGCR, and NPC1L1 on the risk of developing IVDD, sciatica, and LBP, with coronary heart disease risk serving as a positive control. Using summary data from Mendelian randomization (SMR) analysis, we evaluated potential therapeutic targets for IVDD, sciatica, and LBP through protein quantitative trait loci (pQTL). The genetic associations with IVDD, sciatica, LBP, and coronary heart disease were derived from FinnGen (discovery) and UK Biobank (replication). Additionally, a cross-sectional observational study was performed using data from the National Health and Nutrition Examination Survey (NHANES) to further investigate the connection between LBP and statin use, with a sample size of 4343 participants. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the outcomes.ResultsThe NHANES-based cross-sectional study indicated that non-statin use was associated with an increased risk of developing LBP (OR = 1.29, 95% CI [1.04, 1.59], P = 0.019). Moreover, Inverse-variance weighting (IVW) analysis revealed that NPC1L1-mediated reductions in TC, LDL-C, and non-HDL-C concentrations were associated with a decreased risk of developing IVDD (P = 9.956E-03; P = 3.516E-02; P = 1.253E-04). Similarly, PCSK9-mediated reductions in LDL-C and TC concentrations were linked to a lower risk of developing sciatica (P = 3.825E-02; P = 2.709E-02). Sensitivity analysis confirmed the stability and reliability of the MR results. MST1 (macrophage stimulating 1) levels was inversely associated with IVDD, sciatica, and LBP risks.ConclusionThe results of cross-sectional study suggested that non-use of statins was positively correlated with LBP. The results of Mendelian randomization study suggest that NPC1L1 could lower the risk of developing IVDD by reducing TC, LDL-C, and non-HDL-C levels. Additionally, PCSK9 may reduce the risk of developing sciatica by lowering LDL-C and TC levels. In contrast, HMGCR appears to have no significant effect on IVDD, sciatica, or LBP development. Nonetheless, further research is needed to verify these preliminary results. MST1 warrants further exploration as a potential therapeutic target. It is necessary to do further research to validate these findings.

The causal relationship between gut microbiota and lower extremity deep vein thrombosis combined with pulmonary embolism.

Over the years, numerous studies have explored the relationship between gut microbiota and lower extremity deep vein thrombosis (LEDVT) and pulmonary embolism (PE). The present study utilized Mendelian randomization (MR) to assess the causal link between gut microbiota and LEDVT combined with PE. Human gut microbiota genome-wide association study (GWAS) summary data from the MiBioGen consortium (n = 18,340) were utilized. Summary-level data on LEDVT (2,116 cases and 359,078 controls) and LEDVT combined with PE (4,319 cases and 356,875 controls) were obtained from the IEU Open GWAS project. MR analysis was conducted using the inverse variance weighted (IVW) method as the primary analysis. Additionally, MR-Egger, weighted median, weighted mode, and simple mode were employed as supplementary methods. Sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed. Lastly, reverse MR analysis was performed. The IVW analyses revealed seven causal relationships between genetic liability in the gut microbiota and LEDVT and five causal relationships between genetic liability in the gut microbiota and LEDVT combined with PE. The intersection of these outcomes identified that the genus Butyricicoccus reduced the risk of both LEDVT and LEDVT combined with PE, while the genus Clostridium innocuum increased the risk for both conditions. This study demonstrates that the gut microbiota is causally associated with LEDVT and LEDVT combined with PE. Our findings provide valuable insights into the underlying mechanisms and suggest potential avenues for further clinical investigations of these conditions.

Nebulized tranexamic acid for treatment of post-tonsillectomy bleeding: a systematic review and meta-analysis.

Post-tonsillectomy bleeding (PTB) is a significant complication and common reason for emergency department (ED) visits. Limited literature has investigated the clinical efficacy of nebulized tranexamic acid (TXA) for treating PTB; however, the results were conflicting and not comprehensively summarized. This study aimed to provide the first-ever systematic review encompassing all literature exploring the efficacy and safety of nebulized TXA in treating PTB. We screened six databases until 01-July-2024, for relevant studies and assessed their quality using validated tools. We provided a qualitative summary of baseline characteristics and clinical data. The primary endpoint was the reoperation rate to manage PTB, and its effect size was aggregated as a proportion or risk ratio (RR) with a 95% confidence interval (CI) using a random-effects model. We analyzed nine studies (2 case reports, 4 case series, and 3 retrospective comparative studies), all of which demonstrated good quality and low risk-of-bias. In studies using nebulized TXA for treating PTB (n = 9 studies), the pooled proportion of reoperation to control bleeding was 0.27 (95% CI: 0.08-0.5). The rate of reoperation to control bleeding was significantly lower in the nebulized TXA arm compared to the no-TXA arm (n = 3 studies, RR = 0.55, 95% CI [0.39-0.77], p < 0.001). Nebulized TXA is safe and promising for treating PTB. This is evidenced by its high efficacy in achieving hemostasis in acute settings during ED visits and reducing the rate of reoperations needed to control PTB. Further high-quality investigations are warranted to corroborate these findings.

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Circulating levels of micronutrients and risk of osteomyelitis: a Mendelian randomization study.

Few observational studies have investigated the effect of micronutrients on osteomyelitis, and these findings are limited by confounding and conflicting results. Therefore, we conducted Mendelian randomization (MR) analyses to evaluate the association between blood levels of eight micronutrients (copper, selenium, zinc, vitamin B12, vitamin C, and vitamin D, vitamin B6, vitamin E) and the risk of osteomyelitis. We performed the two-sample and multivariable Mendelian randomization (MVMR) to investigate causation, where instrument variables for the predictor (micronutrients) were derived from the summary data of micronutrients from independent cohorts of European ancestry. The outcome instrumental variables were used from the summary data of European-ancestry individuals (n = 486,484). The threshold of statistical significance was set at p < 0.00625. We found a significant causal association that elevated zinc heightens the risk of developing osteomyelitis in European ancestry individuals OR = 1.23 [95% confidence interval (CI) [1.07, 1.43]; p = 4.26E-03]. Similarly, vitamin B6 showed a similar significant causal effect on osteomyelitis as a risk factor OR = 2.78 (95% CI [1.34, 5.76]; p = 6.04E-03; in the secondary analysis). Post-hoc analysis suggested this result (vitamin B6). However, the multivariable Mendelian randomization (MVMR) provides evidence against the causal association between zinc and osteomyelitis OR = 0.98(95% CI [-0.11, 0.07]; p = 7.20E-1). After searching in PhenoScanner, no SNP with confounding factors was found in the analysis of vitamin B6. There was no evidence of a reverse causal impact of osteomyelitis on zinc and vitamin B6. This study supported a strong causal association between vitamin B6 and osteomyelitis while reporting a dubious causal association between zinc and osteomyelitis.

Periodontitis and Hepatocellular Carcinoma: A Two-Sample Mendelian Randomisation Study

Introduction and AimsObservational studies have reported conflicting associations between periodontitis (PD) and hepatocellular carcinoma (HCC). To overcome these limitations, we performed a two-sample Mendelian randomization (MR) analysis to investigate the potential association between PD and HCC. MethodsWe used summary data from genome-wide association studies (GWASs) of European ancestry, integrating data from chronic/acute periodontitis (CP/AP) samples (n1 = 34,615; n2 = 277,036; n3 = 410,811) and HCC samples (n1 = 456,348; n2 = 475,638). The inverse variance-weighted (IVW) approach represents our primary analysis method, supplemented by MR-Egger regression, weighted median, weighted-mode, and simple-mode methods. Pleiotropy and heterogeneity tests were also performed. ResultsIVW analysis suggested that PD had no effect on HCC (Group 1: odds ratio [OR] = 0.912, 95% confidence interval [CI] = 0.690-1.204, P = .514; Group 2: OR = 1.038, 95% CI = 0.895-1.203, P = .623; Group 3: OR = 0.966, 95% CI = 0.851-1.096, P = .591; Group 4: OR = 1.103, 95% CI = 0.576-2.113, P = .768; Group 5: OR = 1.257, 95% CI = 0.511-1.037, P = .540; Group 6: OR = 0.728, 95% CI = 0.511-1.037, P = .079). Four complementary analyses further support this conclusion. Both the IVW and MR-Egger results indicate that the instrumental variables in each group did not exhibit significant pleiotropy. MR-Egger regression analysis showed no evidence of pleiotropic effects. ConclusionOur MR analysis suggests that PD does not significantly impact the risk of developing HCC. These results provide a new perspective on the relationship between these 2 conditions. Clinical RelevanceThis MR study suggests no significant genetic causal relationship between PD and HCC, providing a new perspective. It indicates that clinicians may not need to over-intervene in periodontal disease to prevent liver cancer, thereby avoiding unnecessary psychological burden on patients.

Exploring the complex relationship between attention deficit hyperactivity disorder and the immune system: A bidirectional Mendelian randomization analysis

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that can be accompanied by alterations in immune markers. However, the intricate nature of the association between ADHD and immune markers remains insufficiently elucidated. To explore the currently ambiguous causal relationship between ADHD and the immune system, we performed a bidirectional Mendelian randomization (MR) analysis of immune cell traits and ADHD under the randomized inverse variance weighting (IVW) method based on genome-wide association study (GWAS) summary data. We found ADHD increased the level of 3 immune cell traits including myeloid dendritic cells (β = 0.28, P = 0.008), monocyte (β = 0.25, P = 0.024) and granulocyte (β = 0.2, P = 0.042). We also identified 1 trait which belongs to B cell panel was a risk factor (odds ratio (OR) = 1.07, P = 0.001) for ADHD onset. Other 5 traits including CD14+ monocyte (OR = 0.98, P = 0.002), immature myeloid-derived suppressor cells (MDSC) (OR = 0.98, P = 0.003), monocyte MDSC (OR = 0.95, P = 0.005), CD33br HLA DR+ (OR = 0.97, P = 0.021) and basophil (OR = 0.96, P = 0.022) were protective factors for ADHD. Here we identified a range of causal relationships extending from ADHD to immune cell traits, underscoring the complex interaction patterns between ADHD and the immune system. Enhanced interventions for protective and risk factors may be beneficial in the prevention and treatment of ADHD.

Causal effect of gut microbiota on juvenile idiopathic arthritis: A two-sample Mendelian a randomization study.

There is increasing evidence of a significant association between the gut microbiome and juvenile idiopathic arthritis (JIA). However, whether this association is causal remains to be determined. This study was a two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data to investigate the causal relationship between the gut microbiome and JIA. We used summary data on gut flora and JIA obtained from genome-wide association studies (GWAS) from MiBioGen and NHGRI-EBI, using inverse variance weighting as the main method to analyse causality in the TSMR causality analysis. To check the stability of the TSMR results, we performed several sensitivity analyses and assessed the presence of reverse causality through a reverse TSMR analysis. We calculated the degree of sample overlap where applicable. The current TSMR analyses identified four bacterial taxa associated with JIA. Specifically, two bacteria, Catenibacterium (p = 2 × 10-2) and Holdemania (p = 4 × 10-2), were negatively associated with the risk of developing JIA, suggesting a protective effect, while Olsenella (p = 1 × 10-2) and Rikenellaceae (RC9gutgroup) (p = 1 × 10-2) were positively associated with the risk of JIA, suggesting that these two bacteria may be risk factors for JIA. However, the results for Catenibacterium and Holdemania should be interpreted with caution due to instability observed in 'leave-one-out' sensitivity analyses. Reverse TSMR analyses found no evidence of reverse causality between JIA and gut flora. Our confirmation of a causal relationship between gut flora and JIA provides an innovative perspective for the study of JIA: targeting and modulating dysregulation of specific bacterial taxa to prevent and treat JIA.

Exploration of protein and genetic targets causing atrioventricular block: mendelian-randomization analyses based on eQTL data and pQTL data

BackgroundAtrioventricular block (AVB) is a heterogeneous group of arrhythmias. AVB can lead to sudden arrest of the heart and subsequent syncope or sudden cardiac death. Few scholars have investigated the underlying molecular mechanisms of AVB. Finding molecular markers can facilitate understanding of AVB and exploration of therapeutic targets.MethodsTwo-sample Mendelian randomization (MR) analysis was undertaken with inverse variance weighted (IVW) model and Wald ratio as the primary approach. Reverse MR analysis was undertaken to identify the associated protein targets and gene targets. Expression quantitative trait loci (eQTL) data from the eQTLGen database and protein quantitative trait loci (pQTL) data from three previous large-scale proteomic studies on plasma were retrieved as exposure data. Genome-wide association study (GWAS) summary data (586 cases and 379,215 controls) for AVB were retrieved from the UK Biobank database. Colocalization analyses were undertaken to identify the effect of filtered markers on outcome data. Databases (DrugBank, Therapeutic Target, PubChem) were used to identify drugs that interacted with targets.ResultsWe discovered that 692 genes and 42 proteins showed a significant correlation with the AVB phenotype. Proteins (cadherin-5, sTie-1, Notch 1) and genes (DNAJC30, ABO) were putative molecules to AVB. Drug–interaction analyses revealed anticancer drugs such as tyrosine-kinase inhibitors and TIMD3 inhibitors could cause AVB. Other substances (e.g. toxins, neurological drugs) could also cause AVB.ConclusionsWe identified the proteins (cadherin-5, sTie-1, Notch 1) and gene (DNAJC30, ABO) targets associated with AVB pathogenesis. Anticancer drugs (tyrosine-kinase inhibitors, TIMD3 inhibitors), toxins, or neurological drugs could also cause AVB.

Dietary factors and the incidence of intracranial aneurysms: a Mendelian randomization research

ABSTRACT Background Intracranial aneurysms (IAs) pose a significant threat to morbidity and mortality, yet their etiology remains inadequately comprehended. The present study employs Mendelian randomization (MR) to investigate the relationship among dietary elements with IAs, encompassing unruptured intracranial aneurysms (uIA) as well as aneurysmal subarachnoid hemorrhage (aSAH). Methods The current study employed a double-sample MR test utilizing genome-wide association study (GWAS) summary data from the IEU and IAs’ meta-analysis to investigate the genetically predicted consumption levels of various dietary factors using GWAS data. Causation was assessed by techniques of MR-Egger, weighted mode, and median, as well as IVW. To guarantee the accuracy of the results, pleiotropy and heterogeneity evaluations were also carried out. Results The findings of the study indicate a positive correlation between the intake of alcohol, lamb/mutton, and pork with the risk of IAs (IVW all p < 0.05). Conversely, a negative correlation was observed regarding dried fruit consumption and the risk of aSAH (IVW p < 0.05). There was only scant evidence supporting the association between alcohol intake frequency and an elevated risk of uIA (IVW method p < 0.05). The MR analysis outcomes were authenticated by the MR-PRESSO method and were deemed reliable. Furthermore, sensitivity calculations, such as pleiotropy and homogeneity test, leave-one-out evaluation, and funnel charts, validated the robustness of the results. Conclusions The findings suggest that reducing alcohol, lamb/mutton, and pork intake, and increasing dried fruit intake may be potential strategies for the prevention of IAs and aSAH. Additional research is necessary to validate these outcomes and elucidate the underlying mechanisms.

Evaluating the impacts of surface roughness and microstructure on the size effect in two additively manufactured stainless steels

Laser powder bed fusion (L-PBF) enables direct manufacturing of components with complex geometries and thin walls, but many authors report size-dependent mechanical properties that may complicate design. Size effects are commonly attributed to surface roughness, microstructure, and/or internal defects, but the relative importance of each is still not fully understood. To systematically study these effects, L-PBF specimens made of two microstructurally-distinct stainless steels (17-4PH and 316L) were manufactured and mechanically tested, in varied heat-treatment conditions and across a range of thicknesses and build angles. It was found that the size-dependent mechanical properties are efficiently predicted by the ratio of surface roughness to specimen thickness, Ra/t, in a way that is relatively microstructure-agnostic. This metric is particularly useful for predicting ultimate strength and elongation, while microstructure moderates its predictive power for yield strength, especially in the more processing-sensitive 17-4PH. When considered in isolation, thickness or surface roughness had weaker correlations with mechanical properties and, importantly, tended to correlate much more strongly with one steel's properties than the other's. Comparing this comprehensive dataset with summary data from other researchers highlights the utility of Ra/t, and provides semi-quantitative estimates of the relative impacts of porosity, microstructure, and Ra/t on size-dependent properties.

Expert consensus on the clinical application of bifidobacterium tetravaccine tablets for digestive diseases

Based on the fact that the human gut microbiota dysbiosis can cause various diseases, probiotics have a regulatory effect on human microecological imbalance and can be used to alleviate symptoms of some diseases and/or preventing and treating certain diseases. Probiotics have been widely applied in digestive diseases in both children and adults. Bifidobacterium tetravaccine tablets as a probiotic product contains Bifidobacterium infantis (CGMCC 0460.1), Lactobacillus acidophilus (CGMCC 0460.2), Enterococcus faecalis (CGMCC 0460.3), and Bacillus cereus (CGMCC 0460.4). By combining the unique characteristics of different strains, it exerts therapeutic effects through enhancing intestinal colonization resistance, improving intestinal mucosal barrier function, and modulating immune function, thereby maintaining gut and overall health. Bifidobacterium tetravaccine tablets have been widely used for digestive diseases, with a large number of fundamental and clinical research findings accumulated in the past years, a unified clinical guideline has yet to be achieved. To standardize and guide the rational clinical use of bifidobacterium tetravaccine tablets, this expert consensus have been formulated based on the summary and update of evidence-based medical data, providing a reference for its clinical application.

The complications of traditional uvulectomy and concurrent occurrences of cultural malpractices in Ethiopia: A systematic review and meta-analysis

IntroductionDespite the establishment of a national strategy and plan to eliminate all harmful traditional practices, traditional uvulectomy remains widely practiced in Ethiopia, and there is a lack of comprehensive summary of national data on uvulectomy complications and associated malpractices. Therefore, this study aimed to assess the pooled complications of uvulectomy and concurrent occurrences of traditional malpractices in Ethiopia. MethodsThe following databases were used to retrieve studies: PubMed, EMBASE, CINAHL, Google Scholar, Web of Science, MEDLINE, Cochrane Library, SCOPUS, and Google Search. Manual searches were also utilized to identify relevant articles. Studies reporting traditional uvulectomy complications and malpractices in Ethiopia were considered. STATA Version 17 was utilized for statistical analyses, while heterogeneity and publication bias were assessed using I2 statistics. ResultsFrom a total of 259 studies found in electronic databases, 19 studies (23,559 study participants) were incorporated in the analysis. The pooled incidence of complications following traditional uvulectomy in Ethiopia was 29 % (95 % CI: 14%–44 %). Hemorrhage, transmission of communicable infections, and sepsis are the most common complications of traditional uvulectomy. Concurrent to uvulectomy female genital cutting (23 %), milk tooth extraction (29 %), bloodletting (“mebtat” in Amharic) (11 %), eyebrow incision (10 %), and body tattooing (16 %) were found to be widely practiced in Ethiopia. ConclusionsThe overall pooled results of this study revealed that three out of ten children who underwent traditional uvulectomy experienced complications such as hemorrhage, the spread of contagious infections, and sepsis. Children underwent uvulectomy are also victim to other traditional malpractices including milk teeth extraction, bloodletting, eyebrow incision, tonsillectomy, and body tattooing. Efforts should be made to update strategies to avert malpractices through awareness-creation, social mobilization, and controlling traditional practitioners.

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.