Potential Causality Research Articles

The causal relationship between diabetes mellitus and the risk of sensorineural hearing loss: A Mendelian randomization study.

An increasing body of evidence suggests that diabetes mellitus (DM) plays a role in sensorineural hearing loss (SNHL). However, the specific causal relationship between DM and SNHL remains partially uncertain. This study aimed to investigate the causal relationship between DM and the risk of SNHL using a Mendelian randomization (MR) study. Single nucleotide polymorphisms closely related to DM were selected as instrumental variables using open genome-wide association study datasets. Three methods based on inverse variance weighted were utilized to investigate the causal relationship between DM and SNHL. Subsequently, multivariable MR (MVMR) was executed to adjust for confounding genetic associations. In addition, a range of sensitivity analyses were performed to assess the stability and reliability of the MR results. The inverse variance weighted analysis indicated a potential genetic causality between DM and SNHL (odds ratio [OR]: 2.179; 95% confidence interval [CI]: 1.123-4.231; P = .021). The sensitivity analyses showed that the included single nucleotide polymorphisms had no heterogeneity, horizontal pleiotropy, and outliers (P > .05). Moreover, the leave-one-out method further verified the robustness of the MR analysis results. Finally, the results of the MVMR study predicted that there was a genetic causal relationship between type 1 DM and SNHL (OR: 1.032; 95%CI: 1.018-1.047; P = 5.45 × 10-6), while there was no causality between type 2 DM and SNHL (OR: 1.000; 95%CI: 0.958-1.036; P = .853). Our study suggested that DM and type 1 DM may be genetically responsible for SNHL. Although our study did not detect a genetic causal relationship between type 2 DM and SNHL, this does not rule out a relationship between them at other mechanistic levels. Further studies are required to confirm the findings and look into the physiological and pathological mechanism underlying these relationships.

Revealing the potential causality of suicidal ideation and psychopathic symptoms among survivors 10 years after the Wenchuan earthquake using network analysis.

Little is known about the interactions and causal inference between psychopathic symptoms and suicidal ideation (SI) among earthquake survivors. Using a 10-year large cohort of Chinese adolescents exposed to the Wenchuan earthquake, this study aimed to structure networks of suicidal ideation and some specific symptoms of posttraumatic symptoms and depression among survivors of the Wenchuan earthquake to clarify the interactions and causality between these symptoms. A total of 684 survivors who completed surveys at 6 months and 10 years postearthquake and had one or above psychopathic symptoms were included in the analyses. Sociodemographic, posttraumatic stress symptoms, depressive symptoms, and suicidal ideation were measured at 6 months and/or 10 years postearthquake. Network analyses were performed based on R Version 4.1.3. The Gaussian graphical model network revealed that "depressed mood" had the highest expected influence value. In addition, the directed acyclic graph network revealed that anhedonia could affect "depressed mood," which further leads to "suicidal ideation." The pathway of "anhedonia → depressed mood → suicidal ideation" was a crucial psychopathic mechanism of suicidal ideation. It informs that intervening in anhedonia and depressed mood among earthquake-exposed survivors is necessary to potentially decrease the risk of future suicidal ideation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

How Does Politics Affect Quality of Public Transport Infrastructure?

While prior studies have investigated the impacts of political factors such as the ideological stance on quality of public infrastructure, there is a paucity of research on the political effects of re-election success, party fragmentation (political power), and the formation of new electoral consistency on quality of public transport infrastructure, which is represented in this paper by road maintenance efficiency. We employ an instrumental variable approach to mitigate a potential reverse causality bias inherent in literature. Our empirical results show that local governments whose political representatives were re-elected give rise to lower road maintenance efficiency. Local governments with new electoral constituencies report a higher road maintenance efficiency.

Supplemental Material for Revealing the Potential Causality of Suicidal Ideation and Psychopathic Symptoms Among Survivors 10 Years After the Wenchuan Earthquake Using Network Analysis

Supplemental Material for Revealing the Potential Causality of Suicidal Ideation and Psychopathic Symptoms Among Survivors 10 Years After the Wenchuan Earthquake Using Network Analysis

Interleukin-6 levels in atrium and onset of spontaneous atrial fibrillation: is there a causal relationship

Abstract Background Cumulative evidence suggests that atrial interleukin-6 (IL-6) may play a significant role in the development of spontaneous postoperative atrial fibrillation (sPOAF) in coronary artery bypass grafting (CABG) patients. Our previous studies found that the IL-6 produced by the atrium is positively related to the development of sPOAF. However, the causal relationship between IL-6 and sPOAF is not established. Purpose This study aims to explore the potential causality between atrial IL-6 and spontaneous AF(sAF), alongside assessing the impact of IL-6 on the electrophysiological properties of atrial myocytes (AM). Methods To determine the causal link between IL-6 and sAF, mice were randomly divided into eight groups: seven receiving injections of varying doses of recombinant IL-6 protein groups (15ng/kg to180ng/kg) into the left atrial wall, and one control group (vehicle). Mice were monitored for sAF for 7 days using implanted telemetry device. At 48 hrs post-injection, the left atrial appendages of another set of mice were collected for analyzing levels of IL-6, Myeloperoxidase (MPO), Transforming Growth Factor-β1 (TGF-β1), and Tumor Necrosis Factor-α (TNF-α). To assess the effect of IL-6 on the electrophysiological characteristics of AM, AMs were isolated from the hearts of 12-week-old mice and divided into experimental and control groups for electrophysiological testing. The experimental group was perfused with extracellular solutions containing 100 ng/mL of IL-6 while the control group was perfused with standard extracellular solutions. The measurements focused on action potential (AP), transient outward potassium current (Ito), and inward rectifier potassium current (Ik1) after a 30-minute perfusion. Results As depicted in Fig. 1A, a dose-response relationship between IL-6 levels and sAF occurrence was observed, with incidence increasing from 0% at 15 ng/kg to 75% at 180 ng/kg (χ²= 16.691, P = 0.005). The injection of IL-6 also induced the production of MPO, TGF-β1, and TNF-α with a dose-dependent effects (Fig. 2). In comparison to control, the AP duration at 90% (APD90) and APD50 of repolarization of atrial myocytes were significantly shortened in IL-6 group (Fig. 1B). For voltages from -10mV to +70mV, atrial myocytes in the IL-6 group showed significantly lower Ito current density than those in the control (Fig. 1C). No significant alterations were observed in the impact of IL-6 on Ik1 current density in atrial myocytes (Fig.1D). Conclusion To the best of our knowledge, this is the first study that experimentally tested the causal relation between IL-6 and sAF. The injection of IL-6 could cause the onset of sAF and produce MPO, TGF-β1, and TNF-α with a significant dose-dependent effect. The effect of IL-6 on inducing sAF might be through its effect on reducing APD and Ito current density in mouse atrial myocytes. This suggests that inhibition of atrial IL-6 might be a potential novel sPOAF prevention strategy.

Association Between Glaucoma and Brain Structural Connectivity Based on Diffusion Tensor Tractography: A Bidirectional Mendelian Randomization Study.

Glaucoma is a neurodegenerative ocular disease that is accompanied by cerebral damage extending beyond the visual system. Recent studies based on diffusion tensor tractography have suggested an association between glaucoma and brain structural connectivity but have not clarified causality. To explore the causal associations between glaucoma and brain structural connectivity, a bidirectional Mendelian randomization (MR) study was conducted involving glaucoma and 206 diffusion tensor tractography traits. Highly associated genetic variations were applied as instrumental variables and statistical data were sourced from the database of FinnGen and UK Biobank. The inverse-variance weighted method was applied to assess causal relationships. Additional sensitivity analyses were also performed. Glaucoma was potentially causally associated with alterations in three brain structural connectivities (from the SN to the thalamus, from the DAN to the putamen, and within the LN network) in the forward MR analysis, whereas the inverse MR results identified thirteen brain structural connectivity traits with a potential causal relationship to the risk of glaucoma. Both forward and reverse MR analyses satisfied the sensitivity test with no significant horizontal pleiotropy or heterogeneity. This study offered suggestive evidence for the potential causality between the risk of glaucoma and brain structural connectivity. Our findings also provided novel insights into the neurodegenerative mechanism of glaucoma.

No genetic causal relationship between lung function and osteoporosis ― evidence from a mendelian randomization study

For a long time, the decline in lung function has been regarded as a potential factor associated with the risk of osteoporosis (OP). Although several observational studies have investigated the relationship between lung function and OP, their conclusions have been inconsistent. Given that Mendelian randomization (MR) studies can help reduce the interference of confounding factors on outcomes, we adopted this approach to explore the causal relationship between lung function and OP at the genetic level. To investigate the potential causality between lung function (FVC, FEV1, FEV1/FVC, PEF) and OP, we conducted a MR analysis employing three approaches: inverse variance weighted (IVW), MR-Egger, and weighted median. We used Cochran’s Q test to detect potential heterogeneity, MR-Egger regression to evaluate directional pleiotropy, and the MR-PRESSO method to evaluate horizontal pleiotropy. In addition, we used MR-PRESSO and MR radial methods to exclude SNPs exhibiting pleiotropic outliers. Upon identification of potential outliers, we removed them and subsequently ran MR analysis again to assess the reliability of our findings. The MR analysis suggested that there was no causal effect of lung function (FVC, PEF, FEV1/FVC, FEV1) on OP, which is consistent with the. results after excluding potential outliers using MR-PRESSO and MR radial. methods. Sensitivity analysis confirmed the reliability and consistency of these. results. The study concluded that there is no causal link between lung function and OP. The association found in observational studies might be attributable to shared risk factors.

The Relationship between Negative Emotions and Atrial Fibrillation: A Mendelian Randomization Study.

The relationship between negative emotions and atrial fibrillation (AF) has garnered significant attention, yet observational studies have yielded contradictory findings regarding the causal associations between the two. Our study sought to provide genetic evidence for a causal relationship between negative emotions and AF through Mendelian randomization (MR) study. Utilizing genetic variations associated with negative emotions and AF as instrumental variables (IVs), a two-sample MR study was implemented. The potential causality between the two was initially assessed by using negative emotions as exposure and AF as outcome. Subsequently, potential reverse causality was evaluated by using AF as exposure and negative emotions as outcome. The inverse variance weighted (IVW) method served as the primary analysis for the two-sample MR, supplemented by weighted median method, MR-Egger regression, Simple mode method, and Weighted mode method. Sensitivity analyses were performed using the MR pleiotropy residual sum and outlier test (MR-PRESSO), Cochran Q test, and leave-one-out analysis to ensure the robustness of the results. The two-sample MR analyses revealed that genetic susceptibility to AF had no potential causal effect on negative emotions (p > 0.05). Conversely, genetic susceptibility to negative emotions was positively correlated with an increased relative risk of AF [odds ratio (OR), 1.173, 95% confidence interval (CI): 1.115-1.235, p = 8.475 × 10-10]. Furthermore, neither horizontal pleiotropy nor heterogeneity was detected in the analysis. Genetic evidence from the study supports a potential causal link between negative emotions and AF. The study suggests that negative emotions may elevate the risk of AF, and the escalation of negative emotions in AF patients is more likely attributable to modifiable factors rather than genetically related factors.

Pre-pregnancy BMI, gestational weight gain, and telomere length in amniotic fluid: a causal graph analysis.

Previous investigations have suggested a potential association between pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with telomere length (TL) in various tissues of pregnant women and newborns. Nonetheless, as association does not imply causation, our objective was to investigate the causal connections among pre-pregnancy BMI, GWG, and TL in amniotic fluid. The analysis included 136 mother-child pairs from the Mamma & Bambino cohort, and three causal graph models were developed to depict the interconnections between pre-pregnancy BMI, GWG, and TL. Causal graph analysis was conducted utilizing the do-operator to estimate the causal effect of GWG and the controlled direct effect of pregestational BMI. We revealed that transitioning from non-adequate to adequate GWG had a positive impact on the probability of having "long" TL (i.e., a value greater than the population median) in all three models. When considering the effect of pre-pregnancy BMI, the highest probability of "long" TL was observed in normal weight women with adequate GWG. In contrast, the effect of adequate GWG became minimal among overweight women. These results shed light on the potential causality between pre-pregnancy BMI, GWG, and TL in amniotic fluid, emphasizing the importance of appropriate weight management before and during pregnancy for optimal TL outcomes.

Does Coproduction Enhance Quality of Public Infrastructure?

Coproduction is viewed in this paper as joint effort or cooperation between citizens and public infrastructure service providers. There is a paucity of studies on the impact of coproduction on public infrastructure quality or performance. Poor public infrastructure development poses a financial burden to many developing countries. In this paper, we use road maintenance as the example of public infrastructure. Using the Afro-barometer wave-6 dataset on Uganda, we develop the appropriate coproduction indexes as well as the road maintenance performance indexes from the survey data. Our results show that coproduction has significantly positive impacts on public road maintenance performance (RMP), which raises social welfare and economic development. Our results are robust to various model specifications and the conclusions remain valid after controlling for any potential endogenous influence or reverse causality problem that might arise. Our analysis points to the practical importance of cooperation between community and government in transport infrastructure provision such as road maintenance. It also provides practical implications for policy makers on how coproduction between community and government could be arranged.

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.

Evidence of the association between asthma and lung cancer risk from mendelian randomization analysis

Asthma and lung cancer are both significant public health concerns worldwide. Previous observational studies have indicated a potential link between asthma and an increased risk of lung cancer, whereas the causal relationship remains uncertain. We aimed to investigate the potential causal relationship between asthma and lung cancer risk utilizing Mendelian randomization (MR) design.The present study employed a two-sample MR analysis utilizing summary statistics from genome-wide association studies (GWAS) with European descent of asthma and lung cancer. The MR analysis was performed using inverse variance weighting (IVW), supplemented with MR-Egger regression and weighted median method to investigate the potential causality between asthma and lung cancer. Furthermore, Sensitivity analyses were also conducted to ensure the reliability of the findings. The MR analysis showed that genetically predicted asthma had suggestive causal association with the elevated risk of lung cancer [odds ratio (OR), 1.05 (95%Cl,1.01–1.09), P = 0.01]. The consistent direction of effects observed in the three methods further supported this finding. In addition, sensitivity analyses demonstrated the reliability of the results. This study provided potential evidence supporting a causal association between asthma and lung cancer. These findings highlighted the importance of early detection and prevention strategies for lung cancer in individuals with asthma. Further research was needed to elucidate the underlying mechanisms linking asthma and lung cancer.

A Mendelian analysis of the causality between inflammatory cytokines and digestive tract cancers.

In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs. In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds. Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin. This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs. Key message What is already known on this topic The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.

The Effects of Social Interaction Intervention on Cognitive Functions Among Older Adults Without Dementia: A Systematic Review and Meta-Analysis

Abstract Background and Objectives Previous systemic reviews, predominantly including observational studies, have shown that participation in social activities is a protective factor against cognitive decline. However, this association is subject to potential reverse causality, creating a knowledge gap in our understanding of the effect of social interaction interventions on cognitive function. Therefore, this study aims to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of social interaction interventions on cognitive decline among older adults without dementia. Research Design and Methods This systematic review, registered in PROSPERO (CRD42022367828), systematically searched 6 databases from inception to May 6, 2022, to identify relevant articles on the effects of activities with social interaction components on cognitive function in community-dwelling older adults without dementia aged above 60. Two independent reviewers conducted study selection, data extraction, and bias assessment, with RevMan5.3 used for meta-analysis. Subgroup analysis was conducted to assess variation in intervention effects among subgroups. Results We included 11 studies for qualitative analysis and 8 studies for the meta-analysis. The results showed that social interaction intervention had a significant effect on executive function (standardized mean difference [SMD] = 1.60; 95% CI, 0.50 to 2.70; p = .004), but not attention and memory. The subgroup analysis showed a greater cognitive benefit for healthy older adults, but not those with mild cognitive impairment. Moreover, in-person social interaction positively affected global cognition, whereas online interaction did not. Discussion and Implications Social interaction interventions have a limited impact on cognitive function in older adults without dementia but showed potential effects on executive function. This finding offers insights for implementing social intervention in the community.

Association of metabolic score for visceral fat with all-cause mortality, cardiovascular mortality, and cancer mortality: A prospective cohort study.

Our study aimed to evaluate the association between the metabolic score for visceral fat (METS-VF) and mortality. We conducted a cohort study comprising 11,120 participants. We employed weighted multivariable Cox regression analysis to assess the relationship between METS-VF and mortality. Restricted cubic spline analyses were used to investigate potential non-linear associations. Receiver operating characteristic curves were used to evaluate the predictive value of METS-VF and other obesity-related indicators for mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of the results. Mendelian randomization analysis was utilized to assess potential causality. Over a median follow-up duration of 83 months, a total of 1014 all-cause deaths, 301 cardiovascular deaths,and 262 cancer deaths occurred. For every 0.2-unit increase in METS-VF, the hazard ratios(HRs)of all-cause mortality, cardiovascular mortality, and cancer mortality were 1.13 [95% confidence interval (CI): 1.06, 1.20], 1.18 (95% CI: 1.06, 1.31), and 1.13 (95% CI: 1.03, 1.25), respectively. In addition, restricted cubic spline analyses revealed no significant non-linear associations between METS-VF and all-cause mortality, cardiovascular mortality, and cancer mortality. In multivariate Cox regression models, hazard ratios of all-cause mortality, cardiovascular mortality and cancer mortality were higher in the highest METS-VF group compared to the reference group. Subgroup and sensitivity analyses confirmed that our results were robust. Receiver operating characteristic curves indicated that METS-VF predicted mortality better than other obesity-related indicators. Mendelian randomization analysis confirmed significant causal relationships. METS-VF was positively associated with all-cause mortality, cardiovascular mortality, and cancer mortality. These findings suggest that METS-VF could serve as a straightforward, reliable, and cost-effective marker for identifying individuals at high risk of mortality.

Integration of network pharmacology, metabolomics and lipidomics for clarifying the role of sphingolipid metabolism in the treatment of liver cancer by regorafenib

AimsRegorafenib, an FDA-approved drug for advanced primary liver cancer (PLC), could provide survival benefits for patients. However, markers for its therapeutic sensitivity are lacking. This study seeks to identify sensitive targets of regorafenib in PLC from the perspective of small molecular metabolites. Materials and methodsInitiated with network pharmacology (NP) to map regorafenib's target landscape and metabolic regulatory network in liver cancer. Subsequently, regorafenib's impact on hepatoma cells was evaluated by flow cytometry, western blotting (WB) and cell viability assay. Advanced metabolomics and lipidomics were employed to elucidate regorafenib's metabolic reprogramming effects in liver cancer. Metabolic enzyme expression was assessed by WB, immunohistochemical and immunofluorescence assays. Ultimately, mendelian randomization (MR) analysis was utilized to investigate the potential causality of sphingolipid metabolism in hepatic cancer. Key findingsRegorafenib was observed to inhibit hepatoma cell proliferation and cell cycle progression at G0/G1 phase, resulting in significant alterations in sphingolipid levels. It promoted the significant accumulation of 16:0 dihydroceramide (16:0 dhCer) by upregulating ceramide synthase 6 (CERS6) expression and inhibiting dihydroceramide desaturase 1 (DEGS1) activity. The MR analysis revealed that DEGS1 was a risk factor for the development and progression of liver cancer, while cumulative 16:0 dhCer was a protective factor. SignificanceSphingolipids, particularly dhCer and regulatory enzymes, may be potential sensitive markers of regorafenib in the treatment of liver cancer, providing new insights for enhancing the treated efficacy of regorafenib in liver cancer.

Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank

Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure. Of those proteins, 126 were associated with all three CVD outcomes and 118 were associated with at least one CVD in the China Kadoorie Biobank. Mendelian randomization and colocalization analyses indicated that genetically determined levels of 47 and 18 proteins, respectively, were associated with CVDs, including FGF5, PROCR and FURIN. While the majority of protein–CVD observational associations were noncausal, these three proteins showed evidence to support potential causality and are therefore promising targets for drug treatment for CVD outcomes.

Genetically defined causal effects of natural killer cells related traits in risk of infection: a Mendelian randomization study

BackgroundThe intricate interplay between genetics and immunology often dictates the host’s susceptibility to various diseases. This study explored the genetic causal relationship between natural killer (NK) cell-related traits and the risk of infection.MethodsSingle-nucleotide polymorphisms (SNPs) significantly associated with NK cell-related traits were selected as instrumental variables to estimate their genetic causal effects on infection. SNPs from a genome-wide association study (GWAS) on NK cell-related traits, including absolute cell counts, median fluorescence intensities reflecting surface antigen levels, and relative cell counts, were used as exposure instruments. Summary-level GWAS statistics of four phenotypes of infection were used as the outcome data. The exposure and outcome data were analyzed via the two-sample Mendelian randomization method.ResultsEach one standard deviation increase in the expression level of human leukocyte antigen (HLA)-DR on HLA-DR+ NK cells was associated with a lower risk of pneumonia (P < 0.05). An increased HLA-DR+ NK/CD3− lymphocyte ratio was related to a lower of risk of pneumonia (P < 0.05). Each one standard deviation increase in the absolute count of HLA-DR+ NK cells was associated with a lower risk of both bacterial pneumonia and pneumonia (P < 0.05). An increased HLA-DR+ NK/NK ratio was associated with a decreased risk of both pneumonia and bacterial pneumonia (P < 0.05). The results were robust under all sensitivity analyses. No evidence for heterogeneity, pleiotropy, or potential reverse causality was detected. Notably, our analysis did not reveal any significant associations between NK cell-related traits and other phenotypes of infection, including cellulitis, cystitis, and intestinal infection.ConclusionsHLA-DR+ NK cells could be a novel immune cell trait associated with a lower risk of bacterial pneumonia or pneumonia.

Restriction of salt, alcohol and coffee intake and Ménière's disease: insight from Mendelian randomization study.

Restricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière's disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD. Summary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias. The primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429-1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427-1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555-1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993-1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987-1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985-1.011; p = 0.72). This MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.

Do Illegal Migration Affect Tourism Arrivals in Greece? A Vector Autoregression Analysis

Introduction: This paper explores the impact of illegal migration on the tourism sector in Greece. Utilizing a Vector autoregression (VAR) methodology, the research examines the relationship between the influx of illegal migrants and the number of tourist arrivals. The study presents the migration as a phenomenon that takes place dynamically the last decades in Europe in general and the Greek territory particular. By providing, empirical evidence on the short-term and long-term impacts of illegal migration on tourism in Greece, this study contributes to the broader discourse on migration and economic stability. The research's findings reveal that illegal migration does not significantly influence tourism arrivals in Greece. This indicates that tourists’ decisions to visit Greece are driven by factors other than concerns related to illegal migration. Objective: The objective of this study is to investigate the relationship between the influx of illegal migrants and the number of tourist arrivals Theoretical Framework: In this topic, the main concepts and theories that underpin the research are presented: the Model of cyclicity, Lee’s migration model. Method: The research examines the relationship between the influx of illegal migrants and the number of tourist arrivals over a specific period. The methodology used for this research is Vector autoregression analysis, with monthly data for the period January 2015 to December 2023. This analytical approach allows for the examination of the dynamic interactions and potential causality between the two variables over time. Results and Discussion: The results obtained revealed reveal that illegal migration does not significantly influence tourism arrivals in Greece. Changes in the number of migrants arriving do not predict changes in tourist arrivals, and changes in tourist arrivals do not predict the number of migrants arriving in Greece. The outcome is positive for the Greek tourism industry, which is of a great importance for the country’s GDP and employment politics. Research Implications: The practical and theoretical implications of this research are discussed, providing insights into how the results can be applied or influence practices in the field of tourism. These implications could encompass the socio-economic sector of the country. Originality/Value: This study contributes to the literature by a vector autoregression analysis to the broader discourse on migration and economic stability. The relevance and value of this research are evidenced by the findings, that reveal that illegal migration does not significantly impact tourism arrivals in Greece. This indicates that tourists’ decisions to visit Greece are driven by factors other than concerns related to illegal migration.