A Systematic Review and Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Transforaminal Lumbar Interbody Fusion

Background

Transforaminal lumbar interbody fusion (TLIF) has become one of the most widely used procedures for lumbar spinal disorders. However, it is still unclear whether TLIF with unilateral pedicle screw (PS) fixation is as effective as that with bilateral PS fixation. We performed a meta-analysis of the literatures and aimed to gain a better understanding of whether TLIF with unilateral PS fixation was safe and effective for lumbar diseases.

Methodology/Principal Findings

We systematically searched Ovid, Springer, and Medline databases for relevant randomized controlled trials (RCTs) that compared the clinical and radiological outcomes of unilateral versus bilateral PS fixation in TLIF. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. We generated pooled risk ratios or weighted mean differences across studies. According to our predefined inclusion criteria, seven RCTs with a total of 441 patients were included in this study. Baseline characteristics were similar between the unilateral and bilateral groups. Our meta-analysis showed that no significant difference was detected between the two groups in terms of postoperative clinical function, fusion status, reoperation rate, complication rate, and hospital stay (p>0.05). Pooled estimates revealed that the unilateral group was associated with significantly reduced implant cost, operative time and blood loss (p<0.05).

Conclusions/Significances

Our meta-analysis suggested TLIF with unilateral PS fixation was as safe and effective as that with bilateral PS fixation for lumbar diseases in selected patients. Despite these findings, our meta-analysis was based on studies with small sample size and different study characteristics that might lead to the inconsistent results such as various functional outcomes among the included studies. Therefore, high-quality randomized controlled trials with larger sample size are also needed to further clarify these issues and to provide the long-term outcomes.     

Smoking and Risk of Erectile Dysfunction: Systematic Review of Observational Studies with Meta-Analysis

Background

There are many recent observational studies on smoking and risk of erectile dysfunction (ED) and whether smoking increases the risk of ED is still inconclusive. The objective of this meta-analysis was to synthesize evidence from studies that evaluated the association between smoking and the risk of ED.

Methods

We searched PubMed, Embase, Web of Science, and Scopus in January 2013 to identify cohort and case-control studies that evaluated the association between smoking and ED. Study quality of included studies was assessed by the Newcastle-Ottawa scale. Random-effects meta-analyses were used to combine the results of included studies.

Results

Four prospective cohort studies and four case-control studies involving 28, 586 participants were included. Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Compared with non-smokers, the overall odd ratio of ED in prospective cohort studies was 1.51(95% CI: 1.34 to 1.71) for current smokers, and it was 1.29 (95% CI: 1.07 to 1.47) for former smokers. Evidence of publication bias was not found.

Conclusion

Evidence from epidemiological studies suggests that smoking, especially current smoking, may significantly increase the risk of ED     

Plant diversity enhances provision of ecosystem services: A new synthesis

Biodiversity is known to play a fundamental role in ecosystem functioning and thus may positively influence the provision of ecosystem services with benefits to society. There is a need for further understanding of how specific components of biodiversity are affecting service provision. In this context, terrestrial plants are a particularly important component of biodiversity and one for which a wealth of information on biodiversity–ecosystem functioning relationships is available. In this paper, we consider terrestrial plants as providers of ecosystem services and analyze whether manipulating plant diversity has an effect on the magnitude of ecosystem service provision using a meta-analysis of 197 effect sizes and a vote-counting analysis of 361 significance tests. The results of these analyses are compared with those of a previous meta-analysis that included a wide diversity of service providers. We produce a synthesis table to explicitly link plants as service providers to indicators of ecosystem properties and these to ecosystem services. By focusing on only plants, we found a clear positive effect of biodiversity on six out of eight services analyzed (provisioning of plant products, erosion control, invasion resistance, pest regulation, pathogen regulation and soil fertility regulation). When controlling for pseudoreplication (repeated records from single studies), we found that four of the six positive effects remained significant; only pest regulation and soil fertility showed non-significant effects. Further expanding our basis for inference with the vote-counting analysis corroborated these results, demonstrating that quantitative meta-analysis and vote-counting methods are both useful methods to synthesize biodiversity–ecosystem service studies. Notwithstanding the restricted number of identified services, our results point to the importance of maintaining plant diversity to ensure and increased provision of ecosystem services which benefit human well-being.     

Prognostic significance of the systemic immune‐inflammation index in pancreatic carcinoma patients: a meta-analysis

Background: Systemic immune-inflammation index (SII) is a prognostic indicator for several malignancies, including pancreatic carcinoma; however, there is no consensus on its significance. In the current study, a systematic meta-analysis was used to explore the correlation between SII and prognosis in pancreatic carcinoma patients.Methods: PubMed, Embase and Cochrane Library databases were screened from inception to May 2020. Studies describing the prognostic role of SII in pancreatic carcinoma were then retrieved. The pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated using random- or fixed-effects models to determine the correlation between SII and prognosis.Results: A total of four studies, comprising 1749 patients, met the inclusion criteria of the study and were therefore included in this meta-analysis. The meta-analysis showed that high SII indicated was correlated with worse overall survival (OS) in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24–1.65, P<0.001). These findings were validated through subgroup analyses, stratified by the American Joint Committee on Cancer (AJCC) stage. In addition, patients with high SII showed poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55–3.48, P<0.001). However, analysis showed no significant correlations between SII and disease-free and relapse-free survival (RFS).Conclusion: These findings indicate that SII is a potential non-invasive and a promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, the current research did not explore whether neoadjuvant therapy has an effect on the prognostic value of SII. Further studies using adequate designs and larger sample sizes are required to validate these findings.     

Lack of Association of MiR-34b/c Polymorphism (rs4938723) with Hepatocellular Carcinoma: A Meta-Analysis

Background

Previous studies have focused on the association of miR-34 family members with carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). It has been suggested that miR-34b/c polymorphism (rs4938723) is associated with susceptibility to HCC. In the present study, we performed a meta-analysis to systematically summarize the possible association between rs4938723 and the risk for HCC.

Methodology/Principal Findings

We conducted a search of case-control studies on the associations of rs4938723 with susceptibility to HCC in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, ScienceDirect, Wiley Online Library, Wangfang database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. HCC risk associated with rs4938723 was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). 3 studies on rs4938723 were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distribution of the rs4938723 was associated with risk for HCC in all genetic models.

Conclusions/Significance

This meta-analysis suggests that rs4938723 is not associated with the risk of HCC. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.     

Association Between a Single Nucleotide Polymorphism in the TP53 Region and Risk of Ovarian Cancer

TP53 is known as a tumor suppressor gene involved in cell cycle regulation. Many previous epidemiological and clinical studies have evaluated the effects of rs1042522 polymorphism on risk of ovarian cancer. But the results are conflicting and heterogeneous. The primary objective of this study was to examine whether rs1042522 polymorphism is associated with ovarian cancer risk. We performed a comprehensive meta-analysis of 19 case–control studies that analyzed rs1042522 polymorphism in ovarian cancer risk. Odds ratios (ORs) were calculated using distinct genetic models. Heterogeneity between studies was detected by the χ²-based Q test. Additional analyses such as sensitivity analyses and publication bias were also performed. The rs1042522 polymorphism was not overall associated with ovarian cancer risk. But there was a borderline association in the heterozygote model (OR = 1.09, 95 % CI 0.99–1.21). Similar effects were observed in the subgroup of Caucasian population (the heterozygote model: OR = 1.11, 95 % CI 1.00–1.24). No significant heterogeneity and publication bias were revealed in this meta-analysis. This study provides statistical evidence that TP53 rs1042522 polymorphism may play a role in modulating risk of ovarian cancer. This observation requires further analysis of a larger study size.     

A meta-analysis of glucocorticoids as modulators of oxidative stress in vertebrates

Prolonged high secretion of glucocorticoids normally reflects a state of chronic stress, which has been associated with an increase in disease susceptibility and reduction in Darwinian fitness. Here, we hypothesize that an increase in oxidative stress accounts for the detrimental effects of prolonged high secretion of glucocorticoids. We performed a meta-analysis on studies where physiological stress was induced by administration of glucocorticoids to evaluate the magnitude of their effects on oxidative stress. Glucocorticoids have a significant effect on oxidative stress (Pearson r = 0.552), although this effect depends on the duration of treatment, and is larger in long-term experiments. Importantly, there was a significant effect on tissue, with brain and heart being the most and the least susceptible to GC-induced oxidative stress, respectively. Furthermore, effect size was larger (1) in studies using both sexes compared to males only, (2) when corticosterone rather than dexamethasone was administered and (3) in juveniles than in adults. These effects were not confounded by species, biochemical biomarker, or whether wild or laboratory animals were studied. In conclusion, our meta-analysis suggests that GC-induced oxidative stress could be a further mechanism underlying increases in disease susceptibility and decreases in Darwinian fitness observed under chronic stress.     

Diagnostic Performance of Echocardiography for the Detection of Acute Cardiac Allograft Rejection: A Systematic Review and Meta-Analysis

Objective

Many studies have addressed the diagnostic performance of echocardiography to evaluate acute cardiac allograft rejection compared with endomyocardial biopsy. But the existence of heterogeneity limited its clinical application. Thus, we conducted a comprehensive, systematic literature review and meta-analysis for the purpose.

Methods

Studies prior to September 1, 2014 identified by Medline/PubMed, EMBASE and Cochrance were examined by two independent reviews. We conducted meta-analysis by using Meta-DiSc 1.4 software. An assessment tool of QUADAS-2 was applied to evaluate the risk of bias and applicability of the studies.

Results

Thirty studies met the inclusion criteria of meta-analysis. The four parameters of pressure half time, isovolumic relaxation time, index of myocardial performance and late diastolic mitral annular motion velocity were included in the meta-analysis, with a pooled diagnostic odds ratio of 10.43, 6.89, 15.95 and 5.68 respectively, and the area under the summary receiver operating characteristic curves value of 0.829, 0.599, 0.871 and 0.685 respectively.

Conclusion

The meta-analysis and systematic review demonstrate that no single parameter of echocardiography showed a reliable diagnostic performance for acute cardiac allograft rejection. A result of echocardiography for ACAR should be comprehensively considered by physicians in the context of clinical presentations and imaging feature.     

Time of day difference in postprandial glucose and insulin responses: Systematic review and meta-analysis of acute postprandial studies

ABSTRACT

Current dietary trends show that humans consume up to 40% of their energy intake during the night. Those who habitually eat during the night are observed to have an increased risk of metabolic conditions such as type-2 diabetes and cardiovascular disease. Increasing evidence suggest that a biological consequence of eating during the night is a larger postprandial glucose response, compared to meals eaten earlier in the day. However, findings from individual acute postprandial studies have been inconsistent, due to variations in protocols. Therefore, this review aimed to systematically summarize findings from acute postprandial studies and investigate whether postprandial glucose and insulin response at night differs to during the day in healthy adults. This would indicate a possible physiological mechanism linking habitual nighttime eating and increased risk of metabolic conditions. Seven electronic databases were searched in February 2018. Included studies met the following criteria: had a day-time test between 0700 – 1600h, a nighttime test between 2000 and 0400h, the test meals were identical and consumed by the same participant at both day and night time points, preceded by a 3-h fast (minimum). Primary outcome measures were postprandial glucose and insulin incremental area under the curve (iAUC) or area under the curve (AUC). Studies that reported numerical data were included in the meta-analyses, conducted using Stata statistical software (version 13.0, StataCorp, College Station, TX, USA). For eligible studies that did not report numerical data, their authors’ conclusions on the effect of time of day on the primary outcome measures were summarized qualitatively. Full text of 172 articles were assessed for eligibility. Fifteen studies met the eligibility criteria, ten of which were included in the meta-analyses. Meta-analysis for glucose showed a lower postprandial glucose response in the day compared to during the night, after an identical meal (SMD = ?1.66; 95% CI, ?1.97 to ?1.36; p < .001). This was supported by the findings from included studies ineligible for meta-analysis. Meta-analysis also showed a lower postprandial insulin response in the day compared to during the night (SMD = ?0.35; 95% CI, ?0.63 to ?0.06; p = .016). However, findings from included studies ineligible for meta-analysis were inconsistent. Our results suggest poor glucose tolerance at night compared to the day. This may be a contributing factor to the increased risk of metabolic diseases observed in those who habitually eat during the night, such as shift workers.     

Network-Based Meta-Analyses of Associations of Multiple Gene Expression Profiles with Bone Mineral Density Variations in Women

Background

Existing microarray studies of bone mineral density (BMD) have been critical for understanding the pathophysiology of osteoporosis, and have identified a number of candidate genes. However, these studies were limited by their relatively small sample sizes and were usually analyzed individually. Here, we propose a novel network-based meta-analysis approach that combines data across six microarray studies to identify functional modules from human protein-protein interaction (PPI) data, and highlight several differentially expressed genes (DEGs) and a functional module that may play an important role in BMD regulation in women.

Methods

Expression profiling studies were identified by searching PubMed, Gene Expression Omnibus (GEO) and ArrayExpress. Two meta-analysis methods were applied across different gene expression profiling studies. The first, a nonparametric Fisher’s method, combined p-values from individual experiments to identify genes with large effect sizes. The second method combined effect sizes from individual datasets into a meta-effect size to gain a higher precision of effect size estimation across all datasets. Genes with Q test’s p-values < 0.05 or I² values > 50% were assessed by a random effects model and the remainder by a fixed effects model. Using Fisher’s combined p-values, functional modules were identified through an integrated analysis of microarray data in the context of large protein–protein interaction (PPI) networks. Two previously published meta-analysis studies of genome-wide association (GWA) datasets were used to determine whether these module genes were genetically associated with BMD. Pathway enrichment analysis was performed with a hypergeometric test.

Results

Six gene expression datasets were identified, which included a total of 249 (129 high BMD and 120 low BMD) female subjects. Using a network-based meta-analysis, a consensus module containing 58 genes (nodes) and 83 edges was detected. Pathway enrichment analysis of the 58 module genes revealed that these genes were enriched in several important KEGG pathways including Osteoclast differentiation, B cell receptor signaling pathway, MAPK signaling pathway, Chemokine signaling pathway and Insulin signaling pathway. The importance of module genes was replicated by demonstrating that most module genes were genetically associated with BMD in the GWAS data sets. Meta-analyses were performed at the individual gene level by combining p-values and effect sizes. Five candidate genes (ESR1, MAP3K3, PYGM, RAC1 and SYK) were identified based on gene expression meta-analysis, and their associations with BMD were also replicated by two BMD meta-analysis studies.

Conclusions

In summary, our network-based meta-analysis not only identified important differentially expressed genes but also discovered biologically meaningful functional modules for BMD determination. Our study may provide novel therapeutic targets for osteoporosis in women.     

Serum HER2 Is a Potential Surrogate for Tissue HER2 Status in Gastric Cancer: A Systematic Review and Meta-Analysis

Determining the expression level of human epidermal growth factor receptor 2 (HER2) in tumor tissue is of great importance for personalized therapy in gastric cancer. Although several studies have investigated whether serum HER2 can serve as a surrogate for tissue HER2 status, results have been inconsistent. We therefore performed a meta-analysis of published clinical studies in an attempt to address this problem. PubMed, Embase, Web of Science, the Cochrane Library and Science Direct were queried for eligible studies that could provide sufficient data to construct 2 × 2 contingency tables. The quality of the studies included in the meta-analysis was assessed in accordance with the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were calculated for the eligible studies. The summary receiver operating characteristic (SROC) curve was constructed and the area under the SROC (AUSROC) was used to evaluate overall diagnostic performance. Eight studies comprising a total of 1170 participants were included in our meta-analysis. The pooled sensitivity, specificity and DOR were 0.39 (95% CI: 0.21–0.61), 0.98 (95% CI: 0.87–1.00), and 27 (95% CI: 9–81), respectively. The AUSROC was 0.77 (95% CI: 0.73–0.80) and Deeks funnel plot suggested the absence of publication bias (p = 0.91). Meta-regression analysis indicated that threshold effect was the main source of heterogeneity. Assays for evaluating serum HER2 levels are highly specific and demonstrate moderate diagnostic performance for HER2 tissue status in gastric cancer.     

Serology for the diagnosis of human hepatic cystic echinococcosis and its relation with cyst staging: A systematic review of the literature with meta-analysis

BackgroundThe diagnosis of cystic echinococcosis (CE) is primarily based on imaging, while serology should be applied when imaging is inconclusive. CE cyst stage has been reported among the most important factors influencing the outcome of serodiagnosis. We performed a systematic review and meta-analysis of the relation between cyst stage of hepatic CE and diagnostic sensitivity of serological tests, to evaluate whether their relation is a consistent finding and provide guidance for the interpretation of results of serological tests.Methodology/Principal findingsMEDLINE, EMBASE, CENTRAL, and Lilacs databases were searched on December 1^st 2019. Original studies published after 2003 (year of publication of the CE cyst classification), reporting sensitivity of serological tests applied to the diagnosis of human hepatic CE, as diagnosed and staged by imaging, were included. The quality of studies was assessed using the Newcastle-Ottawa Scale. Data from 14 studies were included in the meta-analysis. Summary estimates of sensitivities and 95% confidence intervals were obtained using random effects meta-analysis. Overall, test sensitivity was highest in the presence of CE2 and CE3 (CE3a and/or CE3b), and lowest in the presence of CE5 and CE4 cysts. ELISA, ICT and WB showed the highest sensitivities, while IHA performed worst.Conclusions/SignificanceThe results of our study confirm the presence of a clear and consistent relation between cyst stage and serological tests results. Limitations of evidence included the heterogeneity of the antigenic preparations used, which prevented to determine whether the relation between cyst stage and sensitivity was influenced by the type of antigenic preparation, the paucity of studies testing the same panel of sera with different assays, and the lack of studies assessing the performance of the same assay in both field and hospital-based settings. Our results indicate the absolute need to consider cyst staging when evaluating serological results of patients with hepatic CE.     

Direct and plant trait‐mediated effects of the local environmental context on butterfly oviposition patterns

Variation in the intensity of plant–animal interactions over different spatial scales is widespread and might strongly influence fitness and trait selection in plants. Differences in traits among plant individuals have been shown to influence variation in interaction intensities within populations, while differences in environmental factors and community composition are shown to be important for variation over larger scales. However, little is still known about the relative importance of the local environmental context vs. plant traits for the outcome of interactions within plant populations. We investigated how oviposition by the seed‐predator butterfly Phengaris alcon on its host plant Gentiana pneumonanthe was related to host plant traits and to local environmental variation, as well as how oviposition patterns translated into effects on host plant fruit set. We considered the local environmental context in terms of height of the surrounding vegetation and abundance of the butterfly's second host, Myrmica ants. The probability of oviposition was higher in plants that were surrounded by lower vegetation, and both the probability of oviposition and the number of eggs increased in early‐flowering and tall plants with many flowers in the three study populations. Flowering phenology, shoot height and flower production were, in turn, related to higher surrounding vegetation. Myrmica abundance was correlated with vegetation height, but had no effect on oviposition patterns. Oviposition and subsequent seed predation by the caterpillars strongly reduced host plant fruit set. Our results show that plant–animal interactions are context‐dependent not only because the context influences the abundance or the behavior of the animal interactor, but also because it influences the expression of plant traits that affect the outcome of the interaction. The results also demonstrate that heterogeneity in environmental conditions at a very local scale can be important for the outcomes of interactions.     

Are older patients less likely to be treated for pancreatic cancer? A systematic review and meta-analysis

Pancreatic cancer is the seventh commonest cause of cancer-related death worldwide. Although prognosis is poor, both surgery and adjuvant chemotherapy improve survival. However, it has been suggested that not all pancreatic cancer patients who may benefit from treatment receive it. This systematic review and meta-analysis investigated the existence of age-related inequalities in receipt of first-line pancreatic cancer treatment. Medline, Embase, Cochrane Library and grey literature were searched for population-based studies investigating treatment receipt, reported by age, for patients with primary pancreatic cancer from inception until 4th June 2020, and updated 5th August 2021. Studies from countries with universal healthcare were included, to minimise influence of health system-related economic factors. A modified version of the Newcastle-Ottawa Scale was used to assess risk of bias. Random-effects meta-analysis was undertaken comparing likelihood of treatment receipt in older versus younger patients. Sensitivity and subgroup analyses were conducted. Eighteen papers were included; 12 independent populations were eligible for meta-analysis. In most studies, < 10% of older patients were treated. Older age (generally ≥65) was significantly associated with reduced receipt of any treatment (OR=0.14, 95% CI 0.10–0.21, n = 12 studies), surgery (OR=0.15, 95% CI 0.09–0.24, n = 9 studies) and chemotherapy as a primary treatment (OR=0.13, 95% CI 0.07–0.24, n = 5 studies). The effect of age was independent of methodological quality, patient population or time-period of patient diagnosis and remained in studies with confounder adjustment. The mean quality score of included studies was 6/8. Inequalities in receipt of healthcare interventions across social groups is a recognised concern internationally. This review shows that older age is significantly, and consistently, associated with non-receipt of treatment in pancreatic cancer. However, there are risks and side-effects associated with pancreatic cancer treatment. Further research on what influences patient and professional treatment decision-making is required to better understand these apparent inequalities.     

Prevalence of primary aldosteronism in patient's cohorts and in population-based studies--a review of the current literature

There is an ongoing controversy on the prevalence of primary aldosteronism (PA). We aimed to update a meta-analysis published in 2008, that compiled studies reporting the prevalence of positive ARR screening tests and PA. We therefore reviewed original studies published in 2008 or later to examine whether current reports provide similar, higher or lower prevalences of elevated ARRs or PA than reports included in the original meta-analysis. A systematic review of English articles using PubMed was conducted. Search and extraction of articles were performed by one review author; the second review author checked all extracted data. We identified 11 eligible studies. The updated, weighted mean prevalences of elevated ARRs and PA in primary care (prevalence of high ARRs 16.5%; prevalence of PA 4.3%) and referred patients (prevalence of high ARRs 19.6%; prevalence of PA 9.5%) were only marginally different from the mean values obtained in the original meta-analysis. Among the current studies the maximum values for the prevalence of elevated ARRs and PA were substantially lower than among the older studies. Our results confirm the main conclusions from the original meta-analysis. The prevalence of PA increases with the severity of hypertension and the inclusion of current study results did not alter the mean prevalences of elevated ARRs and PA in primary care and referred patients. Additionally, we found that current studies focus increasingly on patients in referral centers or special subgroups, while the prevalence of PA in the general hypertensive population is yet unknown.     

The heritability of insomnia: A meta-analysis of twin studies

Twin studies of insomnia exhibit heterogeneity in estimates of heritability. This heterogeneity is likely because of sex differences, age of the sample, the reporter and the definition of insomnia. The aim of the present study was to systematically search the literature for twin studies investigating insomnia disorder and insomnia symptoms and to meta-analyse the estimates of heritability derived from these studies to generate an overall estimate of heritability. We further examined whether heritability was moderated by sex, age, reporter and insomnia symptom. A systematic literature search of five online databases was completed on 24 January 2020. Two authors independently screened 5644 abstracts, and 160 complete papers for the inclusion criteria of twin studies from the general population reporting heritability statistics on insomnia or insomnia symptoms, written in English, reporting data from independent studies. We ultimately included 12 papers in the meta-analysis. The meta-analysis focussed on twin intra-class correlations for monozygotic and dizygotic twins. Based on these intra-class correlations, the meta-analytic estimate of heritability was estimated at 40%. Moderator analyses showed stronger heritability in females than males; and for parent-reported insomnia symptoms compared with self-reported insomnia symptoms. There were no other significant moderator effects, although this is likely because of the small number of studies that were comparable across levels of the moderators. Our meta-analysis provides a robust estimate of the heritability of insomnia, which can inform future research aiming to uncover molecular genetic factors involved in insomnia vulnerability.     

Trans-generational immune priming is not mediated by the sex of the parent primed: a meta-analysis of invertebrate data

Traditionally, only vertebrates were thought capable of acquired immune responses, such as the ability to transfer immunological experience vertically to their offspring (known as trans-generational immune priming, TGIP). Increasing evidence challenges this belief and it is now clear that invertebrates also have the ability to exhibit functionally equivalent TGIP. This has led to a surge in papers exploring invertebrate TGIP, with most focusing on the costs, benefits or factors that affect the evolution of this trait. Whilst many studies have found support for the phenomenon, not all studies do, and there is considerable variation in the strength of positive results. To address this, we conducted a meta-analysis to answer the question: what is the overall effect of TGIP in invertebrates? Then, to understand the specific factors that affect its presence and intensity, we conducted a moderator analysis. Our results corroborate that TGIP occurs in invertebrates (demonstrated by a large, positive effect size). The strength of the positive effect was related to if and how offspring were immune challenged (i.e. whether they were challenged with the same or different insult as their parents or not challenged at all). Interestingly, there was no effect of the ecology or life history of the species or the sex of the parent or the offspring primed, and responses were comparable across different immune elicitors. Our publication bias testing suggests that the literature may suffer from some level of positive-result bias. However, even after accounting for potential bias, our effect size remains positive. Publication bias testing can be influenced by diversity in the data set, which was considerable in our data, even after moderator analysis. It is therefore conceivable that differences among studies could be caused by other moderators that were unable to be included in our meta-analysis. Nonetheless, our results suggest that TGIP does occur in invertebrates, whilst providing some potential avenues to examine the factors that account for variation in effect sizes.     

Lack of Association between Bax Promoter (-248G>A) Single Nucleotide Polymorphism and Susceptibility towards Cancer: Evidence from a Meta-Analysis

Background

The Bcl-2-associated X protein (Bax) is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs) in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer.

Methodology

We conducted a search of case-control studies on the associations of Bax-248G>A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE) in controls, power calculation, heterogeneity analysis, Begg’s funnel plot, Egger’s linear regression test, forest plot and sensitivity analysis were performed in the present study.

Results

Cancer risk associated with Bax-248G>A polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The pooled ORs were calculated in allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive model. Statistical significance was checked through Z and p-value in forest plot. A total of seven independent studies including 1772 cases and 1708 controls were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distributions of this polymorphism were associated with risk for cancer in any of the genetic model. Furthermore, Egger’s test did not show any substantial evidence of publication bias.

Conclusions/Significance

This meta-analysis suggests that the Bax-248G>A polymorphism is not an important cancer risk factor. Nevertheless, additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are required to further validate the results.     

Meta-analyses of adverse effects data derived from randomised controlled trials as compared to observational studies: methodological overview

Background

There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies.

Methods and Findings

Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance.

Conclusions

Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors'' Summary