scholarly journals Meta-analysis based on weighted ordered P-values for genomic data with heterogeneity

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Yihan Li ◽  
Debashis Ghosh
Keyword(s):  
2017 ◽  
Author(s):  
Todd M. Everson ◽  
Tracy Punshon ◽  
Brian P. Jackson ◽  
Ke Hao ◽  
Luca Lambertini ◽  
...  

AbstractBackgroundCadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.MethodsUsing placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.ResultsWe identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7, and lower expression of RORA, were associated with lower birth weight z-scores (p-values < 0.05).ConclusionCd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.SignificanceCadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.


2020 ◽  
Vol 9 (10) ◽  
pp. 719-728
Author(s):  
Jiaqian Wang ◽  
Liang Zhou ◽  
Yong Zhang ◽  
Lixin Huang ◽  
Qin Shi

Aims The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. Methods We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source. Results Seven trials evaluating 256 patients were included in the meta-analysis. MSC treatment significantly improved the VAS (mean difference (MD), –13.24; 95% confidence intervals (CIs) –23.28 to –3.20, p = 0.010) and WOMAC (MD, –7.22; 95% CI –12.97 to –1.47, p = 0.010). The low-dose group with less than 30 million cells showed lower p-values for both the VAS and WOMAC. Adipose and umbilical cord–derived stem cells also had lower p-values for pain scores than those derived from bone marrow. Conclusion Overall, MSC-based cell therapy is a relatively safe treatment that holds great potential for OA, evidenced by a positive effect on pain and knee function. Using low-dose (25 million) and adipose-derived stem cells is likely to achieve better results, but further research is needed. Cite this article: Bone Joint Res 2020;9(10):719–728.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 2-2
Author(s):  
Sepideh Alasvand ◽  
William Bridges ◽  
Vivian Haley-Zitlin

Abstract Objectives This study examined the effect of common spices cardamom, ginger, cumin, curcuminoids and cinnamon on improving glucose levels in individuals with type 2 diabetes by systematic review and meta-analysis. Methods PubMed, FSTA, Web of Science, CINAHEL, MEDLINE and Cochrane Library database of systematic review databases were searched using keywords (fasting blood glucose OR hemoglobin A1c OR HbA1c OR homeostasis) AND (Ginger or zingiber or “zingiber officinale” or “cinnamomum zeylanicum” or “cinnamomum aromaticum” or “cinnamomum cassia” or “cinnamomum verum” or curcumin or turmeric or curcuminoids or “curcuma longa” or langas or “curcuma zedoarias” or turmeric) AND (diabetes* OR “diabetes mellitus” OR “type 2” OR “blood glucose” OR insulin* OR antidiabet* OR “glucose level”) up to January 2020. Statistical calculations used SAS software version 9.2 (SAS, Cary NC, USA). P-values &lt; 0.05 were considered significant, P-values &lt; 0.10 were considered weakly significant. Results Twenty-three studies with 2237 trial participants were selected out of a 512 study pool. Spices decreased FBG and HbA1c %. The estimated reduction in intervention change vs. control change is as follows: A1c was −0.264 mg/dl, 95% CI (−0.5503, −0.02), P value 0.069; FBG was −9.9370 mg/dl, 95% CI (−20.79, 0.91), P value 0.07. A significant heterogeneity was observed overall among the all studies, indicating that not all studies had similar levels of decrease. Conclusions A correlation between consumption of certain common spices and significant reduction in glycemic indices among diabetes patients was proved. Funding Sources Clemson University.


2017 ◽  
Vol 2 (3) ◽  
pp. 2473011417S0000
Author(s):  
Sonya Ahmed ◽  
Kyoung min Lee ◽  
Moon Seok Park ◽  
Ki Hyuk Sung ◽  
Seungbum Koo ◽  
...  

Category: Ankle, Arthroscopy, Trauma Introduction/Purpose: This meta-analysis was performed to determine whether the arthroscopically assisted open reduction and internal fixation (ORIF) for ankle fractures is more beneficial than the conventional ORIF. Methods: Articles in electronic medial databases were searched between March 1983 and August 2016, including Pubmed and SCOPUS. We included the studies with comparative design comparing the surgical outcomes between the arthroscopically assisted ORIF for ankle fractures and the conventional ORIF. Finally, two RCTs and two retrospective comparative studies were included for analysis. Mean and standard deviation (SD) of postoperative functional scores, number of subjects, and P-values were extracted from the studies. In addition, postoperative follow-up period, fracture type, and study quality were collected. Results: The pooled effect size of the four studies 0.535 (95% CI, 0.247 to 0.823) in Hedges’s g, which favored the arthroscopically assisted ORIF over conventional ORIF. There was no evidence of publication bias in funnel plot and in Egger’s test (p=0.534). Conclusion: The arthroscopically assisted ORIF for ankle fractures were more beneficial than the conventional ORIF in the current evidences. However, since it needs more medical cost and longer operation time, possible additional complications and cost effectiveness are to be validated in future studies.


2020 ◽  
Vol 31 (1) ◽  
pp. 23-32
Author(s):  
M. A. Rueda Calderón ◽  
M. Balzarini ◽  
C. Bruno

Genomic selection (GS) is used to predict the merit of a genotype with respect to a quantitative trait from molecular or genomic data. Statistically, GS requires fitting a regression model with multiple predictors associated with the molecular markers (MM) states. The model is calibrated in a population with phenotypic and genomic data. The abundance and correlation of MM information make model estimation challenging. For that reason there are diverse strategies to adjust the model: based on best linear unbiased predictors (BLUP), Bayesian regressions and machine learning methods. The correlation between the observed phenotype and the predicted genetic merit by the fitted model provides a measure of the efficiency (predictive ability) of the GS. The objective of this work was to perform a metaanalysis on the efficiency of GS in cereals. A systematic review of related GS studies and a meta-analysis, in wheat and maize, was carried out to obtain a global measure of GS efficiency under different scenarios (MM quantity and statistical models used in GS). The meta-analysis indicated an average correlation coefficient of 0.61 between observed and predicted genetic merits. There were no significant differences in the efficiency of the GS based on BLUP (RR-BLUP and GBLUP), the most common statistical approach. The increase of MM data, make GS efficiency do not vary widely. Key words: Systematic review; Random effects model; Forest plot; Predictive accuracy.


2021 ◽  
Vol 8 (1) ◽  
pp. 118-127
Author(s):  
Flavio Martinez-Morales ◽  
Saray Aranda Romo ◽  
Othoniel Hugo Aragon-Martinez

Nowadays, there is not a meta-analytic synthesis of the clinical reports that used a cacao bean husk extract (CBHE) solution as an anticariogenic mouth rinse. Thus, the aim of this study was to evaluate that information through a systematic review and meta-analysis methodology, conducted in accordance with PRISMA guidelines. Scientific databases were searched for studies published up to June 2021. Inclusion and exclusion criteria were applied to studies found and then, their data was analyzed. The five selected studies were categorized with a 36.6, 58.5, and 4.9 % of a low, unclear, and high risk of bias, respectively. Under appropriate heterogeneities (I2 values from 0 to 65 %, p values > 0.09) and absent reporting bias (symmetrical funnels), the meta-analyses show that the use of a CBHE mouth rinse reduced the salivary count of Streptococcus mutans (Z values from 2.45 to 10.61, p values < 0.01), similar to the chlorhexidine rinse performance (Z value= 0.55, p value= 0.58), and produced an insignificant presence of adverse events (Z value= 0.92, p value= 0.36) in children and adults, all these effects compared with those volunteers under an ethanol rinse or their pretest conditions. In conclusion, the CBHE mouth rinse reduced a cariogenic bacterium under an acceptable safety profile, but more clinical studies with high quality and more parameters are needed.


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