Antenatal imaging and clinical outcome in congenital CMV infection: A field-wide systematic review and meta-analysis.

OBJECTIVES: Postnatal outcome in fetuses with congenital cytomegalovirus infection (cCMV) varies from asymptomatic infection to severe neurodevelopmental impairment. Αntenatal biomarkers of long-term clinical outcome, have yet to be established. Α systematic review and meta-analysis was performed to examine whether prenatal cerebral ultrasonography (US) and magnetic resonance imaging (MRI) findings in cCMV fetuses may predict clinical outcome. METHODS: PubMed and the Web of Science were systematically searched to identify studies reporting on any prenatal US and/or MRI imaging of fetuses with cCMV as well as their postnatal clinical outcome. All reported associations between imaging and postnatal clinical outcome were systematically extracted. Where appropriate, the reported associations were quantitatively synthesized within Bayesian random-effects meta-analyses. RESULTS: A total of 1336 studies were screened to identify 26 eligible observational studies. Overall, 4181 fetuses were studied, of which 1518 had been diagnosed with cCMV. All studies performed fetal US while in 14 (54%) MRI was also performed. Studies substantially varied in timing of fetal imaging, reporting of abnormalities, definition of poor outcome and statistical analysis. Among studies reporting on statistical significance, 6/6 for US and 3/4 for MRI identified significant associations between imaging findings and outcome. In our meta-analyses, within isolated abnormalities, only microcephaly had greater than 95% probability of being associated with poor outcome (OR 26.7; 95% CI, 1.44-1464.5; I2, 19%). Effect sizes for US were higher than those for MRI findings. CONCLUSIONS: Although studies displayed significant heterogeneity in both methodology and analytical decisions, it became evident that when both prenatal cerebral US and MRI are normal the negative predictive value of poor outcome is high. This is important for clinicians when consulting pregnant women. Need to standardize practices and definitions become evident. FUNDING: There was no source of funding.

Long noncoding RNAs as novel predictors of survival in human cancer: a systematic review and meta-analysis.

BACKGROUND: Expression of various long noncoding RNAs (lncRNAs) may affect cancer prognosis. Here, we aim to gather and examine all evidence on the potential role of lncRNAs as novel predictors of survival in human cancer. METHODS: We systematically searched through PubMed, to identify all published studies reporting on the association between any individual lncRNA or group of lncRNAs with prognosis in human cancer (death or other clinical outcomes). Where appropriate, we then performed quantitative synthesis of those results using meta-analytic methods to identify the true effect size of lncRNAs on cancer prognosis. The reliability of those results was then examined using measures of heterogeneity and testing for selective reporting biases. RESULTS: Three hundred ninety-two studies were screened to eventually identify 111 eligible studies on 127 datasets. In total, these represented 16,754 independent participants pertaining to 53 individual and 6 grouped lncRNAs within a total of 19 cancer sites. Overall, 83 % of the studies we identified addressed overall survival and 32 % of the studies addressed recurrence-free survival. For overall survival, 96 % (88/92) of studies identified a statistically significant association of lncRNA expression to prognosis. Meta-analysis of 6 out of 7 lncRNAs for which three or more studies were available, identified statistically significant associations with overall survival. The lncRNA HOTAIR was by far the most broadly studied lncRNA (n = 29; of 111 studies) and featured a summary hazard ratio (HR) of 2.22 (95 % confidence interval (CI), 1.86-2.65) with modest heterogeneity (I(2) = 49 %; 95 % CI, 14-79 %). Prominent excess significance was demonstrated across all meta-analyses (p-value = 0.0003), raising the possibility of substantial selective reporting biases. CONCLUSIONS: Multiple lncRNAs have been shown to be strongly associated with prognosis in diverse cancers, but substantial bias cannot be excluded in this field and larger studies are needed to understand whether these prognostic information may eventually be useful.

Correction: Risk of Bias in Reports of In Vivo Research: A Focus for Improvement.

[This corrects the article DOI: 10.1371/journal.pbio.1002273.].

Risk of Bias in Reports of In Vivo Research: A Focus for Improvement.

The reliability of experimental findings depends on the rigour of experimental design. Here we show limited reporting of measures to reduce the risk of bias in a random sample of life sciences publications, significantly lower reporting of randomisation in work published in journals of high impact, and very limited reporting of measures to reduce the risk of bias in publications from leading United Kingdom institutions. Ascertainment of differences between institutions might serve both as a measure of research quality and as a tool for institutional efforts to improve research quality.