ObjectiveStudy how to quantify the bias of each study and how to estimate them. MethodIn the random-effect model, it is commonly assumed that the effect size of each study in meta-analysis follows a skew normal distribution which has different shape parameter. Through introducing a shape parameter to quantify the bias and making use of Markov estimation as well as maximum likelihood estimation to estimate the overall effect size, bias of each study, heterogeneity variance. ResultIn simulation study, the result was closer to the real value when the effect size followed a skew normal distribution with different shape parameter and the impact of heterogeneity of random effects meta-analysis model based on the skew normal distribution with different shape parameter was smaller than it in a random effects metaanalysis model. Moreover, in this specific example, the length of the 95%CI of the overall effect size was shorter compared with the model based on the normal distribution. ConclusionIncorporate the bias of each study into the random effects meta-analysis model and by quantifying the bias of each study we can eliminate the influence of heterogeneity caused by bias on the pooled estimate, which further make the pooled estimate closer to its true value.
Compared with traditional head to head meta-analysis, network meta-analysis has more confounding factors and difficulties to handle. Due to the mutual transitivity of evidence in network meta-analysis, heterogeneity may be brought into indirect meta-analysis. Hence, effective differentiation and correct handling of heterogeneity are being current focus. In order to ensure the reliability of the results of network meta-analysis, the concept of homogeneity is proposed and a series of methods are developed for differentiation and handling of homogeneity. Based on the extension of Bucher methods, current methods for differentiation and handling of homogeneity has extended to ten quantitative measures (eg., node analysis method, hypothesis tests, and two-step method). However, because of the differences and the focus of fundamental methodological theories as well as the limitation of statistics power, no highly-effective method has been worked out. Therefore, the exploration of highly-effective, simple and high-resolved methods are still needed.
Neutrophils are the most abundant myeloid-derived eukaryotic cells in human blood with increasingly recognized as important regulators of cancer progression. However, the functional importance of tumor-associated neutrophils (TANs) is often overlooked due to their short-lived, terminally differentiated, non-proliferative properties. In recent years, a wealth of evidences obtained from experimental tumor models and cancer patients had indicated that TANs had obvious heterogeneity in morphology and function, and TANs had dual functions of pro- and anti-tumor in cancer patients. This review provides an adequate overview of the heterogeneity and distinct roles of neutrophils.
Diabetic retinopathy (DR) is one of the main causes of vision loss and irreversible blindness in the working-age population, closely regarded as the destruction of the retinal neurovascular unit (NVU). As an important component of the NVU, retinal microglia (RMG) plays a vital role in the progression of DR. In recent years, single-cell RNA sequencing (scRNA-seq) technology has emerged as an important tool in transcriptomic analysis. This latest method reveals the heterogeneity and complexity of RNA transcriptional profiles within individual cells, as well as the composition of different cell types and functions. Utilizing scRNA-seq technology, researchers have further revealed the role of RMG in the occurrence and development of DR, discovering phenotypic heterogeneity, regional heterogeneity, and cell-to-cell communication in RMG. It is anticipated that in the future, more omics technologies and multi-omics correlation analysis methods will be applied to DR and even other ophthalmic diseases, exploring potential diagnostic and therapeutic targets, providing different perspectives for the clinical diagnosis, treatment, and scientific research of DR, and truly promoting clinical translation through technological innovation, thereby benefiting patients with DR diseases.
Through collecting and synthesizing the paper concerning the method of dealing with heterogeneity in the meta analysis, to introduce the multi-levels statistical models, such as meta regression and baseline risk effect model based on random effects, and random effects model based on hierarchical bayes, and to introduce their application of controlling the meta analysis heterogeneity. The multi-levels statistical model will decompose the single random error in the traditional model to data structure hierarchical. Its fitting effect can not only make the meta-analysis result more robust and reasonable, but also guide clinical issues through the interpretation of association variable.
Many meta-analysis studies evaluate rates as parameter to assess the overall estimate of effects. However, none of these studies address systematic approaches for the meta-analysis of rates. This paper outlines the conditions, analysis and software operation procedures for the meta-analysis of rates. It also compares different operation procedures of three types of commonly-used R software (Comprehensive Meta-Analysis, Stata and MetaAnalyst) through real application examples. The biggest challenge for the meta-analysis of rates is to determine whether rates can be pooled, and how to evaluate heterogeneity between studies' outcomes needs further discussion.
ObjectiveTo understand the single-cell RNA sequencing (scRNA-seq) and its research progress in the tumor microenvironment (TME) of breast cancer, in order to provide new ideas and directions for the research and treatment of breast cancer. MethodThe development of scRNA-seq technology and its related research literature in breast cancer TME at home and abroad in recent years was reviewed. ResultsThe scRNA-seq was a quantum technology in high-throughput sequencing of mRNA at the cellular level, and had become a powerful tool for studying cellular heterogeneity when tissue samples were fewer. While capturing rare cell types, it was expected to accurately describe the complex structure of the TME of breast cancer. ConclusionsAfter decades of development, scRNA-seq has been widely used in tumor research. Breast cancer is a malignant tumor with high heterogeneity. The application of scRNA-seq in breast cancer research can better understand its tumor heterogeneity and TME, and then promote development of personalized diagnosis and treatment.
Randomized controlled trials are the gold standard for evaluating the effects of medical interventions, primarily providing estimates of the average effect of an intervention in the overall study population. However, there may be significant differences in the effect of the same intervention across sub-populations with different characteristics, that is, treatment heterogeneity. Traditional subgroup analysis and interaction analysis tend to have low power to examine treatment heterogeneity or identify the sources of heterogeneity. With the recent development of machine learning techniques, causal forest has been proposed as a novel method to evaluate treatment heterogeneity, which can help overcome the limitations of the traditional methods. However, the application of causal forest in the evaluation of treatment heterogeneity in medicine is still in the beginning stage. In order to promote proper use of causal forest, this paper introduces its purposes, principles and implementation, interprets the examples and R codes, and highlights some attentions needed for practice.
This paper is to discuss the research of heterogeneity in Meta-analysis, including the definition of the heterogeneity in Meta-analysis and classification it into clinical heterogeneity, methodological heterogeneity and statistical heterogeneity, the strategies for diminishing clinical heterogeneity and methodological heterogeneity, the five testing methods in statistical heterogeneity (Q statistic, I2 statistic, H statistic, Galbraith plot and L’Abbe plot) and the examples and applying conditions of the five testing methods, classification of meta-analysis into exploratory meta-analysis and analytic meta-analysis according if the meta-analysis has heterogeneity, and the strategies and the flowchart when existing the heterogeneity in meta-analysis.
Some risks affecting the quality of published systematic reviews and in our teaching practice were listed and compared with the correct concept. The current problems include misunderstanding of the relationship of meta-analysis and systematic review, applying meta-analysis and assessing heterogeneity, randomization, allocate concealment, and how to make inclusion and exclusion criteria, etc. This paper aims to help Chinese reviewers improve the quality of their systematic reviews.