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International Journal of Molecular... Jun 2020The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the... (Meta-Analysis)
Meta-Analysis Review
AIM
The purpose of this review was to evaluate the expression patterns of miRNAs in periodontal and peri-implant diseases, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
MATERIALS AND METHODS
Human and animal studies were included when evaluating expression of miRNAs between health and different forms/stages of diseases, in which microarray and/or real-time polymerase chain reaction (RT-PCR) was carried out to detect fold changes in gene expression. After full-text analysis, 43 articles were considered for a qualitative assessment, and 16 miRNAs were selected to perform meta-analysis.
RESULTS
Based on human studies, results showed an overall upregulation of most of the evaluated miRNAs in periodontitis, with miRNA-142-3p and miRNA-146a being the most conclusive on both microarray and RT-PCR values and potentially serving as diagnostic biomarkers for disease activity. Conversely, miR-155 was the only miRNA revealing a statistically significant difference (SSD) ( < 0.05*) in experimental periodontitis models from RT-PCR values. Scarce scientific evidence is available from peri-implant diseases, however, most explored miRNAs in peri-implantitis were downregulated except for miR-145.
CONCLUSIONS
Although our results revealed that a distinct differential expression of specific miRNAs can be noted between the state of health and disease, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases. MeSH Terms: periodontitis, peri-implantitis, epigenomics, microarray analysis, real-time polymerase chain reaction, microRNAs.
CLINICAL RELEVANCE
Scientific background: Although most research identified different expression levels of miRNAs in periodontal and peri-implant diseases compared to their counterparts, their actual role in the pathogenesis of these conditions remains unclear. Therefore, we aimed to present a systematic review and meta-analysis on the expression patterns of miRNAs in periodontitis and peri-implantitis, while identifying potential miRNAs with the greatest diagnostic ability as an oral fluid biomarker.
PRINCIPAL FINDINGS
In periodontitis-related studies, miRNA-142-3p and miRNA-146a were the most conclusive on both microarray and RT-PCR values. Scarce scientific evidence is available from peri-implant diseases.
PRACTICAL IMPLICATIONS
Both miRNA-142-3p and miRNA-146a might serve as future diagnostic biomarkers for disease activity in periodontitis. Yet, future research remains necessary to explore the functional role of specific miRNAs and their potential as therapeutic targets in periodontal and peri-implant diseases.
Topics: Animals; Biomarkers; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Peri-Implantitis; Periodontitis
PubMed: 32532036
DOI: 10.3390/ijms21114147 -
Ultrasound in Obstetrics & Gynecology :... Mar 2024To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants.
METHODS
A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided for two of them. The increase in diagnostic yield with ES for pathogenic/likely pathogenic (P/LP) variants was assessed in all cases of ACC, isolated ACC, ACC with other cranial anomalies and ACC with extracranial anomalies. To identify all reported genetic variants, the systematic review included all ACC cases; however, for the meta-analysis, only studies with ≥ three ACC cases were included. Meta-analysis of proportions was employed using a random-effects model. Quality assessment of the included studies was performed using modified Standards for Reporting of Diagnostic Accuracy criteria.
RESULTS
A total of 28 studies, encompassing 288 prenatally diagnosed ACC cases that underwent ES following negative CMA, met the inclusion criteria of the systematic review. We classified 116 genetic variants in 83 genes associated with prenatal ACC with a full phenotypic description. There were 15 studies, encompassing 268 cases, that reported on ≥ three ACC cases and were included in the meta-analysis. Of all the included cases, 43% had a P/LP variant on ES. The highest yield was for ACC with extracranial anomalies (55% (95% CI, 35-73%)), followed by ACC with other cranial anomalies (43% (95% CI, 30-57%)) and isolated ACC (32% (95% CI, 18-51%)).
CONCLUSIONS
ES demonstrated an incremental diagnostic yield in cases of prenatally diagnosed ACC following negative CMA. While the greatest diagnostic yield was observed in ACC with extracranial anomalies and ACC with other central nervous system anomalies, ES should also be considered in cases of isolated ACC. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Pregnancy; Agenesis of Corpus Callosum; Corpus Callosum; Exome Sequencing
PubMed: 37519216
DOI: 10.1002/uog.27440 -
Prenatal Diagnosis Aug 2023Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental... (Review)
Review
Unexplained stillbirth is defined as a stillbirth with no known cause after the exclusion of common causes, including obstetric complications, infections, placental insufficiency or abruption, umbilical cord complications, and congenital abnormalities with or without known genetic cause. More than 60% of stillbirth cases remain unexplained. The aim of this systematic review was to investigate the known genetic causes of unexplained stillbirth cases and to evaluate the current position and future directions for the use of genetic and genomic testing in expanding the knowledge in this field. A systematic search through several databases was performed using the keywords genetics and stillbirths in humans. Different methods to detect various types of causal genetic aberrations have been used in the past decades, from standard karyotyping to novel methods such as chromosomal microarray analysis and next generation sequencing technologies. Apart from common chromosomal aneuploidies, a promising hypothesis about genetic causes included genes related to cardiomyopathies and channelopathies. However, these were tested in the research settings, since molecular karyotyping is currently the standard approach in the routine evaluation of genetic causes of stillbirth. Hereby, we provide evidence that expanding knowledge using novel genetic and genomic testing might uncover new genetic causes of unexplained stillbirth.
Topics: Humans; Female; Pregnancy; Stillbirth; Placenta; Aneuploidy; Databases, Factual; Genetic Profile
PubMed: 37072878
DOI: 10.1002/pd.6354 -
Urologic Oncology May 2022Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Determining meta-analysis of transcriptional profiling of muscle-invasive bladder cancer (MIBC) through Gene Expression Omnibus (GEO) datasets has not been investigated. This study aims to define gene expression profiles in MIBC and to identify potential candidate genes and pathways.
OBJECTIVES
To review and evaluate gene expression studies in MIBC through publicly available RNA sequencing (RNA-Seq) and microarray data in order to identify potential prognostic and therapeutic targets for MIBC.
METHODS
A systematic literature search of the Ovid MEDLINE, PubMed, and Wiley Cochrane Central Register of Controlled Trials databases was performed using the terms "gene," "gene expression," and "bladder cancer" January 1, 1990 through March 2021 focused on populations with MIBC.
RESULTS
In the final analysis, GEO datasets were included. Fixed effect model was employed in the meta-analysis. Gene networking connections and gene-set functional analyses of the identified genes as differentially expressed in MIBC were performed using ImaGEO and GeneMANIA software. A heatmap for the upregulated and downregulated genes was generated along with the correlated pathways.
CONCLUSION
A total of 9 genes were reported in this analysis. Six genes were reported as upregulated (ProTα, SPINT1, UBE2E1, RAB25, KPNB1, HDAC1) and 3 genes as downregulated (NUP188, IPO13, NUP124). Genes were found to be involved in "ubiquitin mediated proteolysis," "protein processing in endoplasmic reticulum," "transcriptional misregulation in cancer," and "RNA transport" pathways.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Male; Muscles; Neoplasm Invasiveness; Prognosis; Urinary Bladder Neoplasms; rab GTP-Binding Proteins
PubMed: 35039218
DOI: 10.1016/j.urolonc.2021.11.003 -
Cancers Jan 2023Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has... (Review)
Review
Cervical cancer is the leading cause of cancer-related death among women in developing countries. However, no comprehensive molecular mechanism for cervical cancer has been established, as many studies were small-cohort studies conducted with small sample sizes. A thorough literature search was performed using the PubMed, Scopus, EBSCOhost, and Science Direct databases. Medical Subject Heading (MeSH) terms such as "Uterine Cervical Neoplasms" and "gene expression" were used as the keywords in all fields. A total of 4027 studies were retrieved, and only clinical studies, which used the microarray method to identify differentially expressed genes (DEGs) in the cervical tissue of cervical cancer patients, were selected. Following the screening, 6 studies were selected and 1128 DEGs were extracted from the data. Sixty-two differentially expressed genes from at least two studies were selected for further analysis by DAVID, STRING, and Cytoscape software. In cervical cancer pathogenesis, three significant clusters with high intermolecular interactions from the Protein-Protein Interaction (PPI) network complex revealed three major molecular mechanisms, including cell signaling, cell cycle, and cell differentiation. Subsequently, eight genes were chosen as the candidate genes based on their involvement in the relevant gene ontology (GO) and their interaction with other genes in the PPI network through undirected first neighbor nodes. The present systematic review improves our understanding of the molecular mechanism of cervical cancer and the proposed genes that can be used to expand the biomarker panel in the screening for cervical cancer. The targeted genes may be beneficial for the development of better treatment strategies.
PubMed: 36765810
DOI: 10.3390/cancers15030853 -
Diagnostics (Basel, Switzerland) May 2022Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate... (Review)
Review
Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54-6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.
PubMed: 35741137
DOI: 10.3390/diagnostics12061328 -
Pregnancy Hypertension Jan 2020Preeclampsia (PE) is a serious complication of pregnancy. It is considered a complex condition influenced by maternal genes, environmental factors and a deregulated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Preeclampsia (PE) is a serious complication of pregnancy. It is considered a complex condition influenced by maternal genes, environmental factors and a deregulated immune response of the mother, but the etiology is largely unknown. The aim of this study is to identify differentially expressed genes (DEGs) in PE, to help elucidate the identification of the disease etiological mechanisms.
STUDY DESIGN
The databases Pubmed and GEO were searched according to PRISMA guidelines for the existence of gene expression data on placental samples from case-control studies. After meta-analysis the identified DEGs were further analyzed with STRING and PANTHER to retrieve interaction networks and overrepresented biochemical pathways.
RESULTS
Only 10 gene expression datasets and articles fulfilled inclusion criteria, containing data on 195 patients and 231 controls, and were analyzed. Meta-analysis identified 629 DEGs to be associated with PE at a False Discovery Rate p-value of 0.01. Network analysis showed few highly interconnected genes involved in innate immunity and signal transduction pathways indicative of a multifaceted disease with etiological heterogeneity. over representation analysis revealed that these genes participate mainly in carbohydrates, amino acids and pyrimidine metabolism, circadian clock system and signal transduction pathways.
CONCLUSIONS
This work, combining rigorous methods of meta-analysis and the use of modern bioinformatics tools, proposes the existence of novel, overlooked so far, biochemical pathways and mechanisms to contribute to PE development such as carbohydrate, aminoacids and pyrimidine metabolism. Our findings pave the way for further investigation of the above pathways in experimental efforts to decipher the orchestrating mechanisms for PE development.
Topics: Female; Gene Expression Profiling; Humans; Microarray Analysis; Pre-Eclampsia; Pregnancy
PubMed: 31901653
DOI: 10.1016/j.preghy.2019.12.007 -
BMJ Global Health Oct 2023Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs, including reduced sharps risk, thermostability, no need for reconstitution, tolerability and self-administration. We aimed to explore and evaluate the immunogenicity, safety, usability and acceptability of MAPs for vaccination.
METHODS
We searched CINAHL, Cochrane Library, Ovid Embase, Ovid MEDLINE and Web of Science from inception to January 2023. Eligibility criteria included all research studies in any language, which examined microarrays or microneedles intended or used for vaccination and explored immunogenicity, safety, usability or acceptability in their findings. Two reviewers conducted title and abstract screening, full-text reviewing and data extraction.
RESULTS
Twenty-two studies were included (quantitative=15, qualitative=2 and mixed methods=5). The risk of bias was mostly low, with two studies at high risk of bias. Four clinical trials were included, three using influenza antigens and one with Japanese encephalitis delivered by MAP. A meta-analysis indicated similar or higher immunogenicity in influenza MAPs compared with needle and syringe (N&S) (standardised mean difference=10.80, 95% CI: 3.51 to 18.08, p<0.00001). There were no significant differences in immune cell function between MAPs and N&S. No serious adverse events were reported in MAPs. Erythema was more common after MAP application than N&S but was brief and well tolerated. Lower pain scores were usually reported after MAP application than N&S. Most studies found MAPs easy to use and highly acceptable among healthcare professionals, laypeople and parents.
CONCLUSION
MAPs for vaccination were safe and well tolerated and evoked similar or enhanced immunogenicity than N&S, but further research is needed. Vaccine uptake may be increased using MAPs due to less pain, enhanced thermostability, layperson and self-administration. MAPs could benefit at-risk groups and low and middle-income countries.
PROSPERO REGISTRATION NUMBER
CRD42022323026.
Topics: Humans; Influenza, Human; Vaccination; Vaccines; Pain
PubMed: 37827725
DOI: 10.1136/bmjgh-2023-012247 -
Acta Obstetricia Et Gynecologica... Nov 2019The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes.
MATERIAL AND METHODS
Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data.
RESULTS
Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up.
CONCLUSIONS
Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.
Topics: Conservative Treatment; Female; Follow-Up Studies; Humans; Incidence; Magnetic Resonance Imaging; Orthopedic Procedures; Pregnancy; Pregnancy Outcome; Prenatal Care; Prenatal Diagnosis; Risk Assessment; Talipes; Ultrasonography, Prenatal
PubMed: 31034582
DOI: 10.1111/aogs.13637 -
BJOG : An International Journal of... Nov 2023Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited. (Review)
Review
Diagnostic yield of prenatal exome sequencing in the genetic screening of fetuses with brain anomalies detected by MRI and ultrasonography: A systematic review and meta-analysis.
BACKGROUND
Brain anomalies (BAs) have been the focus of research, as they have a high impact on fetal health but therapeutic and diagnostic approaches are limited.
OBJECTIVES
In this study, the application and efficiency of exome sequencing (ES) in detecting different cases of BAs in fetuses were evaluated and compared with chromosomal microarray analysis (CMA).
SEARCH STRATEGY
To conduct this study, three databases including PubMed, Web of Science and Embase were utilised with the keywords 'prenatal', 'diagnoses', 'brain anomalies' and 'exome sequencing'.
SELECTION CRITERIA
Studies were included based on the STARD checklist, for which the ES and CMA diagnostic yields were calculated.
DATA COLLECTION AND ANALYSIS
Meta-analysis was performed on the included studies using a random-effects model and subgroup analysis to define the risk difference between them.
MAIN RESULTS
We included 11 studies representing 779 fetuses that implemented ES along with imaging techniques. The pooled ES diagnostic yield in fetuses with BAs detected through magnetic resonance imaging (MRI) and ultrasonography was 26.53%, compared with 3.46% for CMA. The risk difference between ES and CMA for complex BAs was 0.36 [95% confidence interval (CI) 0.24-0.47], which was higher than for single BAs (0.22; 95% CI 0.18-0.25].
CONCLUSIONS
ES is a useful method with a significantly higher diagnostic yield than CMA for genetic assessment of fetuses with complex BAs detected by imaging techniques. Moreover, ES could be applied to suspected fetuses with related family histories to predict congenital diseases with high efficiency.
PubMed: 37932235
DOI: 10.1111/1471-0528.17710