-
JAMA Network Open Nov 2023Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).
OBJECTIVE
To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.
DATA SOURCES
PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants.
STUDY SELECTION
Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported.
RESULTS
From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH.
Topics: Female; Pregnancy; Humans; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Patients; Hydrocephalus
PubMed: 37991765
DOI: 10.1001/jamanetworkopen.2023.43384 -
The Journal of Maternal-fetal &... Dec 2023To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype and chromosomal microarray (CMA) analyses in fetuses with isolated increased nuchal translucency (NT) and normal fetal anatomy at the time of 11-14 weeks scan.
MATERIALS AND METHODS
Medline and Embase databases were searched. Inclusion criteria were fetuses with NT >95 percentile, normal karyotype and CMA and no associated structural anomalies at the time of the 11-14 weeks scan. The primary outcome was to estimate the incremental yield of detecting pathogenic or likely pathogenic genetic variants by WES over standard karyotype and CMA analyses in fetuses with isolated increased nuchal translucency. The secondary outcomes were the detection of a genetic variant of unknown significance. Sub-analysis according to different NT cutoffs (between 3.0 and 5.5 mm and > 5.5 mm) and considering fetuses with isolated NT in which fetal anatomy was confirmed to be normal at the anomaly scan were also performed. Random effects model meta-analyses of proportion were used to analyze the data.
RESULTS
Eight articles (324 fetuses) were included in the systematic review. Of the fetuses with negative standard karyotype and CMA analysis, the 8.07% (95% CI 5.4-11.3) had pathogenic or likely pathogenic genetic variants detected exclusively by WES. When stratifying the analysis according to NT cutoffs, genetic anomalies detected exclusively at WES analysis were found in 44.70% (95% CI 26.8-63.4) of fetuses with NT between 3.0 mm and 5.5 mm and 55.3% (95% CI 36.6-73.2) in those fetuses with NT >5.5 mm and positive WES results. The 7.84% (95% CI 1.6-18.2) had variants of unknown significance identified by WES. When considering fetuses with isolated increased NT and normal fetal anatomy at the anomaly scan, the rate of pathogenic or likely pathogenic genetic variants detected by WES was 3.87% (95% CI 1.6-7.1), while variants of unknown significance were detected in 4.27% (95% CI 2.2-7.0) of cases.
CONCLUSIONS
Pathogenic and likely pathogenic genetic variants detected by WES are present in a significant proportion of fetuses with increased NT but normal standard karyotype and CMA analysis, also when no anomalies are detected at the anomaly scan. Further large studies sharing objective protocols of imaging assessment are needed to confirm these findings and to elucidate which gene panels should be assessed in fetuses with isolated increased NT to rule out associated genetic anomalies, which may potentially impact post-natal outcomes.
Topics: Pregnancy; Female; Humans; Nuchal Translucency Measurement; Exome Sequencing; Fetus; Karyotyping; Karyotype; Prenatal Diagnosis
PubMed: 37019452
DOI: 10.1080/14767058.2023.2193285 -
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 -
Journal of Translational Medicine Aug 2023Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate...
BACKGROUND
Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings.
METHODS
Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets.
RESULTS
Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1 neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome.
CONCLUSION
This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.
Topics: Humans; Glioblastoma; Isocitrate Dehydrogenase; Brain Neoplasms; Prognosis; Nomograms; Methyltransferases
PubMed: 37553713
DOI: 10.1186/s12967-023-04382-2 -
Journal of Korean Medical Science Mar 2024Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype.
METHODS
An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study.
RESULTS
Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%).
CONCLUSION
CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.
Topics: Female; Humans; Pregnancy; Fetus; Karyotyping; Microarray Analysis; Ultrasonography, Prenatal
PubMed: 38442716
DOI: 10.3346/jkms.2024.39.e70 -
Prenatal Diagnosis Apr 2024Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.
METHODS
Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model.
RESULTS
Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus.
CONCLUSIONS
Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.
Topics: Pregnancy; Female; Humans; Prospective Studies; Hydrocephalus; Nervous System Malformations; Karyotyping; Karyotype; Fetus; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 38054560
DOI: 10.1002/pd.6466 -
Endocrine, Metabolic & Immune Disorders... 2024Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific...
BACKGROUND
Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific mechanism.
OBJECTIVES
In this study, we aimed to investigate CD163 as a potential biomarker associated with immune inflammation in diabetes mellitus through a systematic review and bioinformatics analysis.
METHODS
We searched PubMed, Web of Science, the Cochrane Library, and Embase databases with a time limit of September 2, 2022. Furthermore, we conducted a systematic search and review based on PRISMA guidelines. Additionally, diabetic gene expression microarray datasets GSE29221, GSE30528, GSE30529, and GSE20966 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) for bioinformatics analysis. The PROSPERO number for this study is CRD420222347160.
RESULTS
Following the inclusion and exclusion criteria, seven articles included 1607 patients, comprising 912 diabetic patients and 695 non-diabetic patients. This systematic review found significantly higher levels of CD163 in diabetic patients compared to non-diabetic patients. People with diabetes had higher levels of CRP expression compared to the control group. Similarly, two of the three papers that used TNF- α as an outcome indicator showed higher expression levels in diabetic patients. Furthermore, IL-6 expression levels were higher in diabetic patients than in the control group. A total of 62 samples were analyzed by bioinformatics (33 case controls and 29 experimental groups), and 85 differential genes were identified containing CD163. According to the immune cell correlation analysis, CD163 was associated with macrophage M2, γδ T lymphocytes, macrophage M1, and other immune cells. Furthermore, to evaluate the diagnostic performance of CD163, we validated it using the GSE20966 dataset. In the validation set, CD163 showed high diagnostic accuracy.
CONCLUSION
This study suggests CD163 participates in the inflammatory immune response associated with diabetes mellitus and its complications by involving several immune cells. Furthermore, the results suggest CD163 may be a potential biomarker reflecting immune inflammation in diabetic mellitus.
Topics: Humans; Biomarkers; Computational Biology; Diabetes Mellitus; Inflammation; Macrophages
PubMed: 37455460
DOI: 10.2174/1871530323666230714162324 -
Biochemistry and Biophysics Reports Mar 2024Papillary thyroid cancer (PTC) is a prevalent kind of thyroid cancer (TC), with the risk of metastasis increasing faster than any other malignancy. So, understanding the...
The role of MAPK, notch and Wnt signaling pathways in papillary thyroid cancer: Evidence from a systematic review and meta-analyzing microarray datasets employing bioinformatics knowledge and literature.
Papillary thyroid cancer (PTC) is a prevalent kind of thyroid cancer (TC), with the risk of metastasis increasing faster than any other malignancy. So, understanding the role of PTC in pathogenesis requires studying the various gene expressions to find out which particular molecular biomarkers will be helpful. The authors conducted a comprehensive search on the PubMed microarray database and a meta-analysis approach on the remaining ones to determine the differentially expressed genes between PTC and normal tissues, along with the analyses of overall survival (OS) and recurrence-free survival (RFS) rates in patients with PTC. We considered the associated genes with MAPK, Wnt, and Notch signaling pathways. Two GEO datasets have been included in this research, considering inclusion and exclusion criteria. Nineteen genes were found to have higher differences through the meta-analysis procedure. Among them, ten genes were upregulated, and nine genes were downregulated. The expression of 19 genes was examined using the GEPIA2 database, and the Kaplan-Meier plot statistics were used to analyze RFS and the OS rates. We discovered seven significant genes with the validation: PRICKLE1, KIT, RPS6KA5, GADD45B, FGFR2, FGF7, and DTX4. To further explain these findings, it was discovered that the mRNA expression levels of these seven genes and the remaining 12 genes were shown to be substantially linked with the results of the experimental literature investigations on the PTC. Our research found nineteen panels of genes that could be involved in the PTC progression and metastasis and the immune system infiltration of these cancers
PubMed: 38371530
DOI: 10.1016/j.bbrep.2023.101606 -
Briefings in Bioinformatics Jan 2024Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients...
Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.
Topics: Humans; Neoplasms, Unknown Primary; Precision Medicine; Gene Expression Profiling; Microarray Analysis
PubMed: 38343328
DOI: 10.1093/bib/bbae028