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Journal of Clinical Oncology : Official... Sep 2022To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
PURPOSE
To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline.
METHODS
An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022.
RESULTS
The search identified 19 studies informing the evidence base.
RECOMMENDATIONS
Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline and pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.
Topics: Adenosine Diphosphate; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Breast Neoplasms; Circulating Tumor DNA; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Immune Checkpoint Inhibitors; Ligands; Phosphatidylinositol 3-Kinases; Poly(ADP-ribose) Polymerase Inhibitors; Prospective Studies; Retrospective Studies; Ribose
PubMed: 35759724
DOI: 10.1200/JCO.22.01063 -
Genes Jan 2023The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly,... (Review)
Review
The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning technologies is also presented in this review. Face-landmarking techniques and face-phenotyping algorithms are discussed in chronological order. Then, the latest approaches in genetic to 3D face shape analysis are emphasized. A systematic review of the current markers that passed the threshold of a genome-wide association (GWAS) of single nucleotide polymorphism (SNP)-face traits from the GWAS Catalog is also provided using the preferred reporting items for systematic reviews and meta-analyses (PRISMA), approach. Finally, the current challenges in forensic DNA phenotyping are analyzed and discussed.
Topics: Humans; Nucleic Acids; Genome-Wide Association Study; Phenotype; Pigmentation; DNA
PubMed: 36672878
DOI: 10.3390/genes14010136 -
Archives of Toxicology Nov 2022Studies suggest that chronic lead (Pb) exposure may induce deoxyribonucleic acid (DNA) damage. However, there is no synthesised evidence in this regard. We... (Meta-Analysis)
Meta-Analysis Review
Studies suggest that chronic lead (Pb) exposure may induce deoxyribonucleic acid (DNA) damage. However, there is no synthesised evidence in this regard. We systematically reviewed existing literature and synthesised evidence on the association between chronic Pb exposure and markers of genotoxicity. Observational studies reporting biomarkers of DNA damage among occupationally Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase databases from inception to January 2022. The markers included were micronucleus frequency (MN), chromosomal aberrations, comet assay, and 8-hydroxy-deoxyguanosine. During the execution of this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Mean differences in the biological markers of DNA damage between Pb-exposed and control groups were pooled using the random-effects model. The heterogeneity was assessed using the Cochran-Q test and I statistic. The review included forty-five studies comparing markers of DNA damage between Pb-exposed and unexposed. The primary studies utilised buccal and/or peripheral leukocytes for evaluating the DNA damage. The pooled quantitative results revealed significantly higher DNA damage characterised by increased levels of MN and SCE frequency, chromosomal aberrations, and oxidative DNA damage (comet assay and 8-OHdG) among Pb-exposed than the unexposed. However, studies included in the review exhibited high levels of heterogeneity among the studies. Chronic Pb exposure is associated with DNA damage. However, high-quality, multicentred studies are required to strengthen present observations and further understand the Pb's role in inducing DNA damage. CRD42022286810.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Chromosome Aberrations; Comet Assay; DNA; DNA Damage; Humans; Lead; Micronucleus Tests; Occupational Exposure
PubMed: 35930012
DOI: 10.1007/s00204-022-03352-9 -
Molecular Ecology Resources Oct 2022Environmental DNA (eDNA) has been used in a variety of ecological studies and management applications. The rate at which eDNA decays has been widely studied but at... (Meta-Analysis)
Meta-Analysis Review
Environmental DNA (eDNA) has been used in a variety of ecological studies and management applications. The rate at which eDNA decays has been widely studied but at present it is difficult to disentangle study-specific effects from factors that universally affect eDNA degradation. To address this, a systematic review and meta-analysis was conducted on aquatic eDNA studies. Analysis revealed eDNA decayed faster at higher temperatures and in marine environments (as opposed to freshwater). DNA type (mitochondrial or nuclear) and fragment length did not affect eDNA decay rate, although a preference for <200 bp sequences in the available literature means this relationship was not assessed with longer sequences (e.g. >800 bp). At present, factors such as ultraviolet light, pH, and microbial load lacked sufficient studies to feature in the meta-analysis. Moving forward, we advocate researching these factors to further refine our understanding of eDNA decay in aquatic environments.
Topics: DNA; DNA, Environmental; Environmental Monitoring; Fresh Water; Temperature; Water
PubMed: 35510730
DOI: 10.1111/1755-0998.13627 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241 -
Molecular Biotechnology Nov 2023To overcome the COVID-19 pandemic, the development of safe and effective vaccines is crucial. With the enormous information available on vaccine development for... (Review)
Review
To overcome the COVID-19 pandemic, the development of safe and effective vaccines is crucial. With the enormous information available on vaccine development for COVID-19, there are still grey areas to be considered when designing a potential vaccine. The rapid regulatory approval of nucleic acid-based vaccines was unique to the COVID-19; these vaccines were rapidly produced cost-effectively and with lesser risk of infectivity. Additionally, they demonstrated relative stability at room temperature (DNA). However, a comparative understanding of the immunogenic impact and efficacy of these vaccines is lacking. Immunogenicity is essential for developing and maintaining effective and long-lasting post-vaccination immunity to pathogenic microorganisms. This systematic review aims to assess and summarize the immunogenicity and protective efficacy of the nucleic acid-based vaccines against COVID-19. The Preferred Reporting Items for Systematic Reviews (PRISMA) recommendations were followed in this review. CASP tool was used for quality assessment of randomized controlled trials. All included studies employed a randomized control method, and the results demonstrated promising immune responses and effectiveness that provided high-level protection against COVID-19 infection. This study offers vital insights for advancing vaccine technology. Furthermore, it guides formulation, informs personalized vaccination strategies, and enhances global health preparedness, particularly in regions with limited vaccine access.
PubMed: 38006520
DOI: 10.1007/s12033-023-00965-y -
Journal of Hepatology Apr 2023Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein,...
BACKGROUND & AIMS
Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility.
METHODS
We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates.
RESULTS
HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance.
CONCLUSIONS
HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution.
IMPACT AND IMPLICATIONS
Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B, Chronic; Hepatitis B Surface Antigens; Hepatitis B e Antigens; DNA, Viral; Biomarkers; Antiviral Agents; RNA; Hepatitis B virus
PubMed: 36586590
DOI: 10.1016/j.jhep.2022.12.017 -
The Journal of Clinical Endocrinology... Dec 2023Mitochondrial DNA (mtDNA) plays a key role in diabetes mellitus and metabolic syndrome (MetS). An increasing number of studies have reported the association between... (Meta-Analysis)
Meta-Analysis
CONTEXT
Mitochondrial DNA (mtDNA) plays a key role in diabetes mellitus and metabolic syndrome (MetS). An increasing number of studies have reported the association between mtDNA copy number (mtDNA-CN) and the risk of diabetes mellitus and MetS; however, the associations remain conflicted and a systematic review and meta-analysis on the association between mtDNA-CN and diabetes mellitus and MetS is lacking.
OBJECTIVE
We aimed to investigate the association of mtDNA-CN and diabetes mellitus and MetS using a systematic review and meta-analysis of observational studies.
METHODS
PubMed, EMBASE, and Web of Science were searched up to December 15, 2022. Random-effect models were used to summarize the relative risks (RRs) and 95% CIs.
RESULTS
A total of 19 articles were included in the systematic review and 6 articles (12 studies) in the meta-analysis involving 21 714 patients with diabetes (318 870 participants) and 5031 MetS (15 040 participants). Compared to the highest mtDNA-CN, the summary RR (95% CIs) for the lowest mtDNA-CN were 1.06 (95% CI, 1.01-1.12; I2 = 79.4%; n = 8) for diabetes (prospective study: 1.11 (1.02-1.21); I2 = 22.6%; n = 4; case-control: 1.27 (0.66-2.43); I2 = 81.8%; n = 2; cross-sectional: 1.01 (0.99-1.03); I2 = 74.7%; n = 2), and 1.03 (0.99-1.07; I2 = 70.6%; n = 4) for MetS (prospective: 2.87 (1.51-5.48); I2 = 0; n = 2; cross-sectional: 1.02 (1.01-1.04); I2 = 0; n = 2).
CONCLUSION
Decreased mtDNA-CN was associated with increased risk of diabetes mellitus and MetS when limited to prospective studies. More longitudinal studies are warranted.
Topics: Humans; Metabolic Syndrome; Prospective Studies; DNA, Mitochondrial; DNA Copy Number Variations; Cross-Sectional Studies; Diabetes Mellitus; Risk Factors
PubMed: 37431585
DOI: 10.1210/clinem/dgad403 -
International Journal of Molecular... Dec 2017Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of... (Review)
Review
Ascending aortic aneurysms are mostly asymptomatic and present a great risk of aortic dissection or perforation. Consequently, ascending aortic aneurysms are a source of lethality with increased age. Biological aging results in progressive attrition of telomeres, which are the repetitive DNA sequences at the end of chromosomes. These telomeres play an important role in protection of genomic DNA from end-to-end fusions. Telomere maintenance and telomere attrition-associated senescence of endothelial and smooth muscle cells have been indicated to be part of the pathogenesis of degenerative vascular diseases. This systematic review provides an overview of telomeres, telomere-associated proteins and telomerase to the formation and progression of aneurysms of the thoracic ascending aorta. A better understanding of telomere regulation in the vascular pathology might provide new therapeutic approaches. Measurements of telomere length and telomerase activity could be potential prognostic biomarkers for increased risk of death in elderly patients suffering from an aortic aneurysm.
Topics: Aging; Animals; Aortic Aneurysm, Thoracic; Biomarkers; DNA; Humans; Mice; Rats; Risk Factors; Telomerase; Telomere; Telomere Shortening
PubMed: 29267201
DOI: 10.3390/ijms19010003 -
Revista Brasileira de Enfermagem 2021Analyze available evidence related to SARS-CoV-2 infection and vertical transmission. (Review)
Review
OBJECTIVE
Analyze available evidence related to SARS-CoV-2 infection and vertical transmission.
METHODS
Scoping review, according to the Joanna Briggs Institute and PRISMA-ScR. Searches were conducted in five electronic databases to find publications about coronavirus infection and vertical transmission. Data were extracted, analyzed and synthesized by three independent researchers using a descriptive approach.
RESULTS
The search resulted in 76 publications. After selective steps, 15 articles - retrospective descriptive or case studies - were analyzed, all in English. In order to track the infection, specimens were collected from neonates through nasal swabs and C-reactive protein from breast milk, cord blood, amniotic fluid, placenta and vaginal secretion was analyzed. A small percentage of neonates tested positive for COVID-19, but these cases were not attributed to vertical transmission.
CONCLUSION
Vertical transmission could not be demonstrated. Research protocol registered with the Open Science Framework (https://osf.io/fawmv).
Topics: C-Reactive Protein; COVID-19; DNA, Viral; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pandemics; Pregnancy; Pregnancy Complications, Infectious; Real-Time Polymerase Chain Reaction; SARS-CoV-2
PubMed: 34037165
DOI: 10.1590/0034-7167-2020-0849