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Journal of Crohn's & Colitis Mar 2023Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease [IBD] patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte [PBL] DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.
METHODS
We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies [BIOCROSS] tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies [EWAS] that included patients with Crohn's disease [CD], ulcerative colitis [UC] and/or healthy controls [HC].
RESULTS
Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from four studies based on a cumulative 552 samples [177 CD, 132 UC and 243 HC]. Consistent differential methylation was identified for 256 differentially methylated probes [DMPs; Bonferroni-adjusted p ≤ 0.05] when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD [CD + UC] with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.
CONCLUSION
Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were able to confirm previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.
Topics: Humans; DNA Methylation; Cross-Sectional Studies; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Membrane Proteins
PubMed: 35998097
DOI: 10.1093/ecco-jcc/jjac119 -
BMC Cancer Oct 2020DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns...
BACKGROUND
DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses.
METHODS
We searched major databases (MEDLINE, EMBASE, Web of Science, CENTRAL) from inception up to 30th June 2019, for observational or intervention studies investigating the association between epigenome-wide DNA methylation (using the HM450k or EPIC BeadChip), measured in any type of human sample, and breast cancer risk. A pre-established protocol was drawn up following the Cochrane Reviews rigorous methodology. Study selection, data abstraction, and risk of bias assessment were performed by at least two investigators. A qualitative synthesis and systematic comparison of the strengths and weaknesses of studies was performed.
RESULTS
Overall, 20 studies using the HM450k BeadChip were included, 17 of which had measured blood-derived DNA methylation. There was a consistent trend toward an association of global blood-derived DNA hypomethylation and higher epigenetic age with higher risk of breast cancer. The strength of associations was modest for global hypomethylation and relatively weak for most of epigenetic age algorithms. Differences in length of follow-up periods may have influenced the ability to detect associations, as studies reporting follow-up periods shorter than 10 years were more likely to observe an association with global DNA methylation. Probe-wise differential methylation analyses identified between one and 806 differentially methylated CpGs positions in 10 studies. None of the identified differentially methylated sites overlapped between studies. Three studies used breast tissue DNA and suffered major methodological issues that precludes any conclusion. Overall risk of bias was critical mainly because of incomplete control of confounding. Important issues relative to data preprocessing could have limited the consistency of results.
CONCLUSIONS
Global DNA methylation may be a short-term predictor of breast cancer risk. Further studies with rigorous methodology are needed to determine spatial distribution of DNA hypomethylation and identify differentially methylated sites associated with risk of breast cancer.
PROSPERO REGISTRATION NUMBER
CRD42020147244.
Topics: Biomarkers, Tumor; Breast Neoplasms; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Genome-Wide Association Study; Humans; Prognosis
PubMed: 33129307
DOI: 10.1186/s12885-020-07543-4 -
The European Respiratory Journal Jan 2017Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin... (Meta-Analysis)
Meta-Analysis Review
Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed.This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing. Results for RIF and INH resistance were compared to phenotypic and composite (incorporating sequencing) reference standards. M. tuberculosis detection results were compared to culture.74 unique studies were included. For RIF resistance (21 225 samples), pooled sensitivity and specificity (with 95% confidence intervals) were 96.7% (95.6-97.5%) and 98.8% (98.2-99.2%). For INH resistance (20 954 samples), pooled sensitivity and specificity were 90.2% (88.2-91.9%) and 99.2% (98.7-99.5%). Results were similar for direct and indirect testing and across LPAs. Using a composite reference standard, specificity increased marginally. For M. tuberculosis detection (3451 samples), pooled sensitivity was 94% (89.4-99.4%) for smear-positive specimens and 44% (20.2-71.7%) for smear-negative specimens.In patients with pulmonary TB, LPAs have high sensitivity and specificity for RIF resistance and high specificity and good sensitivity for INH resistance. This meta-analysis provides evidence for policy and practice.
Topics: Antitubercular Agents; DNA Probes; Drug Resistance, Multiple, Bacterial; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 28100546
DOI: 10.1183/13993003.01075-2016 -
Journal of Diabetes Research 2017The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating... (Meta-Analysis)
Meta-Analysis Review
The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.
Topics: Biomarkers; Calcium-Binding Proteins; DNA-Binding Proteins; Diabetes Mellitus, Type 2; Disease Progression; Down-Regulation; Humans; Hypoglycemic Agents; Nerve Tissue Proteins; Nucleobindins; Reproducibility of Results; Up-Regulation
PubMed: 29445751
DOI: 10.1155/2017/7687098 -
Phenomics (Cham, Switzerland) Apr 2022Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of... (Review)
Review
Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of epigenetic modifications could markedly improve biological investigations and cancer precision medicine. A rapid development of molecular imaging approaches for the diagnosis and prognosis of cancer has been observed during the past few years. Various biomarkers unique to epigenetic modifications and targeted imaging probes have been characterized and used to discriminate cancer from healthy tissues, as well as evaluate therapeutic responses. In this study, we summarize the latest studies associated with optical molecular imaging of epigenetic modification targets, such as those involving DNA methylation, histone modification, noncoding RNA regulation, and chromosome remodeling, and further review their clinical application on cancer diagnosis and treatment. Lastly, we further propose the future directions for precision imaging of epigenetic modification in cancer. Supported by promising clinical and preclinical studies associated with optical molecular imaging technology and epigenetic drugs, the central role of epigenetics in cancer should be increasingly recognized and accepted.
PubMed: 36939779
DOI: 10.1007/s43657-021-00041-y -
Revista de Salud Publica (Bogota,... 2009Avian mycobacteriosis is important for animal and human health; wild birds play an important role in mycobacterial species' ecology and movement. This review was aimed... (Review)
Review
Avian mycobacteriosis is important for animal and human health; wild birds play an important role in mycobacterial species' ecology and movement. This review was aimed at reporting the role of birds in the spread of avian mycobacteriosis in human and animal populations at risk and thus a systematic review was made of PubMed, Science Direct, Scielo and Scirus databases. Mycobacteria are classified into the Mycobacterium tuberculosis complex and non-tuberculous mycobacteria; the Mycobacterium avium complex represents the most important part of the latter because it is primarily responsible for mycobacterial infection in wild birds and is a potential pathogen for mammals, especially for immunocompromised patients. The clinical signs in birds are variable as it is a chronic and debilitating disease, involving emaciated carcasses, white nodules in different organs and microscopically it presents granulomatosous multifocal inflammation. Diagnosis begins by suspicion based on clinical signs and finishes with microbiological confirmation. New diagnostic techniques include testing with DNA-RNA probes. No effective treatment is currently available and chemoprophylaxis on suspicion of infection is not recommended at the start; these factors increase the potential risk of mycobacteriosis becoming one of the most frequently documented zoonotic diseases which is difficult to treat in birds and humans. Recent concern regarding mycobacterial infection lies in the increased frequency of these opportunistic infections occurring in immunocompromised individuals and these infections' potential impact on bird conservation, this being increased by greater contact between humans and wild and captive birds.
Topics: Animals; Birds; Humans; Risk Factors; Tuberculosis, Avian
PubMed: 19721987
DOI: 10.1590/s0124-00642009000100014 -
Frontiers in Oncology 2022Urothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy....
BACKGROUND
Urothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy. Testing for HER2 expression in UC is not part of current routine clinical practice. In consequence, the prevalence of HER2 expression in UC is not well defined.
METHODS
A systematic literature review (SLR) was conducted to characterize HER2 expression in both locally advanced unresectable or metastatic (LA/mUC) and earlier stage UC, classified as HER2+, HER2-low, HER2-. HER2+ was defined as an immunohistochemistry (IHC) score of 3+ or IHC 2+ and ISH/FISH+. HER2-low was defined as an IHC score of 2+ and ISH/FISH- or IHC 1+. HER2- was defined as an IHC score of 0. Weighted averages were calculated to generate an estimate of the population prevalence.
RESULTS
A total of 88 studies were identified, with 45, 30, and 13 studies investigating LA/mUC, earlier stage UC, and mixed stage/unspecified, respectively. The most common assays used were Dako HercepTest and Ventana Pathway anti-HER2/neu (4B5) for IHC to assess HER2 protein expression; Abbott PathVysion HER-2 DNA Probe Kit, FoundationOne CDx, and Guardant360 CDx for assessing HER2 gene amplification. The most frequently cited scoring guidelines were ASCO/CAP guidelines for breast cancer and gastric cancer, though most studies defined their own criteria for HER2 expression. Using the pre-specified definition, HER2+ prevalence ranged from 6.7% to 37.5% with a weighted average of 13.0% in LA/mUC. Only 1 study presented data that could be classified as HER2+ based on pre-specified criteria in earlier stage UC patients, and this study represented a likely outlier, at 76.0%.
CONCLUSION
The results from this SLR help to shed light on HER2 expression in UC, a potentially clinically relevant biomarker-driven subpopulation for emerging HER2-directed regimens. Results of this SLR illuminate the variability in how HER2+ status expression levels are being assessed and how HER2+ is defined. Consensus on standardized HER2 testing and scoring criteria is paramount to better understand the clinical relevance in patients with UC.
PubMed: 36338710
DOI: 10.3389/fonc.2022.1011885 -
Sao Paulo Medical Journal = Revista... 2012The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL)... (Review)
Review
Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests.
CONTEXT AND OBJECTIVE
The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL.
DESIGN AND SETTING
Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved.
METHODS
The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed.
RESULTS
Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%).
CONCLUSIONS
Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.
Topics: Adult; Age Factors; Colposcopy; DNA Probes, HPV; Female; Humans; Papillomavirus Infections; Sensitivity and Specificity; Triage; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 22344359
DOI: 10.1590/s1516-31802012000100008 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470 -
Frontiers in Oral Health 2023Noma is a rapidly progressing periodontal disease with up to 90% mortality in developing countries. Poor, immunocompromised and severely malnourished children (2 to 6... (Review)
Review
Noma is a rapidly progressing periodontal disease with up to 90% mortality in developing countries. Poor, immunocompromised and severely malnourished children (2 to 6 years old) are mostly affected by Noma. Prevention and effective management of Noma is hindered by the lack of sufficient cohesive studies on the microbial etiology of the disease. Research efforts have not provided a comprehensive unified story of the disease. Bridging the gap between existing studies gives an insight on the disease pathogenesis. This current systematic review of etiological studies focuses on the key players of dysbiosis in Noma disease. This review was performed in accordance with the Preferred Reporting Items for Systemic review and Meta-Analyses (PRISMA) statement. Web of Science, MEDLINE PubMed, Cochrane Library, Scopus, and Science Direct were searched electronically for clinical trials which applied culture dependent or molecular techniques to identify oral microbiota from Noma patients. Trials which involved periodontal diseases except Noma were excluded. After screening 275 articles, 153 full-texts articles were assessed for eligibility of which eight full text articles were selected for data extraction and analysis. The results show that 308 samples from 169 Noma participants (6 months to 15 years old) have been used in clinical trials. There was some variance in the microbiome identified due to the use of 3 different types of samples (crevicular fluid, subgingival plaque, and swabbed pus) and the ambiguity of the stage or advancement of Noma in the studies. Other limitations of the studies included in this review were: the absence of age-matched controls in some studies; the constraints of colony morphology as a tool in distinguishing between virulent fusobacterium genus at the species level; the difficulty in culturing spirochaetes in the laboratory; the choice of primers in DNA amplification; and the selection of probe sets in gene sequencing. This systematic review highlights spirochaetes and P. intermedia as putative trigger organisms in Noma dysbiosis, shows that F. nucleatum promotes biofilms formation in late stages of the disease and suggests that future studies should be longitudinal, with high throughput genome sequencing techniques used with gingival plaque samples from early stages of Noma.
PubMed: 36937503
DOI: 10.3389/froh.2023.1095858