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Antimicrobial Agents and Chemotherapy Feb 2021Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms...
Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis.
Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September 2013 and December 2019. The genes , , and , and the intergenic region '- were considered in this review. Fifty-two articles were included that described 9,306 clinical isolates (5,804 INH resistant [INH] and 3,502 INH susceptible [INH]) from 31 countries. The three most frequently mutated loci continue to be locus 315 of (315; = 4,271), locus -15 of (-15; = 787), and locus -8 of (-8; 106). However, the diagnostic value of -8 is far lower than previously thought, as it only appears in 25 (0.4%) of the INH isolates lacking the first two mutations. I catalogued 45 new loci (29 , nine , and seven ) associated with INH resistance and identified 59 loci (common to this and previous reviews) as a reliable basis for molecular diagnostics. Including all observed mutations provides a cumulative sensitivity of 85.6%. In 14.4% of resistant isolates, no mechanism of resistance was detected, making them likely to escape molecular detection, and in the case of INH monoresistance, likely to convert to multidrug-resistant TB (MDR-TB). Integrating the information cataloged in this study into current diagnostic tools is essential for combating the emergence of MDR-TB, and its exclusion can lead to an unintended selection against common mechanisms and to diversifying evolution. Observation of many low-frequency resistance-conferring mutations points to an advantage of whole-genome sequencing (WGS) for diagnostics. Finally, I provide five recommendations for future diagnostic platforms.
Topics: Antitubercular Agents; Bacterial Proteins; DNA, Bacterial; Drug Resistance, Multiple; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 33361298
DOI: 10.1128/AAC.02091-20 -
Scientific Reports Jan 2023The serological diagnostic criteria for the immune-tolerant (IT) phase have not been strictly defined and it is hard to determine an accurate rate for significant... (Meta-Analysis)
Meta-Analysis
The serological diagnostic criteria for the immune-tolerant (IT) phase have not been strictly defined and it is hard to determine an accurate rate for significant histologic changes among IT patients. The aim of this study was to establish a baseline rate of significant histologic changes and to determine the main characteristics of IT patients. We systematically searched PubMed, Embase, and Web of Science. Studies reporting liver biopsy results (inflammation grade or fibrosis stage) for adults with chronic hepatitis B virus (HBV) infection in the IT phase diagnosed by serological criterion were included to pool the rate of significant histologic changes. Studies that enrolled subjects with confirmed chronic HBV infection in the IT phase diagnosed by serological and liver biopsy criteria (dual criteria) were included to pool the mean values of main characteristics among IT patients. Of 319 studies screened, 15 were eventually included in the meta-analysis. The pooled rates of significant liver fibrosis and inflammatory activity for 10 studies were 10% (95% confidence interval [CI] 0.06-0.18) and 16% (95% CI 0.07-0.31), respectively. The pooled mean values of age, alanine aminotransferase level, HBV DNA level, and HBsAg level for another 5 studies with IT patients diagnosed by dual criteria were 30.7 years (95% CI 27.31-34.09), 26.64 IU/mL (95% CI 24.45-28.83), 8.41 log cp/mL (95% CI 7.59-9.23), and 4.24 log IU/mL (95% CI 3.67-4.82), respectively. Significant histologic changes were not rare events among IT patients. Strictly defined serological diagnostic criteria for the IT phase are warranted.
Topics: Adult; Humans; Hepatitis B, Chronic; Hepatitis B virus; DNA, Viral; Hepatitis B Surface Antigens; Liver Cirrhosis; Hepatitis B e Antigens; Alanine Transaminase; Hepatitis B
PubMed: 36627364
DOI: 10.1038/s41598-023-27545-z -
Frontiers in Physiology 2022Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions...
Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions affecting the health of the host. However, difficulties hamper the investigation of microbiota composition in cultivating microorganisms in standard growth media. For this reason, our knowledge of microbiota can benefit from the analysis of microbial macromolecules (DNA, transcripts, proteins, or by-products) present in various samples collected from the host. Various omics technologies are used to obtain different data. Metagenomics provides a taxonomical profile of the sample. It can also be used to obtain potential functional information. At the same time, metatranscriptomics can characterize members of a microbiome responsible for specific functions and elucidate genes that drive the microbiotas relationship with its host. Thus, while microbiota refers to microorganisms living in a determined environment (taxonomy of microorganisms identified), microbiome refers to the microorganisms and their genes living in a determined environment and, of course, metagenomics focuses on the genes and collective functions of identified microorganisms. Metabolomics completes this framework by determining the metabolite fluxes and the products released into the environment. The gallbladder is a sac localized under the liver in the human body and is difficult to access for bile and tissue sampling. It concentrates the bile produced in the hepatocytes, which drains into bile canaliculi. Bile promotes fat digestion and is released from the gallbladder into the upper small intestine in response to food. Considered sterile originally, recent data indicate that bile microbiota is associated with the biliary tract's inflammation and carcinogenesis. The sample size is relevant for omic studies of rare diseases, such as gallbladder carcinoma. Although in its infancy, the study of the biliary microbiota has begun taking advantage of several omics strategies, mainly based on metagenomics, metabolomics, and mouse models. Here, we show that omics analyses from the literature may provide a more comprehensive image of the biliary microbiota. We review studies performed in this environmental niche and focus on network-based approaches for integrative studies.
PubMed: 36111147
DOI: 10.3389/fphys.2022.888233 -
International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Clinical Breast Cancer Dec 2019Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is...
Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is vital for early detection and effective treatment. In this study we explored the advances in trial for the diagnosis of BCBM, with review of the literature. On May 8, 2019, we searched ClinicalTrials.gov for interventional and diagnostic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, experimental interventions, results, and publications were collected and analyzed. In addition, a systematic review of the literature was conducted to explore published studies related to BCBM diagnosis. Only 9 diagnostic trials explored BCBM. Of these, 1 trial was withdrawn because of low accrual numbers. Three trials were completed; however, none had published results. Modalities in trial for BCBM diagnosis entailed magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, nanobodies, and circulating tumor cells (CTCs), along with a collection of novel tracers and imaging biomarkers. MRI continues to be the diagnostic modality of choice, whereas CT is best suited for acute settings. Advances in PET and PET-CT allow the collection of metabolic and functional information related to BCBM. CTC characterization can help reflect on the molecular foundations of BCBM, whereas cell-free DNA offers new genetic material for further exploration in trials. The integration of machine learning in BCBM diagnosis seems inevitable as we continue to aim for rapid and accurate detection and better patient outcomes.
Topics: Brain Neoplasms; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Magnetic Resonance Imaging; Neoplastic Cells, Circulating; Positron Emission Tomography Computed Tomography; Prognosis
PubMed: 31262686
DOI: 10.1016/j.clbc.2019.05.018 -
Genes Sep 2020The abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder... (Meta-Analysis)
Meta-Analysis
The abuse of alcohol, one of the most popular psychoactive substances, can cause several pathological and psychological consequences, including alcohol use disorder (AUD). An impaired ability to stop or control alcohol intake despite adverse health or social consequences characterize AUD. While AUDs predominantly occur in men, growing evidence suggests the existence of distinct cognitive and biological consequences of alcohol dependence in women. The molecular and physiological mechanisms participating in these differential effects remain unknown. Transcriptomic technology permits the detection of the biological mechanisms responsible for such sex-based differences, which supports the subsequent development of novel personalized therapeutics to treat AUD. We conducted a systematic review and meta-analysis of transcriptomics studies regarding alcohol dependence in humans with representation from both sexes. For each study, we processed and analyzed transcriptomic data to obtain a functional profile of pathways and biological functions and then integrated the resulting data by meta-analysis to characterize any sex-based transcriptomic differences associated with AUD. Global results of the transcriptomic analysis revealed the association of decreased tissue regeneration, embryo malformations, altered intracellular transport, and increased rate of RNA and protein replacement with female AUD patients. Meanwhile, our analysis indicated that increased inflammatory response and blood pressure and a reduction in DNA repair capabilities are associated with male AUD patients. In summary, our functional meta-analysis of transcriptomic studies provides evidence for differential biological mechanisms of AUD patients of differing sex.
Topics: Alcohol Drinking; Alcoholism; Humans; Sex Characteristics; Transcriptome
PubMed: 32967293
DOI: 10.3390/genes11091106 -
Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
Frontiers in Oncology 2020Breast cancer is the most common malignancy diagnosed during pregnancy. Strong data on the genomic profile of pregnancy-associated breast cancer are lacking. This...
Breast cancer is the most common malignancy diagnosed during pregnancy. Strong data on the genomic profile of pregnancy-associated breast cancer are lacking. This systematic review aims to integrate and analyze all existing data from the literature regarding the genomic background and the gene mutational patterns of pregnancy-associated breast cancer. Using various genomic analysis methods, multiple differentially expressed genes and numerous non-silent mutations have been detected. More particularly, our review demonstrates the aberrant expression of several oncogenes (e.g., ), tumor suppressor genes (e.g., ), apoptosis regulators (e.g., ), transcription regulators (e.g., ), genes involved in DNA repair mechanisms (e.g., Sig20, ), in cell proliferation (e.g., ), in the immune response (e.g., ), and in other significant biological processes (e.g., protein modification, internal cell motility). Further research on the genomic profile of pregnancy-associated breast cancer is urgently required in order to identify potential biomarkers facilitating early-stage diagnosis and individualized therapy.
PubMed: 33014874
DOI: 10.3389/fonc.2020.01773 -
PloS One 2021Nontuberculous mycobacteria (NTM) infection is similar to Mycobacterium tuberculosis (MTB) infection. Early clinical identification and differentiation of NTM and MTB... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nontuberculous mycobacteria (NTM) infection is similar to Mycobacterium tuberculosis (MTB) infection. Early clinical identification and differentiation of NTM and MTB infections continues to be a major challenge. Nucleic acid amplification tests (NAATs) have the ability to efficiently and rapidly detect pathogens and are widely used in mycobacterial infections. The objective of this study is to estimate the diagnostic accuracy of NAATs for NTM.
METHODS
We will search candidate studies that assessing the accuracy of NAATs for diagnosis of NTM through PubMed, Embase and the Cochrane Library until May 2021. Studies with full text that meet the inclusion criteria will be included. Following a revised tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), two researchers will independently evaluate the study quality. The STATA software (version 15.0) will be used to carry out meta-analyses. When heterogeneity is observed, subgroup analyses and meta-regression analyses will be used to explore sources of heterogeneity. Sensitivity analyses will be used to check the robustness of analyses.
CONCLUSION
We hope that this study will provide meaningful evidence for the early and rapid diagnosis of NAATs for NTM, which will help to guide the treatment of NTM and improve the prognosis of patients.
Topics: DNA, Bacterial; Diagnostic Tests, Routine; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Nucleic Acid Amplification Techniques
PubMed: 33886648
DOI: 10.1371/journal.pone.0250470 -
BMC Microbiology Nov 2021Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although recent studies have indicated that imbalance in the respiratory microbiome composition is linked to several chronic respiratory diseases, the association between the lung microbiome and lung cancer has not been extensively studied. Conflicting reports of individual studies on respiratory microbiome alterations in lung cancer complicate the matter for specifying how the lung microbiome is linked to lung cancer. Consequently, as the first meta-analysis on this topic, we integrate publicly available 16S rRNA gene sequence data on lung tissue samples of lung cancer patients to identify bacterial taxa which differ consistently between case and control groups.
RESULTS
The findings of the current study suggest that the relative abundance of several bacterial taxa including Actinobacteria phylum, Corynebacteriaceae and Halomonadaceae families, and Corynebacterium, Lachnoanaerobaculum, and Halomonas genera is significantly decreased (p < 0.05) in lung tumor tissues of lung cancer patients in comparison with tumor-adjacent normal tissues.
CONCLUSIONS
Despite the underlying need for scrutinizing the findings further, the present study lays the groundwork for future research and adds to our limited understanding of the key role of the lung microbiome and its complex interaction with lung cancer. More data on demographic factors and tumor tissue types would help establish a greater degree of accuracy in characterizing the lung microbial community which accords with subtypes and stages of the disease and fully capturing the changes of the lung microbiome in lung cancer.
Topics: Adult; Aged; Aged, 80 and over; Bacteria; DNA, Bacterial; Female; Humans; Lung; Lung Neoplasms; Male; Microbiota; RNA, Ribosomal, 16S
PubMed: 34763672
DOI: 10.1186/s12866-021-02375-z