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Advances in Clinical Chemistry 2024The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a... (Review)
Review
The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic in March 2020. Reverse transcription-polymerase chain reaction (RT-PCR) is the reference technique for molecular diagnosis of SARS-CoV-2 infection. The SARS-CoV-2 virus is constantly mutating, and more transmissible variants have emerged, making genomic surveillance a crucial tool for investigating virus transmission dynamics, detecting novel genetic variants, and assessing mutation impact. The S gene, which encodes the spike protein, is frequently mutated, and it plays an important role in transmissibility. Spike protein mutations affect infectivity and vaccine effectiveness. SARS-CoV-2 variants are tracked using whole genome sequencing (WGS) and S-gene analysis. WGS, Sanger sequencing, and many S-gene-targeted RT-PCR methods have been developed. WGS and Sanger sequencing are standard methods for detecting mutations and can be used to identify known and unknown mutations. Melting curve analysis, endpoint genotyping assay, and S-gene target failure are used in the RT-PCR-based method for the rapid detection of specific mutations in SARS-CoV-2 variants. Therefore, these assays are suitable for high-throughput screening. The combinatorial use of RT-PCR-based assays, Sanger sequencing, and WGS enables rapid and accurate tracking of SARS-CoV-2 variants. In this review, we described RT-PCR-based detection and surveillance techniques for SARS-CoV-2.
Topics: Humans; SARS-CoV-2; COVID-19; Spike Glycoprotein, Coronavirus; Molecular Biology; Mutation; COVID-19 Testing
PubMed: 38280807
DOI: 10.1016/bs.acc.2023.11.003 -
Pathologie (Heidelberg, Germany) Mar 2024With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of... (Review)
Review
With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).
Topics: Artificial Intelligence; Pathology, Molecular; Hope; Precision Medicine
PubMed: 38315198
DOI: 10.1007/s00292-024-01308-7 -
Taiwanese Journal of Obstetrics &... Nov 2023
Topics: Female; Humans; Pathology, Molecular; Endometrial Neoplasms; Endometrium; Endometrial Hyperplasia
PubMed: 38008493
DOI: 10.1016/j.tjog.2023.09.013 -
Cells Jul 2023This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors,... (Review)
Review
This review discusses the evolving topic of atrial cardiomyopathy concerning valvular heart disease. The pathogenesis of atrial cardiomyopathy involves multiple factors, such as valvular disease leading to atrial structural and functional remodeling due to pressure and volume overload. Atrial enlargement and dysfunction can trigger atrial tachyarrhythmia. The complex interaction between valvular disease and atrial cardiomyopathy creates a vicious cycle of aggravating atrial enlargement, dysfunction, and valvular disease severity. Furthermore, atrial remodeling and arrhythmia can predispose to atrial thrombus formation and stroke. The underlying pathomechanism of atrial myopathy involves molecular, cellular, and subcellular alterations resulting in chronic inflammation, atrial fibrosis, and electrophysiological changes. Atrial dysfunction has emerged as an essential determinant of outcomes in valvular disease and heart failure. Despite its predictive value, the detection of atrial fibrosis and dysfunction is challenging and is not included in the clinical routine. Transthoracic echocardiography and cardiac magnetic resonance imaging are the main diagnostic tools for atrial cardiomyopathy. Recently published data have revealed that both left atrial volumes and functional parameters are independent predictors of cardiovascular events in valvular disease. The integration of atrial function assessment in clinical practice might help in early cardiovascular risk estimation, promoting early therapeutic intervention in valvular disease.
Topics: Humans; Atrial Fibrillation; Heart Valve Diseases; Cardiomyopathies; Heart Failure; Fibrosis; Molecular Biology
PubMed: 37443830
DOI: 10.3390/cells12131796 -
Emerging Microbes & Infections Dec 2023Diagnostic development must occur in parallel with drug development to ensure the longevity of new treatment compounds. Despite an increasing number of novel and...
Diagnostic development must occur in parallel with drug development to ensure the longevity of new treatment compounds. Despite an increasing number of novel and repurposed anti-tuberculosis compounds and regimens, there remains a large number of drugs for which no rapid and accurate molecular diagnostic option exists. The lack of rapid drug susceptibility testing for linezolid, bedaquiline, clofazimine, the nitroimidazoles (i.e pretomanid and delamanid) and pyrazinamide at any level of the healthcare system compromises the effectiveness of current tuberculosis and drug-resistant tuberculosis treatment regimens. In the context of current WHO tuberculosis treatment guidelines as well as promising new regimens, we identify the key diagnostic gaps for initial and follow-on tests to diagnose emerging drug resistance and aid in regimen selection. Additionally, we comment on potential gene targets for inclusion in rapid molecular drug susceptibility assays and sequencing assays for novel and repurposed drug compounds currently prioritized in current regimens, and evaluate the feasibility of mutation detection given the design of existing technologies. Based on current knowledge, we also propose design priorities for next generation molecular assays to support triage of tuberculosis patients to appropriate and effective treatment regimens. We encourage assay developers to prioritize development of these key molecular assays and support the continued evolution, uptake, and utility of sequencing to build knowledge of tuberculosis resistance mechanisms and further inform rapid treatment decisions in order to curb resistance to critical drugs in current regimens and achieve End TB targets. ClinicalTrials.gov identifier: NCT05117788..
Topics: Humans; Antitubercular Agents; Microbial Sensitivity Tests; Pathology, Molecular; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36752055
DOI: 10.1080/22221751.2023.2178243 -
Current Opinion in Infectious Diseases Dec 2023Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical... (Review)
Review
PURPOSE OF REVIEW
Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies.
RECENT FINDINGS
An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required.
SUMMARY
mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.
Topics: Child; Humans; Infant; COVID-19; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization; Molecular Epidemiology
PubMed: 37830952
DOI: 10.1097/QCO.0000000000000967 -
Advances in Experimental Medicine and... 2024X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including...
X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis. Now reaching well into the first quarter of the twenty-first century, X-ray crystallography shares the structural biology stage with cryo-electron microscopy and other innovative structure determination methods, as relevant and central to our understanding of biological function and structure as ever. In this chapter, we provide an overview of modern X-ray crystallography and how it interfaces with other mainstream structural biology techniques, with an emphasis on macromolecular complexes.
Topics: Crystallography, X-Ray; Cryoelectron Microscopy; Proteins; Molecular Biology; Macromolecular Substances
PubMed: 38507204
DOI: 10.1007/978-3-031-52193-5_9 -
Virchows Archiv : An International... Feb 2024Neoplasias of the hepatopancreatobiliary tract are growing in numbers, have the poorest prognosis of all major cancer entities, and thus represent a rising clinical... (Review)
Review
Neoplasias of the hepatopancreatobiliary tract are growing in numbers, have the poorest prognosis of all major cancer entities, and thus represent a rising clinical problem. Their molecular diagnostic has dramatically improved, contributing to tumor subtyping, definition of malignancy, and uncovering cases with hereditary predisposition. Most of all, predictive molecular testing allows to identify cases amenable to treatment with the rising number of approved targeted drugs, immune-oncological treatment, and clinical trials. In this review, the current state of molecular testing and its contribution to clinical decision-making are outlined.
Topics: Humans; Pathology, Molecular; Pancreatic Neoplasms; Genetic Predisposition to Disease; Molecular Diagnostic Techniques; Medical Oncology
PubMed: 38429607
DOI: 10.1007/s00428-024-03744-5 -
Frontiers in Immunology 2023Brain metastases stemming from lung cancer represent a common and challenging complication that significantly impacts patients' overall health. The migration of these... (Review)
Review
Brain metastases stemming from lung cancer represent a common and challenging complication that significantly impacts patients' overall health. The migration of these cancerous cells from lung lesions to the central nervous system is facilitated by diverse molecular changes and a specific environment that supports their affinity for neural tissues. The advent of immunotherapy and its varied combinations in non-small cell lung cancer has notably improved patient survival rates, even in cases involving brain metastases. These therapies exhibit enhanced penetration into the central nervous system compared to traditional chemotherapy. This review outlines the molecular mechanisms underlying the development of brain metastases in lung cancer and explores the efficacy of novel immunotherapy approaches and their combinations.
Topics: Humans; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Immunotherapy; Molecular Biology
PubMed: 38283359
DOI: 10.3389/fimmu.2023.1297988 -
Biotechnology Journal Dec 2023Humans have adopted many different methods to explore matter imaging, among which high content imaging (HCI) could conduct automated imaging analysis of cells while... (Review)
Review
Humans have adopted many different methods to explore matter imaging, among which high content imaging (HCI) could conduct automated imaging analysis of cells while maintaining its structural and functional integrity. Meanwhile, as one of the most important research tools for diagnosing human diseases, HCI is widely used in the frontier of medical research, and its future application has attracted researchers' great interests. Here, the meaning of HCI was briefly explained, the history of optical imaging and the birth of HCI were described, and the experimental methods of HCI were described. Furthermore, the directions of the application of HCI were highlighted in five aspects: protein localization changes, gene identification, chemical and genetic analysis, microbiology, and drug discovery. Most importantly, some challenges and future directions of HCI were discussed, and the application and optimization of HCI were expected to be further explored.
Topics: Humans; Diagnostic Imaging; Image Processing, Computer-Assisted; Drug Discovery; Molecular Biology
PubMed: 37639283
DOI: 10.1002/biot.202300170