Showing papers in "Expert Review of Molecular Diagnostics in 2022"
TL;DR: The emerging biomarkers for ICPI sensitivity in HCC are discussed, including tumor genomic features, perturbation of the gut microbiome, and systemic inflammatory markers.
Abstract: ABSTRACT Introduction Hepatocellular carcinoma (HCC) is the most common primary liver cancer and fourth-leading cause of cancer death. While drug discovery to improve disease survival was historically poor, there is now evidence of significant potential for immune checkpoint inhibitors (ICPIs) in treatment of the disease, and indeed such drug approvals are beginning to emerge. Areas covered HCC typically arises in the context of cirrhosis and chronic liver disease (CLD), and HCC exhibits significant biological heterogeneity, in part reflecting the broad range of etiologies of CLD. Different classes and combinations of ICPI-based therapy exist, but not all patients will respond and predictive biomarkers are not yet available to guide clinician decision-making, unlike some other cancer types. In this review, we discuss the emerging biomarkers for ICPI sensitivity in HCC, including tumor genomic features, perturbation of the gut microbiome, and systemic inflammatory markers. Expert opinion Additional profiling studies are required to appreciate existing trends with clinical outcome and to further drive clinical studies in disease stratification by response. This will only be possible within collaborative and international efforts, especially regarding biopsy collection. A close collaboration between basic scientists and clinicians will be the key to shape the next future of HCC biomarker research.
15 citations
TL;DR: This review summarizes advances in different methods for CRC screening, including stool bacterial and metagenomic markers, fecal proteins, genetic and epigenetic markers in blood and stools, and imaging modalities, and the cost-effectiveness of these methods.
Abstract: ABSTRACT Introduction Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. Nonetheless, with early detection of CRC or its precancerous lesions, mortality, and CRC incidence can be reduced. Although colonoscopy is currently the gold standard for CRC screening and diagnosis, its invasive nature, and troublesome bowel preparation deter patient participation. Therefore, there is a need to expand the use of noninvasive or minimally invasive methods to increase patient compliance. Areas Covered This review summarizes advances in different methods for CRC screening, including stool bacterial and metagenomic markers, fecal proteins, genetic and epigenetic markers in blood and stools, and imaging modalities. The cost-effectiveness of these methods is also discussed. FIT is more cost-effective compared to virtual colonoscopy, mSEPT9 test, and Multitarget Stool DNA test, while the cost-effectiveness of other noninvasive methods requires further evaluation. Expert Opinion Recent evidence has well demonstrated the usefulness of gut microbiome and certain fecal bacterial markers in the noninvasive diagnosis of CRC and its precancerous lesions. Many of the fecal biomarkers, from host cells or the gut environment, show better diagnostic sensitivity than FIT. New screening tests based on these fecal biomarkers can be expected to replace FIT with higher cost-effectiveness in the near future.
14 citations
TL;DR: In this article , a review of the latest developments in m6A modification and highlights the mechanisms underlying ischemic stroke, which may provide novel insights into the mechanisms and therapeutic targets for IS.
Abstract: ABSTRACT Introduction N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has attracted considerable attention recently, and accumulating evidence indicates it has an important role in the progression of ischemic stroke (IS). Areas covered We first reviewed m6A methylation modification enzymes, including m6A methyltransferases (METTL3, METTL14, and WTAP), demethylases (FTO and ALKBH5), m6A-binding proteins (YTH domain containing 1/2 [YTHDC1/2], YTHDF1/2/3, and insulin like growth factor 2 mRNA binding protein 1/2/3 [IGF2BP1/2/3]), and their-related functions. An alteration in the m6A methylation profile of IS has been reported and m6A is differentially expressed in IS. Thus, we then focused on the underlying mechanism of m6A methylation in IS and the involvement of atherosclerosis (AS), cerebral ischemia/reperfusion (IR) injury, inflammation, oxidative stress, and apoptosis. Furthermore, we also elucidated the effect of m6A-associated single-nucleotide polymorphisms (SNPs) on stroke and uncovered new causal variants for IS. The clinical application of m6A targeting drugs is still in its infancy and will be available in the future. Expert opinion Collectively, the information in the present review is a summary of the latest developments in m6A modification and highlights the mechanisms underlying IS pathogenesis, which may provide novel insights into the mechanisms and therapeutic targets for IS.
11 citations
TL;DR: Here, localities that have demonstrated success with saliva-based SARS-CoV-2 testing approaches are reviewed and can serve as models for transforming concepts into globally-implemented best practices.
Abstract: ABSTRACT Introduction Symptomatic testing and asymptomatic screening for SARS-CoV-2 continue to be essential tools for mitigating virus transmission. Though COVID-19 diagnostics initially defaulted to oropharyngeal or nasopharyngeal sampling, the worldwide urgency to expand testing efforts spurred innovative approaches and increased diversity of detection methods. Strengthening innovation and facilitating widespread testing remains critical for global health, especially as additional variants emerge and other mitigation strategies are recalibrated. Areas covered A growing body of evidence reflects the need to expand testing efforts and further investigate the efficiency, sensitivity, and acceptability of saliva samples for SARS-CoV-2 detection. Countries have made pandemic response decisions based on resources, costs, procedures, and regional acceptability – the adoption and integration of saliva-based testing among them. Saliva has demonstrated high sensitivity and specificity while being less invasive relative to nasopharyngeal swabs, securing saliva’s position as a more acceptable sample type. Expert opinion Despite the accessibility and utility of saliva sampling, global implementation remains low compared to swab-based approaches. In some cases, countries have validated saliva-based methods but face challenges with testing implementation or expansion. Here, we review the localities that have demonstrated success with saliva-based SARS-CoV-2 testing approaches and can serve as models for transforming concepts into globally-implemented best practices.
11 citations
TL;DR: Several nucleic acid amplification tests (NAATs), mostly PCRs, to detect antimicrobial resistance determinants and predict AMR in Neisseria gonorrhoeae are promising, and some may be ready to apply at the point-of-care (POC) but important limitations remain with NAATs as mentioned in this paper .
Abstract: Several nucleic acid amplification tests (NAATs), mostly PCRs, to detect antimicrobial resistance (AMR) determinants and predict AMR in Neisseria gonorrhoeae are promising, and some may be ready to apply at the point-of-care (POC), but important limitations remain with NAATs. Next-generation sequencing (NGS) can overcome many of these limitations.Recent advances, with main focus on publications since 2017, in the development and use of NAATs and NGS to predict gonococcal AMR for surveillance and clinical use, and the pros and cons of these tests as well as future perspectives for appropriate use of molecular AMR prediction for gonococci.NAATs and/or NGS for AMR prediction should supplement culture-based AMR surveillance, which will remain because it also detects AMR due to unknown AMR determinants, and translation into POC tests is imperative for the end-goal of individualized treatment, sparing ceftriaxone ± azithromycin. Several challenges for direct testing of clinical, especially pharyngeal, specimens and for accurate prediction of cephalosporins and azithromycin resistance, especially using NAATs, remain. The choice of AMR prediction assay needs to carefully consider the intended use of the assay; limitations intrinsic to the AMR prediction technology, algorithms specific to the chosen methodology; specimen types analyzed; and cost-effectiveness.
10 citations
TL;DR: A review of the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics as mentioned in this paper , with a specific focus on diagnostic and prognostic biomarkers.
Abstract: ABSTRACT Introduction Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell, and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy. Areas covered In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers. Expert Opinion Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings.
10 citations
TL;DR: What is known about monkeypox virus is reviewed, with a focus on recent diagnostics and epidemiologic advances, and how recent advances in the understanding of the virus will be used to combat the expanding outbreak is explored.
Abstract: ABSTRACT Introduction Monkeypox virus is a zoonotic double-stranded DNA poxvirus in the genus Orthopoxvirus, family Poxviridae. Until recently, monkeypox was found primarily in Central and West Africa, where the virus had split into Congo Basin and West African clades. Areas Covered On 6 May 2022, monkeypox was detected in the United Kingdom and the virus has now been detected in every continent except Antarctica. The current outbreak represents the first documentation of widespread community transmission outside of Africa. Expert Opinion On 23 July 2022, the World Health Organization declared monkeypox a public health emergency of international concern and issued a series of guidance and recommendations for governments, health professionals and the public. This manuscript reviews what is known about monkeypox virus, with a focus on recent diagnostics and epidemiologic advances, and explores how recent advances in our understanding of the virus will be used to combat the expanding outbreak.
10 citations
TL;DR: An overview of currently available HRD tests can be found in this article , where the authors discuss the pros and cons of different methodologies including their sensitivity for the identification of HRD tumors, their concordance with other HRd tests, and their capacity to predict therapy response.
Abstract: Carcinomas with defects in the homologous recombination (HR) pathway are sensitive to PARP inhibitors (PARPi). A robust method to identify HR-deficient (HRD) carcinomas is therefore of utmost clinical importance. Currently, available DNA-based HRD tests either scan HR-related genes such as BRCA1 and BRCA2 for the presence of pathogenic variants or identify HRD-related genomic scars or mutational signatures by using whole-exome or whole-genome sequencing data. As an alternative to DNA-based HRD tests, functional HRD tests have been developed that assess the actual ability of tumors to accumulate RAD51 protein at DNA double-strand breaks as a proxy for HR proficiency.This review presents an overview of currently available HRD tests and discusses the pros and cons of the different methodologies including their sensitivity for the identification of HRD tumors, their concordance with other HRD tests, and their capacity to predict therapy response.With the increasing use of PARPi in the treatment of several cancers, there is an urgent need to implement HRD testing in routine clinical practice. To this end, calibration of HRD thresholds and clinical validation of both DNA-based and RAD51-based HRD tests should have top-priority in the coming years.
9 citations
TL;DR: Next-generation sequencing has the potential to significantly improve the understanding of fungal phylogeny, epidemiology, pathogenesis, mycobiome/microbiome, and interactions with the host, while identifying novel and existing mechanisms of antifungal resistance and novel diagnostic/therapeutic targets.
Abstract: ABSTRACT Introduction Fungal PCR has undergone considerable standardization and, together with the availability of commercial assays, external quality assessment schemes, and extensive performance validation data, is ready for widespread use for the screening and diagnosis of invasive fungal disease (IFD). Areas Covered Drawing on the experience and knowledge of the leads of the various working parties of the Fungal PCR initiative, this review will address general considerations concerning the use of molecular tests for the diagnosis of IFD, before focusing specifically on the technical and clinical aspects of molecular testing for the main causes of IFD and recent technological developments. Expert Opinion For infections caused by Aspergillus, Candida, and Pneumocystis jirovecii, PCR testing is recommended, and combination with serological testing will likely enhance the diagnosis. For other IFD (e.g. mucormycosis), molecular diagnostics represent the only non-classical mycological approach toward diagnoses, and continued performance validation and standardization have improved confidence in such testing. The emergence of antifungal resistance can be diagnosed, in part, through molecular testing. Next-generation sequencing has the potential to significantly improve our understanding of fungal phylogeny, epidemiology, pathogenesis, mycobiome/microbiome, and interactions with the host, while identifying novel and existing mechanisms of antifungal resistance and novel diagnostic/therapeutic targets.
9 citations
TL;DR: In this paper , a meta-analysis was performed to assess microRNAs in the blood of patients with brain tumors accurately using MetaDisc V.1.4 and Comprehensive Meta-Analysis V.3.
Abstract: Brain tumors (BT) are among the most prevalent cancers in recent years. Various studies have examined the diagnostic role of microRNAs in different diseases; however, their diagnostic role in BT has not been comprehensively investigated. This meta-analysis was performed to assess microRNAs in the blood of patients with BTs accurately.Twenty-six eligible studies were included for analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), Q*index, summary receiver-operating characteristic (SROC) were assessed using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software.The diagnostic accuracy of microRNA was high in identifying BT based on the pooled sensitivity 0.82 (95%CI: 0.816-0.84), specificity 0.82 (95%CI: 0.817-0.84), PLR 5.101 (95%CI: 3.99-6.51), NLR 0.187 (95%CI: 0.149-0.236), DOR 34.07 (95%CI: 22.56-51.43) as well as AUC (0.92), and Q*-index (0.86). Subgroup analyses were performed for sample types (serum/plasma), reference genes (RNU6, miR-39, and miR-24), and region to determine the diagnostic power of microRNAs in the diagnosis of BT using pooled sensitivity, specificity, PLR, NLR, AUC, and DOR.This meta-analysis suggested that circulating microRNAs might be potential markers for noninvasive early detection of BT.
8 citations
TL;DR: Recombinase polymerase amplification (RPA) is a promising and emerging technology for rapidly amplifying target nucleic acid from minimally processed samples and through small portable instruments as mentioned in this paper .
Abstract: Introduction Recombinase polymerase amplification (RPA) is a promising and emerging technology for rapidly amplifying target nucleic acid from minimally processed samples and through small portable instruments. RPA is suitable for point-of-care testing (POCT) and on-site field testing, and it is compatible with microfluidic devices. Several detection assays have been developed, but limited research has dug deeper into the chemistry of RPA to understand its kinetics and fix its shortcomings.Areas covered This review provides a detailed introduction of RPA molecular mechanism, kits formats, optimization, application, pros, and cons. Moreover, this critical review discusses the nonspecificity issue of RPA, highlights its consequences, and emphasizes the need for more research to resolve it. This review discusses the reaction kinetics of RPA in relation to target length, product quantity, and sensitivity. This critical review also questions the novelty of recombinase-aided amplification (RAA). In short, this review discusses many aspects of RPA technology that have not been discussed previously and provides a deeper insight and new perspectives of the technology.Expert opinion RPA is an excellent choice for pathogen detection, especially in low-resource settings. It has a potential to replace PCR for all purposes, provided its shortcomings are fixed and its reagent accessibility is improved.
TL;DR: Increasing FIR values significantly and independently predicts worse in-hospital prognosis in hospitalized patients with COVID-19, as expressed by serum Ferritin-to-Iron Ratio.
Abstract: ABSTRACT Background Acute viral infections, including coronavirus disease 2019 (COVID-19), are characterized by the dysregulation of iron metabolism, resulting in high serum ferritin and low iron levels. Research design and methods This study aimed to evaluate the prospective impact of iron metabolism dysregulation, as expressed by serum Ferritin-to-Iron Ratio (FIR), on the in-hospital prognosis of patients with COVID-19. Serum levels of ferritin and iron, as well as other iron metabolism markers and recognized prognostic indicators of COVID-19 severity, were measured in 362 patients consecutively hospitalized for COVID-19. The prospective relationship between FIR and the risk of the composite outcome of intensive care unit (ICU) admission/in-hospital death was analyzed. Results In the population examined (mean age 74 ± 15 years, males 55%), the rates of radiographic signs of pneumonia, respiratory distress, and the need for noninvasive ventilation were higher in patients with high FIR (≥29.2, the 75th percentile) than in those with low FIR (<29.2, the 75th percentile) (p < 0.05 for all comparisons). High FIR was associated with a 1.7-fold (HR 1.709, 95% CI 1.017–2.871, p = 0.043) higher risk of ICU admission/in-hospital death. Conclusions Increasing FIR values significantly and independently predicts worse in-hospital prognosis in hospitalized patients with COVID-19.
TL;DR: The 5-mC score can be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy, which can be a decisive factor regarding immune treatment responses.
Abstract: BACKGROUND
Methylation of cytosine residues resulting in 5-methylcytosine (5-mC) is an important epigenetic modification associated with tumorigenesis. The present study explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC).
METHODS
RNA sequencing data and corresponding clinical information were downloaded, and preprocessed, and unsupervised consistent cluster analysis was used to identify 5-mC-related clusters and gene clusters. 5-mC scores were calculated using principal component analysis, and a Boruta algorithm was used to evaluate the relationship between tumor mutation burden (TMB), immune checkpoint inhibitor response, and prognosis of individual LUSC patients.
RESULTS
Two 5-mC clusters and three gene clusters with different prognoses were identified. Patients with higher 5-mC scores showed worse prognoses, which was confirmed in multiple cohorts. Some immune-related biological functions and pathways were enriched in the high-5-mC score subtype.
CONCLUSION
The 5-mC score is a potential biomarker independent of TMB, which can be a decisive factor regarding immune treatment responses. Further, patients with low 5-mC scores may respond better to immunotherapy. The 5-mC score can thus be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy.
TL;DR: Molecular neuroimaging of CTE with Tau-PET is an intriguing tool for the in vivo detection and monitoring of neuropathological hallmarks associated with CTE, and some novel tracers hold the promise to get an insight into the complex physiopathological mechanisms leading from brain injury to symptomatic CTE.
Abstract: ABSTRACT Introduction Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, caused by single or repeated traumatic brain injuries. Since a few years ago, post mortem examination represented the only effective method to diagnose CTE through the detection of its peculiar neuropathological features (i.e. tau protein aggregates) at a macroscopic and microscopic level. Several efforts have been made to develop radiopharmaceuticals characterized by high affinity for tau aggregates, suitable for imaging through positron emission computed tomography (Tau-PET). Areas covered The various radiopharmaceuticals utilized for the molecular imaging of CTE through Tau-PET are covered, with specific reference to their applications in clinical practice. Furthermore, PET probes binding to the translocator protein (TSPO), a marker of brain injury and repair, are reviewed as potential tools for the imaging of neuroinflammatory cascade associated with CTE. Expert opinion Molecular neuroimaging of CTE with Tau-PET is an intriguing, although still not completely explored, tool for the in vivo detection and monitoring of neuropathological hallmarks associated with CTE. Furthermore, some novel tracers, such as TSPO-ligands, hold the promise to get an insight into the complex physiopathological mechanisms leading from brain injury to symptomatic CTE.
TL;DR: In this article , the authors summarized the epidemiology, clinical features, and transmission of female genital tuberculosis (TB) with varied clinical presentations, i.e. infertility, pelvic pain, and menstrual irregularities.
Abstract: Female genital tuberculosis (TB) is a common form of extrapulmonary TB (EPTB) with varied clinical presentations, i.e. infertility, pelvic pain, and menstrual irregularities. Diagnosis of female genital TB is challenging predominantly due to paucibacillary nature of specimens and inconclusive results obtained by most of the routine laboratory tests.This review has briefly summarized the epidemiology, clinical features, and transmission of female genital TB. Commonly used laboratory tests include bacteriological examination (smear/culture), tuberculin skin testing, interferon-γ release assays, imaging, laparoscopy/hysteroscopy, and histopathological/cytological observations. Furthermore, utility of nucleic acid amplification tests (NAATs), like loop-mediated isothermal amplification, PCR, multiplex-PCR, nested PCR, real-time PCR, and GeneXpert® could significantly improve the detection of female genital TB.Currently, there is no single test available for the efficient diagnosis of female genital TB, rather a combination of tests is being employed, which yields moderate diagnostic accuracy. The latest modalities developed for diagnosing pulmonary TB and other clinical EPTB forms, i.e. aptamer-linked immobilized sorbent assay, immuno-PCR (I-PCR), analysis of circulating cell-free DNA by NAATs, and identification of Mycobacterium tuberculosis biomarkers within extracellular vesicles of bodily fluids by I-PCR/nanoparticle-based I-PCR, may also be exploited to further improve the diagnosis of female genital TB.
TL;DR: The aim was to prove that multigene analyses can accurately predict and prognosticate cancer risk, subtype cancer for more personalized and effective treatments, and discover anti-cancer therapies.
Abstract: ABSTRACT Introduction Diseases were initially thought to be the consequence of a single gene mutation. Advances in DNA sequencing tools and our understanding of gene behavior have revealed that complex diseases, such as cancer, are the product of genes cooperating with each other and with their environment in orchestrated communication networks. Seeing that the function of individual genes is still used to analyze cancer, the shift to using functionally interacting groups of genes as a new unit of study holds promise for demystifying cancer. Areas Covered The literature search focused on three types of cancer, namely breast, lung, and prostate, but arguments from other cancers were also included. The aim was to prove that multigene analyses can accurately predict and prognosticate cancer risk, subtype cancer for more personalized and effective treatments, and discover anti-cancer therapies. Computational intelligence is being harnessed to analyze this type of data and is proving indispensable to scientific progress. Expert Opinion In the future, comprehensive profiling of all kinds of patient data (e.g. serum molecules, environmental exposures) can be used to build universal networks that should help us elucidate the molecular mechanisms underlying diseases and provide appropriate preventive measures, ensuring lifelong health and longevity.
TL;DR: CTCs and ctDNA components of liquid biopsy and their clinical application as diagnostic, prognostic, and predictive biomarkers in HCC are focused on.
Abstract: ABSTRACT Introduction The diagnosis of hepatocellular carcinoma (HCC) is made at a relatively advanced stage resulting in poor prognosis. Alpha-fetoprotein and liver ultrasound have limited accuracy as biomarkers in HCC. Liver biopsy provides information on tumor biology; however, it is invasive and holds high threat of tumor seeding. Thus, more accurate and less invasive approaches are needed Areas Covered Highly sensitive liquid biopsy assays have made possible the detection and analysis of cells or organelles such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived exosomes. Here, we focus on CTCs and ctDNA components of liquid biopsy and their clinical application as diagnostic, prognostic, and predictive biomarkers in HCC. Unlike tissue biopsy, liquid biopsy involves attaining a sample at several time frames in an easy and a non-invasive manner. They have been efficacious in detecting and classifying cancer, in predicting treatment response, in monitoring disease relapse and in identifying mechanisms of resistance to targeted therapies. Expert Opinion Although interesting and highly promising, liquid biopsy techniques still have many obstacles to overcome before their wide spread clinical application sees the light. It is expected that these techniques will be incorporated into traditional methodologies for better diagnostic, predictive and prognostic results.
TL;DR: In this article , the authors explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC) using RNA sequencing data and corresponding clinical information.
Abstract: ABSTRACT Background Methylation of cytosine residues resulting in 5-methylcytosine (5-mC) is an important epigenetic modification associated with tumorigenesis. The present study explored the relationship between methylation, prognosis, and immunotherapy of patients suffering from lung squamous cell carcinoma (LUSC). Methods RNA sequencing data and corresponding clinical information were downloaded, and preprocessed, and unsupervised consistent cluster analysis was used to identify 5-mC-related clusters and gene clusters. 5-mC scores were calculated using principal component analysis, and a Boruta algorithm was used to evaluate the relationship between tumor mutation burden (TMB), immune checkpoint inhibitor response, and prognosis of individual LUSC patients. Results : Two 5-mC clusters and three gene clusters with different prognoses were identified. Patients with higher 5-mC scores showed worse prognoses, which was confirmed in multiple cohorts. Some immune-related biological functions and pathways were enriched in the high-5-mC score subtype. Conclusion The 5-mC score is a potential biomarker independent of TMB, which can be a decisive factor regarding immune treatment responses. Further, patients with low 5-mC scores may respond better to immunotherapy. The 5-mC score can thus be used as a potential biomarker for the prognosis of LUSC patients and their response to immunotherapy.
TL;DR: A PubMed-based review of the latest findings on α-syn-related biomarkers for AD, focusing on bodily fluids, found ultrasensitive seed amplification techniques may support a biomarker-drug co-development pathway and may be a pathophysiological candidate biomarker for the evolving ATX(N) system to classify AD and the spectrum of primary NDDs.
Abstract: ABSTRACT Introduction α-syn aggregates represent the pathological hallmark of synucleinopathies as well as a frequent copathology (almost 1/3 of cases) in AD. Recent research indicates a potential role of α-syn species, measured in CSF with conventional analytical techniques, in the differential diagnosis between AD and synucleinopathies (such as DLB). Pioneering studies report the detection of α-syn in blood, however, conclusive investigations are controversial. Ultrasensitive seed amplification techniques, enabling the selective quantification of α-syn seeds, may represent an effective solution to identify the α-syn component in AD and facilitate a biomarker-guided stratification. Areas covered We performed a PubMed-based review of the latest findings on α-syn-related biomarkers for AD, focusing on bodily fluids. A dissertation on the role of ultrasensitive seed amplification assays, detecting α-syn seeds from different biological samples, was conducted. Expert opinion α-syn may contribute to progressive AD neurodegeneration through cross-seeding especially with tau protein. Ultrasensitive seed amplification techniques may support a biomarker-drug co-development pathway and may be a pathophysiological candidate biomarker for the evolving ATX(N) system to classify AD and the spectrum of primary NDDs. This would contribute to a precise approach to AD, aimed at implementing disease-modifying treatments.
TL;DR: This study aimed to help the readers to understand what very likely is behind a bad result of SARS-CoV-2 detection by RT-PCR and what could be done to reach a reliable diagnosis.
Abstract: ABSTRACT Introduction The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease has had a catastrophic impact on the world resulting in several deaths. Since World Health Organization declared the pandemic status of the disease, several molecular diagnostic kits have been developed to help the tracking of viruses spread. Areas Covered This review aims to describe and evaluate the currently reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) diagnosis kit. Several processes used in COVID-19 diagnostic procedures are detailed in further depth to demonstrate optimal practices. Therefore, we debate the main factors that influence the viral detection of SARS-COV-2 and how they can affect the diagnosis of patients. Expert Opinion Here is highlighted and discussed several factors that can interfere in the RT-PCR analysis, such as the viral load of the sample, collection site, collection methodology, sample storage, transport, primer, and probe mismatch/dimerization in different brand kits. This is a pioneer study to discuss the factor that could lead to the wrong interpretation of RT-qPCR diagnosis of SARS-CoV-2. This study aimed to help the readers to understand what very likely is behind a bad result of SARS-CoV-2 detection by RT-PCR and what could be done to reach a reliable diagnosis.
TL;DR: This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways and proposes some WarburgEffect-related metabolites and proteins as promising cancer biomarkers.
Abstract: ABSTRACT Introduction Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells. Areas covered This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways. Expert opinion In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.
TL;DR: This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments.
Abstract: ABSTRACT Introduction Alzheimer’s disease (AD) is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population. Characterized by extracellular accumulation of amyloid-beta (Aβ), intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition. Amyloid/tau/neurodegeneration (ATN) classification is utilized for research purposes and involves amyloid, tau, and neuronal injury staging through MRI, PET scanning, and CSF protein concentration estimations. CSF sampling is invasive, and MRI and PET scanning requires sophisticated radiological facilities which limit its widespread diagnostic use. ATN classification lacks effectiveness in preclinical AD. Areas Covered This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments. Expert Opinion It is an accepted observation that AD-related pathological changes occur over a long period of time before the first symptoms are observed providing ample opportunity for detection of biological alterations in various biological samples that can aid in early diagnosis and modify treatment outcomes.
TL;DR: A review focused on the clinical application of circulating biomarkers in advanced hepatocellular carcinoma patients treated with sorafenib is presented in this article , where the authors investigated the predictive or prognostic value of these biomarkers were included.
Abstract: ABSTRACT Introduction Sorafenib is currently the first-line therapeutic regimen for patients with advanced hepatocellular carcinoma (HCC). However, many patients did not experience any benefit and suffered extreme adverse events and heavy economic burden. Thus, the early identification of patients who are most likely to benefit from sorafenib is needed. Areas covered This review focused on the clinical application of circulating biomarkers (including conventional biomarkers, immune biomarkers, genetic biomarkers, and some novel biomarkers) in advanced HCC patients treated with sorafenib. An online search on PubMed, Web of Science, Embase, and Cochrane Library was conducted from the inception to 15 August 2021. Studies investigating the predictive or prognostic value of these biomarkers were included. Expert opinion The distinction of patients who may benefit from sorafenib treatment is of utmost importance. The predictive roles of circulating biomarkers could solve this problem. Many biomarkers can be obtained by liquid biopsy, which is a less or noninvasive approach. The short half-life of sorafenib could reflect the dynamic changes of tumor progression and monitor the treatment response. Circulating biomarkers obtained from liquid biopsy resulted as a promising assessment method in HCC, allowing for better treatment decisions in the near future.
Abbreviations Alpha-fetoprotein (AFP); American Association for the Study of Liver Diseases (AASLD); Angiopoietin (Ang); Barcelona Clinic Liver Cancer stage (BCLC); Circulating endothelial progenitor (CEP); Circulating free DNA (cfDNA); Complete response (CR); Des-γ-carboxy prothrombin (DCP); Endothelium-derived nitric oxide synthase (eNOS); Hepatocellular carcinoma (HCC); Hepatocyte growth factor (HGF); Hepatoma arterial-embolization prognosis score (HAP); High mobility group box 1 (HMgb1); Interferon-gamma (IFN-γ); Long non-coding RNA (lncRNAs); Micro RNAs (miRNAs); Monocyte-to-lymphocyte ratio (MLR); National Comprehensive Cancer Network (NCCN); Neutrophil-lymphocyte ratio (NLR); Newcastle-Ottawa Scale (NOS); Nitric oxide (NO); Overall survival (OS); Partial response (PR); Platelet-lymphocyte ratio (PLR); Prediction of survival in advanced sorafenib-treated HCC (PROSASH); Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA); Prognostic nutritional index (PNI); Progression-free survival (PFS); Progressive disease (PD); Randomized controlled trials (RCTs); Response Evaluation Criteria in Solid Tumors (RECIST); Single nucleotide polymorphisms (SNPs); Sorafenib advanced HCC prognosis score (SAP); Stable disease (SD); Time to progression (TTP); Transcatheter arterial chemoembolization (TACE); Vascular endothelial growth factor (VEGF).
TL;DR: The development of a consensus set of guidelines is necessary to guide the usage of this new technology and the interpretation of NGS results before clinical adoption of mNGS testing, according to expert opinion.
Abstract: ABSTRACT Introduction Clinical metagenomic next-generation sequencing (mNGS) allows a comprehensive genetic analysis of microbial materials. Different from other traditional target-driven molecular diagnostic tests, such as PCR, mNGS is a hypothesis-free diagnostic approach that allows a comprehensive genetic analysis of the clinical specimens that cover nearly any common, rare, and new pathogens ranging broadly from viruses, bacteria, fungi to parasites. Areas covered In this article, we discussed the clinical application of the mNGS using two clinical cases as examples and described the use of mNGS to assist the diagnosis of parasitic pulmonary infection. The advantages and challenges in implementing mNGS in clinical microbiology are also discussed. Expert opinion mNGS is a promising technology that allows quick diagnosis of infectious diseases. Currently, a plethora of sequencing and analysis methods exists for mNGS, each with individual merits and pitfalls. While standards and best practices were proposed by various metagenomics working groups, they are yet to be widely adopted in the community. The development of a consensus set of guidelines is necessary to guide the usage of this new technology and the interpretation of NGS results before clinical adoption of mNGS testing.
TL;DR: The extracellular nucleases of 15 relevant bacterial pathogens are described and the potential use of nuclease activity as a diagnostic biomarker is discussed, offering new possibilities compared to established biomarkers.
Abstract: ABSTRACT Introduction In the increasingly challenging field of clinical microbiology, diagnosis is a cornerstone whose accuracy and timing are crucial for the successful management, therapy, and outcome of infectious diseases. Currently employed biomarkers of infectious diseases define the scope and limitations of diagnostic techniques. As such, expanding the biomarker catalog is crucial to address unmet needs and bring about novel diagnostic functionalities and applications. Areas covered This review describes the extracellular nucleases of 15 relevant bacterial pathogens and discusses the potential use of nuclease activity as a diagnostic biomarker. Articles were searched for in PubMed using the terms: ‘nuclease,’ ‘bacteria,’ ‘nuclease activity’ or ‘biomarker.’ For overview sections, original and review articles between 2000 and 2019 were searched for using the terms: ‘infections,’ ‘diagnosis,’ ‘bacterial,’ ‘burden,’ ‘challenges.’ Informative articles were selected. Expert opinion Using the catalytic activity of nucleases offers new possibilities compared to established biomarkers. Nucleic acid activatable reporters in combination with different transduction platforms and delivery methods can be used to detect disease-associated nuclease activity patterns in vitro and in vivo for prognostic and diagnostic applications. Even when these patterns are not obvious or of unknown etiology, screening platforms could be used to identify new disease reporters.
TL;DR: The current challenges in diagnosing HMs are summarized, a critical overview of the recent literature about potential diagnostic biomarkers and their subclassifications are provided, and an online search on PubMed, Web of Science, and Google Scholar databases was conducted.
Abstract: ABSTRACT Introduction Hydatidiform moles (HMs) are pathologic conceptions with unique genetic bases and abnormal placental villous tissue. Overlapping ultrasonographical and histological manifestations of molar and non-molar (NM) gestations and HMs subtypes makes accurate diagnosis challenging. Currently, immunohistochemical analysis of p57 and molecular genotyping have greatly improved the diagnostic accuracy. Areas covered The differential expression of molecular biomarkers may be valuable for distinguishing among the subtypes of HMs and their mimics. Thus, biomarkers may be the key to refining HMs diagnosis. In this review, we summarize the current challenges in diagnosing HMs, and provide a critical overview of the recent literature about potential diagnostic biomarkers and their subclassifications. An online search on PubMed, Web of Science, and Google Scholar databases was conducted from the inception to 1 April 2022. Expert opinion The emerging biomarkers offer new possibilities to refine the diagnosis for HMs and pregnancy loss. Although the additional studies are required to be quantified and investigated in clinical trials to verify their diagnostic utility. It is important to explore, validate, and facilitate the wide adoption of newly developed biomarkers in the coming years.
TL;DR: Loop-mediated isothermal amplification (LAMP) has emerged as a potentially effective and affordable technique for infectious disease surveillance, especially in under-resourced settings, and expert opinion LAMP has analytical sensitivity and specificity that are not only higher than culture method but also comparable with conventional and quantitative PCR techniques.
Abstract: ABSTRACT Introduction Non-albicans Candida species (NACS) have emerged as a major public health burden, although they are still underappreciated. Some NACS have intrinsic antifungal resistance, requiring constant surveillance to improve patient care and thwart outbreaks of recalcitrant candida infections. However, effective Candida species surveillance has relied on PCR-based or other high-end techniques that are largely unaffordable in under-resourced countries. Loop-mediated isothermal amplification (LAMP) has emerged as a potentially effective and affordable technique for infectious disease surveillance, especially in under-resourced settings. Areas covered We critically reviewed current literature on the application of LAMP for Candida species identification in pure fungal isolates, and in clinical and non-clinical samples. Expert opinion LAMP has been studied for Candida species identification, including the NACS. Besides a short turnaround time, LAMP has analytical sensitivity and specificity that are not only higher than culture method but also comparable with conventional and quantitative PCR techniques. However, extensive evaluation of LAMP for Candida species detection using various types of clinical and environmental samples is required before deploying the technique for Candida species surveillance.
TL;DR: It is shown that CRISPR technology is a promising molecular method for detecting SARS-CoV-2 and standard methods including comparable sample material, patient selection, operating procedure and operators should be established.
Abstract: ABSTRACT Objective To evaluate the diagnostic accuracy of CRISPR-Cas technology for SARS-CoV-2. Methods RT-qPCR is defined as the reference standard. Data was collected and assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. A bivariate model for pooling was employed and subgroups analysis was used to explore heterogeneity. Results 2264 samples from 28 articles were extracted for evaluating the accuracy of CRISPR technology for diagnosing SARS-CoV-2. The pooled sensitivity and specificity of CRISPR technology were 0.98 (95% CI: 0.95–0.99) and 1.0 (95% CI: 0.98–1.00), respectively. High risks in patient selection bias and unclear risk of index test bias may affect accuracy. Subgroup analysis showed that CRISPR-Cas12 is applicable for molecular diagnostics for its active editing characteristics. RT-LAMP and RT-RPA are usually used for pre-amplification and fluorescence detection to output results quantitatively. Nasopharyngeal swabs and dual-genes perform greatly in our study. Conclusion The results concluded from all studies showed that CRISPR technology is a promising molecular method for detecting SARS-CoV-2. Standard methods including comparable sample material, patient selection, operating procedure and operators should be established.
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Abstract: ABSTRACT Introduction Hereditary spastic paraplegias (HSP) include a clinically and genetically heterogeneous group of conditions. Novel imaging modalities have been increasingly applied to HSP cohorts, which help to develop monitoring markers for both clinical care and future clinical trials. Areas covered Advances in HSP imaging are systematically reviewed with a focus on cohort sizes, imaging modalities, study design, clinical correlates, methodological approaches, and key findings. Expert opinion A wide range of imaging techniques have been recently applied to HSP cohorts. Common shortcomings of existing studies include the evaluation of genetically admixed cohorts, limited sample sizes, lack of postmortem validation, and a limited clinical battery. A number of innovative methodological approaches have also been identified, such as robust longitudinal study designs, the implementation of multimodal imaging protocols, complementary cognitive assessments, and the comparison of HSP cohorts to MND cohorts. Collaborative multicenter initiatives may overcome sample limitations, and comprehensive clinical profiling with motor, extrapyramidal, cerebellar, and neuropsychological assessments would permit systematic clinico-radiological correlations. Academic achievements in HSP imaging have the potential to be developed into viable clinical applications to expedite the diagnosis and monitor disease progression.
TL;DR: Non-conventional ELISA formats are relatively rapid, require low reagent volumes, are multiplexable, and could be performed in a low-cost setup and hold added clinical translational potential for quick, inexpensive, and convenient measurements.
Abstract: ABSTRACT Introduction Enzyme-linked immunosorbent assay (ELISA) is a key bio-analytical technique used for the detection of a large array of antigenic substances of scientific, clinical, food safety, and environmental importance. The assay primarily involves capturing and detecting target analytes using specific antigen-antibody interactions. The wide usage of ELISA results from its high specificity and reproducibility. Notwithstanding, the conventional microwell plate-based format of ELISA has some major drawbacks, such as long assay time (4–18 h), large sample volumes requirement (100–200 μL), lack of multiplicity, and burdensome procedures that limit its utility in rapid and affordable diagnostics. Areas covered Here, we reviewed microfluidic-ELISA, paper-ELISA, aptamer-ELISA, and those based on novel incubation such as heat-ELISA, pressure-ELISA, microwave-ELISA, and sound-ELISA. Further, the current trends and future prospects of these ELISA protocols in clinical diagnostics are discussed. Expert opinion The reviewed non-conventional ELISA formats are relatively rapid, require low reagent volumes, are multiplexable, and could be performed in a low-cost setup. In our opinion, these non-conventional variants of ELISA are on a par with the conventional format for clinical diagnostics and fundamental biological research and hold added clinical translational potential for quick, inexpensive, and convenient measurements.