Applegate TL, Causer LM, Gow I
… +26 more, Alternetti N, Anderson L, Borgnolo B, Cooney L, Cunningham P, Fernando M, Hengel B, Huang RL, Kayago K, King JM, Lew HJ, Martinello M, Milic M, Miller K, O'Connor S, Patel P, Phillips E, Rawlinson W, Sharma A, Shephard MDS, Tangey A, Smith K, Williams AL, Andrewartha K, Guy R, Matthews SJ
INTRODUCTION: Decentralized molecular testing for infectious disease diagnosis at the point-of-care (POC) is critical to address inequities in access to timely, informed health care. The COVID-19 pandemic accelerated the...INTRODUCTION: Decentralized molecular testing for infectious disease diagnosis at the point-of-care (POC) is critical to address inequities in access to timely, informed health care. The COVID-19 pandemic accelerated the demand, development and adoption of POC tests for infectious diseases globally. This has provided opportunities to maximize the individual benefits and public health impact of POC testing, particularly in remote and resource-limited primary care settings. Despite this, there remains a lack of harmonized, regulatory compliance and quality management frameworks for the delivery of molecular POC testing networks outside the laboratory setting. AREAS COVERED: This Perspective describes real-world lessons and experiences of delivering a fit-for-purpose, quality framework for one of the world's largest decentralized molecular POC testing programs for infectious disease across rural and remote Australian communities. Here we detail unique, key considerations to ensure the quality of POC testing in primary health settings with global application. EXPERT OPINION: There is an ethical and public health imperative to provide sustained access to decentralized POC testing for infectious disease in primary care. Genuine partnerships across stakeholders and disciplines are essential to deliver well governed, fit-for-purpose quality management POC testing frameworks and increase equitable access to timely, high-quality person-centered care.
INTRODUCTION: The liquid biopsy is a breakthrough in the field of medical diagnostics. It serves as a sentinel that can quietly detect even the subtlest aberrations that indicate the presence of disease. They make it pos...INTRODUCTION: The liquid biopsy is a breakthrough in the field of medical diagnostics. It serves as a sentinel that can quietly detect even the subtlest aberrations that indicate the presence of disease. They make it possible to uncover relevant genetic factors of tumors with minimal to no risk to cancer patients. Liquid biopsies allow detailed diagnosis, dynamic treatment monitoring, and accurate prognosis. They are also invaluable in diagnosing other diseases such as infectious diseases and aberrant gene mutations. AREAS COVERED: The present review undertakes an in-depth analysis of the existing status of liquid biopsy diagnostic tools, focusing on their principal components. Furthermore, the review highlights pertinent and recent research in this field to provide a comprehensive understanding of the current state of this technology and its prospects. EXPERT OPINION: Despite new and upcoming research in liquid biopsies, multiple areas need to be further explored before the viable transition into the clinical arena. With the advancements in tools such as artificial intelligence and machine learning and the integration of these technologies with liquid biopsies, these challenges are being addressed and will eventually lead to the development of a highly evolved liquid biopsy diagnostic tools.
INTRODUCTION: Rapid and accurate detection of group A (GAS) pharyngitis allows for timely initiation of appropriate antibiotic treatment. This is important to prevent empiric antibiotic overuse while simultaneously lowe...INTRODUCTION: Rapid and accurate detection of group A (GAS) pharyngitis allows for timely initiation of appropriate antibiotic treatment. This is important to prevent empiric antibiotic overuse while simultaneously lowering the risk of post-infection sequelae. Timely treatment may also reduce forward transmission, which could prevent cases of devastating invasive infections. The need for timely and accurate diagnosis of GAS pharyngitis has created an ideal environment for molecular diagnostic (MDx) testing. The high sensitivity of MDx tests mean no culture confirmation is required for negative results in most situations, and several MDx tests are approved for point-of-care (PoC) use. As such, MDx technology can lower the barriers to treatment in remote areas of high incidence, where resources are limited. We believe it is time for widespread adoption of MDx testing for GAS pharyngitis. AREAS COVERED: Here, we highlight the advantages of MDx GAS pharyngitis testing and discuss challenges to implementation - as well as solutions to these challenges. EXPERT OPINION: In the face of increased GAS-induced disease following the end of the COVID-19 pandemic, evidence supporting the clinical validity and cost-effectiveness of MDx testing for GAS pharyngitis continues to grow. Although hurdles to implementation exist, broad-based implementation of this technology is within practical reach.
OBJECTIVES: Krüppel‑like factors (KLFs) are implicated in the progression of endometrial cancer (EC). This present study explored the correlation between variants of KLF5, KLF12 and EC risk in the Chinese population. MET...OBJECTIVES: Krüppel‑like factors (KLFs) are implicated in the progression of endometrial cancer (EC). This present study explored the correlation between variants of KLF5, KLF12 and EC risk in the Chinese population. METHODS: The Agena MassARRAY technology platform was utilized to genotype six single nucleotide polymorphisms (SNPs) in KLF5 and KLF12 genes among 509 women diagnosed with EC and 506 age-matched healthy women. Subsequently, the relationship between SNPs in KLF5 and KLF12 and EC risk was calculated using logistic regression analysis. The interactions between SNPs in KLF5 and KLF12 were analyzed to predict EC risk using multifactor dimensionality reduction (MDR) analysis. RESULTS: KLF12 rs12429889 was significantly associated with EC risk (codominant: OR = 1.53, = 0.003; dominant: OR = 1.54, = 0.004). In addition, rs7329599 was significantly associated with EC risk in participants aged ≤55 years (codominant: OR = 0.63, = 0.014; dominant: OR = 0.67, = 0.024), whereas rs12429889 was significantly associated with EC risk in participants aged >55 years (codominant: OR = 1.98, = 0.004; dominant: OR = 2.06, = 0.002). CONCLUSION: Our findings revealed a significant correlation between KLF12 rs12429889 and rs7329599 and EC risk, highlighting their potential as diagnostic biomarkers. [Figure: see text].
BACKGROUND: The development of coronary artery disease (CAD) is influenced by sex and genetic factors. Genome-wide association studies (GWAS) have linked genetic loci to CAD, mostly in European populations. The study aim...BACKGROUND: The development of coronary artery disease (CAD) is influenced by sex and genetic factors. Genome-wide association studies (GWAS) have linked genetic loci to CAD, mostly in European populations. The study aims to find sex-related genetic differences in the Iranian population. RESEARCH DESIGN AND METHODS: We conducted a sex-stratified GWAS with 4519 subjects (1832 males and 2687 females) in the discovery group and 922 subjects (495 males and 427 females) in the confirmation group of an Iranian cohort. We analyzed 9,141,124 variants using a genome-wide complex trait analysis (GCTA) tool. RESULTS: We detected distinct genetic variants associated with CAD in males: rs34952209 [OR = 1.79; = 5.216E-8], rs1432687863 [OR = 1.95; = 8.477E-8], and in females, rs7314741 [OR = 1.67; = 7.142-8E] positively influenced CAD risk. The CAD-associated SNPs that were obtained have been confirmed using independent samples. Rs3495229 May impact histone mark and Pou2f2 motifs, while rs7314741 in the LEM Domain Containing 3 (LEMD3) promoter may affect a regulatory motif for the STAT transcription factor. According to Roadmap and ENCODE data, Rs1432687863 is a new variant affecting CAD in males, potentially through H3K9me3 in the heart. CONCLUSIONS: Our findings highlight the role of sex-specific genetic differences in CAD development, providing novel insights into disease pathways which is not appropriate using a sex-combined strategy. [Figure: see text].
BACKGROUND: This study aimed to validate HNF1B single nucleotide polymorphisms (SNPs) associated with endometrial cancer risk in a Chinese Han population and explore novel SNPs. Our findings enhance the understanding of...BACKGROUND: This study aimed to validate HNF1B single nucleotide polymorphisms (SNPs) associated with endometrial cancer risk in a Chinese Han population and explore novel SNPs. Our findings enhance the understanding of genetic components and are crucial for detection strategies and personalized medicine. METHODS: We genotyped four HNF1B SNPs in 637 patients and 667 controls using Agena MassARRAY. Logistic regression calculated odds ratios (ORs) and 95% CI. Forest plots visualize stratified analyses. Multiple comparisons tested genetic loci-clinical indicator associations. RESULTS: The study confirmed that rs4430796 (A>G) reduced endometrial cancer risk (OR = 0.83, 95% CI: 0.70-0.99, = 0.041). Additionally, novel HNF1B mutations were associated with endometrial cancer risk: rs7405776 in individuals under the age of 55 (OR = 047, 95% CI: 0.25-0.91, = 0.025) and nonsmokers (OR = 0.42, 95% CI: 0.23-0.75, = 0.004), and rs11651755 in drinkers (OR = 0.39, 95% CI: 0.17-0.90, = 0.027) and nonsmokers (OR = 0.43, 95% CI: 0.23-0.81, = 0.009). The SNP rs4430796 was also associated with the CA125 level ( < 0.05). CONCLUSION: HNF1B polymorphisms influence endometrial cancer risk in the Chinese Han population. Further studies are needed to explore the functional roles and clinical practicality of these SNPs.
Babady NE, Chiu CY, Craney A
… +5 more, Gaston DC, Hicklen RS, Hogan CA, John TM, Stewart AG
Expert Rev Mol Diagn
· 2024 Dec · PMID 39623670
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INTRODUCTION: Invasive fungal diseases (IFDs) are a serious threat to immunocompromised patients. Routine diagnostic methods have limited performance in identifying IFDs. Next-generation sequencing (NGS), including metag...INTRODUCTION: Invasive fungal diseases (IFDs) are a serious threat to immunocompromised patients. Routine diagnostic methods have limited performance in identifying IFDs. Next-generation sequencing (NGS), including metagenomic NGS (mNGS) and whole-genome sequencing (WGS), recently emerged as diagnostic methods that could provide more accurate and timely diagnoses and management of IFDs. AREAS COVERED: This article describes the emergence of NGS as a diagnostic tool to address the limitations of current tests. The literature regarding its application and clinical utility in the diagnosis of IFDs is reviewed. Practical considerations, challenges, and opportunities as they relate to the development and implementation of mNGS and WGS for fungal pathogens are discussed. EXPERT OPINION: NGS emerged over a decade ago with the potential to solve many of the challenges in diagnosing infectious diseases, including IFDs. However, published literature has yielded conflicting data about its clinical utility. The increased clinical adoption of NGS is improving our understanding of how to interpret and use its results to guide actionable decisions. Still, several gaps remain. As the cost, effort, and expertise involved in performing NGS decrease and the reporting of its results becomes standardized, NGS is poised to fill current gaps in the diagnosis of IFDs.
INTRODUCTION: Overexpression of tribbles homolog 3 (TRIB3) has been reported in various cancers, yet its clinical significance remains contentious. This study aims to elucidate the association between TRIB3 overexpressio...INTRODUCTION: Overexpression of tribbles homolog 3 (TRIB3) has been reported in various cancers, yet its clinical significance remains contentious. This study aims to elucidate the association between TRIB3 overexpression and the progression and prognosis of solid tumors. METHODS: A comprehensive analysis was conducted using data from published studies and The Cancer Genome Atlas (TCGA) up to May 2023. We evaluated the impact of high TRIB3 expression on tumor malignancy and survival outcomes across different cancer types. RESULTS: Seventeen studies met the inclusion criteria. Our findings revealed that TRIB3 overexpression is significantly associated with increased distant metastasis (OR = 4.01, 95% CI: 2.36-6.74, < 0.001) and advanced histological stage (OR = 2.68, 95% CI: 1.50-4.78, < 0.001). Additionally, high TRIB3 expression significantly elevated the risk of reduced overall survival (OS) in cancer patients (HR = 1.52, 95% CI: 1.05-2.20, < 0.001), indicating a poor prognosis. Analyses of TCGA data among various prognostic indicators corroborated these findings. CONCLUSIONS: TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors. These results suggest that TRIB3 holds promise as a biomarker and therapeutic target in human cancers.
INTRODUCTION: Currently the diagnosis of Kawasaki disease is still heavily reliant on clinical criteria which may be subject to interpretation or mimic other common febrile diseases of childhood. Biomarkers that can aid...INTRODUCTION: Currently the diagnosis of Kawasaki disease is still heavily reliant on clinical criteria which may be subject to interpretation or mimic other common febrile diseases of childhood. Biomarkers that can aid in the accurate and timely diagnosis of KD are of great clinical utility. AREAS COVERED: A literature search of PubMed was performed using the key words: Kawasaki disease, diagnosis, biomarkers, proteomics and transcriptomics. In this article we review biomarkers that are widely clinically available including NT-ProBNP and ferritin. We also include promising novel biomarkers that have been identified through newer transcriptomic and proteomic techniques. EXPERT OPINION: While the identification of biomarkers that can accurately assist in diagnosing patients with KD is a promising field of research, more still remains to be done to in order to validate new biomarkers in larger cohorts, and to set standardized cutoff values for potential biomarkers that are currently clinically available. Further research is needed before KD biomarkers that are consistent, readily available, and cost-effective can be a clinical reality.
INTRODUCTION: While pneumonia (PcP) remains a major AIDS-defining disease, the majority of cases of PcP now present in the HIV-negative cohort, causing significant mortality. PcP PCR diagnosis is not novel, and the opti...INTRODUCTION: While pneumonia (PcP) remains a major AIDS-defining disease, the majority of cases of PcP now present in the HIV-negative cohort, causing significant mortality. PcP PCR diagnosis is not novel, and the optimal route of diagnosis remains unclear, with an imperfect reference method and complexity in result interpretation for alternative tests. AREAS COVERED: This extensive review utilizing a literature search underpinning a recent systematic review/meta-analysis discusses the technical and clinical performance of PcP PCR, the added benefits of PCR testing, future aspects/considerations, and how PCR may be best used in clinical algorithms to provide a probability of PcP. EXPERT OPINION: Given the current imperfect reference test for PcP, an alternative would be beneficial. Concerns over PcP PCR generating false positive results are valid but can be resolved by using positivity thresholds that drive specificity. Unfortunately, the extensive range of PCR assays complicates the provision of a PCR reference method. Combination testing incorporating PCR and B-D-Glucan, along with clinical and host risk factors, is key to understanding the individual probability of PcP. It is critical that access to PcP PCR testing is improved through technical and logistical development. Conversely, syndromic approaches including PcP need to be fully evaluated.
INTRODUCTION: Parkinson's disease (PD) is a complex disorder with vast clinical heterogeneity. Recent genetic, imaging and clinical evidence suggest that there are multiple subtypes of PD, and perhaps even distinct clini...INTRODUCTION: Parkinson's disease (PD) is a complex disorder with vast clinical heterogeneity. Recent genetic, imaging and clinical evidence suggest that there are multiple subtypes of PD, and perhaps even distinct clinical entities, which are being diagnosed under the umbrella of PD. These might have similar clinical presentation, but potentially different underlying mechanisms, which, in future, will require different treatments. Despite extensive genetic research progress, genetic testing is still not a common practice in clinical patient care. AREAS COVERED: This review examines the numerous genes that have been discovered to affect the risk of, or cause, PD. We also outline genetic variants that affect PD age at onset, its progression, and the presence or severity of motor and non-motor symptoms. We differentiate between PD, other synucleinopathies, and atypical parkinsonism syndromes, and describe genes responsible for familial forms of typical PD and atypical parkinsonism. Lastly, we present current clinical trails that are underway for targeted therapies, particularly for GBA1-PD and LRRK2-PD which are the most significant subtypes. EXPERT OPINION: While genetic studies alone cannot be diagnostic for PD, proper utilization of genetic screening for PD could improve diagnostic accuracy and predictions for prognosis, guide treatment, and identify individuals that qualify for clinical trials.
INTRODUCTION: There have been many recent advancements in the treatment of bladder cancer including the approval of novel intravesical agents for non-muscle-invasive disease and systemic-targeted therapeutics for muscle-...INTRODUCTION: There have been many recent advancements in the treatment of bladder cancer including the approval of novel intravesical agents for non-muscle-invasive disease and systemic-targeted therapeutics for muscle-invasive and advanced disease. However, treatment strategies for bladder cancer are still largely based on clinicopathologic characteristics. AREAS COVERED: Based on primary literature sourced from PubMed, Embase, and Cochrane Library, we review the current status of molecular markers and biomarker panels with respective to their value in predicting response to standard chemotherapeutics and novel agents in non-muscle-invasive, muscle-invasive, and advanced bladder cancer. EXPERT OPINION: Several biomarkers based on molecular characterization of tumors and quantification of circulating tumor DNA have been associated with response or resistance to standard chemotherapeutics. More recent investigations have reported on predictive biomarkers for novel therapeutics in bladder cancer, although large-scale validation is still needed. Given the increasing therapeutic options for this disease, employment of such predictive biomarkers may help guide treatment selection and sequencing.
BACKGROUND: This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clini...BACKGROUND: This study investigated the relationship between lipid-associated loci identified through genome-wide association studies (GWAS) and the risk of peripheral artery disease (PAD), its severity, as well as clinical and laboratory features. RESEARCH DESIGN AND METHODS: A study included 1263 unrelated Russian subjects, consisting of 620 patients diagnosed with PAD and 643 healthy controls. Thirteen single nucleotide polymorphisms (SNP) were genotyped using the MassArray-4 system. RESULTS: Polymorphisms rs1689800, rs55730499 and rs881844 were found to be associated with an increased risk of PAD, whereas SNPs rs1883025, rs3136441, rs3764261 and rs6065906 showed protective effects against disease (P ≤ 0.05). SNPs rs1689800, rs217406, rs1883025, and rs3136441 exhibited combined effects with cigarette smoking on the PAD risk (P ≤ 0.05). Polymorphisms rs55730499 (beta = 0.124, P = 0.04), rs9987289 (beta = 0.558, P = 0.03), and rs881844 beta = -0.171, P = 0.03) correlated with the ankle-brachial index. Multiple associations have been found between the SNPs and clinically significant characteristics, including disease severity, risk of gangrene, early disease onset, plasma procoagulant and atherogenic lipid changes (P ≤ 0.05). CONCLUSIONS: We identified novel genetic markers associated with PAD susceptibility and disease-related clinical and laboratory features. The identified biomarkers enhance the potential for predictive genetic testing related to the risk and progression of PAD, facilitating the integration of molecular diagnostics into clinical decision-making processes.
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medi...INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a common metabolism-related disease worldwide. Although studies have shown that some medications may be effective for treating NAFLD, they do not satisfy the medical requirements, and lifestyle changes are the most basic strategy. Thus, early detection of NAFLD and timely lifestyle interventions are highly important. AREAS COVERED: The traditional diagnostic methods for NAFLD are limited by accuracy, cost, and security issues. Cytokeratin 18 (CK18), which is a marker of apoptosis and overall cell death, is an excellent biomarker for NAFLD. Liver fat accumulation in NAFLD triggers the activation of caspases, which increases the CK18 cleavage and its release into the blood. CK18 can help diagnose different stages of NAFLD, especially the nonalcoholic steatohepatitis (NASH) stage. In evaluating the efficacy of the NAFLD treatment and predicting the risk of NAFLD-related diseases, CK18 plays a significant role. EXPERT OPINION: CK18 can non-invasively monitor the pathological conditions of NAFLD patients and provide new hope for the early diagnosis of NAFLD. Adding CK18 to the NAFLD diagnostic criteria that are widely used in clinical settings may be efficient for the detection of NAFLD and early effective intervention.
INTRODUCTION: Non-coding RNAs (ncRNAs) comprise a heterogeneous cluster of RNA molecules. Emerging evidence suggests their involvement in various aspects of tumorigenesis, particularly in gynecological malignancies. Nota...INTRODUCTION: Non-coding RNAs (ncRNAs) comprise a heterogeneous cluster of RNA molecules. Emerging evidence suggests their involvement in various aspects of tumorigenesis, particularly in gynecological malignancies. Notably, ncRNAs have been implicated as mediators within tumor signaling pathways, exerting their influence through interactions with RNA or proteins. These findings further highlight the hypothesis that ncRNAs constitute therapeutic targets and point out their clinical potential as stratification biomarkers. AREAS COVERED: The review outlines the use of small ncRNAs, including miRNAs, tRNA-derived small RNAs, PIWI-interacting RNAs and circular RNAs, for diagnostic, prognostic, and predictive purposes in gynecological cancers. It aims to increase our knowledge of their functions in tumor biology and their translation into clinical practice. EXPERT OPINION: By leveraging interdisciplinary collaborations, scientists can decipher the riddle of small ncRNA biomarkers as diagnostic, prognostic and predictive biomarkers of gynecological tumors. Integrating small ncRNA-based assays into clinical practice will allow clinicians to provide cure plans for each patient, reducing the likelihood of adverse responses. Nevertheless, addressing challenges such as standardizing experimental methodologies and refining diagnostic assays is imperative for advancing small ncRNA research in gynecological cancer.
INTRODUCTION: Approximately 15 million deaths occur globally each year due to infectious diseases. Timely diagnosis is crucial in promoting cure and preventing disease transmission. Currently, molecular diagnostics have...INTRODUCTION: Approximately 15 million deaths occur globally each year due to infectious diseases. Timely diagnosis is crucial in promoting cure and preventing disease transmission. Currently, molecular diagnostics have replaced many conventional diagnostic tools due to their inherent limitations. However, the full potential of Immuno Polymerase Chain Reaction (IPCR) remains largely untapped. AREAS COVERED: This review focuses on the use of IPCR in the diagnosis of different bacterial diseases, highlighting its advantages over traditional methods. EXPERT OPINION: Early and accurate diagnosis of infectious diseases is crucial because it enhances treatment effectiveness, reduces morbidity and mortality, helps identify potential causes of sepsis earlier, and reduces the risk of unknowingly spreading the disease to others. IPCR in turn has shown promise for the early diagnosis of bacterial diseases as an alternative to conventional culture-based or serological diagnostic assays leading to delayed diagnosis and treatment. IPCR has the potential to revolutionize the diagnostic field due to its increased sensitivity and specificity. Although efforts are needed to reduce the time of the assay and to reduce background noise, IPCR can be combined with other platforms like lateral flow assay/biosensors/automation to improve its use as a point-of-care assay, especially in resource-limited settings.
INTRODUCTION: SARS-CoV-2, seasonal influenza, and respiratory syncytial virus (RSV) are major causes of acute respiratory infections in all age groups and responsible for an enormous socio-economic burden. The recently c...INTRODUCTION: SARS-CoV-2, seasonal influenza, and respiratory syncytial virus (RSV) are major causes of acute respiratory infections in all age groups and responsible for an enormous socio-economic burden. The recently coined term 'tripledemic' describes co-circulation of these three viruses, a novel epidemiological paradigm that poses profound public health implications. AREAS COVERED: Real-time reverse transcription polymerase chain reaction (RT-PCR) is now considered the reference method for the diagnosis of SARS-CoV-2, influenza, and RSV infections. Syndromic-based multiplex RT-PCR panels that simultaneously detect several respiratory viruses have become increasingly common. This review explores available molecular diagnostics (MDx) platforms for the diagnosis of SARS-CoV-2, influenza, and RSV in the same biological sample. Within some limitations of the published validation and diagnostic accuracy studies, both laboratory-based and point-of-care multiplex panels proved highly performant in identifying SARS-CoV-2, influenza A, influenza B, and RSV. Improved operational efficiency and faster turnaround times make these assays potentially cost-effective or even cost-saving. EXPERT OPINION: The adoption of multiplex MDx assays for the contemporary detection of SARS-CoV-2, influenza, RSV, and other respiratory pathogens will likely increase in the next few years. To maximize the clinical usefulness and cost-effectiveness of these assays, locally issued guidelines and protocols on their implementation should be adopted.