INTRODUCTION: Cancer remains one of the leading causes of death worldwide, with outcomes improving significantly when the disease is detected at an early stage. Screening programs have demonstrated clear benefits, yet th...INTRODUCTION: Cancer remains one of the leading causes of death worldwide, with outcomes improving significantly when the disease is detected at an early stage. Screening programs have demonstrated clear benefits, yet they often struggle with limited accuracy, unequal participation, and substantial demands on health care systems. Artificial intelligence (AI) has entered this space as a promising tool, aiming to improve detection, reduce workload, and support more individualized screening approaches. AREAS COVERED: This review explores the application of AI across different aspects of cancer screening. We discuss its use in established imaging modalities such as mammography and low-dose CT, explore early developments in liquid and blood-based assays, and highlight efforts to harness routine clinical and laboratory data to better identify people at risk. EXPERT OPINION: AI is beginning to move beyond experimental settings and into real-world clinical practice. Early evidence suggests that it can enhance both accuracy and efficiency. At the same time, important challenges remain, including risks of bias, overdiagnosis, and uneven performance across clinical environments. However, sustainable progress will require robust validation, careful integration into clinical workflows, and policies that ensure the technology benefits patients across diverse settings.
INTRODUCTION: Since 1993, when a polymorphic CAG trinucleotide repeat was established as the cause of Huntington's disease (HD), fragment analysis has been the first-tier test in genetic diagnosis of HD. However, in rece...INTRODUCTION: Since 1993, when a polymorphic CAG trinucleotide repeat was established as the cause of Huntington's disease (HD), fragment analysis has been the first-tier test in genetic diagnosis of HD. However, in recent years it has become increasingly clear that, in addition to the repeat length itself, sequence variations within the repeat and elsewhere in the genome also play a crucial role in the onset and clinical presentation of the disease. AREAS COVERED: Sequence interruptions or non-canonical repeat motifs have historically been difficult to identify, as PCR cannot distinguish an interrupted repeat tract when assessed by capillary electrophoresis. However, these non-canonical interruptions may directly affect the phenotype or result in an underestimation of the uninterrupted CAG repeat length. While next-generation sequencing (NGS) with short read lengths has revolutionized genetic diagnostics, it faces limitations in diagnosing repeat expansion diseases. The literature search methodology involved a review of relevant studies and clinical data. EXPERT OPINION: In contrast, long-read sequencing (LRS) generates read lengths of over 10 kb and can thus overcome the limitations associated with short reads. This enables detailed investigation of repeat sequences and the identification of complex patterns of alternating sequence motifs, potentially providing additional clinically relevant information.
INTRODUCTION: The SARS-CoV-2 pandemic forced a radical expansion of essential public health laboratory services that went beyond basic testing. This perspective highlights key shifts in laboratory function, specifically...INTRODUCTION: The SARS-CoV-2 pandemic forced a radical expansion of essential public health laboratory services that went beyond basic testing. This perspective highlights key shifts in laboratory function, specifically toward decentralized testing, self-sampling, less invasive specimen types, point-of-care devices, and novel surveillance strategies. AREAS COVERED: The surge in testing demand favored decentralized solutions, including rapid lateral flow tests, due to their flexibility, speed, and affordability. However, several challenges arose from the variable diagnostic accuracy of rapid self-tests and alternative specimen types when compared to reference laboratory-based molecular assays using nasopharyngeal swabs. For instance, the use of self-collected saliva, which is often preferred by patients, was hindered by a lack of internationally standardized processing protocols. A post-pandemic rebound in the circulation of respiratory pathogens other than SARS-CoV-2 was likely driven by both immunity debt and increased testing, including of less severe cases, commonly performed through more costly multiplex respiratory panels. EXPERT OPINION: Moving forward, while over-the-counter self-tests for common respiratory viruses are now common, stricter regulatory oversight and improved data connectivity are essential. Local decision-makers must weigh the trade-offs between broad testing access and clinical performance, and implement robust diagnostic stewardship programs for acute respiratory infections.
INTRODUCTION: Ovarian cancer is a leading cause of cancer-related death in women, primarily due to nonspecific symptoms and diagnosis at an advanced stage. Improving outcomes through earlier diagnosis and effective popul...INTRODUCTION: Ovarian cancer is a leading cause of cancer-related death in women, primarily due to nonspecific symptoms and diagnosis at an advanced stage. Improving outcomes through earlier diagnosis and effective population screening remains a global priority. CONTEXT: Existing modalities ,including CA125 and transvaginal ultrasound (TVUS), lack sufficient specificity and sensitivity, and no screening strategy has demonstrated a reduction in mortality. Multivariate Index Assays (MIAs), that combine multiple biomarker results into a single risk score, have emerged as a promising approach for differential diagnosis of adnexal masses, early detection, and screening. AREAS COVERED: This review summarizes current literature and clinical trial data on MIAs in ovarian cancer, describing their advantages over single biomarkers, their potential to improve patient outcomes, and their role in personalized medicin. Successful clinical adoption of MIAs will depend on well-designed prospective studies that robustly validate their clinical utility. EXPERT OPINION/COMMENTARY: It is also critical to clearly distinguish between diagnostic and screening applications, as each requires different performance characteristics, regulatory pathways, and target populations, and no ovarian cancer screening test is currently approved for routine use.
INTRODUCTION: Sepsis, a life-threatening condition characterized by dysregulated host immune and metabolic responses to infection, is associated with high mortality, making accurate diagnosis and targeted treatment cruci...INTRODUCTION: Sepsis, a life-threatening condition characterized by dysregulated host immune and metabolic responses to infection, is associated with high mortality, making accurate diagnosis and targeted treatment crucial. Sepsis often induces a notable reduction in serum high-density lipoprotein (HDL) levels. As the fundamental structural and functional components of HDL, apolipoproteins play pivotal roles in mediating the function of HDL. Therefore, these apolipoproteins can serve as potential biomarkers in sepsis. AREAS COVERED: This review systematically synthesizes current evidence on the dynamic expression profiles of these apolipoproteins in sepsis, highlighting the relation of their single nucleotide polymorphisms (SNPs) with sepsis and clinical relevance in diagnosis and prognosis. Furthermore, it also summarizes the underlying mechanisms by which these apolipoproteins are involved in the progression of sepsis. EXPERT OPINION: The changes in the levels of HDL-associated apolipoproteins can characterize the progression of sepsis and the type of infecting bacteria, and provide therapeutic targets for the treatment of sepsis. Therefore, the comprehensive understanding of their integrated effects holds promise for developing precision interventions to improve clinical outcomes of sepsis.
INTRODUCTION: Early diagnosis and treatment initiation are essential to prevent ongoing tuberculosis (TB) transmission and reduce the disease burden. Smear microscopy, which is widely used test for diagnosis, has limited...INTRODUCTION: Early diagnosis and treatment initiation are essential to prevent ongoing tuberculosis (TB) transmission and reduce the disease burden. Smear microscopy, which is widely used test for diagnosis, has limited sensitivity and does not detect rifampicin resistance. Truenat is a portable, battery-operated, chip-based test that can be placed in peripheral laboratories, serving as a point-of-care test. It also detects rifampicin resistance, which is crucial in the management of TB. AREAS COVERED: Our review comprehensively covers the functionality and workflow of the Truenat MTB assay, in addition to its cost-effectiveness and diagnostic accuracy, based on recent evidence. We also discuss the merits and drawbacks of alternative diagnostic tests available for detecting TB and rifampicin resistance. EXPERT OPINION: Truenat assays are rapid molecular tests that revolutionized TB diagnosis, moving toward peripheral testing. Evidence indicates that the Truenat MTB Plus performs better than the original Truenat MTB, with an approximate LOD of 30 CFU/ml. The 2025 WHO guidelines rely exclusively on data from Truenat MTB Plus. We need larger studies on the newer Truenat MTB Ultima to evaluate its performance on tongue swabs. Additionally, data on the accuracy of Truenat MTB in children remains scarce, emphasizing the importance of further research in this group. Evidence regarding its accuracy in detecting rifampicin resistance is also limited, requiring larger studies and technological advancements. Truenat MTB will remain crucial in the fight to eliminate TB in the future.
INTRODUCTION: MUC4 is overexpressed in gastric cancer and its precursor lesions and plays an essential role in disease progression. AREA COVERED: In this review, we describe the diagnostic and prognostic value of MUC4 ex...INTRODUCTION: MUC4 is overexpressed in gastric cancer and its precursor lesions and plays an essential role in disease progression. AREA COVERED: In this review, we describe the diagnostic and prognostic value of MUC4 expression in gastric cancer. First, we provide a summary of gastric cancer pathogenesis and its intricate relationship with mucin expression. We will then provide an extensive description of MUC4 expression in gastric cancer and its diagnostic and therapeutic significance. EXPERT OPINION: Apart from its protective role in normal physiology, MUC4 contributes to disease progression and metastasis in several malignancies, including gastric cancer. MUC4 is expressed at negligible levels in normal gastric mucosa. However, some patients with intestinal metaplasia and gastric cancer have high levels of MUC4 expression, particularly in the pit cell compartment. The expression of MUC4 in metaplastic pit cells is associated with increased proliferation, inflammation, and epithelial-to-mesenchymal transition. Hence, evaluating MUC4 expression in precursor lesions may help stratify disease and identify cases in which curative surgery should be performed. MUC4 expression in gastric cancer is associated with disease aggressiveness, lymphatic invasion, and nodal metastasis. Due to its role in disease pathobiology, it is a promising target for the diagnosis and therapy of gastric cancer.
INTRODUCTION: Infections caused by different Leishmania species are considered as neglected diseases and are prevalent in many tropical and temperate regions worldwide. Extracellular vehicles (EVs) transport different na...INTRODUCTION: Infections caused by different Leishmania species are considered as neglected diseases and are prevalent in many tropical and temperate regions worldwide. Extracellular vehicles (EVs) transport different nanoparticles for extracellular medium as enzymes, proteins, lipids, nucleic acids and others for cellular metabolic activities. However, the precise role of EVs in infections caused by Leishmania species is not totally established. This article revised the significance of EVs in pathogenesis, diagnosis and treatment strategies for the different forms of leishmaniasis. AREAS COVERED: EVs of Leishmania spp. may be considered as potential drug targets in treatment, as they can encapsulate small molecules or drugs for more effective delivery to specific cells or tissues. The perspectives on EVs research in Leishmania facilitate the understanding of the role of these nanoparticles in parasite-host interactions and the development of diagnostic and therapeutic strategies, as vaccine development, and enhancing drug delivery systems. EXPERT OPINION: The knowledge of the participation of EVs in Leishmania species offers opportunities to further our understanding in pathogenesis and in the development of innovative diagnostic tools and treatments and to explore new approaches to disease.
BACKGROUND: Intrinsic capacity (IC) decline is a key marker of aging-related functional loss, yet sex-specific biomarkers remain poorly characterized. This cross-sectional study of 1014 community-dwelling older adults in...BACKGROUND: Intrinsic capacity (IC) decline is a key marker of aging-related functional loss, yet sex-specific biomarkers remain poorly characterized. This cross-sectional study of 1014 community-dwelling older adults investigated the associative strength and potential statistical intermediaries of insulin-like growth factor binding protein 2 (IGFBP2) and growth differentiation factor 15 (GDF-15) in IC impairment, with sex-stratified analyses. RESEARCH DESIGN AND METHODS: Dose-response relationships were assessed using restricted cubic splines. Multivariable logistic regression evaluated independent associations after adjusting for covariates. Mediation analysis explored roles of renal, muscular, metabolic, and oxidative stress indicators. RESULTS: IC impairment was associated with higher IGFBP2 and GDF-15 (all < 0.001). In males, IGFBP2 showed a reverse L-shaped association (inflection at 310 ng/mL; AUC = 0.75), partially explained by renal function (β2-MG), muscle damage (CK, LDH), oxidative stress (SOD), and nutrition (ALB), with 11.02% mediation. In females, GDF-15 had a nonlinear relationship (inflection at 1.99 ng/mL; AUC = 0.76), attributable in part to glucose (FBG), lipids (FFA), and renal function (BUN), accounting for 19.8% of the effect. Fully adjusted ORs were 2.41 (IGFBP2 in males) and 4.27 (GDF-15 in females), both < 0.001. CONCLUSION: IGFBP2 and GDF-15 are sex-specific biomarkers for IC decline, operating through distinct pathways, and may aid early screening and targeted interventions.
BACKGROUND: Critically ill patients have high mortality influenced by insulin resistance (IR)and inflammation.The C-reactive protein-triglyceride-glucose index (CTI), integrating IR and inflammation, has unclear prognost...BACKGROUND: Critically ill patients have high mortality influenced by insulin resistance (IR)and inflammation.The C-reactive protein-triglyceride-glucose index (CTI), integrating IR and inflammation, has unclear prognostic value in this population compared to the traditional triglyceride-glucose index (TyG). METHODS: This cohort study analyzed 1963 critically ill patients from MIMIC-IV. Outcomes included in-hospital mortality, acute kidney injury (AKI), and length of stay. Analyses employed multivariable regression, mediation, and machine learning. RESULTS: Elevated CTI showed a graded association with mortality. Per unit increase conferred 22% higher risk (OR 1.22, 95% CI 1.08-1.38); the top quartile had double the risk (OR 2.07, 1.36-3.13) and a mortality rate of 26.48% vs. 9.98% in the lowest quartile. CTI also independently predicted higher AKI risk (OR 1.28, 1.13-1.45; incidence 91.24% vs. 73.32% in Q4 vs. Q1) and prolonged ICU/hospital stay (β 1.99 and 3.71 days, < 0.05). AKI mediated 5.53% of the CTI-mortality relationship. CTI's discriminative power surpassed TyG (DeLong = 0.001). In prognostic modeling, CTI was a key feature, with the Gradient Boosting Machine model achieving optimal performance (AUC 0.789). CONCLUSION: CTI is strongly associated with adverse outcomes and may outperform TyG in critically ill patients, supporting its utility for risk stratification.
INTRODUCTION: Bladder cancer (BC) is a prevalent urinary tract malignancy, characterized by high recurrence rates and heterogeneous disease progression. Non-muscle invasive bladder cancer (NMIBC) and muscle-invasive blad...INTRODUCTION: Bladder cancer (BC) is a prevalent urinary tract malignancy, characterized by high recurrence rates and heterogeneous disease progression. Non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) present distinct clinical challenges, and conventional clinicopathological parameters are often insufficient to predict recurrence or progression accurately. Long non-coding RNAs (lncRNAs) have emerged as key regulators of tumor biology, influencing proliferation, migration, epithelial-mesenchymal transition, and therapy resistance, with potential in risk stratification, prognostic prediction and guidance of therapy de-escalation or intensification. AREAS COVERED: This narrative review examines the role of lncRNAs in BC, focusing on their biological functions, prognostic significance, and potential to guide personalized treatment strategies. We discuss lncRNA involvement in NMIBC and MIBC, highlight molecular profiling studies enabling risk stratification and molecular subtyping for guiding treatment de-escalation or intensification. Finally, we address the challenges and future directions for integrating lncRNA profiling into routine clinical practice. EXPERT OPINION: LncRNAs offer a promising approach for precision oncology in bladder cancer, providing insights beyond traditional clinical parameters. Integrating lncRNA profiling into routine practice could optimize risk stratification, guide therapy intensity, and reduce overtreatment. Although current evidence is encouraging, large-scale prospective trials are needed to validate lncRNA signatures and fully realize their potential in personalized bladder cancer management.
INTRODUCTION: Transfer RNA-derived small RNAs (tsRNAs) have emerged as critical regulators in cancer biology, influencing gene expression, protein synthesis, and cellular signaling. Their unique expression patterns and f...INTRODUCTION: Transfer RNA-derived small RNAs (tsRNAs) have emerged as critical regulators in cancer biology, influencing gene expression, protein synthesis, and cellular signaling. Their unique expression patterns and functional diversity highlight their potential for diagnostic, prognostic, and therapeutic potential, particularly in hepatocellular carcinoma (HCC), a major cause of cancer-related mortality worldwide. AREAS COVERED: This review provides the first integrative overview of tsRNAs in HCC, encompassing their biogenesis, classification, molecular functions, and involvement in tumor hallmarks, including proliferation, metastasis, apoptosis, metabolism, angiogenesis, and immune modulation. We also summarize current advances in detection methods and databases and highlight the translational potential of tsRNAs as diagnostic, prognostic, and therapeutic targets. This work emphasizes unexplored dimensions of tsRNA-mediated regulation, connecting mechanistic insights with clinical applications. EXPERT OPINION: Although tsRNAs show great promise in HCC diagnosis, prognosis, and therapy, clinical translation remains hindered by gaps in mechanistic understanding, technical challenges in detection, and a lack of large-scale validation. Overcoming these limitations through standardized methodologies and multi-omics integration could unlock their full potential in precision cancer medicine.
INTRODUCTION: New research has shown an intriguing link between the gut bacteria and the thyroid. A gut-thyroid relationship affects energy production, immunological function, and inflammation. As a result, disrupted gut...INTRODUCTION: New research has shown an intriguing link between the gut bacteria and the thyroid. A gut-thyroid relationship affects energy production, immunological function, and inflammation. As a result, disrupted gut flora harmony is associated with an increased/altered risk of thyroid dysfunction, autoimmune disorders, and metabolic imbalance. In addition to current diagnostic technology, understanding the gut flora-thyroid relationship could assist in the detection of thyroid-related conditions and modify patient treatment. AREAS COVERED: This review explores state-of-the-art molecular techniques, e.g. metagenomics profiling and metabolomics, to uncover clinically relevant microbiota-driven biomarkers related to thyroid disorders. EXPERT OPINION: Revealing potential microbiota-driven biomarker candidates is pivotal in enhancing our understanding of the mechanisms of thyroid disorders more precisely and identifying diagnostic and prognostic markers with clinical potential. Precisely, the individualization in the approach to patients with thyroid disorder, inevitably considering the harmonization of the gut microbiota-thyroid hormone relationship, is the basis of rational pharmacotherapy.
BACKGROUND: Oral squamous cell carcinoma, the most common head and neck cancer, is characterized by aggressive invasion, frequent lymph node metastasis, and high recurrence. OBJECTIVE: This review explores the role of mi...BACKGROUND: Oral squamous cell carcinoma, the most common head and neck cancer, is characterized by aggressive invasion, frequent lymph node metastasis, and high recurrence. OBJECTIVE: This review explores the role of microbial dysbiosis in shaping the immune landscape of oral squamous cell carcinoma. It aims to identify key microbial taxa altered in Oral squamous cell carcinoma, examine the immunological pathways they influence, and assess their impact on tumor progression and immune evasion. METHODS: A comprehensive literature search was conducted across three major databases: PubMed, Scopus, and Embase. A total of 300 records were initially identified (PubMed: = 68; Scopus: = 63; Embase: = 169). After screening and eligibility assessment, 17 studies meeting inclusion criteria were selected for final analysis. RESULTS: Fusobacterium was the most frequently enriched genus in Oral squamous cell carcinoma, followed by Peptostreptococcus, Prevotella, Porphyromonas, Campylobacter, Treponema, Capnocytophaga, and Dialister. Streptococcus was the most consistently depleted, along with Rothia, Veillonella, Leptotrichia, Capnocytophaga, and Neisseria. CONCLUSION: Cancer remains a leading cause of death. Oral microbial dysbiosis, with loss of beneficial species and enrichment of pathogens, has been linked to oral cancer, but its mechanistic role remains hypothetical and requires validation.
BACKGROUND: This systematic review and meta-analysis of diagnostic test accuracy evaluated the performance of noninvasive liquid biopsy methods for diagnosis of meningioma, the most common primary intracranial neoplasm i...BACKGROUND: This systematic review and meta-analysis of diagnostic test accuracy evaluated the performance of noninvasive liquid biopsy methods for diagnosis of meningioma, the most common primary intracranial neoplasm in adults. RESEARCH DESIGN AND METHODS: Following PRISMA-DTA guidelines, we searched three databases. Data for 2 × 2 contingency tables were extracted, methodological quality was assessed using QUADAS-2, and a bivariate meta-analysis was performed. RESULTS: A total of 23 studies with 27 datasets were included. Pooled sensitivity was 0.78 (95% CI: 0.71 - 0.83) and specificity was 0.82 (95% CI: 0.76 - 0.86), with an area under the curve (AUC) of 0.86. Subgroup analysis showed that seroreactivity assays had the highest accuracy (diagnostic odds ratio or DOR = 67), while emerging technologies like cfDNA methylation showed high potential but were supported by limited data. The evidence was limited by significant publication bias (Deeks' test, < 0.001), and meta-regression revealed that studies with a lower risk of bias reported significantly lower specificity ( = 0.008). CONCLUSIONS: Fluid-based biomarkers show good overall accuracy for meningioma diagnosis, but the current evidence is compromised by methodological bias, suggesting that true performance is more modest than reported. Rigorous, prospective validation of promising approaches like cfDNA methylation and seroreactivity is essential to clarify their clinical utility.
Expert Rev Mol Diagn
· 2025 Dec · PMID 41275384
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INTRODUCTION: Pediatric tuberculosis (TB), especially among children co-infected with HIV, remains a significant global health challenge. Traditional sputum-based diagnostics are less effective in this population due to...INTRODUCTION: Pediatric tuberculosis (TB), especially among children co-infected with HIV, remains a significant global health challenge. Traditional sputum-based diagnostics are less effective in this population due to difficulties in sample collection and paucibacillary disease, necessitating alternative non-sputum diagnostic approaches. AREAS COVERED: This review examines recent advances in non-sputum biosignatures for pediatric TB diagnosis, including host- and pathogen-based biomarkers detectable in blood, urine, stool and breath. EXPERT OPINION: Despite rapid advances in TB biosignature discovery, translation into usable diagnostics lags behind - especially for children and those with HIV. Studies often exclude these key populations, lack diverse validation, and depend on complex laboratory platforms. Bridging this gap requires early integration of feasibility, usability, and health system factors into product development. Multimodal, point-of-care tools adapted for low-resource settings and inclusive of high-risk children are essential. Implementation science and technology adaptation are critical to ensure real-world impact of these promising innovations.To summarize, non-sputum biosignatures offer an opportunity for early diagnosis of TB in children with HIV. However, these signatures need to be validated and be translated into affordable point-of-care tools that can be integrated with current diagnostic approaches and implemented in low resource settings.
INTRODUCTION: CRISPR-based genome editing has revolutionized molecular diagnostics and therapeutic applications, offering precise genetic modifications. However, off-target effects remain a significant challenge, potenti...INTRODUCTION: CRISPR-based genome editing has revolutionized molecular diagnostics and therapeutic applications, offering precise genetic modifications. However, off-target effects remain a significant challenge, potentially leading to unintended mutations and genomic instability. Addressing these concerns is crucial for ensuring the clinical safety and efficacy of CRISPR technologies. AREAS COVERED: This review provides a comprehensive analysis of strategies for detecting and mitigating off-target effects in CRISPR genome editing. We discuss in silico, in vitro, and in vivo detection methods, highlighting their strengths and limitations. Additionally, we examine advancements in guide RNA (gRNA) engineering, improved Cas variants, optimized delivery systems, base and prime editing technologies, and anti-CRISPR proteins as key approaches to enhance genome-editing precision. EXPERT OPINION: While significant progress has been made in off-target detection and mitigation, challenges remain in accurately assessing unintended genomic modifications in vivo and ensuring long-term safety in clinical applications. Future research should focus on developing high-fidelity CRISPR variants, refining computational prediction models, and integrating multi-modal detection systems. Advancing delivery mechanisms and regulatory strategies will be essential for translating CRISPR into safe and effective therapeutic interventions.