Critical reviews in clinical laboratory sciences最新文献

This review attempts to find a crucial set of criteria that can be applied to diagnose infections caused by Trichophyton indotineae, based on laboratory and clinical characteristics derived from other studies. T. indotineae has emerged as a new species from the anthropophilic Trichophyton mentagrophytes and Trichophyton interdigitale. The close relationship between T. indotineae and these two species makes it difficult to distinguish them based on morphological and physiological features. Resistance to terbinafine was first observed in T. indotineae, and later to other antifungals, which increased the treatment failure rate in several dermatophytoses. In conclusion; identifying criteria specific to infections with T. indotineae can provide a framework for physicians to readily diagnose such infections and distinguish them from other dermatophytoses. Categorization guidelines for all diagnostic characteristics of T. indotineae and its infection can make a forward step in prescribing effective therapies.

Implementing DP on a large scale is a complex, multi-dimensional process that requires strategic planning, technological adaptation, and change management. We provide a detailed account of the full-scale implementation of DP at the University Health Network (UHN), a multi-site tertiary clinical center in Canada, highlighting practical lessons learned, ongoing challenges, and mitigation strategies.

A phased implementation approach was adopted, involving pre-implementation planning, procurement, infrastructure development, and optimized validation protocols. Significant focus was placed on technical considerations, including system interoperability, storage capacity, and image quality. Procurement was structured to ensure vendor neutrality and long-term sustainability.A critical component of the implementation was "change management", addressing resistance to change through extensive training, real-time troubleshooting, utilizing "super users" as change champions. Attention was paid to pathologist office configuration.

A dual workflow model, with simultaneous access to both glass and digital slides, facilitated smoother transition. As of this writing all histopathology H&E cases and tissue hematopathology are being scanned. Efforts to implement digital liquid hematopathology and cytopathology are ongoing.

The financial implications of DP implementation were evaluated, including direct and indirect costs. While initial investments in scanners, storage, and software infrastructure were substantial, long-term savings are anticipated through increased efficiency, reduced physical slide storage, enhanced workload distribution and the integration of AI-based tools.

Continuous monitoring and feedback were established to assess system performance and address emerging challenges. Scalability and future applications of DP remain a priority. The adoption of AI-driven pathology tools, remote diagnostics, and cross-institutional data sharing are anticipated to further enhance the value of DP. UHN's experience underscores the importance of a structured, multidisciplinary approach to DP implementation.

Our experience offers a realistic and evolving roadmap for institutions considering DP adoption. We provide practical guidance, highlight persistent challenges and emphasize the importance of continuous evaluation and adaptation.

Non-coding RNAs (ncRNAs) are a class of functional transcripts that are not translated into proteins and primarily include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In recent years, as therapeutic challenges such as tumor heterogeneity and drug resistance have become increasingly prominent, ncRNAs have emerged as pivotal targets in cancer mechanistic research and precision intervention strategies due to their central roles in tumor initiation, progression, metastasis, and therapeutic resistance. Given the limitations of conventional treatments, inadequate early detection methods, and significant inter-individual variability, elucidating the regulatory functions of ncRNA networks have become an urgent imperative for advancing cancer diagnosis and treatment. This review systematically integrates the regulatory mechanisms of miRNAs, lncRNAs, and circRNAs in key oncogenic processes from a pan-cancer perspective, including cell proliferation, cell cycle control, apoptosis evasion, metastatic activation, and resistance reprogramming, while highlighting their hub-like roles in multi-pathway crosstalk,the application of ncRNA in cancer diagnosis and its role in treatment and prognosis. Furthermore, future research must strive for breakthroughs in areas such as the optimization of nanodelivery systems, AI-driven target identification, and dynamic multi-omics integration, with the ultimate goal of achieving the systematic translation of ncRNAs into actionable strategies for personalized precision medicine-transforming "functional transcriptional regulation" into "targetable therapeutic intervention."

Blood-based biomarkers are an easily available and practical tool for Alzheimer's disease (AD) screening and diagnosis. Plasma phosphorylated Tau217 (p-tau217) is the front-runner candidate for AD diagnosis due to its strong correlation with core AD pathology determined either by cerebrospinal fluid biomarker (CSF) and positron emission tomography (PET) or postmortem examination. While plasma p-tau217 is firmly associated with AD pathology, it is crucial to evaluate its performance in distinguishing AD from mixed pathologies, as brain autopsies have shown the coexisting of AD pathology with other related types of dementia. Moreover, the measurement of AD biomarkers will be a crucial element in defining eligibility for disease-modifying treatment in clinical practice. Moreover, plasma p-tau217 is a highly efficacious biomarker in the early detection of Aβ pathology, making it a feasible test for AD screening in clinical practice. Several assays, including the ALZpath p-tau217 assay and the Fujirebio plasma p-tau217 assay, have been made commercially available for research use. A few studies analytically and clinically have validated these immunoassays as laboratory diagnostic tests for AD diagnosis and differentiating from non-AD neurodegenerative disorders in clinical practice.

Cancer is a major global public health problem. Epigenetic regulation, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA) dysregulation, is a main driver of tumorigenesis and progression. Recent studies are suggesting that the human microbiota, commonly referred to as a "super-organ," are not only associated with tumors but play an active role in regulating the epigenetic state of the host. The aim of this review is to systematically explain the main regulatory mechanisms of the "microbiota-epigenetic-cancer regulatory axis", their heterogeneous manifestations across various tumors, and the exploration of novel diagnostic biomarkers and therapeutic strategies of this regulatory axis. Microbiota mainly drive tumor epigenetic remodeling through three levels. First, microbial metabolites (e.g., butyrate) can act as natural histone deacetylase inhibitors (HDACis), or tryptophan metabolites can directly regulate the host chromatin state by activating the aryl hydrocarbon receptor (AhR) pathway. Second, bacterial structures such as lipopolysaccharide (LPS) can induce inflammation and disease by activating inflammatory signaling pathways. Third, specific pathogens like HBV and Helicobacter pylori can hijack the host's epigenetic machinery or induce epigenetic reprogramming via virulence factors. The tumor-resident microbiota (TRM) is an emerging and important field. TRM that actively partake in the tumor microenvironment (TME) may promote immune evasion through in situ mechanisms (e.g., lactylation), thereby confirming a direct and causal role for microbes within tumors. The epigenetic therapeutic strategies based on these mechanisms are being rapidly developed, including, for example, the regulation of microbial community structure (e.g., FMT), the targeting of microbial metabolic pathways, and TRM-specific approaches and key pathways (e.g., engineered bacteria). These strategies also have great potential as biomarkers for tumor prognosis prediction and therapy response evaluation. Overall, microbes and tumor epigenetics are part of a network that brings together their metabolism, inflammation, immunity, and gene regulation. Future research will shift from exploring the correlation of the gut microbiota at the macro level to exploring TRM's causality within the TME. By using gnotobiotic mouse models, organoid co-cultures, and multiomics, we will deeply analyze the microenvironment specificity of this network and develop precision interventions targeting TRM that could transform cancer therapy.

Laboratory diagnostics of diseases have improved significantly with modern laboratory techniques offering greater accuracy, earlier detection, and opportunities for personalized diagnosis. This review highlights the key techniques used in the diagnostics of autoimmune rheumatic diseases. Detection of autoantibodies is the basis for modern laboratory diagnostics of autoimmune rheumatic diseases. Immunofluorescent analysis, enzyme-linked immunosorbent assay, chemiluminescent immunoassay, and immunoblotting are nowadays common methods for differential diagnostics, screening, and monitoring the progression of autoimmune diseases. Polymerase chain reaction methods allow the identification of genetic markers associated with autoimmune disorders, which facilitates early diagnosis. Next Generation Sequencing allows for comprehensive analysis of genetic variants, identifying novel biomarkers, and furthering our understanding of disease mechanisms. Diagnostics and treatment are now approaching personalized medicine based mainly on modern molecular discoveries. Such an approach aims to determine disease risk, tailor treatment to individual patient needs, improve safety and efficacy, and reduce treatment costs. This review covers essential laboratory techniques for diagnosing autoimmune rheumatic diseases and aims to serve as a reliable resource for clinicians, including rheumatologists, and researchers.

Loop-mediated isothermal amplification (LAMP) has emerged as a rapid and accessible alternative to traditional polymerase chain reactions (PCR) for nucleic acid amplification in research, significantly enhancing pathogen detection in infectious disease diagnostics. This review aims to bridge the gap in the literature regarding the real-world applications of LAMP assays and their potential to improve infectious disease diagnostics across various healthcare settings. We evaluated the current landscape of United States Food and Drug Administration (FDA)-authorized LAMP-based microbial tests, categorizing 30 such tests and detailing their regulatory pathways, such as 510(k) clearance and Emergency Use Authorization (EUA), particularly in response to the COVID-19 pandemic. We comprehensively examine the technical characteristics of LAMP assays, including sample collection, nucleic acid extraction, amplification processes, signal detection, device automation, and their analytical and clinical performance. We highlight the versatility of LAMP assays in diagnostic applications and their growing role in rapid infectious disease. We discuss the advantages and limitations of LAMP technology and identify future directions for its development in infectious disease diagnostics. By analyzing FDA-authorized LAMP-based microbial tests, this review aims to guide healthcare professionals and support future research and product development, ultimately improving patient care.

Several immune/inflammatory components have been associated with arthritis. The role of monocytes/macrophages in inflammatory arthritis has been explored over the last years; however, the role of other myeloid cells, such as neutrophils and dendritic cells, in driving the pathophysiology of arthritis is largely overlooked. In this article, we aim to discuss literature pointing to the role of these immune cells in inflammatory arthritis and emphasize the multiple and dynamic phenotypic roles these cells can hold either in the persistence or in the resolution of inflammation. We also highlight the interactions between neutrophils, macrophages, and/or dendritic cells in the arthritic joint space. We further discuss pathways and features that may be of importance for characterizing neutrophils and dendritic cells, the phenotype of which can be "reprogrammed" to direct the resolution of inflammation efficiently in the arthritic joint. Identifying novel and patient-tailored approaches for addressing persistent or recurrent inflammation through these cellular pathways, might address unmet needs in arthritis management. Types of arthritides discussed in this review include osteoarthritis, spondyloarthritis and rheumatoid arthritis. Brief reference to the role of these immune cells in the acute gouty inflammation is also included.

Raman spectroscopy is an important diagnostic method that extracts molecular-level information from biological specimens, with distinct potential for disease diagnoses. However, its clinical application has been limited by the challenges associated with spectral interpretation. Deep learning (DL) represents an important new approach in which selected Raman spectroscopy experiments can be automated, offering the potential for higher classification accuracy. This paper highlights recent efforts toward the integration of Raman spectroscopy and DL for medical applications and elaborates on key DL models, including Convolutional Neural Networks (CNNs), Long Short-Term Memory (LSTMs), and Generative Adversarial Networks (GANs), which can collect relevant features, denoise spectra, and provide enhanced diagnostic value from biological specimens. The use of DL in Raman spectroscopy has produced impressive results in cancer diagnosis, bacterial identification, and viral diagnostics. Therefore, this paper provides an organized introduction to explore existing DL architectures used in Raman spectroscopy, their advantages and limitations, and opportunities for clinical applications. Collectively, DL with Raman spectroscopy provides a unique approach for noninvasive and reliable diagnostics.

Over the past 60 years, preventative public health screening programs have evolved since their inception and now include newborn screening (NBS) aimed at identifying infants after birth for a number of rare, congenital, inherited diseases. Most of the conditions detected through NBS are autosomal recessive disorders or exhibit X-linked inheritance, meaning that family members of individuals with these conditions have a higher risk for being either affected or obligate heterozygotes. For example, the X-linked adrenoleukodystrophy (X-ALD) in the screening panel identifies affected newborns and asymptomatic relatives through subsequent testing. Thus, NBS becomes a gateway to family-wide prevention, through the application of reverse cascade testing (RCS). In this paper we examined the scenarios where RCS may be appropriate. Accordingly, we have identified a list of criteria assessing whether a NBS disease would benefit from RCS: (1) autosomal recessive or X-linked inheritance; (2) high carrier rates, (3) variable expressivity, (4) mild or late-onset forms; and (5) association with diagnostic delays and recent addition to the screening panel. More than one criterion usually needs to be met for a disease to benefit from RCS. We have identified a list of diseases and highlighted the potential benefits of RCS: X-ALD, Cystic Fibrosis, Sickle Cell Disease, Spinal Muscular Atrophy and Pompe disease. There are additional scenarios within NBS where disease maternal conditions (3-methylcrotonyl-CoA carboxylase deficiency and carnitine uptake deficiency) or nutritional maternal conditions (vitamin B12 deficiency) may cause a screen-positive NBS result. Whenever a maternal nutritional deficiency is a potential reason for a positive NBS, this is indicative of a non-inherited condition that may require treatment in the newborn owing to possible neurological damage and delay in normal growth in newborns with certain secondary deficiencies. For these cases RCS is recommended, as the mother's status may put her at risk for future adverse events (i.e. cardiovascular and musculoskeletal disorders, hepatic involvement, and neurodegeneration). The RCS-NBS strategy discussed in this paper offers a set of criteria against which diseases can be assessed for the potential need for RCS. Implementation of this strategy requires several considerations including educational needs, ethical issues, uptake of testing, logistics and costs for this expanded screening and counseling, and availability of appropriate specialists for ongoing management.