Clinica Chimica Acta最新文献

The detection of 17β-estradiol (E2), a potent endocrine-disrupting compound, is critical for both environmental monitoring and biomedical diagnostics. Traditional detection methods often suffer from limitations in sensitivity, selectivity, and cost-effectiveness. Aptasensors, which utilize aptamers as biorecognition elements, offer promising alternatives because of their high specificity, stability, and adaptability. This paper explores recent advancements in aptasensor technologies for E2 detection, highlighting optical, electrochemical, and surface-enhanced Raman scattering (SERS)-based platforms. The integration of nanomaterials such as gold nanoparticles, carbon dots, and conductive polymers significantly enhances sensor performance, achieving ultralow detection limits and broad dynamic ranges. By leveraging these innovations, aptasensors provide scalable solutions for real-time monitoring of E2 in environmental, food, and clinical samples, paving the way for improved endocrine regulation and public health safety.

Sickle cell disease (SCD) is a severe hereditary hemoglobinopathy with the highest burden in sub-Saharan Africa. Timely diagnosis via newborn screening is critical to enabling low-cost, life-saving interventions, yet its implementation remains inconsistent worldwide. This study assessed the performance and analytical stability of dried blood spot (DBS) samples collected on Guthrie cards for quantifying hemoglobin S (Hb S), using three high-performance liquid chromatography (HPLC) platforms and one capillary electrophoresis system. Simulated neonatal samples at three Hb S concentrations (non-carrier, carrier, and affected) were analyzed at three timepoints (immediate, 1 week, and 2 weeks post-collection). Across all methods, Hb S quantification was highly reproducible, with inter-timepoint variation remaining within the predefined critical threshold for the vast majority of the measurements. While minor discrepancies were observed for fetal hemoglobin (Hb F), all methods correctly classified samples for SCD screening purposes. These findings confirm that Guthrie card-based DBS is a robust and practical matrix for Hb S detection, suitable for transport and delayed analysis-even across different analytical platforms. Limitations include the use of spiked rather than native SCD neonatal samples and ambient-temperature shipping. Nonetheless, the results support broader adoption of DBS in SCD screening programs, particularly in low-resource or decentralized settings, and highlight the need for further standardization of Hb F quantification.

The irreversibility and lethality of Spinal Muscular Atrophy (SMA) underscore the urgency of newborn screening, as diagnostic delay in neonates causes irreversible motor neuron degeneration and poor outcomes. Current SMA detection methods are hindered by high costs, dependence on specialized equipment, and technical complexity, restricting their implementation in primary care setting. Here, we proposed a fast and sensitive SMA-(Recombinase Polymerase Amplification) RPA-Cas12a detection assay based on suboptimal protospacer adjacent motif (sPAM) and 3'-end ssDNA-modified crRNA, named SPSMC. The crRNA is designed based on the sPAM to enhance the specificity of SMN1 gene detection. The competition between RPA and Cas12a digestion for target DNA was resolved by using 3'-end ssDNA-modified crRNA. With ALB as a reference gene, this method can detect DNA at concentrations as low as 1.8 pM within 1 h. The sensitivity and specificity of the proposed method in differentiating SMA patients from non-SMA individuals were both 100 %. This strategy has been used for the detection of the SMN1 gene, which saves time, reduces contamination risks, and offers new possibilities for future point-of-care screening of SMA. In addition, the SPSMC system was successfully adapted to SMA lateral flow assay format and validated using 66 clinical samples, demonstrating 100 % sensitivity and specificity. The method is straightforward to perform, requires no bulky equipment, maintains full portability, and is more suitable for large-scale neonatal screening scenarios compared with traditional methods.

Background: Biological reference intervals (RIs) are fundamental tools in clinical diagnostics, traditionally derived from geographically and ethnically homogeneous populations, predominantly of Western origin. Such generalized RIs often fail to account for variations arising from genetic, environmental, and lifestyle factors, which can impact clinical decision-making and contribute to health inequities, particularly in countries across Africa, India, and many other Southeast Asian nations. This scoping review investigates ethnicity-based variations in RIs for a range of biomarkers to highlight the importance of population-specific RIs.

Methods: Adhering to the Joanna Briggs Institute (JBI) guidelines, this scoping review examined the literature on ethnicity-based RI variations across multiple biomarkers, including Von Willebrand factor, C-reactive protein, thyroid-stimulating hormone, albumin, creatinine, and more. Studies were identified via searches in MEDLINE (via PubMed), Embase, Scopus, and Web of Science up to December 30, 2024. Eligibility was determined using the Population-Concept-Context (PCC) framework, focusing on observational studies analysing ethnicity-specific differences. Data extraction and charting were performed using CADIMA software, with independent review by two authors to ensure consistency.

Results: Out of 4,514 articles, a total of 15 studies met the inclusion criteria, encompassing multi-ethnic populations. Significant variations in biomarker levels were observed across ethnic groups, highlighting the inadequacy of generalized RIs. Notable differences included variations in lipid profiles, vitamin B12, and anti-Mullerian hormone levels. Regional distribution analysis highlighted gaps in research from underrepresented ethnic populations.

Conclusion: This review emphasizes the critical need for ethnicity-specific RIs to improve diagnostic accuracy and promote equitable healthcare outcomes. Further research should focus on developing robust methodologies for establishing inclusive and representative RIs.

Traumatic brain injury (TBI) poses a significant global health challenge, leading to high mortality and morbidity rates. Despite extensive research, effective diagnostic and therapeutic strategies remain limited. This review explores the emerging roles of exosomal non-coding RNAs (ncRNAs) as biomarkers and therapeutic agents in TBI. Exosomes, small extracellular vesicles secreted by various cell types, facilitate intercellular communication and carry diverse ncRNAs that modulate gene expression and cellular functions. The pathogenesis of TBI involves complex inflammatory cascades, in which exosomal ncRNAs play pivotal roles in neuroinflammation, neuronal apoptosis, and secondary injury mechanisms. Key ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been identified as potential biomarkers for diagnosing TBI and predicting outcomes. Additionally, exosomal ncRNAs derived from mesenchymal stem cells (MSCs) show promise in promoting neuroprotection and enhancing recovery through various mechanisms. The review highlights the potential of exosomal ncRNAs in addressing critical unmet needs in TBI management, emphasizing their stability, accessibility, and relevance to disease pathophysiology. However, challenges in standardization, validation, and regulatory pathways must be addressed to facilitate their clinical application. This comprehensive examination underscores the transformative potential of exosomal ncRNAs in TBI diagnosis and treatment, paving the way for future research and clinical innovations.

Objective: This study aimed to assess the infection status and clinical manifestations of Pseudomonas aeruginosa (P.a.) in hospitalized children with respiratory tract infections.

Methods: Between April 2021 and November 2023, a total of 5,021 hospitalized children with acute respiratory tract infections were collected at the Guangxi Maternal and Child Health Hospital. tNGS was used to detect pathogens in their respiratory samples.

Results: Among the 5,021 hospitalized children with acute respiratory tract infections, P.a. was detected in 113 cases, with a detection rate of 2.25 %. The infected children were mainly infants under 1 year old, and males were predominant. Among the 113 P.a. positive cases, there was 1 case of single P.a. infection and 112 cases of co-infection with other pathogens. In infection patterns, the P.a.-bacteria-virus co-infection is relatively common. A total of 53 different pathogens were identified in children with mixed P. aeruginosa infections, with Human Herpesvirus 5 (observed in 40 cases) being the most prevalent, followed by Acinetobacter baumannii (39 cases) and Mycoplasma pneumoniae (24 cases). Among children with P. aeruginosa infection, the most common respiratory complications included sinusitis, respiratory failure, and pulmonary consolidation. In contrast, the most frequent complications affecting other systems were electrolyte disturbances, gastrointestinal dysfunction, anemia, and myocardial damage. The median duration of hospitalization for the 113 children was 8 days. Out of 113 children with P.a. infection, 55 cases (48.67 %) required respiratory support and 18 cases (15.93 %) required intensive care unit (ICU) admission.

Conclusion: The detection rate of P.a. in hospitalized children with respiratory tract infections was 2.25 %. Almost all hospitalized children with P.a. respiratory tract infections had co-infections with other pathogens. The median duration of hospitalization was 8 days. 15.93 % of hospitalized children with P.a. infection required intensive care.

Quantitation of fecal elastase 1 (FE-1) is a non-invasive test for pancreatic function to detect moderate or severe exocrine insufficiency. The enzyme-linked immunosorbent assays (ELISA) are well-established tests for FE-1 detection. Traditional sample preparation by manual weighing and extraction is laborious, but new sample devices allow more effective sample preparation. FE-1 in stool has good stability but systematic studies on FE-1 stability in sampling and extraction devices are lacking. We examined the stability of FE-1 in the IDK Extract® device and intact stool samples at room temperature, 4 °C or -20 °C. Furthermore, we assessed the suitability of the IDK Extract® device for FE-1 testing and compared the performance of IDK FE-1 ELISA to that of the established ScheBo assay. FE-1 is stable in IDK Extract® device and intact stool for at least 29 days at all storage temperatures tested with deviation < 20 % from day zero concentration. When compared to weighing, the IDK Extract® device proved to be a reliable tool for sample preparation. Based on common clinical decision limits of pancreatic exocrine function, the ScheBo and IDK assays showed good agreement. In conclusion, IDK FE-1 assay together with the IDK Extract® device offers an effective and reliable method to determine exocrine pancreatic insufficiency. FE-1 is stable at various temperatures and the IDK and ScheBo assays perform equally. Thus, stool samples from outpatient clinics can be transported to the analytical laboratory cost-effectively at room temperature.

Despite the central role of biological samples in biomedical discovery, many research laboratories operate without robust sample storage systems. This compromises sample integrity, reproducibility, biosafety, and the long-term utility of the data. Implementing structured sample storage policies and infrastructure is crucial for maintaining scientific quality, ensuring regulatory compliance, and promoting responsible research conduct. It would be highly beneficial for any research laboratory to transition from sample storage to the implementation of a formal biobank. Biobanks constitute a critical infrastructure for biomedical research, as they systematically store biological specimens and databases, which are essential for maximizing utility in clinical investigations and facilitating international collaborative efforts. Most countries lack biobank-specific regulatory frameworks, which limits the ability to implement concurrent initiatives in line with international standards. Integrating quality management systems is essential for ensuring specimen quality and security. In this study, we analyzed the importance of the sample storage conditions and the steps required to transition to a formal biobank. We proposed a guide for doing so in the absence of a regulatory framework, based on the ISO 20387:2018 model, and included an example of successful implementation. We integrated environmental sustainability considerations and inter-institutional networking as a strategy for enhancing operational efficiency. Transforming an internal sample storage system into a formal biobank is a strategic and scientific advancement. It ensures that biological materials are managed with the rigor, transparency, and ethical responsibility required by contemporary biomedical research. By doing so, research institutions strengthen their capacity for innovation and collaboration.

Viral pandemics pose severe threats to human health and societal stability, exemplified by the COVID-19 outbreak in 2019. Conventional viral detection methods such as Polymerase chain reaction (PCR) typically require trained personnel, expensive equipment, and 2-4 h for processing. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) and Argonaute (Ago) system-based detection methods achieve attomolar sensitivity or single-copy detection limits with single-base specificity within 1 h, without requiring complex or costly instruments. This review firstly introduces the mechanisms and functions of CRISPR/Cas systems (Cas9, Cas12, Cas13) and Ago systems. It also introduces viruses with significant social impact, and continued with reviewing applications of these systems in single and multiplex virus detection. Single viral detection includes recently developed DNA/RNA-activated Cas9 detection (DACD/RACD) using Cas9 trans-cleavage activity, Cas12-based DNA Endonuclease-targeted CRISPR Trans Reporter (DETECTR) with attomolar sensitivity, CRISPR/Cas13a-based Fluorescent Nanoparticle SARS-CoV-2 (CFNS) achieving 1 copy/mL sensitivity with quantum dot reporters, and amplification-free mobile phone detection detecting 31 copies/μL without amplification. Multiplex viral detection includes Microfluidic Device Integrated with CRISPR/Cas12a and Multiplex Recombinase Polymerase Amplification (MiCaR) enabling 30-plex detection through microfluidic chips with spatial discrimination, PfAgo-mediated Nucleic acid Detection (PAND) utilizing Ago-produced guide sequences for 5-plex detection, Specific High-Sensitivity Enzymatic Reporter UnLOCKing v2 (SHERLOCKv2) achieving 4-plex detection with multi-enzyme single-reaction systems, and Multiplexed Evaluation of Nucleic acids (CARMEN) supporting over 100 target assays. Finally, this review discusses challenges in CRISPR/Cas and Ago-based detection methods, including Protospacer Adjacent Motif (PAM) sequence requirements for Cas9/12, prolonged reaction times due to nucleic acid extraction/amplification, and instability of core components like nucleases and crRNAs. Detection specificity and multiplex capabilities could be further improved. Future directions are outlined for improving detection specificity, developing multiplex capabilities and advancing POCT. Developing diagnostic tools using CRISPR/Cas and Ago systems could transform molecular diagnostics, such tools promise to be easily accessible worldwide. They are essential for precise identification and strategic containment of infectious disease transmission.