Diagnostic Tool Research Articles

Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.

Thermophoretic Aggregation Imaging of Tumor-Derived Exosomes by CRISPR-Cas13a-Based Nanoprobes.

The inherent heterogeneity of tumor-derived exosomes holds great promise for enhancing the precision of cancer diagnostics. MicroRNAs (miRNAs) encapsulated in tumor-associated exosomes have emerged as valuable biomarkers for the early detection of cancers. Nevertheless, the flexible structure and inherent instability of RNA limit its application in biological diagnostics. The CRISPR-Cas13a system, distinguished by its target-responsive "collateral effect", represents a powerful tool for advancing cancer diagnostics. In this study, we harness the CRISPR-Cas13a system as an innovative signal amplification tool to image cancer-related exosomal miRNA in situ. Furthermore, we capitalize on the thermophoretic aggregation effect exhibited by gold nanoparticles (Au NPs) to consolidate the fluorescent signals generated by the CRISPR-Cas13a system. Subsequently, the developed nanoprobe is applied to detect lung cancer-related exosomal miRNA from human serum, enabling the aggregated visualization of low-abundance cancer exosomes in individuals with lung cancer compared with healthy individuals. This sensitive thermophoretic aggregation assay provides a diagnostic tool for lung cancer in the clinic.

A review of ADHD detection studies with machine learning methods using rsfMRI data.

Attention deficit hyperactivity disorder (ADHD) is a common mental health condition that significantly affects school-age children, causing difficulties with learning and daily functioning. Early identification is crucial, and reliable and objective diagnostic tools are necessary. However, current clinical evaluations of behavioral symptoms can be inconsistent and subjective. Functional magnetic resonance imaging (fMRI) is a non-invasive technique that has proven effective in detecting brain abnormalities in individuals with ADHD. Recent studies have shown promising outcomes in using resting state fMRI (rsfMRI)-based brain functional networks to diagnose various brain disorders, including ADHD. Several review papers have examined the detection of other diseases using fMRI data and machine learning or deep learning methods. However, no review paper has specifically addressed ADHD. Therefore, this study aims to contribute to the literature by reviewing the use of rsfMRI data and machine learning methods for detection of ADHD. The study provides general information about fMRI databases and detailed knowledge of the ADHD-200 database, which is commonly used for ADHD detection. It also emphasizes the importance of examining all stages of the process, including network and atlas selection, feature extraction, and feature selection, before the classification stage. The study compares the performance, advantages, and disadvantages of previous studies in detail. This comprehensive approach may be a useful starting point for new researchers in this area.

The challenge of diagnosing cultural syndromes: A narrative review.

In 2022 the total world migrant population was 281 million (an increase of approximately 62% compared to year 2000), of whom 169 million were migrant workers. The number of refugees, asylum seekers and others in need of international protection increased by 22% compared to 2021. Research has shown that the forcibly displaced have high rates of mental disorders (including depression, post-traumatic stress disorder (PTSD) and anxiety), with an estimated prevalence almost 6 to 7 times higher than the general population. Given the increase of the overall migration phenomenon and the challenge raised by the cultural features concerning mental health, we consider that this is an area that requires close attention to ensure that culturally sensitive health services be available to the migrant and displaced population. The aim of this narrative review is to provide a background to the issue and take stock of what is currently available in the literature regarding culture-bound illnesses and the relevant diagnostic tools. A comprehensive search was performed in PubMed, Psychinfo, Embase, Google Scholar, organized in stages to assure inclusion of all the relevant studies. Of the 703 papers initially identified, only 30 papers finally satisfied the inclusion criteria. Eleven diagnostic scales were found, only two of which are being used for displaced people. Further work is required in this field, including a debate as to whether scales are indeed an appropriate tool for use with this population.

High-frequency ultrasound imaging findings in the diagnosis of segmental schwannomatosis of the ulnar nerve: case report and literature review.

Schwannomatosis is characterized by the development of multiple schwannomas without evidence of vestibular tumors. Segmental schwannomatosis is defined as being limited to one limb or five or fewer contiguous segments of the spine. We report a case of a 20-year-old male with the painful masses of the left upper extremity with associated numbness and paresthesia in the ulnar nerve distribution. The high-frequency ultrasound showed that the ulnar nerve fascicles were enlarged and expanded with beadlike growth. The patient underwent surgery twice and all the tumors were pathologically confirmed to be schwannomas. Together, the medical history, imaging, and pathology findings indicated the diagnosis of segmental schwannomatosis. By the imaging diagnostic tools, MRI is the most commonly used in assistance with diagnosis of segmental schwannomatosis while high-frequency ultrasonography is rare. In this paper, we discuss the value of high-frequency ultrasonography in the diagnosis of this rare disease. This case report provides a deeper understanding of segmental schwannomatosis and may help improve the accuracy of preoperative diagnosis.

Automatic classification of seizure and seizure-free EEG signals based on phase space reconstruction features.

Epilepsy is a type of brain disorder triggered by an abrupt electrical imbalance of neuronal networks. An electroencephalogram (EEG) is a diagnostic tool to capture the underlying brain mechanisms and detect seizure onset in epileptic patients. To detect seizures, neurologists need to manually monitor EEG recordings for long periods, which is challenging and susceptible to errors depending on expertise and experience. Therefore, automatic identification of seizure and seizure-free EEG signals becomes essential. This study introduces a method based on the features extracted from the phase space reconstruction for classifying seizure and seizure-free EEG signals. The computed features are derived from the elliptical area and interquartile range of the Euclidean distance by varying percentage values of data points ranging from 50 to 100%. We consider two public datasets and evaluate these features in each EEG epoch that includes the healthy, interictal, preictal, and ictal stages of epileptic subjects, utilizing the K-nearest neighbor classifier for classification. Results show that the features have higher values during the seizure than the seizure-free EEG signals and healthy subjects. Furthermore, the proposed features can effectively discriminate seizure EEG signals from the seizure-free and normal subjects with 100% accuracy, sensitivity, and specificity in both datasets. Likewise, the classification between the preictal stage and seizure EEG signals attains 98% accuracy. Overall, the reconstructed phase space features significantly enhance the accuracy of detecting epileptic EEG signals compared with existing methods. This advancement holds great potential in assisting neurologists in swiftly and accurately diagnosing epileptic seizures from EEG signals.

Identifying and Validating Alcohol Diagnostics for Injury-Related Trauma in South Africa: Protocol for a Mixed Methods Study.

The burden of alcohol use among patients with trauma and the relative injury risks is not routinely measured in South Africa. Given the prominent burden of alcohol on hospital trauma departments, South Africa needs practical, cost-effective, and accurate alcohol diagnostic tools for testing, surveillance, and clinical management of patients with trauma. This study aims to validate alcohol diagnostics for injury-related trauma and assess its use for improving national health practice and policy. The Alcohol Diagnostic Validation for Injury-Related Trauma study will use mixed methods across 3 work packages. Five web-based focus group discussions will be conducted with 6 to 8 key stakeholders, each across 4 areas of expertise (clinical, academic, policy, and operational) to determine the type of alcohol information that will be useful for different stakeholders in the injury prevention and health care sectors. We will then conduct a small pilot study followed by a validation study of alcohol diagnostic tools (clinical assessment, breath analysis, and fingerprick blood) against enzyme immunoassay blood concentration analysis in a tertiary hospital trauma setting with 1000 patients. Finally, selected alcohol diagnostic tools will be tested in a district hospital setting with a further 1000 patients alongside community-based participatory research on the use of the selected tools. Pilot data are being collected, and the protocol will be modified based on the results. Through this project, we hope to identify and validate the most appropriate methods of diagnosing alcohol-related injury and violence in a clinical setting. The findings from this study are likely to be highly relevant and could influence our primary beneficiaries-policy makers and senior health clinicians-to adopt new practices and policies around alcohol testing in injured patients. The findings will be disseminated to relevant national and provincial government departments, policy experts, and clinicians. Additionally, we will engage in media advocacy and with our stakeholders, including community representatives, work through several nonprofit partners to reach civil society organizations and share findings. In addition, we will publish findings in scientific journals. DERR1-10.2196/52949.

Uses and limitations of small-volume biopsies for the diagnosis of lymphoma.

Although surgical biopsy remains the gold standard for the diagnosis of lymphoma, small-volume biopsies including fine-needle aspiration and core needle biopsy are increasingly being used as a first line diagnostic tool. Small-volume biopsies are safe, rapid and cost effective; however, diagnostic utility varies by lymphoma subtype. It is important for pathologists and clinicians to recognize both the strengths and limitations of such biopsies.

Unveiling the Potential of VELScope in Potentially Malignant Oral Lesion Early Detection for Future Dental Diagnosis Technology

Introduction: Oral lesions range from innocuous to possibly dangerous, including oral cancer, which is the world's 16th most common malignancy. Early detection of oral cancer can enhance a patient's life expectancy by a decade, emphasizing the need of diagnostic instruments like VELScope. VELScope is a portable device that employs blue light to examine oral tissue, exposing natural fluorescence and emphasizing aberrant regions that would otherwise be invisible without the use of specialized equipment. Objectives: This review looks at the possibility of the VELScope for identifying oral lesions, since it has the potential to be a future dental diagnostic tool. Method: We began with 88 findings and reduced them down to 33 research regarding VELScope technology published in the previous five years. Following screening, we chose ten articles using the same criteria for all research. Results: VELScope uses fluorescence to identify both obvious and concealed oral lesions, which is especially useful when collagen loss occurs in normal tissues. While using autofluorescence requires knowledge, it assists in analyzing margins in probable pre- malignant oral conditions. VELScope, despite its limitations, has promise for early cancer diagnosis as technology develops. Conclusion: When utilized for early diagnosis, VELScope helps to reduce oral cancer mortality, reaching an 83% 5-year survival rate. While it has limits, continuous technical improvements have the potential to improve its accuracy, making it a vital tool for accurate early diagnosis and lowering oral cancer mortality.

Inappropriate wrist MRI: did guidelines have an impact?

To assess the national prevalence and cost of inappropriate MRI in patients with wrist pain prior to and following American College of Radiology (ACR) guidelinepublication. We used administrative claims from the IBM MarketScan Research Databases to evaluate the appropriateness of wrist MRI in a national cohort of patients with commercial insurance or Medicare Advantage. Adult patients with a diagnosis of wrist pain between 2016 and 2019 were included and followed for 1year. We made assessments of appropriateness based on ACR guidelines for specific wrist pain etiologies. We tabulated the total costs and out-of-pocket expenses associated with inappropriate MRI studies using weighted mean payments for facility and professional fees. We performed segmented logistic regression on interrupted time series data to identify predictors of receiving inappropriate imaging and the impact of guideline publication on MRI use. The study cohort consisted of 867,119 individuals. Of these, 40,164 individuals (4.6%) had MRI, of whom 52.6% received an inappropriate study. Inappropriate studies accounted for $44,493,234 in total payments and $8,307,540 in out-of-pocket expenses. The interrupted time series found an approximately 1% monthly decrease in the odds of receiving an inappropriate study after guidelinedissemination. MRI as a diagnostic tool for wrist pain is often inappropriate and expensive. Our findings support interventions to increase guideline adherence, such as integrated clinical decision support tools.

Targeting the Warburg Effect in Cancer: Where Do We Stand?

The Warburg effect, characterized by the preferential conversion of glucose to lactate even in the presence of oxygen and functional mitochondria, is a prominent metabolic hallmark of cancer cells and has emerged as a promising therapeutic target for cancer therapy. Elevated lactate levels and acidic pH within the tumor microenvironment (TME) resulting from glycolytic profoundly impact various cellular populations, including macrophage reprogramming and impairment of T-cell functionality. Altogether, the Warburg effect has been shown to promote tumor progression and immunosuppression through multiple mechanisms. This review provides an overview of the current understanding of the Warburg effect in cancer and its implications. We summarize recent pharmacological strategies aimed at targeting glycolytic enzymes, highlighting the challenges encountered in achieving therapeutic efficacy. Additionally, we examine the utility of the Warburg effect as an early diagnostic tool. Finally, we discuss the multifaceted roles of lactate within the TME, emphasizing its potential as a therapeutic target to disrupt metabolic interactions between tumor and immune cells, thereby enhancing anti-tumor immunity.

Lectin: A Molecular Tool in Cancer Diagnosis and Therapy with Special Reference to Reproductive Cancers.

The prevalence of cancer deaths globally and domestically is higher especially due to the deferment of diagnosis and lack of facilities for women's reproductive cancers. The present review focussed to explore the application of lectins in cancer theranostics. Though there is cancer diagnostic and treatment available there is no promising early diagnostic tool and effective treatment available for the cancer which is the major concern. Lectins are cellulose-binding proteins that are strongly determined in saccharide groups of glycans, glycopeptides, or glycolipids. In the concomitance of events in cells, carbohydrates, and proteins, lectins play an important role. Lectins bind superiorly to the cancer cell membrane and their receptors induce the cytotoxic effect, which results in caspase-mediated cell death, and prohibits tumour development. Lectin snuffing also reveals polyamine stocks and impedes the growth of cancerous cells. They affect the cell cycle by non-apoptotic aggregation, seizure of the cell cycle phase G2, M, and the mediation of caspases. It can also adversely affect the action of telomerase and hinder vascularisation. They promote immunomodulation and adversely limit protein synthesis. Their easy availability and its characteristics support its use in cancer diagnosis and therapy, despite their small corollary effects. Future investigations recommend focussing more on the key applications of lectin by reducing its concurrent effects and carrying out more in-vitro investigations. However, the use of lectin formulations for cancer theranostics is a new area in cancer detection and treatment. In this review, plant lectin appears to be a potential target for cancer research in the fields of diagnosis and theranostics.

Decrease of exosomal miR-21-5p and the increase of CD62p+ exosomes are associated with the development of sepsis in polytraumatized patients

Sepsis as a severe systemic inflammation leads oftentimes to organ dysfunction and subsequently to death. In polytrauma patients, septic complications represent with 45% the predominant cause of late death and are responsible for extremely high costs in the healthcare system. Therefore, clinicians have to detect as early as possible the begin of sepsis to improve the patient's outcome. One new promising diagnostic tool to diagnose septic complications in polytraumatized patients are exosomes.Plasma samples from polytraumatized patients (Injury Severity Score (ISS) ≥16) which developed sepsis (n = 10) and without sepsis (n = 10), were collected at emergency room (ER), 24h and 5 days after trauma. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with plasma EVs from healthy controls (n = 10). Moreover, exosomal cytokine concentrations were measured via high-sensitive ELISA and were correlated with systemic concentrations. For miRNA cargo analysis, we analysed the miRNAs miR-1298-5p, miR-1262, miR-125b-5p, miR-92a-3p, miR-93-5p, miR-155-5p and miR-21-5p and compared their exosomal concentrations by means of RT-qPCR.CD62p + exosomes were significantly increased in septic polytrauma-patients (p ≤ 0.05), while CD40+exosomes, as well as CD49e + exosomes were diminished (p ≤ 0.05). Furthermore, we observed that the exosomal IL-6 concentration reflects the systemic IL-6 concentration (r2 = 0.63) and did not significantly alter between patients with and without sepsis. The exosomal IL-10 concentration seemed to be constant in all patients and healthy controls. We observed that a decrease of miR-21-5p in exosomes was associated with the development of sepsis (p ≤ 0.05), while exosomal miR-93-5p, miR-155-5p and miR-92a-3p were not specifically altered in septic patients.Taken together, the present study in polytraumatized patients demonstrated that the development of sepsis is associated with an increase of CD62p + exosomes. Furthermore, the exosomal cargo was changed in septic patients: miR-21-5p was diminished.

Article Review: Multiple Sclerosis

Neurology still puzzles about multiple sclerosis (MS). This comprehensive overview explores MS's history, epidemiology, etiology, clinical manifestations, diagnostic tools, and treatment options. From historical awareness to cutting-edge research, we traverse MS's complex world with a focus on the past and future. Genetics, environment, and migration interact to create geographic riddles in MS prevalence. MS's sensory and cognitive symptoms show its significant influence. Advanced imaging technology and diagnostic criteria enable accurate and quick identification. While transformational, disease-modifying treatments require a tailored approach. Advances have left crucial gaps, prompting researchers, physicians, and policymakers to continue. This in-depth investigation of MS combines historical and future perspectives to emphasize the urgency and possibility of solving this complicated neurological puzzle.

TFCP2 as a therapeutic nexus: unveiling molecular signatures in cancer.

Tumor suppressor genes and proto-oncogenes comprise most of the complex genomic landscape associated with cancer, with a minimal number of genes exhibiting dual-context-dependent functions. The transcription factor cellular promoter 2 (TFCP2), a pivotal transcription factor encoded by the alpha globin transcription factor CP2 gene, is a constituent of the TFCP2/grainyhead family of transcription factors. While grainyhead members have been extensively studied for their crucial roles in developmental processes, embryogenesis, and multiple cancers, the TFCP2 subfamily has been relatively less explored. The molecular mechanisms underlying TFCP2's involvement in carcinogenesis are still unclear even though it is a desirable target for cancer treatment and a therapeutic marker. This comprehensive literature review summarizes the molecular functions of TFCP2, emphasizing its involvement in cancer pathophysiology, particularly in the epithelial-mesenchymal transition and metastasis. It highlights TFCP2's critical function as a regulatory target and explores its potential as a prognostic marker for survival and inflammation in carcinomas. Its ambiguous association with carcinomas underlines the urgent need for an in-depth understanding to facilitate the development of more efficacious targeted therapeutic modality and diagnostic tools. This study aims to elucidate the multifaceted effects of TFCP2 regulation, through a comprehensive integration of the existing knowledge in cancer therapeutics. Furthermore, the clinical relevance and the inherent challenges encountered in investigating its intricate role in cancer pathogenesis have been discussed in this review.

Design of sonochemical assisted synthesis of Zr-MOF/g-C3N4-modified electrode for ultrasensitive detection of antipsychotic drug chlorpromazine from biological samples.

Therapid fabrication is describedof binary electrocatalyst based on a highly porous metal-organic framework with zirconium metal core (Zr-MOF) decorated over the graphitic carbon nitride (g-C3N4) nanosheets via facile ultrasonication method. It is used for the robust determination of antipsychotic drug chlorpromazine (CLP) from environmental samples. The electrochemical behaviour of 2D Zr-MOF@g-C3N4 was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) studies. The crystalline and porous nature of the composite was characterized by XRD and SEM analysis. The functional groups and surface characteristics were investigated by FT-IR, Raman and XPS. The major electrochemical properties of the Zr-MOF@g-C3N4 composite towards CLP detection were analyzed by CV, chronocoulometric (CC), chronoamperometric (CA) and differential pulse voltammetry (DPV) techniques. The composite exhibits a low detection limit (LOD) of 2.45nM with a linear range of 0.02 to 2.99µM and attractive sensitivity for CLP. The sensor system shows higher selectivity towards the possible interferences of CLP drug and exhibits betterrepeatability and stability. Finally, the fabricated sensor system shows a high recovery range varying from 96.2 to 98.9% towards the real samples. The proposed electrochemical probe might be a promising alternative to the prevailing diagnostic tools for the detection of CLP.

Hybrid Materials From Peptide Nanofibrils and Magnetic Beads to Concentrate and Isolate Virus Particles

AbstractPeptide nanofibrils (PNFs) are considered a novel and highly efficient class of retroviral transduction enhancers due to their ability to efficiently bind virus particles and promote their attachment to the membrane of target cells. In this study, the virus‐binding properties of enhancing factor C (EF‐C) PNFs are used to develop a method for concentrating and isolating HIV‐1 particles without the need for centrifugation. Upon incubation in a virus‐laden sample, PNF‐coated magnetic beads facilitate magnetic separation, effectively depleting virus particles from the solution and consequently reducing its infectious nature. Remarkably, the isolated virus particles maintain their infectivity and exhibit an enhanced ability to infect target cells due to the complexation with EF‐C PNFs. This enhancement is pivotal for further virus propagation in cell cultures or detailed analysis. The presented method addresses the urgent need for more rapid, sensitive detection, and purification technologies for viral agents. It provides a tool to efficiently capture, isolate, and concentrate HIV‐1 particles. This may significantly improve the sensitivity of existing diagnostic tools and analytical tests.

Comparison of the Discrimination Performance of AI Scoring and the Brixia Score in Predicting COVID-19 Severity on Chest X-Ray Imaging: Diagnostic Accuracy Study.

The artificial intelligence (AI) analysis of chest x-rays can increase the precision of binary COVID-19 diagnosis. However, it is unknown if AI-based chest x-rays can predict who will develop severe COVID-19, especially in low- and middle-income countries. The study aims to compare the performance of human radiologist Brixia scores versus 2 AI scoring systems in predicting the severity of COVID-19 pneumonia. We performed a cross-sectional study of 300 patients suspected with and with confirmed COVID-19 infection in Jakarta, Indonesia. A total of 2 AI scores were generated using CAD4COVID x-ray software. The AI probability score had slightly lower discrimination (area under the curve [AUC] 0.787, 95% CI 0.722-0.852). The AI score for the affected lung area (AUC 0.857, 95% CI 0.809-0.905) was almost as good as the human Brixia score (AUC 0.863, 95% CI 0.818-0.908). The AI score for the affected lung area and the human radiologist Brixia score had similar and good discrimination performance in predicting COVID-19 severity. Our study demonstrated that using AI-based diagnostic tools is possible, even in low-resource settings. However, before it is widely adopted in daily practice, more studies with a larger scale and that are prospective in nature are needed to confirm our findings.

Performance evaluation of the SMG HHV-6 Q Real-Time PCR Kit for quantitative detection and differentiation of human herpesvirus 6A and 6B.

The aim of this study was to compare the performance of the newly developed SMG HHV-6 Q Real-Time PCR Kit (SMG assay) with the RealStar HHV-6 PCR Kit (RealStar assay). The analytical sensitivity and specificity, linearity, and precision of the SMG assay were evaluated. The clinical performance of the SMG assay was assessed and compared with that of the RealStar assay using 207 clinical specimens (HHV-6A positive, n = 51; HHV-6B positive, n = 64; HHV-6A/B negative, n = 92). The limit of detection of the SMG assay was 2.92 log10 copies/mL for HHV-6A DNA and 2.88 log10 copies/mL for HHV-6B DNA. The linear range was determined to be 3.40-9.00 log10 copies/mL for both viruses. Intra- and inter-assay variability were below 5% at concentrations ranging from 4 to 9 log10 copies/mL. No cross-reactivity was observed with the 25 microorganisms included in the specificity panel. The clinical sensitivity and specificity of the SMG and RealStar assays compared to in-house polymerase chain reaction and sequencing were as follows: SMG assay, 98.0% and 100% for HHV-6A DNA, respectively, and 96.9% and 100% for HHV-6B DNA, respectively; RealStar assay, 98.0% and 100% for HHV-6A DNA, respectively, and 90.6% and 100% for HHV-6B DNA, respectively. The correlation coefficients between viral loads measured by the two assays were 0.948 and 0.975, with mean differences of 0.62 and 0.32 log10 copies/mL for HHV-6A and HHV-6B DNA, respectively. These results demonstrate that the SMG assay is a sensitive and reliable tool for the quantitative detection and differentiation of HHV-6A and HHV-6B DNA.IMPORTANCEQuantitative real-time PCR (qPCR) that can distinguish between HHV-6A and HHV-6B DNA is recommended for diagnosis of active infection. The SMG HHV-6 Q Real-Time PCR Kit (SMG assay) is a newly developed qPCR assay that can differentiate between HHV-6A and HHV-6B DNA; however, little is known about its performance. In this study, we assessed the performance of the SMG assay and compared it with that of a commercially available qPCR assay, the RealStar HHV-6 PCR Kit (RealStar assay). The SMG assay demonstrated excellent analytical sensitivity and specificity, precision, and linearity. Furthermore, the viral loads measured by the SMG assay were highly correlated with those measured by the RealStar assay. Our results suggest that the SMG assay is a useful diagnostic tool for quantitative detection and differentiation of HHV-6A and HHV-6B DNA.

Diagnosis of human brucellosis: Systematic review and meta-analysis.

Brucellosis, a widely spread zoonotic disease, poses significant diagnostic challenges due to its non-specific symptoms and underreporting. Timely and accurate diagnosis is crucial for effective patient management and public health control. However, a comprehensive comparative review of available diagnostic tests is lacking. This systematic review addressed the following question: 'What is the accuracy of the available tests to confirm human brucellosis?' Two independent reviewers examined articles published up to January 2023. The review included original studies reporting symptomatic patients with brucellosis suspicion, through any index test, with sensitivity and/or specificity as outcomes. As exclusion criteria were considered: sample size smaller than 10 patients, studies focusing on complicated brucellosis, and those lacking essential information about index or comparator tests. Sensitivity and specificity were assessed, with consideration for the index test, and 'culture' and 'culture and standard tube agglutination test (SAT)' were used as reference standards. Bias assessment and certainty of evidence were carried out using the QUADAS-2 and GRADE tools, respectively. A total of 38 studies reporting diagnostic test performance for human brucellosis were included. However, the evidence available is limited, and significant variability was observed among studies. Regarding the reference test, culture and/or SAT are deemed more appropriate than culture alone. Rose Bengal, IgG/IgM ELISA, and PCR exhibited equally high performances, indicating superior overall diagnostic accuracy, with very low certainty of the evidence. This systematic review underscores the potential of the Rose Bengal test, IgG/IgM ELISA, and PCR as promising diagnostic tools for brucellosis. However, the successful implementation and recommendations for their use should consider the local context and available resources. The findings highlight the pressing need for standardization, improved reporting, and ongoing advancements in test development to enhance the accuracy and accessibility of brucellosis diagnosis.