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Search Results (1,234)

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Keywords = point-of-care diagnostics

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14 pages, 1250 KiB  
Article
Acute Coronary Syndrome After Aneurysmal Subarachnoid Hemorrhage: Incidence, Risk Factors and Impact on the Outcome
by Džiugas Meška, Sebastian Schroer, Svenja Odensass, Meltem Gümüs, Christoph Rieß, Thiemo F. Dinger, Laurèl Rauschenbach, Adrian Engel, Marvin Darkwah Oppong, Yahya Ahmadipour, Yan Li, Philipp Dammann, Ulrich Sure and Ramazan Jabbarli
Medicina 2024, 60(11), 1862; https://doi.org/10.3390/medicina60111862 - 14 Nov 2024
Viewed by 310
Abstract
Background and Objectives: Development of acute coronary syndrome (ACS) after aneurysmal subarachnoid hemorrhage (aSAH) strongly affects further neuro-intensive care management. We aimed to analyze the incidence, risk factors and clinical impact of ACS in aSAH patients. Materials and Methods: This retrospective analysis included [...] Read more.
Background and Objectives: Development of acute coronary syndrome (ACS) after aneurysmal subarachnoid hemorrhage (aSAH) strongly affects further neuro-intensive care management. We aimed to analyze the incidence, risk factors and clinical impact of ACS in aSAH patients. Materials and Methods: This retrospective analysis included 855 aSAH cases treated between 01/2003 and 06/2016. The occurrence of ACS during 3 weeks of aSAH was documented. Patients’ demographic, clinical, radiographic and laboratory characteristics at admission were collected as potential ACS predictors. The association between ACS and the aSAH outcome was analyzed as the occurrence of cerebral infarcts in the computed tomography scans and unfavorable outcome (modified Rankin scale > 3) at 6 months after aSAH. Univariable and multivariable analyses were performed. Results: ACS was documented in 28 cases (3.3%) in the final cohort (mean age: 54.9 years; 67.8% females). In the multivariable analysis, there was a significant association between ACS, an unfavorable outcome (adjusted odds ratio [aOR] = 3.43, p = 0.027) and a borderline significance with cerebral infarcts (aOR = 2.5, p = 0.066). The final prediction model for ACS occurrence included five independent predictors (age > 55 years [1 point], serum sodium < 142 mmol/L [3 points], blood sugar ≥ 170 mg/dL [2 points], serum creatine kinase ≥ 255 U/L [3 points] and gamma-glutamyl transferase ≥ 36 U/L [1 point]) and showed high diagnostic accuracy for ACS prediction (AUC = 0.879). Depending on the cumulative score value, the risk of ACS in the cohort varied between 0% (0 points) and 66.7% (10 points). Conclusions: ACS is a rare, but clinically very relevant, complication of aSAH. The development of ACS can reliably be predicted by the presented prediction model, which enables the early identification of aSAH individuals at high risk for ACS. External validation of the prediction model is mandatory. Full article
(This article belongs to the Section Neurology)
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<p>Histogram representing ACS risk score value distribution in the study population.</p>
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<p>ROC curve showing a good diagnostic accuracy of the novel risk score for ACS prediction, with the area under the curve of 0.897 (<span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Bar chart showing the rates of ACS (gray bars) in the study population depending on the value of the ACS risk score.</p>
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14 pages, 623 KiB  
Review
The Unique Challenge of Coronary Artery Disease in Adult Patients with Congenital Heart Disease
by Nunzia Borrelli, Assunta Merola, Rosaria Barracano, Michela Palma, Ippolita Altobelli, Massimiliana Abbate, Giovanni Papaccioli, Giovanni Domenico Ciriello, Carmen Liguori, Davide Sorice, Lorenzo De Luca, Giancarlo Scognamiglio and Berardo Sarubbi
J. Clin. Med. 2024, 13(22), 6839; https://doi.org/10.3390/jcm13226839 - 14 Nov 2024
Viewed by 368
Abstract
Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review [...] Read more.
Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review provides insight into the complex interactions between coronary artery disease and CHD in adults. We describe the peculiar features of cardiac anatomy in these patients, the possible role cardiac sequelae may play in an increased risk of myocardial ischemia, and the diagnostic challenges in this patient group. Furthermore, this review outlines the risk factors and potential mechanisms of accelerated atherosclerosis in adults with CHD by pointing out areas where current knowledge is incomplete and highlighting areas for further research. The review concludes by examining potential management strategies for this particular population, emphasizing the necessity for a multidisciplinary approach. Understanding the unique coronary risks that adults with CHD experience can enhance patient care and improve long-term results. Full article
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<p>Coronary artery disease determinants in patients with congenital heart disease.</p>
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19 pages, 9106 KiB  
Review
Chemical Heating for Minimally Instrumented Point-of-Care (POC) Molecular Diagnostics
by Michael G. Mauk, Felix Ansah and Mohamed El-Tholoth
Biosensors 2024, 14(11), 554; https://doi.org/10.3390/bios14110554 - 13 Nov 2024
Viewed by 415
Abstract
The minimal instrumentation of portable medical diagnostic devices for point-of-care applications is facilitated by using chemical heating in place of temperature-regulated electrical heaters. The main applications are for isothermal nucleic acid amplification tests (NAATs) and other enzymatic assays that require elevated, controlled temperatures. [...] Read more.
The minimal instrumentation of portable medical diagnostic devices for point-of-care applications is facilitated by using chemical heating in place of temperature-regulated electrical heaters. The main applications are for isothermal nucleic acid amplification tests (NAATs) and other enzymatic assays that require elevated, controlled temperatures. In the most common implementation, heat is generated by the exothermic reaction of a metal (e.g., magnesium, calcium, or lithium) with water or air, buffered by a phase-change material that maintains a near-constant temperature to heat the assay reactions. The ability to incubate NAATs electricity-free and to further to detect amplification with minimal instrumentation opens the door for fully disposable, inexpensive molecular diagnostic devices that can be used for pathogen detection as needed in resource-limited areas and during natural disasters, wars, and civil disturbances when access to electricity may be interrupted. Several design approaches are reviewed, including more elaborate schemes for multiple stages of incubation at different temperatures. Full article
(This article belongs to the Special Issue Biosensors Based on Isothermal Nucleic Acid Amplification Strategies)
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<p>Electrical heating vs. chemical heating for point-of-care testing (POCT).</p>
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<p>(<b>A</b>) Sample time–temperature profiles for chemical self heating showing various figures of merit: rise time <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>t</mi> </mrow> <mrow> <mi>R</mi> </mrow> </msub> </mrow> </semantics></math>, overshoot <math display="inline"><semantics> <mrow> <mo>∆</mo> <mi>M</mi> </mrow> </semantics></math>, tolerance band <math display="inline"><semantics> <mrow> <mo>Δ</mo> <mi>T</mi> </mrow> </semantics></math>, and incubation time <math display="inline"><semantics> <mrow> <msub> <mrow> <mi>t</mi> </mrow> <mrow> <mi>I</mi> </mrow> </msub> </mrow> </semantics></math> (time spent within tolerance temperature range). Two example cases: Curve 1 shows a fast ramp-up, but with overshoot and a long incubation time. Curve 2 shows a slow ramp-up and insufficient incubation time before cooling below the tolerance band. (<b>B</b>) Example of the optimization of the time–temperature in the system shown: 10.5 g of PCM, 1.4 g of Mg:Fe powder, and 4 mL, 6 mL, and 8 mL of water added [<a href="#B37-biosensors-14-00554" class="html-bibr">37</a>].</p>
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<p>Three configurations for chemical heating with PCMs. (<b>A</b>) sample embedded in reactants and temperature buffered by thermal contact with phase-change material (PCM), (<b>B</b>) sample surrounded by PCM, which in turn is melted through contact with reactants, and (<b>C</b>) mixture of fuel and PCM powders (e.g., Li et al. [<a href="#B37-biosensors-14-00554" class="html-bibr">37</a>]). Sample can be viewed (to monitor fluorescence of color change) either through tube lid, or from side through viewing port.</p>
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34 pages, 4136 KiB  
Review
Synthesis, Functionalization, and Biomedical Applications of Iron Oxide Nanoparticles (IONPs)
by Mostafa Salehirozveh, Parisa Dehghani and Ivan Mijakovic
J. Funct. Biomater. 2024, 15(11), 340; https://doi.org/10.3390/jfb15110340 - 12 Nov 2024
Viewed by 657
Abstract
Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including [...] Read more.
Iron oxide nanoparticles (IONPs) have garnered significant attention in biomedical applications due to their unique magnetic properties, biocompatibility, and versatility. This review comprehensively examines the synthesis methods, surface functionalization techniques, and diverse biomedical applications of IONPs. Various chemical and physical synthesis techniques, including coprecipitation, sol–gel processes, thermal decomposition, hydrothermal synthesis, and sonochemical routes, are discussed in detail, highlighting their advantages and limitations. Surface functionalization strategies, such as ligand exchange, encapsulation, and silanization, are explored to enhance the biocompatibility and functionality of IONPs. Special emphasis is placed on the role of IONPs in biosensing technologies, where their magnetic and optical properties enable significant advancements, including in surface-enhanced Raman scattering (SERS)-based biosensors, fluorescence biosensors, and field-effect transistor (FET) biosensors. The review explores how IONPs enhance sensitivity and selectivity in detecting biomolecules, demonstrating their potential for point-of-care diagnostics. Additionally, biomedical applications such as magnetic resonance imaging (MRI), targeted drug delivery, tissue engineering, and stem cell tracking are discussed. The challenges and future perspectives in the clinical translation of IONPs are also addressed, emphasizing the need for further research to optimize their properties and ensure safety and efficacy in medical applications. This review aims to provide a comprehensive understanding of the current state and future potential of IONPs in both biosensing and broader biomedical fields. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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<p>The crystal structure of (<b>a</b>) magnetite and (<b>b</b>) maghemite, where Fe<sup>2+</sup> ions are represented by black spheres, Fe<sup>3+</sup> ions by green spheres, and O<sup>2−</sup> ions by red spheres. Reprinted from reference [<a href="#B2-jfb-15-00340" class="html-bibr">2</a>].</p>
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<p>An overview diagram of this paper including the synthesis, functionalization, and biomedical applications of iron oxide nanoparticles (IONPs).</p>
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<p>A schematic illustration of the synthesis of IONPs. (<b>a</b>) The synthesis of iron oxide nanoparticles via the sol–gel method: iron nitrate and citric acid are mixed, forming an iron oxide gel, followed by drying, annealing, and grinding to obtain α-Fe<sub>2</sub>O<sub>3</sub> nanoparticles. (<b>b</b>) The synthesis of iron oxide nanoparticles via the green chemistry method: ferrous sulfate is combined with plant extract and sodium hydroxide, centrifuged, and oven-dried to produce a brownish-black powder for storage [<a href="#B29-jfb-15-00340" class="html-bibr">29</a>,<a href="#B30-jfb-15-00340" class="html-bibr">30</a>].</p>
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<p>Schematic illustration of IONPs synthesis via coprecipitation technique. Reprinted from reference [<a href="#B49-jfb-15-00340" class="html-bibr">49</a>].</p>
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<p>Schematic illustration of IONPs synthesis via sol–gel technique.</p>
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<p>Schematic illustration of IONPs synthesis via thermal breakdown technique. Reprinted from reference [<a href="#B49-jfb-15-00340" class="html-bibr">49</a>].</p>
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<p>Schematic illustration of IONPs synthesis via microemulsion technique.</p>
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<p>Multiple surface functionalizations of magnetic IONPs.</p>
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<p>The timeline of magnetic nanoparticles in therapeutic and imaging applications. Reprinted from reference [<a href="#B212-jfb-15-00340" class="html-bibr">212</a>].</p>
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24 pages, 3186 KiB  
Review
3D-Printed Electrochemical Sensors: A Comprehensive Review of Clinical Analysis Applications
by Thaís Cristina de Oliveira Cândido, Daniela Nunes da Silva, Marcella Matos Cordeiro Borges, Thiago Gabry Barbosa, Scarlat Ohanna Dávila da Trindade and Arnaldo César Pereira
Analytica 2024, 5(4), 552-575; https://doi.org/10.3390/analytica5040037 - 11 Nov 2024
Viewed by 427
Abstract
Three-dimensional printing technology has emerged as a versatile and cost-effective alternative for the fabrication of electrochemical sensors. To enhance sensor sensitivity and biocompatibility, a diverse range of biocompatible and conductive materials can be employed in these devices. This allows these sensors to be [...] Read more.
Three-dimensional printing technology has emerged as a versatile and cost-effective alternative for the fabrication of electrochemical sensors. To enhance sensor sensitivity and biocompatibility, a diverse range of biocompatible and conductive materials can be employed in these devices. This allows these sensors to be modified to detect a wide range of analytes in various fields. 3D-printed electrochemical sensors have the potential to play a pivotal role in personalized medicine by enabling the real-time monitoring of metabolite and biomarker levels. These data can be used to personalize treatment strategies and optimize patient outcomes. The portability and low-cost nature of 3D-printed electrochemical sensors make them suitable for point-of-care (POC) diagnostics. These tests enable rapid and decentralized analyses, aiding in diagnosis and treatment decisions in resource-limited settings. Among the techniques widely reported in the literature for 3D printing, the fused deposition modeling (FDM) technique is the most commonly used for the development of electrochemical devices due to the easy accessibility of equipment and materials. Focusing on the FDM technique, this review explores the critical factors influencing the fabrication of electrochemical sensors and discusses potential applications in clinical analysis, while acknowledging the challenges that need to be overcome for its effective adoption. Full article
(This article belongs to the Special Issue Feature Papers in Analytica)
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Graphical abstract
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<p>Stages involved in manufacturing objects using 3D printing technology.</p>
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<p>Three-dimensional printing technologies; deposition methods and materials used.</p>
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<p>Illustration of a FDM 3D printer, highlighting in the zoomed-in image the layer-by-layer deposition process, forming the final object.</p>
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<p>Illustration of conductive networks with (<b>A</b>) low fraction of conductive particles, (<b>B</b>) the critical value, (<b>C</b>) small gaps, and (<b>D</b>) insufficient conductive material. The blue highlights indicate the conductive pathways for electron transfer, considering the arrangement of conductive particles within the polymeric matrix.</p>
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<p>Illustrative diagram showing the 3D printing process of the electrode.</p>
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<p>Representation of biorecognition elements for different types of biosensors.</p>
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<p>Schematic representation of the development of (<b>A</b>) the genosensor for detection of the biomarker HSP90, (<b>B</b>) the enzymatic biosensor for H<sub>2</sub>O<sub>2</sub>, and (<b>C</b>) the immunosensor for detection of <span class="html-italic">Hantavirus Nucleoprotein</span>.</p>
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16 pages, 2197 KiB  
Article
Real-Life Diagnostic Accuracy and Clinical Utility of Hepatitis B Virus (HBV) Nucleic Acid Testing Using the GeneXpert Point-of-Care Test System from Fresh Plasma and Dry Blood Spot Samples in The Gambia
by Amie Ceesay, Sainabou Drammeh, Gibril Ndow, Alpha Omar A. Jallow, Haddy Nyang, Baboucarr Bittaye, Francis S. Mendy, Ousman Secka, Umberto D’Alessandro, Yusuke Shimakawa, Erwan Vo-Quang, Barbara Testoni, Mark Thursz, Maud Lemoine and Isabelle Chemin
Microorganisms 2024, 12(11), 2273; https://doi.org/10.3390/microorganisms12112273 - 9 Nov 2024
Viewed by 762
Abstract
The GeneXpert HBV Viral Load test is a simplified tool to scale up screening and HBV monitoring in resource-limited settings, where HBV is endemic and where molecular techniques to quantify HBV DNA are expensive and scarce. However, the accuracy of field diagnostics compared [...] Read more.
The GeneXpert HBV Viral Load test is a simplified tool to scale up screening and HBV monitoring in resource-limited settings, where HBV is endemic and where molecular techniques to quantify HBV DNA are expensive and scarce. However, the accuracy of field diagnostics compared to gold standard assays in HBV-endemic African countries has not been well understood. We aim to validate the diagnostic performance of the GeneXpert HBV Viral Load test in freshly collected and stored plasma and dried blood spot (DBS) samples to assess turn-around-time (TAT) for sample processing and treatment initiation, to map GeneXpert machines and to determine limitations to its use in The Gambia. Freshly collected paired plasma and DBS samples (n = 56) were analyzed by the GeneXpert test. Similarly, stored plasma and DBS samples (n = 306, n = 91) were analyzed using the GeneXpert HBV test, in-house qPCR and COBAS TaqMan Roche. The correlation between freshly collected plasma and DBS is r = 0.88 with a mean bias of −1.4. The GeneXpert HBV test had the highest quantifiable HBV DNA viremia of 81.4% (n = 249/306), and the lowest was detected by in-house qPCR at 37.9% (n = 116/306) for stored plasma samples. Bland–Altman plots show strong correlation between GeneXpert and COBAS TaqMan and between GeneXpert and in-house qPCR with a mean bias of +0.316 and −1.173 log10 IU/mL, respectively. However, paired stored plasma and DBS samples had a lower mean bias of 1.831 log10 IU/mL, which is almost significant (95% limits of agreement: 0.66–3.001). Patients (n = 3) were enrolled in the study within a TAT of 6 days. The GeneXpert HBV test displayed excellent diagnostic accuracy by detecting HBV viremia in less than 10 IU/mL. Full article
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<p>Correlation between DBS and plasma of fresh samples. (<b>A</b>) Scatter plot of DBS and plasma viral loads. (<b>B</b>) Bland–Altman plot of the mean difference of plasma minus DBS viral loads. The correlation coefficient r = 0.88, the bias is −1.4 and 3/56 falls outside of the limits of agreement; the maximum measurement lies between 1 and 7.94 log 10 IU/mL.</p>
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<p>Assay comparison analysis using linear regression methods and Bland–Altman plot of HBV DNA viral load levels measured by GeneXpert HBV viral load and in-house PCR assay. (<b>A</b>) Simple linear regression (scatter plot) of 109 specimens with numerical viral load quantified by both assays. (<b>B</b>) Bland–Altman plot of 109 serum samples with detectable viral load by GeneXpert- minus in-house PCR-measured plasma viral load (vertical axis) against mean of GeneXpert- and in-house PCR-measured plasma viral loads (horizontal axis); the data (dotted) represent mean differences of −1.173 at limits of agreement at 95% CI of −2.474 and +0.128, average viral load is between 1.352 and 8.033 log<sub>10</sub> IU/mL and 4.59% (5/109) of the data are found outside the limits of agreement.</p>
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<p>Assay accuracy and concordance determined using scatter plots and Bland–Altman plots of detectable viral load by GeneXpert HBV DNA viral test and COBAS TaqMan PCR. (<b>A</b>) Comparison of the sensitivity and correlation of 110 serum samples of numerical results for the two assays using a scatter plot. (<b>B</b>) Bland–Altman plot of 110 serum samples viral load by GeneXpert minus COBAS TaqMan PCR measured plasma of quantifiable viral load (vertical axis) against mean of GeneXpert and COBAS TaqMan PCR plasma measured viral loads (horizontal axis), the dotes represent mean difference of +0.316 at 95% limits of agreement of 1.188 to 1.820, an average is between 1.44 and 8.485 log<sub>10</sub> IU/mL and 5.45% (6/110) of samples are found outside the limits of agreement.</p>
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<p>Accuracy, correlation and sensitivity of the two assays using plasma sample viral loads using scatter plot or linear regression and Bland–Altman plot. (<b>A</b>) Scatter plot of 79 serum samples quantified by COBAS TaqMan and in-house PCR test. (<b>B</b>) Bland–Altman plot analysis of 79 samples with detectable viral loads of in-house PCR minus COBAS TaqMan PCR (vertical axis) against the mean of the in-house PCR- and COBAS TaqMan PCR-measured plasma viral loads (horizontal axis); the data represent the mean difference of +1.421 at 95% limits of agreement of 0.129 to 2.713, the average lies between log<sub>10</sub> IU/mL 2.358 and 7.853 and 6.33% (5/79) are found outside the limits of agreement.</p>
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<p>Comparison and correlation of DBS and plasma paired samples using scatter and Bland–Altman plots of detectable viral loads by GeneXpert HBV DNA test. (<b>A</b>) Linear regression of 34 paired DBS–plasma samples with detectable viral loads by GeneXpert. (<b>B</b>) Bland–Altman plot analysis of GeneXpert viral load of DBS minus plasma viral loads (vertical axis) against GeneXpert viral load mean of DBS and plasma viral loads (horizontal axis); mean difference of 1.831 at limits of agreement of 0.660 to 3.001; the average lies between log<sub>10</sub> IU/mL 1.151 and 6.311 and 11.76% of the data are outside of the limits of agreement. Samples that had numerical results by both methods are presented (n = 34).</p>
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20 pages, 6476 KiB  
Systematic Review
An Assessment of the Feasibility, Patient Acceptance, and Performance of Point-of-Care Transient Elastography for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review and Meta-Analysis
by Taranika Sarkar Das, Xucong Meng, Mohamed Abdallah, Mohammad Bilal, Raiya Sarwar and Aasma Shaukat
Diagnostics 2024, 14(22), 2478; https://doi.org/10.3390/diagnostics14222478 - 6 Nov 2024
Viewed by 391
Abstract
Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE’s ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing [...] Read more.
Background: Vibration-Controlled Transient Elastography (VCTE) with FibroScan is a non-invasive, reliable diagnostic tool for Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD), enabling early detection and management to prevent severe liver diseases. VCTE’s ease and portability suit primary care, streamlining referrals, promoting lifestyle changes, reducing costs, and benefiting underserved communities. Methods: Studies on point-of-care VCTE were systematically reviewed, followed by meta-analysis using a random-effects model. Pooled proportions with 95% confidence intervals were reported, and heterogeneity was assessed using I2%. Results: A total of twenty studies from 14 countries, including 6159 patients, were analyzed, with three studies from France, two from the U.S., and four from China. The population had a slight male preponderance, with a mean age range of 35–73 years and a BMI range of 24.4–41.1%. The diagnostic accuracy for detecting any fibrosis (≥F1) was reported in four studies (n = 210) with an AUC of 0.74, sensitivity of 69.5%, and specificity of 70.6%. For significant fibrosis (≥F2), eight studies (n = 650) reported an AUC of 0.69, sensitivity of 81.7%, and specificity of 64.6%. Advanced fibrosis (≥F3) was evaluated in 10 studies (n = 619), with an AUC of 0.84, sensitivity of 88.1%, and specificity of 63.8%. Cirrhosis (F4) was assessed in nine studies (n = 533), with an AUC of 0.65, sensitivity of 87.5%, and specificity of 62.6%. Steatosis diagnoses across stages S1 to S3 showed increasing diagnostic accuracies, with AUCs of 0.85, 0.76, and 0.80, respectively. Probe type and BMI were significant covariates influencing diagnostic performance for both fibrosis and steatosis, while the percentage of male participants also showed significant associations. Conclusions: VCTE shows high diagnostic accuracy for fibrosis and steatosis in MASLD patients at the point of care. Future research should assess its implementation in fibroscan settings. Full article
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<p>The bar chart above visualizes the comparison of bias levels across different studies. Blue bars represent the risk of bias in patient selection, which is consistently low across all studies. Green bars indicate the risk of bias in result interpretation, with only Karlas et al. [<a href="#B18-diagnostics-14-02478" class="html-bibr">18</a>] showing a high level of bias in this category. Red bars represent the risk of bias in test and reference test interpretation. Several studies, including Boursier et al. [<a href="#B9-diagnostics-14-02478" class="html-bibr">9</a>], Siddiqui et al. [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Lai et al. [<a href="#B11-diagnostics-14-02478" class="html-bibr">11</a>], and both Chan et al. [<a href="#B12-diagnostics-14-02478" class="html-bibr">12</a>,<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>] studies, exhibit high bias here, while others, like Jung et al. [<a href="#B14-diagnostics-14-02478" class="html-bibr">14</a>] and Wong et al. [<a href="#B24-diagnostics-14-02478" class="html-bibr">24</a>], show low bias [<a href="#B15-diagnostics-14-02478" class="html-bibr">15</a>,<a href="#B17-diagnostics-14-02478" class="html-bibr">17</a>,<a href="#B18-diagnostics-14-02478" class="html-bibr">18</a>,<a href="#B19-diagnostics-14-02478" class="html-bibr">19</a>,<a href="#B20-diagnostics-14-02478" class="html-bibr">20</a>,<a href="#B21-diagnostics-14-02478" class="html-bibr">21</a>,<a href="#B22-diagnostics-14-02478" class="html-bibr">22</a>,<a href="#B23-diagnostics-14-02478" class="html-bibr">23</a>,<a href="#B25-diagnostics-14-02478" class="html-bibr">25</a>,<a href="#B27-diagnostics-14-02478" class="html-bibr">27</a>,<a href="#B28-diagnostics-14-02478" class="html-bibr">28</a>,<a href="#B29-diagnostics-14-02478" class="html-bibr">29</a>].</p>
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<p>Forest plots for sensitivity of any degree of fibrosis (F0 vs. F1–4) along with their 95% confidence intervals (CIs). The plot includes four studies: Siddiqui 2019 [<a href="#B9-diagnostics-14-02478" class="html-bibr">9</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Kwok 2015 [<a href="#B15-diagnostics-14-02478" class="html-bibr">15</a>], and Liu 2021 [<a href="#B28-diagnostics-14-02478" class="html-bibr">28</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (66%) and τ<sup>2</sup> (0.3995), with a <span class="html-italic">p</span>-value of 0.03 indicating significant heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of any degree of fibrosis (F0 vs. F1–4). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of significant fibrosis (F0–1 vs. F2–4) along with their 95% confidence intervals (CIs). The plot includes four studies: Boursier 2022 [<a href="#B9-diagnostics-14-02478" class="html-bibr">9</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Kwok 2014 [<a href="#B15-diagnostics-14-02478" class="html-bibr">15</a>], Wong 2010 [<a href="#B24-diagnostics-14-02478" class="html-bibr">24</a>], Bertrot 2023 [<a href="#B26-diagnostics-14-02478" class="html-bibr">26</a>], Lee 2022 [<a href="#B27-diagnostics-14-02478" class="html-bibr">27</a>], and Liu 2021 [<a href="#B28-diagnostics-14-02478" class="html-bibr">28</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (85%) and τ<sup>2</sup> (1.4346), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mo>&lt;</mo> </mrow> </semantics></math>0.01 indicating significant heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of fignificant fibrosis (F0–1 vs. F2–4). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of advanced fibrosis (F0–2 vs. F3–4) along with their 95% confidence intervals (CIs). The plot includes four studies: Boursier 2022 [<a href="#B9-diagnostics-14-02478" class="html-bibr">9</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Lai 2019 [<a href="#B11-diagnostics-14-02478" class="html-bibr">11</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Kwok 2014 [<a href="#B15-diagnostics-14-02478" class="html-bibr">15</a>], Wong 2010 [<a href="#B24-diagnostics-14-02478" class="html-bibr">24</a>], Tapper 2016 [<a href="#B25-diagnostics-14-02478" class="html-bibr">25</a>], Bertrot 2023 [<a href="#B26-diagnostics-14-02478" class="html-bibr">26</a>], Lee 2022 [<a href="#B27-diagnostics-14-02478" class="html-bibr">27</a>], and Liu 2021 [<a href="#B28-diagnostics-14-02478" class="html-bibr">28</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (65%) and τ<sup>2</sup> (0.7620), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mo>&lt;</mo> </mrow> </semantics></math>0.01 indicating significant heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of advanced fibrosis (F0–2 vs. F3–4). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of cirrhosis (F0–3 vs. F4) along with their 95% confidence intervals (CIs). The plot includes four studies: Boursier 2022 [<a href="#B9-diagnostics-14-02478" class="html-bibr">9</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Lai 2019 [<a href="#B11-diagnostics-14-02478" class="html-bibr">11</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Kwok 2014 [<a href="#B15-diagnostics-14-02478" class="html-bibr">15</a>], Wong 2010 [<a href="#B24-diagnostics-14-02478" class="html-bibr">24</a>], Tapper 2016 [<a href="#B25-diagnostics-14-02478" class="html-bibr">25</a>], Bertrot 2023 [<a href="#B26-diagnostics-14-02478" class="html-bibr">26</a>], Lee 2022 [<a href="#B27-diagnostics-14-02478" class="html-bibr">27</a>], and Liu 2021 [<a href="#B28-diagnostics-14-02478" class="html-bibr">28</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (65%) and τ<sup>2</sup> (0.7620), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mo>&lt;</mo> </mrow> </semantics></math>0.01 indicating significant heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of cirrhosis (F0–3 vs. F4). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of mild steatosis (CAP &lt; 33%, S1) along with their 95% confidence intervals (CIs). The plot includes four studies: Sasso 2010 [<a href="#B16-diagnostics-14-02478" class="html-bibr">16</a>], Jung 2014 [<a href="#B14-diagnostics-14-02478" class="html-bibr">14</a>], Chan 2014 [<a href="#B12-diagnostics-14-02478" class="html-bibr">12</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Shen 2014 [<a href="#B17-diagnostics-14-02478" class="html-bibr">17</a>], Karlas 2014 [<a href="#B18-diagnostics-14-02478" class="html-bibr">18</a>], Chon 2014 [<a href="#B19-diagnostics-14-02478" class="html-bibr">19</a>], Masaki 2013 [<a href="#B20-diagnostics-14-02478" class="html-bibr">20</a>], and Caussy 2018 [<a href="#B23-diagnostics-14-02478" class="html-bibr">23</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (3%) and τ<sup>2</sup> (0.0564), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mn>0.41</mn> </mrow> </semantics></math> indicating low heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of mild steatosis (CAP &lt; 33%, S1). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of moderate steatosis (CAP 34–66%, S2) along with their 95% confidence intervals (CIs). The plot includes four studies: Sasso 2010 [<a href="#B16-diagnostics-14-02478" class="html-bibr">16</a>], Jung 2014 [<a href="#B14-diagnostics-14-02478" class="html-bibr">14</a>], Chan 2014 [<a href="#B12-diagnostics-14-02478" class="html-bibr">12</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Shen 2014 [<a href="#B17-diagnostics-14-02478" class="html-bibr">17</a>], Karlas 2014 [<a href="#B18-diagnostics-14-02478" class="html-bibr">18</a>], Chon 2014 [<a href="#B19-diagnostics-14-02478" class="html-bibr">19</a>], Masaki 2013 [<a href="#B20-diagnostics-14-02478" class="html-bibr">20</a>], Kumar 2013 [<a href="#B21-diagnostics-14-02478" class="html-bibr">21</a>], Friedrich-Rust 2008 [<a href="#B22-diagnostics-14-02478" class="html-bibr">22</a>], and Caussy 2018 [<a href="#B23-diagnostics-14-02478" class="html-bibr">23</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (0%) and τ<sup>2</sup> (0.0136), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mn>0.69</mn> </mrow> </semantics></math> indicating low heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of moderate steatosis (CAP 34–66%, S2). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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<p>Forest plots for sensitivity of severe steatosis (CAP &gt; 67%, S3) along with their 95% confidence intervals (CIs). The plot includes four studies: Sasso 2010 [<a href="#B16-diagnostics-14-02478" class="html-bibr">16</a>], Jung 2014 [<a href="#B14-diagnostics-14-02478" class="html-bibr">14</a>], Chan 2014 [<a href="#B12-diagnostics-14-02478" class="html-bibr">12</a>], Chan 2017 [<a href="#B13-diagnostics-14-02478" class="html-bibr">13</a>], Siddiqui 2019 [<a href="#B10-diagnostics-14-02478" class="html-bibr">10</a>], Shen 2014 [<a href="#B17-diagnostics-14-02478" class="html-bibr">17</a>], Karlas 2014 [<a href="#B18-diagnostics-14-02478" class="html-bibr">18</a>], Chon 2014 [<a href="#B19-diagnostics-14-02478" class="html-bibr">19</a>], Masaki 2013 [<a href="#B20-diagnostics-14-02478" class="html-bibr">20</a>], Kumar 2013 [<a href="#B21-diagnostics-14-02478" class="html-bibr">21</a>], Friedrich-Rust 2008 [<a href="#B22-diagnostics-14-02478" class="html-bibr">22</a>], and Caussy 2018 [<a href="#B23-diagnostics-14-02478" class="html-bibr">23</a>]. Each study’s sensitivity is represented by a square, with the square size reflecting the study weight in the random effects model. Horizontal lines indicate the 95% CI for each study. The diamond at the bottom represents the pooled sensitivity estimate and its 95% CI, based on the random effects model. Heterogeneity among studies is quantified by I<sup>2</sup> (0%) and τ<sup>2</sup> (0.0259), with a <span class="html-italic">p</span>-value of <math display="inline"><semantics> <mrow> <mn>0.63</mn> </mrow> </semantics></math> indicating low heterogeneity.</p>
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<p>Summary Receiver Operating Characteristic (SROC) curve for diagnostic test accuracy of moderate steatosis (CAP &gt;67%, S3). The curve plots sensitivity (y-axis) against false positive rate (x-axis), providing an overall measure of test performance across studies. The central curve represents the relationship between sensitivity and false positive rate, while the surrounding shaded region illustrates the 95% confidence region, indicating the variability in diagnostic accuracy.</p>
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19 pages, 1503 KiB  
Article
Application of Monoclonal Anti-Mycolate Antibodies in Serological Diagnosis of Tuberculosis
by Alma Truyts, Ilse Du Preez, Eldas M. Maesela, Manfred R. Scriba, Les Baillie, Arwyn T. Jones, Kevin J. Land, Jan A. Verschoor and Yolandy Lemmer
Trop. Med. Infect. Dis. 2024, 9(11), 269; https://doi.org/10.3390/tropicalmed9110269 - 6 Nov 2024
Viewed by 575
Abstract
Patient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial cell [...] Read more.
Patient loss to follow-up caused by centralised and expensive diagnostics that are reliant on sputum is a major obstacle in the fight to end tuberculosis. An affordable, non-sputum biomarker-based, point-of-care deployable test is needed to address this. Serum antibodies binding the mycobacterial cell wall lipids, mycolic acids, have shown promise as biomarkers for active tuberculosis. However, anti-lipid antibodies are of low affinity, making them difficult to detect in a lateral flow immunoassay—a technology widely deployed at the point-of-care. Previously, recombinant monoclonal anti-mycolate antibodies were developed and applied to characterise the antigenicity of mycolic acid. We now demonstrate that these anti-mycolate antibodies specifically detect hexane extracts of mycobacteria. Secondary antibody-mediated detection was applied to detect the displacement of the monoclonal mycolate antibodies by the anti-mycolic acid antibodies present in tuberculosis-positive guinea pig and human serum samples. These data establish proof-of-concept for a novel lateral flow immunoassay for tuberculosis provisionally named MALIA—mycolate antibody lateral flow immunoassay. Full article
(This article belongs to the Section Infectious Diseases)
Show Figures

Figure 1

Figure 1
<p>Mycolate Antibody Lateral Flow Immunoassay (MALIA) schematic. Monoclonal anti-mycolic acid (MA) antibody, ‘gallibody’ (Gb), binds to the MA antigen-coated test line and is bound by the anti-chicken (AC) antibody on the control line. In the case of TB-positive sera, biomarker anti-MA antibodies present in sera displace bound gallibody on the test line. Gold (Au)-labelled anti-chicken antibody binds gallibody on the test and control lines providing visible lines. TB—tuberculosis.</p>
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<p>Whole-cell detection using gallibody. Single-cell suspensions of four mycobacterial species and <span class="html-italic">E. coli</span> were dried in triplicate wells, fixed in 70% methanol and blocked with 1% casein (in PBS at pH 7). Wells were probed with gallibody 12-2 at 0.04 mg/mL (<b>A</b>) or a polyclonal rabbit anti-<span class="html-italic">M. tuberculosis</span> (ab905) at 1:200 dilution (<b>B</b>). Binding was detected using relevant secondary antibodies conjugated to horseradish peroxidase. Average absorbance at 450 nm (bar heights) and standard deviation (error bars) with <span class="html-italic">n</span> = 3 shown. MA – mycolic acid; PBS – phosphate buffered saline CFU—colony-forming units.</p>
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<p>Mycobacterial species specificity of gallibodies. Crude hexane extracts (1× and 0.1×) of 4 species of mycobacteria as well as <span class="html-italic">E. coli</span> were probed with all 6 gallibodies (<b>A</b>–<b>F</b>) in ELISA. Three replicate extracts (shown separately) and controls were coated in triplicate wells (technical repeats). Technical replicates averaged for each coating; standard deviation presented as error bars. Data are represented as a percentage of the signal obtained for 62.5 µg/mL commercially purified MA (100%) with the average of the <span class="html-italic">E. coli</span> extract and the hexane-only signals as the inner 0% circle. Three further concentrations of purified MA (0.78, 1.041 and 3.125 µg/mL) were also probed for comparison. Key is listed clockwise from 12 o’clock. MA—mycolic acid.</p>
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<p>Reduction in MA signal by serum samples from TB-positive guinea pigs. (<b>A</b>) Scanned test sections. Gallibodies at 0.06 mg/mL diluted in membrane blocker was flowed on tests striped with anti-chicken IgG (Fc) antibody (top line) at 0.25 mg/mL and mycolic acid (bottom line) at 3 × 0.5 mg/mL for ~15 min. Subsequently, 50 µL of 10% guinea pig serum (pooled serum from TB-negative animals—‘TB−’, two TB-positive animals—‘TB+ (x)’ and ‘TB+ (y)’ diluted in membrane blocker containing a rheumatoid factor interference blocker (1 mg/mL) was flowed until absorbed, followed by 50 µL of membrane blocker containing 3 µL of anti-chicken-gold conjugate. Cropped scans of the test section of duplicate tests are shown; (<b>B</b>) heatmap of MA test line intensity from tests in (<b>A</b>). Fiji software analysis was performed on the scanned tests to quantify the intensity of the mycolic acid (MA) test line. The average of the red, green and blue pixels for the selected region of interest (in the test line) were used to generate the heatmap and are given in the bottom right of each block; (<b>C</b>) normalised MA test line intensity values. MA test line intensity (as in (<b>B</b>)) of individual replicate tests was normalised to the average of the MA test line intensity obtained using buffer only (no serum) for each gallibody. Buffer-only tests and test line intensity values are shown in <a href="#app1-tropicalmed-09-00269" class="html-app">Supplementary Figure S3 and Table S3</a>. TB—tuberculosis.</p>
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<p>Titration of gallibody 16-1 concentration for optimal detection of anti-MA antibody in TB-positive guinea pig sera. (<b>A</b>) Gallibody 16-1 at 0.06, 0.04, 0.02 and 0.01 mg/mL diluted in membrane blocker was flowed on tests striped with anti-chicken IgG (Fc) antibody (top line) at 0.25 mg/mL and mycolic acid (bottom line) at 3 × 0.5 mg/mL for ~15 min. Subsequently, 50 µL of 10% guinea pig serum (pooled serum from TB-negative animals—‘TB−’, and two TB-positive animals denoted x and z—‘TB+ (x)’ and ‘TB+ (z)’ diluted in membrane blocker containing a rheumatoid factor inhibition blocker (1 mg/mL) was flowed until absorbed, followed by 50 µL of membrane blocker containing 3 µL of anti-chicken-gold conjugate. Cropped scans of the test section of duplicate tests are shown; (<b>B</b>) heatmap of MA test line intensity from tests in (<b>A</b>). FIJI software analysis was performed on the scanned tests to quantify the intensity of the mycolic acid (MA) test line. The average of the red, green and blue pixels for the selected region of interest (in the test line) were used to generate the heatmap and are given in the bottom right of each block; (<b>C</b>) normalised MA test line intensity values. MA test line intensity (as in (<b>B</b>)) of individual replicate tests was normalised to the average of the MA test line intensity obtained using buffer only (no serum) for each concentration. Buffer-only tests and test line intensity values are shown in <a href="#app1-tropicalmed-09-00269" class="html-app">Supplementary Figure S4 and Table S4</a>. TB—tuberculosis.</p>
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<p>MALIA diagnostic differentiates TB-positive and -negative human serum samples. (<b>A</b>) Gallibody 16-1 at 0.04 and 0.02 mg/mL diluted in membrane blocker was flowed on tests striped with anti-chicken IgG (Fc) antibody (top line) at 0.25 mg/mL and mycolic acid (bottom line) at 3 × 0.5 mg/mL for ~15 min. Subsequently, 50 µL of 10% human serum (TB− or TB+) diluted in membrane blocker containing a rheumatoid factor inhibition blocker (1 mg/mL) was flowed until absorbed. Tests were then developed with 50 µL of membrane blocker containing 3 µL of anti-chicken-gold conjugate. Cropped scans of the test section of duplicate tests are shown. (<b>B</b>) Heatmap of MA test line intensity from tests in (<b>A</b>). FIJI software analysis was performed on the scanned tests to quantify the intensity of the mycolic acid (MA) test line. The average of the red, green and blue pixels for the selected region of interest (in the test line) were used to generate the heatmap and are given in the bottom right of each block; (<b>C</b>) normalised MA test line intensity values. MA test line intensity (as in (<b>B</b>)) of individual replicate tests was normalised to the average of the MA test line intensity obtained using buffer only (no serum) for each concentration. Buffer-only tests and test line intensity values are shown in <a href="#app1-tropicalmed-09-00269" class="html-app">Supplementary Figure S5 and Table S5</a>. * Test removed from analysis due to scan artefact. TB—tuberculosis.</p>
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14 pages, 2414 KiB  
Article
Development of a Recombinase Polymerase Amplification-Coupled CRISPR/Cas12a Platform for Rapid Detection of Antimicrobial-Resistant Genes in Carbapenem-Resistant Enterobacterales
by Ji Woo Yang, Heesu Kim, Lee-Sang Hyeon, Jung Sik Yoo and Sangrim Kang
Biosensors 2024, 14(11), 536; https://doi.org/10.3390/bios14110536 - 5 Nov 2024
Viewed by 657
Abstract
The worldwide spread of carbapenemase-producing Enterobacterales (CPE) represents a significant threat owing to the high mortality and morbidity rates. Traditional diagnostic methods are often too slow and complex for rapid point-of-care testing. Therefore, we developed a recombinase polymerase amplification (RPA)-coupled CRISPR/Cas12a system (RCCS), [...] Read more.
The worldwide spread of carbapenemase-producing Enterobacterales (CPE) represents a significant threat owing to the high mortality and morbidity rates. Traditional diagnostic methods are often too slow and complex for rapid point-of-care testing. Therefore, we developed a recombinase polymerase amplification (RPA)-coupled CRISPR/Cas12a system (RCCS), a rapid, accurate, and simple diagnostic platform for detecting antimicrobial-resistant genes. The RCCS detected carbapenemase genes (blaKPC and blaNDM) within 50 min, including 10 min for DNA extraction and 30–40 min for RCCS reaction (a 20 min RPA reaction with a 10–20-min CRISPR/Cas12a assay). Fluorescence signals obtained from the RCCS platform were visualized using lateral-flow test strips (LFSs) and real-time and endpoint fluorescence. The LFS clearly displayed test lines while detecting carbapenemase genes. Furthermore, the RCCS platform demonstrated high sensitivity by successfully detecting blaKPC and blaNDM at the attomolar and picomolar levels, respectively. The accuracy of the RCCS platform was validated with clinical isolates of Klebsiella pneumoniae and Escherichia coli; a 100% detection accuracy was achieved, which has not been reported when using conventional PCR. Overall, these findings indicate that the RCCS platform is a powerful tool for rapid and reliable detection of carbapenemase-encoding genes, with significant potential for implementation in point-of-care settings and resource-limited environments. Full article
(This article belongs to the Section Biosensors and Healthcare)
Show Figures

Figure 1

Figure 1
<p>Schematic overview of RPA-CRISPR Cas12a/crRNA (RCCS) assay for rapid detection of carbapenemase genes. RPA was used for amplification of <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> genes. The RPA products were subsequently added to the CRISPR/Cas12a system that can specifically recognize <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> genes, respectively. Finally, the results can be interpreted using real-time PCR and UV trans-illuminator or LFS.</p>
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<p>Screening of the PRA primer and crRNA sequence for <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> gene detection using the RCCS platform. (<b>A</b>) An overview of the crRNA and RPA primer design. (<b>B</b>) Amplification of <span class="html-italic">bla</span><sub>KPC</sub> (left) and <span class="html-italic">bla</span><sub>NDM</sub> (right) using RPA-1/2/3/ primer pairs. (<b>C</b>) <span class="html-italic">Cis</span>-cleavage assay using two crRNA candidates, visualizing the agarose gel electrophoresis. Red arrows point to cleaved fragments of template DNA. (<b>D</b>) <span class="html-italic">trans</span>-cleavage assay using two crRNA candidates and ssDNA probes. (left) Monitoring the fluorescence signal by real-time PCR and (right) endpoint fluorescence signal by UV trans-illuminator. Error bars represent standard deviation.</p>
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<p>Optimization of the RCCS reaction conditions for <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> genes detection. (<b>A</b>) Optimization of the Cas12a:crRNA ratio. (<b>B</b>) Optimization of the concentration of ssDNA probe. The endpoint fluorescence was measured by UV trans-illuminator after 30 min of incubation at 37 °C. (<b>C</b>) Detection of <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> genes using RCCS platform under optimal conditions. Fluorescence signal was obtained using real-time PCR. All experiments were conducted three times, and the error bars indicate the standard deviation. Statistical analysis used the <span class="html-italic">t</span>-test for multiple comparisons with NTC (*** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Determination of specificity and sensitivity of the RCCS platform for the detection of <span class="html-italic">bla</span><sub>KPC</sub> (left) and <span class="html-italic">bla</span><sub>NDM</sub> (right). NC, negative control; NTC, non-template control reaction. (<b>A</b>) The <span class="html-italic">trans</span>-cleavage activity of the RCCS platform targeting subtypes of <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> genes-containing plasmids. (<b>B</b>) Specificity test of the RCCS platform through endpoint imaging and LFS assay. The specificity was determined using clinical isolates, including carbapenemase genes or non-CPE strain. (<b>C</b>) The relative quantifications of band intensities obtained from the C-line and T-line of LFS. (<b>D</b>) Sensitivity test of the RCCS platform using ten-fold serially diluted plasmid containing <span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub> as a template. All experiments were conducted three times, and the error bars indicate the standard deviation. The <span class="html-italic">t</span>-test for multiple comparisons was used for statistical analysis (* <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Detection of carbapenemase genes (<span class="html-italic">bla</span><sub>KPC</sub> and <span class="html-italic">bla</span><sub>NDM</sub>) by using RCCS in bacteria-spiked urine samples. The endpoint fluorescence was detected by UV trans-illuminator after 30 min. (<b>A</b>) <span class="html-italic">bla</span><sub>KPC</sub>. (<b>B</b>) <span class="html-italic">bla</span><sub>NDM</sub>. <span class="html-italic">bla</span><sub>KPC</sub> was detected at levels up to 10<sup>3</sup> CFU/mL, and <span class="html-italic">bla</span><sub>NDM</sub> was detected at levels up to 10<sup>6</sup> CFU/mL.</p>
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33 pages, 6915 KiB  
Review
Conventional and Emerging Diagnostic Approaches for Differentiated Thyroid Carcinoma
by Kathelina Kristollari, Abraham Abbey Paul, Sagi Angel and Robert S. Marks
Chemosensors 2024, 12(11), 229; https://doi.org/10.3390/chemosensors12110229 - 1 Nov 2024
Viewed by 1183
Abstract
Differentiated thyroid carcinoma (DTC) is among the most prevalent endocrine cancers. The diagnosis of DTC has witnessed tremendous progress in terms of technological advancement and clinical operational guidelines. DTC diagnostics have evolved significantly over centuries, from early clinical examinations to modern molecular testing [...] Read more.
Differentiated thyroid carcinoma (DTC) is among the most prevalent endocrine cancers. The diagnosis of DTC has witnessed tremendous progress in terms of technological advancement and clinical operational guidelines. DTC diagnostics have evolved significantly over centuries, from early clinical examinations to modern molecular testing and imaging modalities. The diagnosis and management of DTC are currently dependent on the international histological classification and identification of specific genetic abnormalities in tumor tissue, as well as the prognostic implications that can inform treatment decisions. This study goes down the memory lanes of various diagnostic methods for DTCs, highlighting recent advancements in molecular testing and point-of-care (POC) technology. Beginning with conventional methods like fine needle aspiration biopsy (FNAB), fine needle aspiration cytology (FNAC), and ultrasound (US) and moving to contemporary innovative approaches such as POC-thyroglobulin (POC-Tg) and liquid biopsy, this review showcases the current trends in DTC diagnostics. Although considerable progress has been achieved in early malignancy detection, patient stratification, prognosis, and personalized treatment, there is a need to refine the mainstay diagnostic procedures. Finally, future perspectives were provided, and emerging roles of artificial intelligence in DTC diagnostics were explored. Full article
(This article belongs to the Special Issue Rapid Point-of-Care Testing Technology and Application)
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<p>Schematic overview of pathways leading to PTC and FTC development. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Stimulatory and inhibitory pathways: regulated (<b>A</b>) in normal cells and dysregulated (<b>B</b>) in abnormal cells, leading to tumor formation. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Flowchart schematically showing the diagnostic steps in patients presenting with a thyroid nodule. Adapted from [<a href="#B7-chemosensors-12-00229" class="html-bibr">7</a>], Copyright (2022) with permission from Elsevier.</p>
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<p>Thyroid cancer staging: (<b>1</b>) Cancer is confined to the thyroid and &lt;2 cm in diameter; (<b>2</b>) Cancer is confined to the thyroid and 2–4 cm in diameter; (<b>3</b>) Cancer has spread to lymph nodes or local organs, or the tumor is localized and &gt;4 cm; (<b>4</b>) Cancer has metastasized to distant organs or invades significant blood vessels. Adapted from “Thyroid Cancer Staging” by <a href="http://BioRender.com" target="_blank">BioRender.com</a> (2024). Retrieved from <a href="https://app.biorender.com/biorender-templates" target="_blank">https://app.biorender.com/biorender-templates</a> (accessed 31 July 2024).</p>
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<p>Fine-needle aspiration smears of well-differentiated thyroid carcinomas. Exhibit (<b>A</b>) displays the typical cytological appearance of PTC with papillary structures and nuclear pseudo inclusion, while exhibit (<b>B</b>) displays a typical follicular-patterned lesion. Obtained from [<a href="#B28-chemosensors-12-00229" class="html-bibr">28</a>], Copyright (2013) with permission from Spring Nature.</p>
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<p>PTC histopathology showing “Orphan Annie Eye”. Taken from [<a href="#B30-chemosensors-12-00229" class="html-bibr">30</a>], Copyright (2016), printed with permission from Elsevier.</p>
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<p>Timeline highlighting the evolution of DTC diagnostics over the centuries. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Images of scintigraphy showing: (<b>a</b>) A Tc-99m scintigraphy image showing an underactive (cold) thyroid nodule (arrow) in the right lobe of the thyroid gland. (<b>b</b>) An ultrasonography scan showing a well-defined, iso/hyperechogenic, heterogeneous mass containing large calcifications (arrow) on the right lobe of the thyroid gland. (<b>c</b>,<b>d</b>) Dual-phase Tl-201 scintigraphy images showing that the uptake in the nodules is higher on both the (<b>c</b>) early and (<b>d</b>) delayed phase images compared with the surrounding parenchyma. This finding was defined as a delayed accumulation pattern. Follicular adenoma was diagnosed on histopathologic examination. Retrieved from [<a href="#B47-chemosensors-12-00229" class="html-bibr">47</a>], Copyright (2018), reprinted with permission from Springer Nature.</p>
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<p>Illustration of fine-needle aspiration biopsy, material handling, and further analysis. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Cytological analysis of FNA: (<b>A</b>) Arrows pointing at typical characteristics of PTC, such as nuclear grooves, pseudoinclusions, and ground-glass chromatin. (<b>B</b>) Further evidence of PTC is highlighted by arrowhead (Diff-Quik-stained, intermediate power). (<b>C</b>) Papillary formation (Diff-Quik -stained, low power). Retrieved from [<a href="#B67-chemosensors-12-00229" class="html-bibr">67</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>Comparison of FNA-Tg levels in metastatic and non-metastatic cervical lymph nodules. Retrieved from [<a href="#B65-chemosensors-12-00229" class="html-bibr">65</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>Immunohistochemical investigation of PTC and FTC samples through the expression of markers such as cyclin D1, p21, and CDK4. Retrieved from [<a href="#B71-chemosensors-12-00229" class="html-bibr">71</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>Principle of detection behind ultrasound technology. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Axial CT scan image with arrows pointing at (<b>a</b>) recurrent DTC affecting great blood vessels and (<b>b</b>) DTC invading the internal jugular vein and esophagus. Retrieved from [<a href="#B93-chemosensors-12-00229" class="html-bibr">93</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>MRI imaging of PTC in the right lobe: (<b>A</b>) Axial T1-weighted image showing a heterogeneous isointense nodule (long arrowhead) with patchy hyperintense signal (white arrow) in the left lobe. (<b>B</b>) Axial T2-weighted image showing a heterogeneous hyperintense nodule with cystic change (white arrow) in the left lobe. (<b>C</b>) Axial DWI image showing a hyperintense nodule (white arrow) with ADC value of 1.990 × 10<sup>−3</sup> mm<sup>2</sup>/s. (<b>D</b>) Axial contrast-enhanced image showing a heterogeneous hyperintense lesion with a regular shape and clear margin in the left thyroid lobe during the early phase. (<b>E</b>) Axial contrast-enhanced image showing the pseudocapsule sign (white arrow) in the left thyroid lobe during delayed phase. (<b>F</b>) Histopathological hematoxylin and eosin (H&amp;E, ×40) staining showing heterogeneous follicular hyperplasia with colloid and hemorrhage (white arrow). Retrieved from [<a href="#B94-chemosensors-12-00229" class="html-bibr">94</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>Configuration of a classical lateral flow immunoassay compartmentalized into 4 main pads (sample pad, conjugation pad, membrane, absorbent pad) and displaying the location of control/test line. Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Right thyroid lobe with DTC: Image visualized to differentiate between shear-wave elastography [m/s] (in colors) and B-mode ultrasound (black and white). Arrowheads pointing at irregular hard areas. Adapted from [<a href="#B130-chemosensors-12-00229" class="html-bibr">130</a>], under CC BY-NC 4.0 (Deed—Attribution 4.0 International—Creative Commons).</p>
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<p>(<b>A</b>) ECL responses of the immuno-DNA sensors in the absence and presence of the 5-mC RASSF1A target in buffer solution and in undiluted human plasma samples. (<b>B</b>) ECL responses of sandwich-type immune-DNA sensor versus different amounts of DNA in undiluted human plasma and (<b>C</b>) calibration plot obtained from panel (<b>B</b>). (<b>D</b>) Clinical assay performance of DNA methylation normal and thyroid cancer patients’ circulating DNA from their plasma. The threshold value is calculated from three times the normal control signal’s standard deviation. Adapted from [<a href="#B137-chemosensors-12-00229" class="html-bibr">137</a>], Copyright (2022), with permission from Elsevier.</p>
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22 pages, 1489 KiB  
Review
AI-Reinforced Wearable Sensors and Intelligent Point-of-Care Tests
by Ghita Yammouri and Abdellatif Ait Lahcen
J. Pers. Med. 2024, 14(11), 1088; https://doi.org/10.3390/jpm14111088 - 1 Nov 2024
Viewed by 818
Abstract
Artificial intelligence (AI) techniques offer great potential to advance point-of-care testing (POCT) and wearable sensors for personalized medicine applications. This review explores the recent advances and the transformative potential of the use of AI in improving wearables and POCT. The integration of AI [...] Read more.
Artificial intelligence (AI) techniques offer great potential to advance point-of-care testing (POCT) and wearable sensors for personalized medicine applications. This review explores the recent advances and the transformative potential of the use of AI in improving wearables and POCT. The integration of AI significantly contributes to empowering these tools and enables continuous monitoring, real-time analysis, and rapid diagnostics, thus enhancing patient outcomes and healthcare efficiency. Wearable sensors powered by AI models offer tremendous opportunities for precise and non-invasive tracking of physiological conditions that are essential for early disease detection and personalized treatments. AI-empowered POCT facilitates rapid, accurate diagnostics, making these medical testing kits accessible and available even in resource-limited settings. This review discusses the key advances in AI applications for data processing, sensor fusion, and multivariate analytics, highlighting case examples that exhibit their impact in different medical scenarios. In addition, the challenges associated with data privacy, regulatory approvals, and technology integrations into the existing healthcare system have been overviewed. The outlook emphasizes the urgent need for continued innovation in AI-driven health technologies to overcome these challenges and to fully achieve the potential of these techniques to revolutionize personalized medicine. Full article
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<p>General principle of biosensors. Reused with permission from Elsevier publisher [<a href="#B34-jpm-14-01088" class="html-bibr">34</a>].</p>
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<p>A schematic illustration of the AI/ML-assisted POCT-based biosensing devices used for clinical decision-making. Reused with permission from ACS publisher [<a href="#B2-jpm-14-01088" class="html-bibr">2</a>].</p>
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<p>A compact and ultrasensitive bioelectrochemical patch was based on boronate-affinity amplified organic electrochemical transistors (BAAOECTs) for the POC sensing of glycoproteins. The figure is reused with permission from the publisher, Elsevier [<a href="#B92-jpm-14-01088" class="html-bibr">92</a>].</p>
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13 pages, 3380 KiB  
Article
A Loop-Mediated Isothermal Amplification Assay Utilizing Hydroxy Naphthol Blue (LAMP-HNB) for the Detection of Treponema pallidum Subspp. pallidum
by Saranthum Phurijaruyangkun, Pongbun Tangjitrungrot, Pornpun Jaratsing, Suphitcha Augkarawaritsawong, Khurawan Kumkrong, Sawanya Pongparit, Pawita Suwanvattana, Supatra Areekit, Kosum Chansiri and Somchai Santiwatanakul
Pathogens 2024, 13(11), 949; https://doi.org/10.3390/pathogens13110949 - 31 Oct 2024
Viewed by 404
Abstract
Treponema pallidum subspp. pallidum is a spirochaete bacterium that causes syphilis, one of the most common sexually transmitted diseases. Syphilis progresses through four distinct stages, each characterized by specific symptoms, namely primary, secondary, latent, and late (tertiary) syphilis. Serology has been considered the [...] Read more.
Treponema pallidum subspp. pallidum is a spirochaete bacterium that causes syphilis, one of the most common sexually transmitted diseases. Syphilis progresses through four distinct stages, each characterized by specific symptoms, namely primary, secondary, latent, and late (tertiary) syphilis. Serology has been considered the primary diagnostic approach. However, it is plagued by problems such as the limited specificity of nontreponemal tests and the inadequate correlation of treponemal tests with disease activity. In this study, we focused on the development of a loop-mediated isothermal amplification assay utilizing hydroxy naphthol blue (LAMP-HNB) for the diagnosis of T. pallidum subspp. pallidum. Specifically, this study seeks to determine the analytical sensitivity (limit of detection; LOD) and analytical specificity. Four hundred clinical serum samples were analyzed for diagnostic sensitivity, specificity, and predictive value, and each technique’s 95% confidence intervals (95% CI, p < 0.05) were evaluated. The limit of detection for polymerase chain reaction with agarose gel electrophoresis (PCR-AGE), the loop-mediated isothermal amplification assay combined with agarose gel electrophoresis (LAMP-AGE), and LAMP-HNB were 116 pg/µL, 11.6 pg/µL, and 11.6 pg/ µL, respectively. Analytical specificity examinations indicated the absence of cross-reactivity with Leptospira interrogans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, human immunodeficiency virus (HIV), and healthy human serum in PCR-AGE, LAMP-AGE, and LAMP-HNB. The diagnostic sensitivity, diagnostic specificity, positive predictive value (PPV), and negative predictive value (NPV) for PCR-AGE were 100.00 (100.00)%, 94.50 (94.40–94.60)%, 94.79 (94.69–94.88)%, and 100.00 (100.00)%, respectively. While, for LAMP-AGE and LAMP-HNB, they were 100.00 (100.00)%, 91.00 (90.87–91.13)%, 91.74 (91.63–91.86)%, and 100.00 (100.00)%, respectively. The LAMP-HNB test is simple, rapid, highly sensitive, and highly specific, without requiring expensive equipment. In the future, the LAMP-HNB assay may develop into a single-step diagnostic process, enabling the use as point-of-care testing for the diagnosis, prevention, and management of syphilis infection. Full article
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<p>The change in the color of hydroxy naphthol blue (HNB) is attributed to the decrease in magnesium. The concentration of Mg<sup>2+</sup> in the solution decreases during the LAMP process, the color of the HNB solution changes from purple to blue, which can be observed with the naked eye after amplification.</p>
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<p>The optimization of the LAMP assay in the range of 4.5–5.5 mM. Lane “M” represents a 100 bp plus DNA ladder marker of Vivantis, Darul Ehsan, Malaysia, and “N” is the negative control.</p>
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<p>The optimization of thermal conditions ranging between 60 and 65 °C. Lane “M” represents a 100 bp plus DNA ladder marker of Vivantis, Darul Ehsan, Malaysia, and “Neg” is the negative control.</p>
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<p>The optimal reaction durations were observed at 45 and 60 min. Lane “M” represents a 100 bp plus DNA ladder marker of Vivantis, Darul Ehsan, Malaysia, and “Neg” is the negative control.</p>
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<p>The optimization of LAMP-HNB, ranging from 1 to 20 µM.</p>
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<p>The analytical sensitivity and specificity tests and DNA analysis using 10-fold dilution. In the agarose gel electrophoresis (AGE) results, lanes 1–9: 11.6 ng/µL, 1.16 ng/µL, 116 pg/µL, 11.6 pg/µL, 1.16 pg/µL, 116 fg/µL, 11.6 fg/µL, 1.16 fg/µL, and negative control, respectively. Lane “M” represent a 100 bp plus DNA ladder marker of Vivantis. (<b>a</b>) PCR with agarose gel electrophoresis (PCR-AGE). (<b>b</b>) LAMP with agarose gel electrophoresis (LAMP-AGE). (<b>c</b>) LAMP utilizing hydroxy naphthol blue (LAMP-HNB).</p>
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<p>In the agarose gel electrophoresis (AGE) results, lanes 1–11: <span class="html-italic">T. pallidum</span> subspp. <span class="html-italic">pallidum</span>, <span class="html-italic">Leptospira interrogans</span>, <span class="html-italic">Staphylococcus aureus</span>, <span class="html-italic">Enterococcus faecalis</span>, <span class="html-italic">Escherichia coli</span>, <span class="html-italic">Klebsiella pneumoniae</span>, <span class="html-italic">Acinetobacter baumannii</span>, <span class="html-italic">Pseudomonas aeruginosa</span>, Human Immunodeficiency Virus (HIV), healthy human serum, and negative control, respectively. Lane “M” represent a 100 bp plus DNA ladder marker of Vivantis. (<b>a</b>) PCR with agarose gel electrophoresis (PCR-AGE). (<b>b</b>) LAMP with agarose gel electrophoresis (LAMP-AGE). (<b>c</b>) LAMP utilizing hydroxy naphthol blue (LAMP-HNB).</p>
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28 pages, 38866 KiB  
Review
CMOS Point-of-Care Diagnostics Technologies: Recent Advances and Future Prospects
by Tania Moeinfard, Ebrahim Ghafar-Zadeh and Sebastian Magierowski
Micromachines 2024, 15(11), 1320; https://doi.org/10.3390/mi15111320 - 29 Oct 2024
Viewed by 693
Abstract
This review provides a comprehensive overview of point-of-care (PoC) devices across several key diagnostic applications, including blood analysis, infectious disease detection, neural interfaces, and commercialized integrated circuits (ICs). In the blood analysis section, the focus is on biomarkers such as glucose, dopamine, and [...] Read more.
This review provides a comprehensive overview of point-of-care (PoC) devices across several key diagnostic applications, including blood analysis, infectious disease detection, neural interfaces, and commercialized integrated circuits (ICs). In the blood analysis section, the focus is on biomarkers such as glucose, dopamine, and aptamers, and their respective detection techniques. The infectious disease section explores PoC technologies for detecting pathogens, RNA, and DNA, highlighting innovations in molecular diagnostics. The neural interface section reviews advancements in neural recording and stimulation for therapeutic applications. Finally, a survey of commercialized ICs from companies such as Abbott and Medtronic is presented, showcasing existing PoC devices already in widespread clinical use. This review emphasizes the role of complementary metal-oxide-semiconductor (CMOS) technology in enabling compact, efficient diagnostic systems and offers insights into the current and future landscape of PoC devices. Full article
(This article belongs to the Special Issue The 15th Anniversary of Micromachines)
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<p>Various point-of-care devices, illustrating the integration of sensors for different health monitoring applications. The point-of-care block diagram on the right shows the main blocks and communication with our devices for real-time analysis and remote healthcare management.</p>
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<p>Blood analysis principle.</p>
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<p>A schematic representation of an optical sensing system for health monitoring. Light is transmitted through the finger and detected by a sensor, followed by signal processing through a front-end circuit and analog-to-digital converter (ADC). The processed data are transmitted via a processor and data telemetry to external devices, such as a computer or smartwatch, for real-time monitoring and analysis.</p>
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<p>(<b>a</b>) OG-ISFET transistors for ultrasensitive dopamine detection [<a href="#B37-micromachines-15-01320" class="html-bibr">37</a>]. (<b>b</b>) ADPLL-based implantable amperometric biosensor interface [<a href="#B48-micromachines-15-01320" class="html-bibr">48</a>]. (<b>c</b>) Traditional interface of biochemical sensor for drug-monitoring applications [<a href="#B41-micromachines-15-01320" class="html-bibr">41</a>]. (<b>d</b>) Injectable BioMote for continuous alcohol interface [<a href="#B52-micromachines-15-01320" class="html-bibr">52</a>].</p>
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<p>Block diagram of infectious disease detection PoC devices.</p>
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<p>(<b>a</b>) ADC-direct interface of the fluorescence biochip for DNA and RNA testing [<a href="#B62-micromachines-15-01320" class="html-bibr">62</a>]. (<b>b</b>) A patch-clamp ASIC interface for nanopore-based DNA analysis [<a href="#B65-micromachines-15-01320" class="html-bibr">65</a>]. (<b>c</b>) OG-JFET interface for biochemical sensing [<a href="#B74-micromachines-15-01320" class="html-bibr">74</a>].</p>
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<p>Block diagram of conventional neural interface microsystems.</p>
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<p>(<b>a</b>) Second-order <math display="inline"><semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi mathvariant="sans-serif">Σ</mi> </mrow> </semantics></math> ADC [<a href="#B85-micromachines-15-01320" class="html-bibr">85</a>]. (<b>b</b>) VCO-based <math display="inline"><semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi mathvariant="sans-serif">Σ</mi> </mrow> </semantics></math> ADC [<a href="#B86-micromachines-15-01320" class="html-bibr">86</a>]. (<b>c</b>) SAR-assisted <math display="inline"><semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi mathvariant="sans-serif">Σ</mi> </mrow> </semantics></math> ADC [<a href="#B87-micromachines-15-01320" class="html-bibr">87</a>]. (<b>d</b>) SNDR Gm-C-based <math display="inline"><semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi mathvariant="sans-serif">Σ</mi> </mrow> </semantics></math> modulator with a feedback-assisted Gm linearization [<a href="#B88-micromachines-15-01320" class="html-bibr">88</a>]. (<b>e</b>) Dynamic-zoom <math display="inline"><semantics> <mrow> <mi mathvariant="sans-serif">Δ</mi> <mi mathvariant="sans-serif">Σ</mi> </mrow> </semantics></math> ADC [<a href="#B89-micromachines-15-01320" class="html-bibr">89</a>].</p>
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<p>(<b>a</b>) Overview of closed-loop neuromodulation SoC of [<a href="#B90-micromachines-15-01320" class="html-bibr">90</a>]. (<b>b</b>) High dynamic range neural recording chip experimental setup on a mouse illustration of [<a href="#B88-micromachines-15-01320" class="html-bibr">88</a>]. (<b>c</b>) Time-based neural-recording IC with degeneration test setup illustration [<a href="#B54-micromachines-15-01320" class="html-bibr">54</a>]. (<b>d</b>) Wireless electro-optic headstage in vivo setup [<a href="#B94-micromachines-15-01320" class="html-bibr">94</a>].</p>
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<p>Commercialized PoC devices: (<b>a</b>) i-STAT Abbot [<a href="#B108-micromachines-15-01320" class="html-bibr">108</a>]; (<b>b</b>) Cepheid’s GeneXpert [<a href="#B109-micromachines-15-01320" class="html-bibr">109</a>]; (<b>c</b>) Medtronic’s Percept PC Neurostimulation [<a href="#B110-micromachines-15-01320" class="html-bibr">110</a>]; (<b>d</b>) Neuralink Brain Implant [<a href="#B111-micromachines-15-01320" class="html-bibr">111</a>]; (<b>e</b>) Tendem Diabetes Care T:Slim X2 Insuling Pump [<a href="#B112-micromachines-15-01320" class="html-bibr">112</a>]; (<b>f</b>) Abbot FreeStyle Libre [<a href="#B113-micromachines-15-01320" class="html-bibr">113</a>]; (<b>g</b>) Medtronics MiniMed 770G [<a href="#B114-micromachines-15-01320" class="html-bibr">114</a>]; (<b>h</b>) Omnipod DASH Insulin Management System [<a href="#B115-micromachines-15-01320" class="html-bibr">115</a>]; (<b>i</b>) OrSense NBM 200 [<a href="#B103-micromachines-15-01320" class="html-bibr">103</a>]; (<b>j</b>) CNOGA MTX [<a href="#B102-micromachines-15-01320" class="html-bibr">102</a>]; (<b>k</b>) Samsung LABGEO PT10 [<a href="#B104-micromachines-15-01320" class="html-bibr">104</a>]; (<b>l</b>) Pathfast [<a href="#B105-micromachines-15-01320" class="html-bibr">105</a>]; (<b>m</b>) RAMP system [<a href="#B106-micromachines-15-01320" class="html-bibr">106</a>]; (<b>n</b>) Aspect Plus—ST2 [<a href="#B107-micromachines-15-01320" class="html-bibr">107</a>].</p>
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19 pages, 1306 KiB  
Review
AI in Prosthodontics: A Narrative Review Bridging Established Knowledge and Innovation Gaps Across Regions and Emerging Frontiers
by Laura Iosif, Ana Maria Cristina Țâncu, Oana Elena Amza, Georgiana Florentina Gheorghe, Bogdan Dimitriu and Marina Imre
Prosthesis 2024, 6(6), 1281-1299; https://doi.org/10.3390/prosthesis6060092 - 28 Oct 2024
Viewed by 1043
Abstract
As the discipline of prosthodontics evolves, it encounters a dynamic landscape characterized by innovation and improvement. This comprehensive analysis underscores future developments and transformative solutions across its various subspecialties: fixed, removable, implant, and maxillofacial prosthodontics. The narrative review examines the latest advancements in [...] Read more.
As the discipline of prosthodontics evolves, it encounters a dynamic landscape characterized by innovation and improvement. This comprehensive analysis underscores future developments and transformative solutions across its various subspecialties: fixed, removable, implant, and maxillofacial prosthodontics. The narrative review examines the latest advancements in prosthetic technology, focusing on several critical areas. The integration of artificial intelligence and machine learning into prosthetic design and fitting processes is revolutionizing the field, serving as a common thread that links these innovative technologies across all subspecialties. This includes advancements in automated diagnostics, predictive analysis, and treatment planning. Furthermore, the review offers a forward-looking perspective on how these innovations are influencing each prosthetic dentistry domain, patient outcomes, and current clinical practices. By thoroughly analyzing contemporary research and emerging technologies, the study illustrates how these advancements represent a growing focal point of interest in developing countries, such as Romania, with the potential to redefine the trajectory of prosthetic rehabilitation and enhance patient care not only within this country but also beyond. Full article
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<p>Number of articles on the topic “AI in Prosthodontics”—source: PubMed/Medline.</p>
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<p>Current AI applications in prosthodontics.</p>
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11 pages, 2911 KiB  
Review
Challenges Associated with Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) Management—A Case Report with Comprehensive Literature Review
by Jakub Kwiatkowski, Nicole Akpang, Lucja Zaborowska, Marcelina Grzelak, Iga Lukasiewicz and Artur Ludwin
J. Clin. Med. 2024, 13(21), 6443; https://doi.org/10.3390/jcm13216443 - 28 Oct 2024
Viewed by 657
Abstract
Background: Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a poorly studied neoplasm that does not fulfill the definition of either leiomyoma or leiomyosarcoma. STUMP symptoms are indistinguishable from those of benign lesions; it has no specific biochemical markers or ultrasound presentations. [...] Read more.
Background: Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a poorly studied neoplasm that does not fulfill the definition of either leiomyoma or leiomyosarcoma. STUMP symptoms are indistinguishable from those of benign lesions; it has no specific biochemical markers or ultrasound presentations. The management of this type of tumor is particularly challenging due to significant heterogeneity in its behavior and the lack of clear guidelines; moreover, the lesion may recur after excision. Case Report: We report on a case of a 42-year-old patient diagnosed with a STUMP. The preliminary diagnosis was a submucous leiomyoma, which was removed hysteroscopically due to menorrhagia resulting in anemia. The histopathological examination of the resected myoma pointed to the diagnosis of STUMP. The hysterectomy was performed as the patient had completed her reproductive plans. There were no complications. The patient is currently recurrence-free after a 9-month follow-up. Discussion and Conclusions: The care of a patient diagnosed with STUMP requires a personalized approach and the cooperation of various medical disciplines, including molecular diagnostics, imaging techniques, and minimally invasive surgery. Management of STUMP must consider the patient’s plans for childbearing. All cases of tumors with “uncertain malignant potential” are a challenge in the context of patient-physician communication. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Treatment of Gynecologic Oncology)
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<p>Transvaginal ultrasound (TVS) image showing a sagittal view of the patient’s uterus. A well-defined, solid lesion (red arrow) of mixed echogenicity is visualized within the borders of the uterine cavity. No evident acoustic shadow is present. The myometrium surrounding the lesion displays visible heteroechogenity with rich vascularization.</p>
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<p>A coronal plane view of the patient’s uterus obtained with a 3D-TVS. The lesion (red arrow) protruding from the uterine fundus exerts a visible mass effect on the endometrial cavity.</p>
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