DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111436
Fu-Ming Zhou
{"title":"Whole-Brain Confocal Imaging Provides an Accurate Global View of the Nigral Dopamine System.","authors":"Fu-Ming Zhou","doi":"10.3390/diagnostics15111436","DOIUrl":"10.3390/diagnostics15111436","url":null,"abstract":"<p><p>Clinicopathological studies and the effectiveness of dopaminergic replacement therapy establish that dopamine loss is the key pathology causing motor symptoms in Parkinson's disease. The dopamine neurons that are impaired in Parkinson's disease reside in the substantia nigra and ventral tegmental area in the midbrain. These neurons project into the striatum, where dopamine axons bifurcate repeatedly and form dense axon networks (the striatum is separated into the caudate nucleus and putamen by the internal capsule). Midbrain dopamine neurons also innervate many other areas of the brain, including the cerebral cortex. Therefore, there are preclinical and clinical studies investigating extrastriatal dopamine mechanisms in motor control and Parkinson's disease pathophysiology and treatment. While extrastriatal dopamine can contribute, this contribution needs to be compared with the contribution of the striatal dopamine system. An isolated view of the extrastriatal dopamine system is like examining only the ear of an elephant and may lead to distorted assessments for preclinical and clinical research and diagnostic work. Thus, photographs of the whole brain dopamine system are important. For these reasons, we photographed the dopamine systems in whole mouse brain sagittal sections, showing clearly that, under identical imaging conditions, dopamine innervation is highly concentrated and intense in the striatum but sparse and weak in the cerebral cortex.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111441
Ehssan Aljanabi, İlker Türker
{"title":"Connectogram-COH: A Coherence-Based Time-Graph Representation for EEG-Based Alzheimer's Disease Detection.","authors":"Ehssan Aljanabi, İlker Türker","doi":"10.3390/diagnostics15111441","DOIUrl":"10.3390/diagnostics15111441","url":null,"abstract":"<p><p><b>Background:</b> Alzheimer's disease (AD) is a neurological disorder that affects the brain in the elderly, resulting in memory loss, mental deterioration, and loss of the ability to think and act, while being a cause of death, with its rates increasing dramatically. A popular method to detect AD is electroencephalography (EEG) signal analysis thanks to its ability to reflect neural activity, which helps to identify abnormalities associated with the disorder. Originating from its multivariate nature, EEG signals are generally handled as multidimensional time series, and the related methodology is employed. <b>Methods</b>: This study proposes a new transformation strategy that generates a graph representation with time resolution, which handles EEG recordings as relatively small time windows and converts these segments into a similarity graph based on signal coherence between available channels. The retrieved adjacency matrices are further flattened to form a 1-pixel image column, which represents the coherence activity from the available electrodes within the given time window. These pixel columns are concatenated horizontally for all available sliding time windows with 50% overlap, resulting in a grayscale image representation that can be input to well-known deep learning architectures specialized for images. We name this representation Connectogram-COH, a coherence-based version of the previously proposed time graph representation, Connectogram. <b>Results</b>: The experimental results demonstrate that the proposed Connectogram-COH representation effectively captures the coherence dynamics of multichannel EEG data and achieves high accuracy in detecting Alzheimer's disease. The time graph images serve as robust input for deep learning classifiers, outperforming traditional EEG representations in terms of classification performance. <b>Conclusions</b>: Connectogram-COH offers a powerful and interpretable approach for transforming EEG signals into image representations that are well suited for deep learning. The method not only improves the detection of AD but also shows promise for broader applications in EEG-based and general time series classification tasks.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111440
Laura Büttner, Annette Aigner, Regina Stegherr, Simon Iseke, Martin Jonczyk, Willie Magnus Lüdemann, Timo Alexander Auer, Federico Collettini, Dirk Schnapauff, Maximilian de Bucourt, Bernhard Gebauer, Dominik Geisel, Georg Böning
{"title":"Sarcopenia as a Risk Factor in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt (TIPS) Implantation.","authors":"Laura Büttner, Annette Aigner, Regina Stegherr, Simon Iseke, Martin Jonczyk, Willie Magnus Lüdemann, Timo Alexander Auer, Federico Collettini, Dirk Schnapauff, Maximilian de Bucourt, Bernhard Gebauer, Dominik Geisel, Georg Böning","doi":"10.3390/diagnostics15111440","DOIUrl":"10.3390/diagnostics15111440","url":null,"abstract":"<p><p><b>Background</b>: Prior studies suggest that patients' body composition changes following transjugular intrahepatic portosystemic shunt (TIPS) implantation, potentially influencing complications and survival. <b>Method</b>: A prototype artificial intelligence (AI)-based, automated computed tomography (CT) body composition analysis tool was used to assess body composition imaging parameters in pre- and postinterventional scans of TIPS patients: visceral (VAT) and subcutaneous adipose tissue (SAT) areas, psoas muscle area (PMA), and total abdominal muscle area (TAMA). Sarcopenia was defined as a lumbar skeletal muscle index (LSMI) ≤ 38.5 cm<sup>2</sup>/m<sup>2</sup> in women and ≤52.4 cm<sup>2</sup>/m<sup>2</sup> in men. We analyzed longitudinal changes in body composition and investigated the impact of sarcopenia at TIPS implantation on the risk of TIPS thrombosis, hepatic encephalopathy, complications, and death using Cox regression models. <b>Results</b>: No clear trend emerged regarding changes in body composition parameters during postinterventional follow-up. Sarcopenia at TIPS implantation increased the instantaneous risk of postinterventional complications (hazard ratio (HR) 1.67; 95% confidence interval (CI) 0.95-2.93), development of hepatic encephalopathy (HR 1.65; 0.81-3.33), as well as the risk of dying within one year (HR 1.39; 0.66-2.92). <b>Conclusions</b>: CT body composition analysis may help in identifying high-risk patients undergoing TIPS implantation. Sarcopenia was associated with increased mortality and a higher incidence of postinterventional complications, particularly hepatic encephalopathy.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111438
Jasna Mihailović
{"title":"Evolving Paradigm in Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Historical Perspectives, Current Practices and Future Directions.","authors":"Jasna Mihailović","doi":"10.3390/diagnostics15111438","DOIUrl":"10.3390/diagnostics15111438","url":null,"abstract":"<p><p>Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed by tumor biology, patient risk stratification and evolving clinical guidelines. This review examines the changing landscape of I-131 therapy, tracing its historical foundations, current indications, and future directions shaped by molecular medicine. We discuss the transition from a standardized, one-size-fits-all treatment approach to an individualized, dynamic stratification model that allows for ongoing risk reassessment and tailored treatment strategies. Key updates in clinical practice, such as the 2015 ATA Guidelines, the 2022 ETA Consensus Statement, and joint SNMMI and EANM nuclear medicine recommendations, are critically examined. We also address ongoing controversies in the management of low- and intermediate-risk patients, including the roles of I-131 whole-body scanning, activity selection, and overall treatment approach. Molecular theranostics is ushering in a new era in DTC management, enabling improved patient selection and more precise treatment. Advances in molecular profiling, imaging, and targeted therapies support a personalized treatment approach that aims to optimize therapeutic decisions while minimizing side effects and enhancing long-term safety.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111434
Maddalena Calvo, Gaetano Maugeri, Dafne Bongiorno, Giuseppe Migliorisi, Stefania Stefani
{"title":"Integrating an LFA Carbapenemase Detection System into the Laboratory Diagnostic Routine: Preliminary Data and Effectiveness Against Enzyme Variants.","authors":"Maddalena Calvo, Gaetano Maugeri, Dafne Bongiorno, Giuseppe Migliorisi, Stefania Stefani","doi":"10.3390/diagnostics15111434","DOIUrl":"10.3390/diagnostics15111434","url":null,"abstract":"<p><p><b>Background/Objectives</b>. Carbapenemase production is the most diffused carbapenem-resistance mechanism among <i>Enterobacterales</i>, with <i>Klebsiella pneumoniae</i> carbapenemase (KPC), Verona-imipenemase (VIM), New-Delhi metallo-β-lactamase (NDM), imipenemase (IMP), and oxacillinase (OXA-48) being reported as the main types within Europe. Particularly, Southern Italy holds a concerningly high percentage of carbapenemases-producing <i>Enterobacterales</i> diffused among different hospital settings. These strains may colonize critical patients' gastrointestinal tracts, often causing disseminations and severe complications. Scientific data recently reported carbapenemase variants' worldwide diffusion and several double-carbapenemases reports. The diagnostic routine needs devices whose detection rates are extended to similar epidemiological conditions, avoiding a lack of specificity and potential negative results. <b>Methods</b>. We planned a retrospective study including carbapenem- and/or ceftazidime/avibactam-resistant <i>Enterobacterales</i> (62) which were tested with the KPC/IMP/NDM/VIM/OXA-48 Combo Test Kit (KINVO, Medomics Medical Technology, Nanjing, Jiangsu, China) based on the lateral flow assay (LFA) method. <b>Results</b>. We compared its results to the phenotypic antimicrobial susceptibility testing (AST) MIC results, obtaining a 100% agreement rate. The LFA kit reported carbapenemases in all the tested strains, also identifying cases of KPC variants and double-carbapenemases production. <b>Conclusions</b>. Our data demonstrated how LFAs may represent a reliable alternative requiring minimum economic and personnel resources along with simple result interpretations. Future studies will be necessary to further investigate the system effectiveness on a larger isolates' number and a broad carbapenemase variant spectrum.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111435
Andrea Capponi, Carlo Rostagno
{"title":"Trauma-Induced Coagulopathy: A Review of Specific Molecular Mechanisms.","authors":"Andrea Capponi, Carlo Rostagno","doi":"10.3390/diagnostics15111435","DOIUrl":"10.3390/diagnostics15111435","url":null,"abstract":"<p><p>Trauma remains a leading cause of death and disability in adults, and about 20% of deaths occur due to intractable bleeding. Trauma-induced coagulopathy (TIC) is a complex hemostatic disorder characterized by an abnormal coagulation response, which can manifest as either a hypo-coagulable state, leading to excessive bleeding, or a hypercoagulable state, resulting in thromboembolic events and multiple organ failure. Early diagnosis and correction of hypocoagulability may be lifesaving. Replacement of coagulation factors using blood components as well as counteracting enhanced fibrinolysis with tranexamic acid in association with a strategy of damage control are the current practices in the management of TIC. Nevertheless, the improved comprehension of the several mechanisms involved in the development of TIC might offer space for a tailored treatment with improvement of clinical outcome. This review aims to outline the pathophysiology of TIC and evaluate both established and emerging management strategies. A thorough literature review was made with a specific emphasis on articles discussing the molecular mechanisms of trauma-induced coagulopathy. We utilized PubMed, Scopus, and Web of Science with the main search terms \"trauma-induced coagulopathy\", \"molecular mechanisms\", and \"coagulation pathways\".</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Variation in CBC-Derived Inflammatory Biomarkers Across Histologic Subtypes of Lung Cancer: Can Histology Guide Clinical Management?","authors":"Claudia Raluca Mariean, Oana Mirela Tiuca, Alexandru Mariean, Ovidiu Simion Cotoi","doi":"10.3390/diagnostics15111437","DOIUrl":"10.3390/diagnostics15111437","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The early detection of high levels of CBC-derived inflammatory biomarkers and cellular lines, as well as their variations across different histological subtypes of lung cancer, may aid in the early identification of high-risk lung cancer patients and further guide their clinical approach. <b>Methods</b>: A retrospective descriptive study was conducted and included 202 patients diagnosed with lung carcinoma at the Clinical County Hospital Mureș. The main analyzed parameters were the histological subtype and the stage of the tumor at diagnosis, white blood cell counts, and platelet counts, as well as nine CBC-derived inflammatory indexes like neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI). The statistical analysis was performed using the MedCalc software, version 23.0.2. Logarithmic ANOVA was used to compare groups. Normality was tested using the Shapiro-Wilk test. The Chi-square test compared categorical variables, while the independent Mann-Whitney test was used for continuous variables. <b>Results</b>: The inflammatory response increased as disease severity progressed, with NSCLC-NOS being the histological subtype with the most numerous patients outside the normal ranges. Eosinophil count differed significantly across the histologic subtypes of NSCLC, with adenocarcinoma and adenosquamous patients exhibiting the highest values. In adenocarcinoma patients, we observed that NLR and MLR levels increased progressively as the tumor stage advanced. Based on severity, differences were observed across the histological subtypes of lung cancer in stage III patients for ENR, EMR, AISI, eosinophil count, and platelet count, as well as in stage IV patients for AISI, SIRI, and SII. Disease severity impacts the associated inflammatory response in all histologic subtypes of lung cancer to varying degrees. <b>Conclusions</b>: Histological subtype might have a decisive role in shaping the systemic inflammatory profile of lung cancer patients. CBC-derived indices serve as accessible, cost-effective biomarkers for early risk assessment, aiding in the prognosis evaluation and monitoring of therapeutic response. Future studies are needed to further evaluate the histology-specific inflammatory profiles as adjunctive tools in precision oncology.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111442
Aslı Tatlıparmak, Murat Doğan, Zafer Türkoğlu
{"title":"Preoperative Tunnel Measurement in Hidradenitis Suppurativa: Comparison of Palpation and Ultrasound.","authors":"Aslı Tatlıparmak, Murat Doğan, Zafer Türkoğlu","doi":"10.3390/diagnostics15111442","DOIUrl":"10.3390/diagnostics15111442","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The accurate measurement of tunnel lengths in hidradenitis suppurativa (HS) is critical for surgical planning. This study aimed to evaluate the agreement between palpation and high-frequency ultrasound (USG) for assessing tunnel lengths in HS patients. <b>Methods</b>: This prospective study included patients who underwent the surgical excision of tunnels between May 2024 and July 2024 at a referral dermatology clinic. Tunnel lengths were measured preoperatively using palpation and USG. Clinical and demographic data, including lesion localization and disease severity, were prospectively recorded and analyzed. <b>Results</b>: This study analyzed 121 lesions from patients undergoing surgical excision for HS. Tunnel lengths measured by palpation had a median of 30 mm [IQR 18-40], while USG measurements had a median of 36 mm [IQR 24-51.5], with USG identifying tunnels 10.3 mm longer on average (95% CI: 8.2-12.3). Axillary lesions were most frequent (53.7%), followed by inguinal (32.2%) and sacral regions (6.6%). Most lesions were classified as Hurley stage 2 (59.5%) and stage 3 (37.2%), with a median IHS4 score of 8 [IQR 7-11]. <b>Conclusions</b>: High-frequency USG offers greater precision than palpation in measuring tunnel lengths, indicating its potential to enhance disease assessments in HS.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Insights into the Phosphatidylinositol-Specific Phospholipase C Gene Family in <i>Leishmania major</i> and <i>Leishmania infantum</i>: Expression Patterns and Potential Association with Drug Resistance.","authors":"Serhat Sirekbasan, Samatar Samaleh Osman, Tuğba Gürkök-Tan","doi":"10.3390/diagnostics15111433","DOIUrl":"10.3390/diagnostics15111433","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Timely and effective clinical management of leishmaniasis depends on a deep understanding of parasite biology and drug resistance mechanisms. Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes are critical for parasite survival and immune evasion and possibly influence treatment outcomes. This study aimed to characterize the PI-PLC gene family in the <i>Leishmania infantum</i> and <i>Leishmania major</i> genomes, with a focus on their expression profiles in antimony-susceptible and -resistant strains to uncover their diagnostic and prognostic relevance. <b>Methods</b>: This study conducted a comprehensive genome-wide screening to identify PI-PLC genes in <i>L. infantum</i> and <i>L. major</i>, followed by detailed analyses of their gene structures, conserved motifs, chromosomal localization, and phylogenetic relationships. To explore potential roles in drug resistance and clinical prognosis, RNA-seq data from antimony-resistant and -susceptible <i>L. infantum</i> strains were analyzed for differential gene expression. <b>Results</b>: Twenty-two PI-PLC genes were identified in each species, displaying conserved catalytic domains and diverse biochemical characteristics. Phylogenetic and chromosomal analyses revealed gene clustering and distribution patterns. Importantly, expression profiling highlighted several PI-PLC genes with differential regulation in resistant strains, suggesting a role in treatment response and potential as molecular markers. <b>Conclusions</b>: Our findings suggest that PI-PLC genes may be associated with drug susceptibility in <i>L. infantum</i>, warranting further functional investigation to validate their role as potential molecular markers.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiagnosticsPub Date : 2025-06-05DOI: 10.3390/diagnostics15111443
Jessica L Keane, Mahashweta Bose, Barbara J Molini, Kelika A Konda, Silver K Vargas, Michael Reyes Diaz, Carlos F Caceres, Jeffrey D Klausner, Rebecca S Treger, Lorenzo Giacani
{"title":"B-Cell Epitope Mapping of the <i>Treponema pallidum</i> Tp0435 Immunodominant Lipoprotein for Peptide-Based Syphilis Diagnostics.","authors":"Jessica L Keane, Mahashweta Bose, Barbara J Molini, Kelika A Konda, Silver K Vargas, Michael Reyes Diaz, Carlos F Caceres, Jeffrey D Klausner, Rebecca S Treger, Lorenzo Giacani","doi":"10.3390/diagnostics15111443","DOIUrl":"10.3390/diagnostics15111443","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Syphilis, a chronic sexually transmitted disease caused by the spirochete <i>Treponema pallidum</i> subspecies <i>pallidum</i> (<i>T. pallidum</i>), is still endemic in low- and middle-income countries and has been resurgent for decades in many high-income nations despite being treatable. Improving our understanding of syphilis pathogenesis, immunology, and <i>T. pallidum</i> biology could result in novel measures to curtail syphilis spread, including new therapeutics, a preventive vaccine, and, most importantly, improved diagnostics. <b>Methods:</b> Using overlapping synthetic peptides spanning the length of the <i>T. pallidum</i> Tp0435 mature lipoprotein, an abundant antigen known to induce an immunodominant humoral response during both natural and experimental infection, we evaluated which Tp0435 linear epitopes are most significantly recognized by antibodies from an infected host. Specifically, we used sera from 63 patients with syphilis at different stages, sera from non-syphilis patients (<i>n</i> = 40), and sera longitudinally collected from 10 rabbits infected with either the Nichols or SS14 isolates of <i>T. pallidum</i>, which represent the model strains for the two known circulating clades of this pathogen, to further evaluate the use of this animal model for syphilis studies. Recognized amino acid sequences were then mapped to the experimentally determined Tp0435 structure. <b>Results:</b> Reactive epitopes in both serum groups mapped predominantly to the α-helix preceding Tp0435 soluble β-barrel and the loops of the barrel. <b>Conclusions:</b> In the current effort to improve current syphilis diagnostics, the peptides corresponding to these immunodominant epitopes could help develop epitope-based assays such as peptide-based ELISAs and lateral flow point-of-care tests to improve the performance of treponemal tests and expedite diagnosis in low-income settings, where the infection is still a significant concern for public health and access to facilities with laboratories equipped to perform complex procedures might be challenging.</p>","PeriodicalId":11225,"journal":{"name":"Diagnostics","volume":"15 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}