Diagnostics

15 pages, 1516 KiB

Open AccessArticle

B-Cell Epitope Mapping of the Treponema pallidum Tp0435 Immunodominant Lipoprotein for Peptide-Based Syphilis Diagnostics

by 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 and Lorenzo Giacani

Diagnostics 2025, 15(11), 1443; https://doi.org/10.3390/diagnostics15111443 - 5 Jun 2025

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Abstract

Background/Objectives: Syphilis, a chronic sexually transmitted disease caused by the spirochete Treponema pallidum subspecies pallidum (T. pallidum), 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 [...] Read more.

Background/Objectives: Syphilis, a chronic sexually transmitted disease caused by the spirochete Treponema pallidum subspecies pallidum (T. pallidum), 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 T. pallidum biology could result in novel measures to curtail syphilis spread, including new therapeutics, a preventive vaccine, and, most importantly, improved diagnostics. Methods: Using overlapping synthetic peptides spanning the length of the T. pallidum 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 (n = 40), and sera longitudinally collected from 10 rabbits infected with either the Nichols or SS14 isolates of T. pallidum, 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. Results: Reactive epitopes in both serum groups mapped predominantly to the α-helix preceding Tp0435 soluble β-barrel and the loops of the barrel. Conclusions: 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. Full article

(This article belongs to the Special Issue Dermatology and Venereology: Diagnosis and Management)

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13 pages, 3586 KiB

Open AccessArticle

Preoperative Tunnel Measurement in Hidradenitis Suppurativa: Comparison of Palpation and Ultrasound

by Aslı Tatlıparmak, Murat Doğan and Zafer Türkoğlu

Diagnostics 2025, 15(11), 1442; https://doi.org/10.3390/diagnostics15111442 - 5 Jun 2025

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Abstract

Background/Objectives: 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. Methods: This prospective study included [...] Read more.

Background/Objectives: 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. Methods: 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. Results: 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]. Conclusions: High-frequency USG offers greater precision than palpation in measuring tunnel lengths, indicating its potential to enhance disease assessments in HS. Full article

(This article belongs to the Special Issue Advances in Imaging Diagnosis of Dermatology)

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22 pages, 2225 KiB

Open AccessArticle

Connectogram-COH: A Coherence-Based Time-Graph Representation for EEG-Based Alzheimer’s Disease Detection

by Ehssan Aljanabi and İlker Türker

Diagnostics 2025, 15(11), 1441; https://doi.org/10.3390/diagnostics15111441 - 5 Jun 2025

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Abstract

Background: 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 [...] Read more.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

(This article belongs to the Special Issue EEG Analysis in Diagnostics)

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11 pages, 1848 KiB

Open AccessArticle

Sarcopenia as a Risk Factor in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt (TIPS) Implantation

by 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 and Georg Böning

Diagnostics 2025, 15(11), 1440; https://doi.org/10.3390/diagnostics15111440 (registering DOI) - 5 Jun 2025

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Abstract

Background: Prior studies suggest that patients’ body composition changes following transjugular intrahepatic portosystemic shunt (TIPS) implantation, potentially influencing complications and survival. Method: A prototype artificial intelligence (AI)-based, automated computed tomography (CT) body composition analysis tool was used to assess body composition [...] Read more.

Background: Prior studies suggest that patients’ body composition changes following transjugular intrahepatic portosystemic shunt (TIPS) implantation, potentially influencing complications and survival. Method: 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 cm²/m² in women and ≤52.4 cm²/m² 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. Results: 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). Conclusions: 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. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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15 pages, 2602 KiB

Open AccessArticle

The Role of Muscle Density in Predicting the Amputation Risk in Peripheral Arterial Disease: A Tissue Composition Study Using Lower Extremity CT Angiography

by Yueh-Hung Lin, Pei-Shan Tsai, Chung-Lieh Hung, Mirza Faisal Beg, Hung-I Yeh, Chun-Ho Yun and Ming-Ting Wu

Diagnostics 2025, 15(11), 1439; https://doi.org/10.3390/diagnostics15111439 - 5 Jun 2025

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Abstract

Objectives: Peripheral arterial disease (PAD) is a common vascular condition with amputation as a major complication. While muscle volume and vascular severity is often considered in risk prediction, the prognostic value of muscle density remains underexplored. Methods: In this exploratory study, we [...] Read more.

Objectives: Peripheral arterial disease (PAD) is a common vascular condition with amputation as a major complication. While muscle volume and vascular severity is often considered in risk prediction, the prognostic value of muscle density remains underexplored. Methods: In this exploratory study, we retrospectively analyzed 134 patients undergoing lower-limb computed tomography angiography between January 2018 and December 2023. Muscle density (MD), muscle volume, intermuscular adipose tissue (IMAT), and vascular severity scores were quantified using deep learning software. Patients were stratified into non-PAD, mild PAD, and critical limb ischemia (CLI) groups. Multivariate Cox regression assessed associations with amputation risk. Results: PAD patients, especially those with CLI, had lower muscle volumes (e.g., total leg: 7945.3 ± 2012.5 cm³ in CLI vs. 11,161.6 ± 4670.4 cm³ in non-PAD), lower muscle densities (e.g., lower leg: 34.0 ± 10.5 HU in CLI vs. 44.1 ± 6.9 HU in non-PAD), higher intermuscular adipose tissue volume percentage (e.g., total leg: 15.6 ± 5.4% in CLI vs. 10.5 ± 3.6% in non-PAD), and higher vascular severity scores (e.g., total leg: 12.6 ± 5.0 in CLI vs. 0.1 ± 0.3 in non-PAD), compared to non-PAD individuals. Only muscle density (MD) including that of abdominal muscle, thigh muscle, and lower leg muscle remained significant predictors of amputation risk after adjusting for confounders. Multivariate Cox regression models, adjusted for demographics and comorbidities, revealed that lower MD of abdomen (<18.7 HU; HR, 6.50, 95% CI, 1.95–21.77), thigh (<27.8 HU; HR, 5.00, 95% CI, 1.60–15.66), and lower leg (<32.4 HU; HR, 6.89, 95% CI, 2.17–21.93) muscles were independently associated with increased amputation risk. Conclusions: Muscle density, reflecting muscle quality rather than quantity, was an independent predictor of amputation risk in PAD. These findings highlight the prognostic value of muscle quality and support the integration of advanced imaging techniques, such as automated CTA-based body composition analysis, for risk stratification in PAD patients. Full article

(This article belongs to the Special Issue Diagnosis and Management of Vascular Diseases)

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29 pages, 770 KiB

Open AccessReview

Evolving Paradigm in Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Historical Perspectives, Current Practices and Future Directions

by Jasna Mihailović

Diagnostics 2025, 15(11), 1438; https://doi.org/10.3390/diagnostics15111438 - 5 Jun 2025

Viewed by 293

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Applications of PET/CT in Clinical Diagnostics)

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19 pages, 2179 KiB

Open AccessArticle

Variation in CBC-Derived Inflammatory Biomarkers Across Histologic Subtypes of Lung Cancer: Can Histology Guide Clinical Management?

by Claudia Raluca Mariean, Oana Mirela Tiuca, Alexandru Mariean and Ovidiu Simion Cotoi

Diagnostics 2025, 15(11), 1437; https://doi.org/10.3390/diagnostics15111437 - 5 Jun 2025

Viewed by 209

Abstract

Background/Objectives: 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 [...] Read more.

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

(This article belongs to the Special Issue Prognostic and Predictive Biomarkers of Lung Cancer)

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6 pages, 4382 KiB

Open AccessInteresting Images

Whole-Brain Confocal Imaging Provides an Accurate Global View of the Nigral Dopamine System

by Fu-Ming Zhou

Diagnostics 2025, 15(11), 1436; https://doi.org/10.3390/diagnostics15111436 - 5 Jun 2025

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Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomedical Optics)

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19 pages, 1239 KiB

Open AccessReview

Trauma-Induced Coagulopathy: A Review of Specific Molecular Mechanisms

by Andrea Capponi and Carlo Rostagno

Diagnostics 2025, 15(11), 1435; https://doi.org/10.3390/diagnostics15111435 - 5 Jun 2025

Viewed by 217

Abstract

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, [...] Read more.

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”. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

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8 pages, 636 KiB

Open AccessCommunication

Integrating an LFA Carbapenemase Detection System into the Laboratory Diagnostic Routine: Preliminary Data and Effectiveness Against Enzyme Variants

by Maddalena Calvo, Gaetano Maugeri, Dafne Bongiorno, Giuseppe Migliorisi and Stefania Stefani

Diagnostics 2025, 15(11), 1434; https://doi.org/10.3390/diagnostics15111434 - 5 Jun 2025

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Abstract

Background/Objectives. Carbapenemase production is the most diffused carbapenem-resistance mechanism among Enterobacterales, with Klebsiella pneumoniae 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 [...] Read more.

Background/Objectives. Carbapenemase production is the most diffused carbapenem-resistance mechanism among Enterobacterales, with Klebsiella pneumoniae 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 Enterobacterales 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. Methods. We planned a retrospective study including carbapenem- and/or ceftazidime/avibactam-resistant Enterobacterales (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. Results. 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. Conclusions. 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. Full article

(This article belongs to the Special Issue Microbiology Laboratory: Sample Collection and Diagnosis Advances, 2nd Edition)

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12 pages, 2311 KiB

Open AccessArticle

Genomic Insights into the Phosphatidylinositol-Specific Phospholipase C Gene Family in Leishmania major and Leishmania infantum: Expression Patterns and Potential Association with Drug Resistance

by Serhat Sirekbasan, Samatar Samaleh Osman and Tuğba Gürkök-Tan

Diagnostics 2025, 15(11), 1433; https://doi.org/10.3390/diagnostics15111433 - 5 Jun 2025

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Abstract

Background/Objectives: 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 [...] Read more.

Background/Objectives: 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 Leishmania infantum and Leishmania major genomes, with a focus on their expression profiles in antimony-susceptible and -resistant strains to uncover their diagnostic and prognostic relevance. Methods: This study conducted a comprehensive genome-wide screening to identify PI-PLC genes in L. infantum and L. major, 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 L. infantum strains were analyzed for differential gene expression. Results: 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. Conclusions: Our findings suggest that PI-PLC genes may be associated with drug susceptibility in L. infantum, warranting further functional investigation to validate their role as potential molecular markers. Full article

(This article belongs to the Special Issue Clinical Diagnosis, Prognosis and Data Analysis of Medical Parasites and Arthropods)

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18 pages, 3798 KiB

Open AccessArticle

Assessment of the Diagnostic Accuracy of Artificial Intelligence Software in Identifying Common Periodontal and Restorative Dental Conditions (Marginal Bone Loss, Periapical Lesion, Crown, Restoration, Dental Caries) in Intraoral Periapical Radiographs

by Wael I. Ibraheem, Saurabh Jain, Mohammed Naji Ayoub, Mohammed Ahmed Namazi, Amjad Ismail Alfaqih, Aparna Aggarwal, Abdullah A. Meshni, Ammar Almarghlani and Abdulkareem Abdullah Alhumaidan

Diagnostics 2025, 15(11), 1432; https://doi.org/10.3390/diagnostics15111432 - 4 Jun 2025

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Abstract

Objectives: The purpose of the study is to evaluate the diagnostic accuracy of artificial intelligence (AI) software in detecting a common set of periodontal and restorative conditions, including marginal bone loss, dental caries, periapical lesions, calculus, endodontic treatment, crowns, restorations, and open crown [...] Read more.

Objectives: The purpose of the study is to evaluate the diagnostic accuracy of artificial intelligence (AI) software in detecting a common set of periodontal and restorative conditions, including marginal bone loss, dental caries, periapical lesions, calculus, endodontic treatment, crowns, restorations, and open crown margins, using intraoral periapical radiographs. Additionally, the study will assess how this AI software influences the diagnostic accuracy of dentists with varying levels of experience in identifying these conditions. Methods: A total of three hundred digital IOPARs representing 1030 teeth were selected based on predetermined selection criteria. The parameters assessed included (a) calculus, (b) periapical radiolucency, (c) caries, (d) marginal bone loss, (e) type of restorative (filling) material, (f) type of crown retainer material, and (g) detection of open crown margins. Two oral radiologists performed the initial diagnosis of the selected radiographs and independently labeled all the predefined parameters for the provided IOPARs under standardized conditions. This data served as reference data. A pre-trained AI-based computer-aided detection (“CADe”) software (Second Opinion^®, version 1.1) was used for the detection of the predefined features. The reports generated by the AI software were compared with the reference data to evaluate the diagnostic accuracy of the AI software. In the second phase of the study, thirty dental interns and thirty dental specialists were randomly selected. Each participant was randomly assigned five IOPARs and was asked to detect and diagnose the predefined conditions. Subsequently, all the participants were requested to reassess the IOPARs, this time with the assistance of the AI software. All the data was recorded using a self-designed Performa. Results: The sensitivity of the AI software in detecting caries, periapical lesions, crowns, open crown margins, restoration, endodontic treatment, calculus, and marginal bone loss was 91.0%, 86.6%, 97.1%, 82.6%, 89.3%, 93.4%, 80.2%, and 91.1%, respectively. The specificity of the AI software in detected caries, periapical lesions, crowns, open crown margins, restoration, endodontic treatment, calculus, and marginal bone loss was 87%, 98.3%, 99.6%, 91.9%, 96.4%, 99.3%, 97.8%, and 93.1%, respectively. The differences between the AI software and radiologist diagnoses of caries, periapical lesions, crowns, open crown margins, restoration, endodontic treatment, calculus, and marginal bone loss were statistically significant (all p values < 0.0001). The results showed that the diagnostic accuracy of operators (interns and specialists) with AI software revealed higher accuracy, sensitivity, and specificity in detecting caries, PA lesions, restoration, endodontic treatment, calculus, and marginal bone loss compared to that without using AI software. There were variations in the improvements in the diagnostic accuracy of interns and dental specialists. Conclusions: Within the limitations of the study, it can be concluded that the tested AI software has high accuracy in detecting the tested dental conditions in IOPARs. The use of AI software enhanced the diagnostic capabilities of dental operators. The present study used AI software to detect a clinically useful set of periodontal and restorative conditions, which can help dental operators in fast and accurate diagnosis and provide high-quality treatment to their patients. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

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18 pages, 690 KiB

Open AccessReview

The Lung Microbiome and Its Impact on Obstructive Sleep Apnea: A Diagnostic Frontier

by Aliki Karkala, Serafeim-Chrysovalantis Kotoulas, Asterios Tzinas, Eleni Massa, Eleni Mouloudi, Foteini Gkakou and Athanasia Pataka

Diagnostics 2025, 15(11), 1431; https://doi.org/10.3390/diagnostics15111431 - 4 Jun 2025

Viewed by 281

Abstract

Obstructive sleep apnea (OSA), a prevalent disorder characterized by recurrent upper airway collapse, is increasingly recognized as a systemic inflammatory condition influenced by microbial dysregulation. Emerging evidence underscores the lung microbiome as a mediator in OSA pathophysiology, where dysbiotic shifts driven by intermittent [...] Read more.

Obstructive sleep apnea (OSA), a prevalent disorder characterized by recurrent upper airway collapse, is increasingly recognized as a systemic inflammatory condition influenced by microbial dysregulation. Emerging evidence underscores the lung microbiome as a mediator in OSA pathophysiology, where dysbiotic shifts driven by intermittent hypoxia, oxidative stress and mechanical airway trauma amplify inflammatory cascades and perpetuate respiratory instability. This review synthesizes current knowledge on the bidirectional interplay between OSA and lung microbial communities. It aims to highlight how hypoxia-induced alterations in microbial ecology disrupt immune homeostasis, while inflammation-driven mucosal injury fosters pathogenic colonization. Clinical correlations between specific taxa like Streptococcus and Prevotella, and disease severity, suggest microbial signatures as novel biomarkers for OSA progression and treatment response. Furthermore, oxidative stress markers and pro-inflammatory cytokines emerge as potential diagnostic tools that bridge microbial dysbiosis with sleep-related outcomes. However, challenges persist in sampling standardization of the low-biomass lower airways, as well as in causative mechanisms linking microbial dysbiosis to OSA pathophysiology. By integrating microbial ecology with precision sleep medicine, this paradigm shift promises to transform OSA management from mechanical stabilization to holistic ecosystem restoration. Full article

(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)

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15 pages, 7556 KiB

Open AccessArticle

Comparison of Tomographic Findings in Patients with Influenza A (H1N1) and COVID-19

by Lourdes Noemí Vélez-Ramírez, Omar Jiménez-Zarazúa, Luis Ernesto González-Najera, Gustavo Adolfo Flores-Saldaña, Adolfo Valdez-Escobedo and Jaime Daniel Mondragón

Diagnostics 2025, 15(11), 1430; https://doi.org/10.3390/diagnostics15111430 - 4 Jun 2025

Viewed by 230

Abstract

Objectives: The objective of this study was to identify CT-based predictors of mechanical ventilation and mortality in patients with severe and critical viral pneumonia and to examine the association between imaging severity and outcomes in ventilated patients. Methods: We analyzed pulmonary [...] Read more.

Objectives: The objective of this study was to identify CT-based predictors of mechanical ventilation and mortality in patients with severe and critical viral pneumonia and to examine the association between imaging severity and outcomes in ventilated patients. Methods: We analyzed pulmonary CT scans from 148 patients with severe or critical pneumonia caused by COVID-19 (n = 98) or influenza A H1N1 (n = 50). Patients were assessed based on tomographic patterns, demographics, clinical severity scores (Charlson Comorbidity Index, SOFA, and APACHE IV), and biomarkers. Survival analyses were performed using Kaplan–Meier curves and multivariable Cox regression. Results: Bilateral, peripheral, and basal lung involvement was common across both groups. Ground-glass opacities (89.62%, p ≤ 0.001) and consolidation (61.54%, p = 0.001) were more prevalent in COVID-19, whereas pleural effusion was significantly more frequent in H1N1 (76.92%, p ≤ 0.001). COVID-19 cases more often presented with bilateral (96.94%) and peripheral lesions (77.87%). H1N1 patients were more likely to develop severe ARDS and require mechanical ventilation. In COVID-19, higher APACHE IV scores and pulmonary damage severity index were independently associated with increased mortality. Conclusions: Radiologic and clinical severity profiles differ between COVID-19 and H1N1 pneumonia. CT-based assessments combined with prognostic scores may aid early risk stratification and guide treatment decisions in patients with severe viral pneumonia. Full article

(This article belongs to the Special Issue Diagnostics in the Emergency and Critical Care Medicine)

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9 pages, 766 KiB

Open AccessArticle

Comparison of Aqueous Depth Changes Following Cataract Surgery in Vitrectomized and Non-Vitrectomized Fellow Eyes

by Mercè Guarro, Laura Sararols, Elena López, Meritxell Vázquez, Sergi Ruiz and Marc Biarnés

Diagnostics 2025, 15(11), 1429; https://doi.org/10.3390/diagnostics15111429 - 4 Jun 2025

Viewed by 218

Abstract

Background/Objectives: The role of the vitreous in the effective lens position (ELP) is controversial in patients undergoing phacovitrectomy. The aim of this study was to compare the change in aqueous depth (AD), a surrogate of the ELP, in non-vitrectomized and vitrectomized fellow [...] Read more.

Background/Objectives: The role of the vitreous in the effective lens position (ELP) is controversial in patients undergoing phacovitrectomy. The aim of this study was to compare the change in aqueous depth (AD), a surrogate of the ELP, in non-vitrectomized and vitrectomized fellow eyes. Methods: Post-hoc analysis of a prospective study conducted in OMIQ facilities (Barcelona, Spain) between 2021 and 2023. Patients with bilateral cataracts and a unilateral grade 2/3 epiretinal membrane underwent phacoemulsification in one eye and phacovitrectomy without endotamponade in the fellow eye. All eyes were implanted with an extended depth-of-focus intraocular lens after power calculation using the same biometer, technicians, formula, and surgeon. We compared the change in AD (mm and percentage) from baseline, and the role of vitrectomy without endotamponade on AD with a mixed-effects models. Results: We included 40 eyes (20 patients) with a mean age of 71.6 years, with 55% females. The mean change in AD was +1.51 (vitrectomized) and +1.42 mm (non-vitrectomized eyes), p = 0.33. The percent of change in AD was not different between groups (p ≥ 0.38) and phacovitrectomy had no effect on the change in AD on mixed-effects models (p > 0.10). Conclusions: The absence of the vitreous had a minimal influence on AD in these patients undergoing standard phacoemulsification or phacovitrectomy. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

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13 pages, 751 KiB

Open AccessArticle

The Impact of Alveolar Recruitment Strategies on Perioperative Outcomes in Obese Patients Undergoing Major Gynecologic Cancer Surgeries: A Prospective Randomized Controlled Trial

by Duygu Akyol and Funda Gümüş Özcan

Diagnostics 2025, 15(11), 1428; https://doi.org/10.3390/diagnostics15111428 - 4 Jun 2025

Viewed by 215

Abstract

Background/Objectives: Lung-protective ventilation (LPV) reduces postoperative pulmonary complications (PPCs) in obese patients. While the roles of low tidal volume and positive end-expiratory pressure (PEEP) in LPV have been established in patients with healthy lungs, the protective effect of alveolar recruitment strategies (ARSs) [...] Read more.

Background/Objectives: Lung-protective ventilation (LPV) reduces postoperative pulmonary complications (PPCs) in obese patients. While the roles of low tidal volume and positive end-expiratory pressure (PEEP) in LPV have been established in patients with healthy lungs, the protective effect of alveolar recruitment strategies (ARSs) remains a subject of debate. This study aims to evaluate the benefit of ARSs in patients with low-to-moderate risk according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score undergoing gynecologic cancer surgery with LPV and low tidal volume intraoperatively. Methods: A total of 88 obese patients were evaluated in this study. They were divided into two groups as the non-ARS group (non-ARS) and the ARS group (ARS). Intraoperative hemodynamics, blood gas analyses, respiratory mechanics, mechanical ventilator parameters, and postoperative outcomes were compared in these obese patients. Results: A total of 40 obese patients undergoing major gynecological cancer surgery were included in this study. Although the non-ARS group presented with higher weight (p < 0.05), body mass indexes were similar to the ARS group. Intraoperative blood gas analysis revealed higher end-tidal carbon dioxide (etCO₂) levels in the non-ARS group during the T2 and T3 time intervals (p < 0.05). In the ARS group, peak inspiratory pressure (PIP) at T3 was lower, while drive pressures at T1 and T2 and dynamic compliance at T3 were higher (p < 0.05). Radiologic atelectasis scores were higher in the non-ARS group, indicating more atelectatic lung images (p < 0.05). PPC rates were similar across both groups. Conclusions: Although the ARS demonstrated positive effects on lung mechanics and radiologic atelectasis scores in major open gynecologic cancer surgeries, it did not effectively reduce postoperative pulmonary complications. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

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13 pages, 969 KiB

Open AccessArticle

Ultrasound Evaluation of Internal Jugular Venous Insufficiency and Its Association with Cognitive Decline

by Jiu-Haw Yin, Nai-Fang Chi, Wen-Yung Sheng, Pei-Ning Wang, Yueh-Feng Sung, Giia-Sheun Peng and Han-Hwa Hu

Diagnostics 2025, 15(11), 1427; https://doi.org/10.3390/diagnostics15111427 - 4 Jun 2025

Viewed by 292

Abstract

Background: Prior studies have shown an association between jugular venous reflux and age-related neurological conditions, including cognitive decline and potentially incident dementia. However, a relationship between internal jugular vein (IJV) outflow disturbance and cognitive impairment has yet to be elucidated. This study evaluates [...] Read more.

Background: Prior studies have shown an association between jugular venous reflux and age-related neurological conditions, including cognitive decline and potentially incident dementia. However, a relationship between internal jugular vein (IJV) outflow disturbance and cognitive impairment has yet to be elucidated. This study evaluates the relationship between impaired IJV drainage and cognitive function. Methods: We recruited a prospective sample of 106 participants with subjective memory complaints. Subjects underwent neuropsychological assessments and ultrasound examination of IJV, including time-averaged mean velocity (TAMV) and the cross-sectional area of the IJV at the middle (J2) and distal (J3) segments. Impaired IJV drainage was defined by either of the following: (1) TAMV < 4 cm/s at the J2 or J3 segment on either side, or (2) IJV lumen collapse during inspiration at the J2 segment on either side. Results: The impaired cognition group had a significantly higher prevalence of both impaired flow velocity and impaired IJV drainage compared to the normal cognition group (34% vs. 16%, p = 0.032; 68% vs. 30%, p < 0.001). Furthermore, the impaired IJV drainage group demonstrated lower scores across all neuropsychological tests, with statistical significance observed in the Mini-Mental State Examination (median (IQR) 27 vs. 29, p = 0.013), Montreal Cognitive Assessment (median (IQR) 23 vs. 26, p < 0.001) and Chinese Version of the Verbal Learning Test (median (IQR) 23.5 vs. 27, p = 0.024). Notably, incorporating IJV lumen collapse during deep inspiration into the definition of impaired IJV drainage further increased its prevalence in the impaired cognition group. Conclusions: Our results revealed that the impaired cognition group exhibited a higher prevalence of impaired outflow in the bilateral IJV, while the impaired IJV drainage group scored lower on all neuropsychological tests compared to the normal group. These findings support the hypothesis that impaired IJV drainage is correlated with global cognitive decline. Full article

(This article belongs to the Special Issue Current Challenges and Perspectives of Ultrasound, 2nd Edition)

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13 pages, 1392 KiB

Open AccessArticle

Prognostic Significance of RBM3 Expression in Epithelial Ovarian Cancer: A Tissue Microarray-Based Study

by Hyeong Chan Shin, Hye Won Lee, So-Jin Shin and Sun Young Kwon

Diagnostics 2025, 15(11), 1426; https://doi.org/10.3390/diagnostics15111426 - 3 Jun 2025

Viewed by 194

Abstract

Background/Objectives: RNA-binding motif protein 3 (RBM3) is a cold-shock protein associated with a favorable prognosis in various malignancies. However, its role in epithelial ovarian cancer (OC) remains unclear. This study aimed to evaluate the prognostic significance of RBM3 expression in OC and its [...] Read more.

Background/Objectives: RNA-binding motif protein 3 (RBM3) is a cold-shock protein associated with a favorable prognosis in various malignancies. However, its role in epithelial ovarian cancer (OC) remains unclear. This study aimed to evaluate the prognostic significance of RBM3 expression in OC and its association with clinicopathological features. Methods: We retrospectively analyzed 183 cases of OC. Tissue microarrays were constructed using paired 2 mm tumor cores, and RBM3 expression was assessed by immunohistochemistry. Nuclear staining was semi-quantitatively scored based on intensity and proportion, generating a nuclear score (NS). Cases were classified as high (NS > 1) or low (NS ≤ 1) expression. Associations with clinicopathological parameters and survival outcomes were analyzed using chi-square tests, Kaplan–Meier survival curves, and Cox regression models. Results: High RBM3 expression was observed in 51.4% of cases and was significantly associated with favorable histologic subtypes (mucinous, endometrioid, clear cell), early International Federation of Gynecology and Obstetrics (FIGO) stage, and the absence of distant metastasis. Subgroup survival analyses stratified by histologic subtype revealed no significant differences in survival outcomes. RBM3 expression was correlated with prolonged disease-free and overall survival, although it did not retain significance in multivariate analysis. Conclusions: RBM3 expression is strongly associated with favorable pathological features in epithelial ovarian cancer. Although not an independent prognostic marker, RBM3 may serve as a complementary biomarker for risk stratification and prognosis in clinical practice. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

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10 pages, 692 KiB

Open AccessArticle

GM-VGG-Net: A Gray Matter-Based Deep Learning Network for Autism Classification

by Ebenezer Daniel, Anjalie Gulati, Shraya Saxena, Deniz Akay Urgun and Biraj Bista

Diagnostics 2025, 15(11), 1425; https://doi.org/10.3390/diagnostics15111425 - 3 Jun 2025

Viewed by 259

Abstract

Background: Around 1 in 59 individuals is diagnosed with Autism Spectrum Disorder (ASD), according to CDS statistics. Conventionally, ASD has been diagnosed using functional brain regions, regions of interest, or multi-tissue-based training in artificial intelligence models. The objective of the exhibit study is [...] Read more.

Background: Around 1 in 59 individuals is diagnosed with Autism Spectrum Disorder (ASD), according to CDS statistics. Conventionally, ASD has been diagnosed using functional brain regions, regions of interest, or multi-tissue-based training in artificial intelligence models. The objective of the exhibit study is to develop an efficient deep learning network for identifying ASD using structural magnetic resonance imaging (MRI)-based brain scans. Methods: In this work, we developed a VGG-based deep learning network capable of diagnosing autism using whole brain gray matter (GM) tissues. We trained our deep network with 132 MRI T1 images from normal controls and 140 MRI T1 images from ASD patients sourced from the Autism Brain Imaging Data Exchange (ABIDE) dataset. Results: The number of participants in both ASD and normal control (CN) subject groups was not statistically different (p = 0.23). The mean age of the CN subject group was 14.62 years (standard deviation: 4.34), and the ASD group had mean age of 14.89 years (standard deviation: 4.29). Our deep learning model accomplished a training accuracy of 97% and a validation accuracy of 96% over 50 epochs without overfitting. Conclusions: To the best of our knowledge, this is the first study to use GM tissue alone for diagnosing ASD using VGG-Net. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

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10 pages, 416 KiB

Open AccessArticle

Imaging and Clinical Outcomes Six Months After Middle Meningeal Artery Embolization with Squid for Chronic Subdural Hematoma: A Prospective Study

by Ángela H. Schmolling, Carlos Pérez-García, Isabel Bérmudez, Alfonso López-Frías, Eduardo Fandiño, Carmen Trejo, Santiago Rosati, Daniel Padrón, Lara Guardado, José Carlos Méndez, Juan Arrazola and Manuel Moreu

Diagnostics 2025, 15(11), 1424; https://doi.org/10.3390/diagnostics15111424 - 3 Jun 2025

Viewed by 199

Abstract

Background: Chronic subdural hematoma (CSDH) is a common condition in older adults with rising rates of incidence. While burr hole drainage remains the standard treatment, it is associated with significant recurrence and complications. This study assesses MMA embolization with Squid, both as a [...] Read more.

Background: Chronic subdural hematoma (CSDH) is a common condition in older adults with rising rates of incidence. While burr hole drainage remains the standard treatment, it is associated with significant recurrence and complications. This study assesses MMA embolization with Squid, both as a standalone procedure and as an adjunct to surgery. Methods: Our prospective registry included 101 patients with 134 CSDH cases treated at two tertiary care centers from December 2020 to January 2024. Patients were divided into two groups: embolization alone and embolization combined with surgery. Demographic, clinical, radiological, and procedural data were collected. Follow-up imaging was conducted at 1, 3, and 6 months. Treatment failure was defined as rescue surgery, hematoma thickness ≥ 10 mm, midline shift > 3 mm at 6 months, or procedure-related death. Results: Fifty-two patients (51.5%) underwent combined treatment, and forty-nine (48.5%) received embolization alone. Most were men (68.3%) and the median age was 82 years. Combined-treatment patients had larger hematomas and more symptoms. Procedures were performed under general anesthesia in 72.3% of patients, with radial and femoral access used equally frequently, and 32.7% underwent bilateral embolization. Patients’ hematoma thickness in follow-up imaging showed a significant decrease (p = 0.000), reaching a median of 0 mm at six months, with no significant difference between groups. Complications occurred in 5.9%, and treatment failure in 4%. Mortality was higher in the embolization-only group, likely reflecting greater rates of comorbidities. Conclusions: This study supports the use of MMA embolization with Squid as a safe and effective treatment for CSDH. Comparable procedural and radiological outcomes in both groups suggest embolization alone may suffice in select patients, offering a less invasive alternative. Full article

(This article belongs to the Special Issue Chronic Subdural Hematoma: Diagnosis and Management, 2nd Edition)

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10 pages, 1972 KiB

Open AccessCase Report

Fetal Death Due to an Unusual Coexistence of Two Umbilical Cord Anomalies: Analysis in a Forensic Perspective

by Alice Ferretti, Maria Paola Bonasoni, Benedetta Petrachi, Giuseppina Comitini, Immacolata Blasi, Arianna Giorgetti, Paolo Fais, Susi Pelotti and Lorenzo Aguzzoli

Diagnostics 2025, 15(11), 1423; https://doi.org/10.3390/diagnostics15111423 - 3 Jun 2025

Viewed by 220

Abstract

Background and Clinical Significance: In stillbirth, bereaved parents must be promptly taken in by healthcare staff, and their requests to understand what happened must be fully explained and discussed. Empathic and open communication with the parents is fundamental in avoiding time-consuming lawsuits for [...] Read more.

Background and Clinical Significance: In stillbirth, bereaved parents must be promptly taken in by healthcare staff, and their requests to understand what happened must be fully explained and discussed. Empathic and open communication with the parents is fundamental in avoiding time-consuming lawsuits for investigating medical liability. Herein, we describe a case of stillbirth in which many elements exemplify potential concerns, either from a parental or judicial context. All these hypothetical questions will be addressed and discussed. Case presentation: A female stillbirth was vaginally delivered at 41 weeks of gestation after induction of labor. The baby was normally grown for gestational age, and the umbilical cord examination disclosed a length of 90 cm (75 cm attached to the placenta and 15 cm to the fetus), two tight knots, and a furcate insertion into the chorionic plate. Histologically, non-occlusive luminal thrombosis was found in the umbilical vein, extended to the cord insertion, and was in a few chorionic vessels. The knots showed myonecrosis in the vascular wall, widespread in the first one and more focal in the second, indicating prolonged contraction. Conclusions: The case we described, though fully diagnostically explained, raised many hypothetical questions that might have been brought up either in a judicial context or during communication with the parents of the autopsy results. Frequent questions may include what the cause of death was, when the baby died, if the death might have been avoidable, and, in the latter, potential medical liability. Full article

(This article belongs to the Special Issue Diagnostic Methods in Forensic Pathology, Third Edition)

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13 pages, 1113 KiB

Open AccessArticle

Automated Detection of the Kyphosis Angle Using a Deep Learning Approach: A Cross-Sectional Study on Young Adults

by Onur Kocak, Cansel Ficici, Ilknur Ezgi Dogan, Ziya Telatar and Nihan Ozunlu Pekyavas

Diagnostics 2025, 15(11), 1422; https://doi.org/10.3390/diagnostics15111422 - 3 Jun 2025

Viewed by 191

Abstract

Objectives: In healthy young adults, thoracic kyphosis can be attributed to a number of factors, including a sedentary lifestyle, stress, poor posture, activity and daily habits, muscle pain, fatigue, and anxiety. In regard to clinical diagnosis and evaluation methods, high-cost radiological measurements and [...] Read more.

Objectives: In healthy young adults, thoracic kyphosis can be attributed to a number of factors, including a sedentary lifestyle, stress, poor posture, activity and daily habits, muscle pain, fatigue, and anxiety. In regard to clinical diagnosis and evaluation methods, high-cost radiological measurements and a variety of non-radiological clinical methods are employed. In this study, a decision support system that performs automatic thoracic kyphosis angle measurements has been developed with the objective of avoiding exposure of the human body to radiation and reducing the time required for measurements. Methods: The features were determined with reference to the thoracic kyphosis measurements that were manually marked by the expert on the subjects. The kyphosis angle was calculated by automatically identifying the T1 and T12 points through image segmentation using a convolutional neural network (CNN), which is a type of deep learning algorithm. Results: Intra-class consistency of ICC > 0.95 (p < 0.05) and internal consistency reliability of Cronbach’s α = 0.947 are obtained. Conclusions: The results demonstrate that the proposed algorithm exhibits high intra-class consistency and high internal consistency reliability to provide an automated thoracic kyphosis angle measurement system. Full article

(This article belongs to the Special Issue Artificial Intelligence and Deep Learning in Clinical Classification and Prediction)

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14 pages, 1392 KiB

Open AccessArticle

A Five-Gene Signature for the Prediction of Event-Free Survival of Both Pediatric and Adult Acute Myeloid Leukemia

by Dechang Chen, Alvin J. Liu, Li Sheng, Zhenqiu Liu and Irina Elcheva

Diagnostics 2025, 15(11), 1421; https://doi.org/10.3390/diagnostics15111421 - 3 Jun 2025

Viewed by 205

Abstract

Background: While adult and pediatric acute myeloid leukemia (AML) exhibit genetic distinctions, investigating their common gene expression program is critical for understanding the fundamental biological mechanisms that drive diverse cellular responses. However, existing gene signatures, predominantly tailored for overall survival (OS), may not [...] Read more.

Background: While adult and pediatric acute myeloid leukemia (AML) exhibit genetic distinctions, investigating their common gene expression program is critical for understanding the fundamental biological mechanisms that drive diverse cellular responses. However, existing gene signatures, predominantly tailored for overall survival (OS), may not adequately forecast event-free survival (EFS). EFS represents the time patients survive without disease recurrence, progression, or further treatment, a crucial metric for evaluating drug efficacy and assessing the clinical benefits of treatment. Methods: We performed an integrated analysis of adult TCGA and pediatric TARGET expression datasets to pinpoint genes and pathways associated with EFS in both adult and pediatric AML. Additionally, we constructed a predictive model using one dataset and validated it on the other to unveil a novel gene signature. Results: A five-gene signature comprising F2RL3, IL2RA, MYH15, SIX3, and SOBP was identified for EFS for both adult and pediatric AML. The test Area Under the ROC Curves (AUCs) for the 2-year and 5-year cutoffs of adult TCGA data were 0.851 (95% CI (Confidence Interval): 0.778–0.923) and 0.848 (95% CI: 0.729–0.968), respectively. Similarly, the test AUCs for the 2-year and 5-year cutoffs of Pediatric TARGET data were 0.725 (95% CI: 0.640–0.811) and 0.695 (95% CI: 0.59–0.80), respectively. When patients were stratified into three equal-sized prognostic subtypes based on the five-gene test risk scores, the P-values of tertile partitions for TARGET and TCGA data were 2.32e−6 and 5.12e−14, respectively, indicating superior performance compared to cytogenetic risk stratification within the same data (TARGET: P = 0.0019; TCGA: P = 0.0086). Despite being identified for EFS, the five-gene signature successfully stratified patients into distinct OS groups across two additional independent datasets. Conclusions: This five-gene signature demonstrates robust performance in both EFS and OS risk prediction and might be clinically significant. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis of Hematological Disease)

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30 pages, 1174 KiB

Open AccessReview

PAX Family, Master Regulator in Cancer

by Erica Giacobbi, Maria Paola Scioli, Francesca Servadei, Valeria Palumbo, Rita Bonfiglio, Pierluigi Bove, Alessandro Mauriello and Manuel Scimeca

Diagnostics 2025, 15(11), 1420; https://doi.org/10.3390/diagnostics15111420 - 3 Jun 2025

Viewed by 180

Abstract

PAX genes, known as master regulators, encode paired box (PAX) proteins that govern key processes in organ development and are widely expressed in normal tissues. Notably, PAX proteins also play a pivotal role in both promoting and suppressing tumorigenesis. They influence essential cellular [...] Read more.

PAX genes, known as master regulators, encode paired box (PAX) proteins that govern key processes in organ development and are widely expressed in normal tissues. Notably, PAX proteins also play a pivotal role in both promoting and suppressing tumorigenesis. They influence essential cellular functions such as survival, proliferation, fate determination, differentiation, invasion, metastasis, and the formation of oncogenic fusion proteins. In this review, we summarize the current understanding of these transcription factors. First, we provide a brief overview of their molecular structure, which underlies their classification into four subgroups. Then, we examine the expression patterns of each PAX gene across organ systems and explore their biological roles in the most relevant malignant neoplasms affecting human health. Additionally, we highlight their diagnostic, prognostic, and predictive significance in the context of cancer. Full article

(This article belongs to the Special Issue Advances in Cancer Biomarkers)

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14 pages, 1010 KiB

Open AccessArticle

Is UA/HDL-C a Reliable Surrogate Marker for Fatty Liver? A Comparative Evaluation with Metabolic Scores in a Mexican Population: The Genetics of Atherosclerotic Disease Study

by Rosalinda Posadas-Sánchez, Giovanny Fuentevilla-Álvarez, Gilberto Vargas-Alarcón and Guillermo C. Cardoso-Saldaña

Diagnostics 2025, 15(11), 1419; https://doi.org/10.3390/diagnostics15111419 - 3 Jun 2025

Viewed by 243

Abstract

Background: Fatty liver disease (FLD), the most common liver disease worldwide, is associated with cardiometabolic diseases and increases the risk of cardiovascular disease. It remains asymptomatic in its early stages, and late diagnosis heightens the likelihood of progression to severe liver diseases. Objectives: [...] Read more.

Background: Fatty liver disease (FLD), the most common liver disease worldwide, is associated with cardiometabolic diseases and increases the risk of cardiovascular disease. It remains asymptomatic in its early stages, and late diagnosis heightens the likelihood of progression to severe liver diseases. Objectives: We aimed to evaluate the utility of serum uric acid to HDL cholesterol ratio (UA/HDL-C) as a biomarker for FLD and compare its diagnostic utility versus established liver disease index (FLI, LAP, HSI, NAFLD score (FLS), and ALT/AST ratio). Methods: This cross-sectional study, conducted between 2009 and 2013, included 1470 adults, 50.2% women and 49.8% men between 20 and 75 years old. FLD was diagnosed using non-contrast computed tomography. The population was stratified by sex and FLD. The associations with UA/HDL-C were analyzed using ROC curves and logistic regression analysis to evaluate and compare the predictive capacity of various indices for FLD. Results: Anthropometric, physiologic, biochemical variables, ratios, and indices were significantly higher in subjects with FLD (p < 0.001). In the unadjusted logistic regression model, UA/HDL-C is strongly associated with FLD (co-efficient 2.5, p < 0.001). The FLS, HSI, and ALT/AST ratios were also significant, whereas FLI and LAP showed no clear relationship. In the sex-adjusted model, the UA/HDL-C ratio remained strongly associated with FLD (3.47, p < 0.001). Conclusions: Our results suggest that the UA/HDL-C ratio is associated with FLD as an established liver disease index and may be a practical, useful marker for FLD. The results highlight its potential as a scrutiny and early biomarker for effective preventive strategies for FLD. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

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21 pages, 374 KiB

Open AccessReview

Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease

by Rahul Kumar, Kyle Sporn, Aryan Borole, Akshay Khanna, Chirag Gowda, Phani Paladugu, Alex Ngo, Ram Jagadeesan, Nasif Zaman and Alireza Tavakkoli

Diagnostics 2025, 15(11), 1418; https://doi.org/10.3390/diagnostics15111418 - 3 Jun 2025

Viewed by 387

Abstract

Degenerative joint disease remains a leading cause of global disability, with early diagnosis posing a significant clinical challenge due to its gradual onset and symptom overlap with other musculoskeletal disorders. This review focuses on emerging diagnostic strategies by synthesizing evidence specifically from studies [...] Read more.

Degenerative joint disease remains a leading cause of global disability, with early diagnosis posing a significant clinical challenge due to its gradual onset and symptom overlap with other musculoskeletal disorders. This review focuses on emerging diagnostic strategies by synthesizing evidence specifically from studies that integrate biochemical biomarkers, advanced imaging techniques, and machine learning models relevant to osteoarthritis. We evaluate the diagnostic utility of cartilage degradation markers (e.g., CTX-II, COMP), inflammatory cytokines (e.g., IL-1β, TNF-α), and synovial fluid microRNA profiles, and how they correlate with quantitative imaging readouts from T2-mapping MRI, ultrasound elastography, and dual-energy CT. Furthermore, we highlight recent developments in radiomics and AI-driven image interpretation to assess joint space narrowing, osteophyte formation, and subchondral bone changes with high fidelity. The integration of these datasets using multimodal learning approaches offers novel diagnostic phenotypes that stratify patients by disease stage and risk of progression. Finally, we explore the implementation of these tools in point-of-care diagnostics, including portable imaging devices and rapid biomarker assays, particularly in aging and underserved populations. By presenting a unified diagnostic pipeline, this article advances the future of early detection and personalized monitoring in joint degeneration. Full article

(This article belongs to the Special Issue Advances in Musculoskeletal Imaging: From Diagnosis to Treatment)

16 pages, 2228 KiB

Open AccessArticle

Potential Use of a New Energy Vision (NEV) Camera for Diagnostic Support of Carpal Tunnel Syndrome: Development of a Decision-Making Algorithm to Differentiate Carpal Tunnel-Affected Hands from Controls

by Dror Robinson, Mohammad Khatib, Mohammad Eissa and Mustafa Yassin

Diagnostics 2025, 15(11), 1417; https://doi.org/10.3390/diagnostics15111417 - 3 Jun 2025

Viewed by 246

Abstract

Introduction: Carpal Tunnel Syndrome (CTS) is a prevalent neuropathy requiring accurate, non-invasive diagnostics to minimize patient burden. This study evaluates the New Energy Vision (NEV) camera, an RGB-based multispectral imaging tool, to detect CTS through skin texture and color analysis, developing a machine [...] Read more.

Introduction: Carpal Tunnel Syndrome (CTS) is a prevalent neuropathy requiring accurate, non-invasive diagnostics to minimize patient burden. This study evaluates the New Energy Vision (NEV) camera, an RGB-based multispectral imaging tool, to detect CTS through skin texture and color analysis, developing a machine learning algorithm to distinguish CTS-affected hands from controls. Methods: A two-part observational study included 103 participants (50 controls, 53 CTS patients) in Part 1, using NEV camera images to train a Support Vector Machine (SVM) classifier. Part 2 compared median nerve-damaged (MED) and ulnar nerve-normal (ULN) palm areas in 32 CTS patients. Validations included nerve conduction tests (NCT), Semmes–Weinstein monofilament testing (SWMT), and Boston Carpal Tunnel Questionnaire (BCTQ). Results: The SVM classifier achieved 93.33% accuracy (confusion matrix: [[14, 1], [1, 14]]), with 81.79% cross-validation accuracy. Part 2 identified significant differences (p < 0.05) in color proportions (e.g., red_proportion) and Haralick texture features between MED and ULN areas, corroborated by BCTQ and SWMT. Conclusions: The NEV camera, leveraging multispectral imaging, offers a promising non-invasive CTS diagnostic tool using detection of nerve-related skin changes. Further validation is needed for clinical adoption. Full article

(This article belongs to the Special Issue New Trends in Musculoskeletal Imaging)

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12 pages, 854 KiB

Open AccessArticle

Forensic Cases in the Emergency Department: Associations Between Life-Threatening Risk, Medical Treatability, and Patient Outcomes

by Harun Yildirim and Murtaza Kaya

Diagnostics 2025, 15(11), 1416; https://doi.org/10.3390/diagnostics15111416 - 2 Jun 2025

Viewed by 248

Abstract

Background: This study aimed to evaluate the clinical and forensic characteristics of cases admitted to a high-volume tertiary emergency department, focusing on severity-based classification using treatability with simple medical intervention (SMI) and life-threatening status. Methods: We retrospectively analyzed 3014 forensic cases over one [...] Read more.

Background: This study aimed to evaluate the clinical and forensic characteristics of cases admitted to a high-volume tertiary emergency department, focusing on severity-based classification using treatability with simple medical intervention (SMI) and life-threatening status. Methods: We retrospectively analyzed 3014 forensic cases over one year. Patients were classified based on injury severity, anatomical region, and clinical outcomes. Documentation practices and report types were also reviewed. Results: Among all the cases, 60.4% were treatable with SMI, and 10.5% were identified as life threatening. Notably, all patients who died (1.3% mortality) were in the life-threatening group, and none of the SMI-treated patients died, underscoring the accuracy of early triage and alignment between documentation and outcomes. Road traffic accidents were the leading cause of life-threatening injury and hospitalization, while assault cases were predominantly minor and managed conservatively. Seasonal variation peaked in July, and sex-based differences revealed a higher SMI eligibility among female patients. Final forensic reports were more frequently issued in SMI cases, while preliminary reports were predominant in severe trauma. Conclusions: Severity-based classification using SMI and life-threatening categories offers valuable insight for clinical decision-making and forensic documentation. Integrating structured triage, anatomical injury mapping, and standardized report templates can enhance both patient safety and legal reliability. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management in Emergency and Hospital Medicine)

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21 pages, 6594 KiB

Open AccessArticle

Three-Dimensional Semantic Segmentation of Palatal Rugae and Maxillary Teeth and Motion Evaluation of Orthodontically Treated Teeth Using Convolutional Neural Networks

by Abdul Rehman El Bsat, Elie Shammas, Daniel Asmar, Kinan G. Zeno, Anthony T. Macari and Joseph G. Ghafari

Diagnostics 2025, 15(11), 1415; https://doi.org/10.3390/diagnostics15111415 - 2 Jun 2025

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Abstract

Background: The segmentation of individual teeth in three-dimensional (3D) dental models is a key step in orthodontic computer-aided design systems. Traditional methods lack robustness when handling challenging cases such as missing or misaligned teeth. Objectives: to semantically segment maxillary teeth and palatal rugae [...] Read more.

Background: The segmentation of individual teeth in three-dimensional (3D) dental models is a key step in orthodontic computer-aided design systems. Traditional methods lack robustness when handling challenging cases such as missing or misaligned teeth. Objectives: to semantically segment maxillary teeth and palatal rugae in 3D textured scans using Convolutional Neural Networks (CNNs) and assess tooth movement after orthodontic treatment using stable rugae references. Methods: Building on the robustness of two-dimensional image semantic segmentation, we developed a method to convert 3D textured palate scans into two-dimensional images for segmentation, then back projected them onto the original 3D meshes. A dataset of 100 textured scans from 100 patients seeking orthodontic treatment was manually segmented by orthodontic experts. The proposed 3D segmentation method was applied to these scans. Finally, each pair of segmented 3D scans from the same patient, before and after treatment, was aligned by superimposing them on the stable rugae region. Results: The 3D segmentation method achieved an accuracy of 98.69% and an average Intersection over Union (IoU) of 84.5%. The common stable coordinate frame for both scans using the rugae area as a stable reference enabled the computation of the 3D translational and rotational motions of each maxillary tooth. Neither pre- nor post-processing of the data was required to enhance segmentation. Conclusions: The proposed method enabled successful motion measurement of teeth using the rugal area as a stable reference and providing rotation and translational measurements of the maxillary teeth. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

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Open AccessArticle

ECG Signal Analysis for Detection and Diagnosis of Post-Traumatic Stress Disorder: Leveraging Deep Learning and Machine Learning Techniques

by Parisa Ebrahimpour Moghaddam Tasouj, Gökhan Soysal, Osman Eroğul and Sinan Yetkin

Diagnostics 2025, 15(11), 1414; https://doi.org/10.3390/diagnostics15111414 - 2 Jun 2025

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Abstract

Background: Post-traumatic stress disorder (PTSD) is a serious psychiatric condition that can lead to severe anxiety, depression, and cardiovascular complications if left untreated. Early and accurate diagnosis is critical. This study aims to develop and evaluate an artificial intelligence-based classification system using electrocardiogram [...] Read more.

Background: Post-traumatic stress disorder (PTSD) is a serious psychiatric condition that can lead to severe anxiety, depression, and cardiovascular complications if left untreated. Early and accurate diagnosis is critical. This study aims to develop and evaluate an artificial intelligence-based classification system using electrocardiogram (ECG) signals for the detection of PTSD. Methods: Raw ECG signals were transformed into time–frequency images using Continuous Wavelet Transform (CWT) to generate 2D scalogram representations. These images were classified using deep learning-based convolutional neural networks (CNNs), including AlexNet, GoogLeNet, and ResNet50. In parallel, statistical features were extracted directly from the ECG signals and used in traditional machine learning (ML) classifiers for performance comparison. Four different segment lengths (5 s, 10 s, 15 s, and 20 s) were tested to assess their effect on classification accuracy. Results: Among the tested models, ResNet50 achieved the highest classification accuracy of 94.92%, along with strong MCC, sensitivity, specificity, and precision metrics. The best performance was observed with 5-s signal segments. Deep learning (DL) models consistently outperformed traditional ML approaches. The area under the curve (AUC) for ResNet50 reached 0.99, indicating excellent classification capability. Conclusions: This study demonstrates that CNN-based models utilizing time–frequency representations of ECG signals can effectively classify PTSD with high accuracy. Segment length significantly influences model performance, with shorter segments providing more reliable results. The proposed method shows promise for non-invasive, ECG-based diagnostic support in PTSD detection. Full article

(This article belongs to the Special Issue Artificial Intelligence in Biomedical Diagnostics and Analysis 2024)

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Diagnostics, Volume 15, Issue 11 (June-1 2025) – 144 articles

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