Diagnostics

11 pages, 771 KiB

Open AccessArticle

Potential for Misinterpretation in the Laboratory Diagnosis of Clostridioides difficile Infections

by Alexandra Kalacheva, Metodi Popov, Valeri Velev, Rositsa Stoyanova, Yordanka Mitova-Mineva, Tsvetelina Velikova and Maria Pavlova

Diagnostics 2025, 15(9), 1166; https://doi.org/10.3390/diagnostics15091166 (registering DOI) - 3 May 2025

Abstract

Background/Objective. Toxin-producing strains of Clostridioides difficile (C. diff) are the most commonly identified cause of healthcare-associated infection in the elderly. Risk factors include advanced age, hospitalization, prior or concomitant systemic antibacterial therapy, chemotherapy, and gastrointestinal surgery. Patients with unspecified and [...] Read more.

Background/Objective. Toxin-producing strains of Clostridioides difficile (C. diff) are the most commonly identified cause of healthcare-associated infection in the elderly. Risk factors include advanced age, hospitalization, prior or concomitant systemic antibacterial therapy, chemotherapy, and gastrointestinal surgery. Patients with unspecified and new-onset diarrhea with ≥3 unformed stools in 24 h are the target population for C. diff infection (CDI) testing. To present data on the risks of laboratory misdiagnosis in managing CDI. Materials. In two general hospitals, we examined 116 clinical stool specimens from hospitalized patients with acute diarrhea suspected of nosocomial or antibiotic-associated diarrhea (AAD) due to C. diff. Enzyme immunoassay (EIA) tests for the detection of C. diff toxins A (cdtA) and B (cdtB) in stool, automated CLIA assay for the detection of C. diff GDH antigen and qualitative determination of cdtA and B in human feces and anaerobic stool culture were applied for CDI laboratory diagnosis. MALDI-TOF (Bruker) was used to identify the presumptive anaerobic bacterial colonies. The following methods were used as confirmatory diagnostics: the LAMP method for the detection of Salmonella spp. and simultaneous detection of C. jejuni and C. coli, an E. coli Typing RT-PCR detection kit (ETEC, EHEC, STEC, EPEC, and EIEC), API 20E and aerobic stool culture methods. Results. A total of 40 toxigenic strains of C. diff were isolated from all 116 tested diarrheal stool samples, of which 38/40 produced toxin B and 2/40 strains were positive for both cdtA and cdtB. Of the stool samples positive for cdtA (6/50) and/or cdtB (44/50) by EIA, 33 were negative for C. diff culture but positive for the following diarrheal agents: Salmonella enterica subsp. arizonae (1/33, LAMP, culture, API 20E); C. jejuni (2/33, LAMP, culture, MALDI TOF); ETEC O142 (1/33), STEC O145 and O138 (2/33, E. coli RT-PCR detection kit, culture); C. perfringens (2/33, anaerobic culture, MALDI TOF); hypermycotic enterotoxigenic K. pneumonia (2/33) and enterotoxigenic P. mirabilis (2/33, culture; PCR encoding LT-toxin). Two of the sixty-six cdtB-positive samples (2/66) showed a similar misdiagnosis when analyzed using the CLIA method. However, the PCR analysis showed that they were cdtB-negative. In contrast, the LAMP method identified a positive result for C. jejuni in one sample, and another was STEC positive (stx1+/stx2+) by RT-PCR. We found an additional discrepancy in the CDI test results: EPEC O86 (RT-PCR eae+) was isolated from a fecal sample positive for GHA enzyme (CLIA) and negative for cdtA and cdtB (CLIA and PCR). However, the culture of C. diff was negative. These findings support the hypothesis that certain human bacterial pathogens that produce enterotoxins other than C. diff, as well as intestinal commensal microorganisms, including Klebsiella sp. and Proteus sp., contribute to false-positive EIA card tests for C. diff toxins A and B, which are the most widely used laboratory tests for CDI. Conclusions. CDI presents a significant challenge to clinical practice in terms of laboratory diagnostic management. It is recommended that toxin-only EIA tests should not be used as the sole diagnostic tool for CDI but should be limited to detecting toxins A and B. Accurate diagnosis of CDI requires a combination of laboratory diagnostic methods on which proper infection management depends. Full article

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

14 pages, 555 KiB

Open AccessArticle

Leveraging Subjective Parameters and Biomarkers in Machine Learning Models: The Feasibility of lnc-IL7R for Managing Emphysema Progression

by Tzu-Tao Chen, Tzu-Yu Cheng, I-Jung Liu, Shu-Chuan Ho, Kang-Yun Lee, Huei-Tyng Huang, Po-Hao Feng, Kuan-Yuan Chen, Ching-Shan Luo, Chien-Hua Tseng, Yueh-His Chen, Arnab Majumdar, Cheng-Yu Tsai and Sheng-Ming Wu

Diagnostics 2025, 15(9), 1165; https://doi.org/10.3390/diagnostics15091165 (registering DOI) - 3 May 2025

Abstract

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, with emphysema progression providing valuable insights into disease development. Clinical assessment approaches, including pulmonary function tests and high-resolution computed tomography, are limited by accessibility constraints and radiation exposure. This study, [...] Read more.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, with emphysema progression providing valuable insights into disease development. Clinical assessment approaches, including pulmonary function tests and high-resolution computed tomography, are limited by accessibility constraints and radiation exposure. This study, therefore, proposed an alternative approach by integrating the novel biomarker long non-coding interleukin-7 receptor α-subunit gene (lnc-Il7R), along with other easily accessible clinical and biochemical metrics, into machine learning (ML) models. Methods: This cohort study collected baseline characteristics, COPD Assessment Test (CAT) scores, and biochemical details from the enrolled participants. Associations with emphysema severity, defined by a low attenuation area percentage (LAA%) threshold of 15%, were evaluated using simple and multivariate-adjusted models. The dataset was then split into training and validation (80%) and test (20%) subsets. Five ML models were employed, with the best-performing model being further analyzed for feature importance. Results: The majority of participants were elderly males. Compared to the LAA% <15% group, the LAA% ≥15% group demonstrated a significantly higher body mass index (BMI), poor pulmonary function, and lower expression levels of lnc-Il7R (all p < 0.01). Fold changes in lnc-IL7R were strongly and negatively associated with LAA% (p < 0.01). The random forest (RF) model achieved the highest accuracy and area under the receiver operating characteristic curve (AUROC) across datasets. A feature importance analysis identified lnc-IL7R fold changes as the strongest predictor for emphysema classification (LAA% ≥15%), followed by CAT scores and BMI. Conclusions: Machine learning models incorporated accessible clinical and biochemical markers, particularly the novel biomarker lnc-IL7R, achieving classification accuracy and AUROC exceeding 75% in emphysema assessments. These findings offer promising opportunities for improving emphysema classification and COPD management. Full article

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

► Show Figures

Figure 1

17 pages, 7042 KiB

Open AccessReview

Multimodal Imaging Approach to MEN-1 Syndrome-Associated Tumors

by Alice Carli, Elisa Boffa, Matteo Bonatti, Marco Chincarini, Maria Vittoria Davì and Giulia A. Zamboni

Diagnostics 2025, 15(9), 1164; https://doi.org/10.3390/diagnostics15091164 (registering DOI) - 3 May 2025

Abstract

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant inherited syndrome characterized by a genetic predisposition for the development of specific hormone-secreting tumors. Effective diagnosis and management of MEN-1 require genetic testing, regular surveillance, and imaging follow-up to detect and monitor tumor [...] Read more.

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant inherited syndrome characterized by a genetic predisposition for the development of specific hormone-secreting tumors. Effective diagnosis and management of MEN-1 require genetic testing, regular surveillance, and imaging follow-up to detect and monitor tumor growth or recurrence and to plan for surgical intervention. The aim of this narrative review is to provide an overview of the current imaging modalities and their role in the diagnosis and follow-up of patients affected by MEN-1, focusing on the detection and characterization of associated neoplasms. The knowledge of the most frequent MEN-1 associated neoplasms and their imaging features is crucial for an accurate diagnosis, management, and treatment. Full article

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

► Show Figures

Figure 1

22 pages, 37030 KiB

Open AccessReview

The Many Faces of the Angry Peritoneum

by Maria Chiara Ambrosetti, Matilde Bariani, Giulia Angela Zamboni, Riccardo Valletta and Matteo Bonatti

Diagnostics 2025, 15(9), 1163; https://doi.org/10.3390/diagnostics15091163 (registering DOI) - 3 May 2025

Abstract

The peritoneum is a thin membrane that lines the abdominal cavity and covers the abdominal organs. It serves as a conduit for the spread of various pathological processes, including gas and fluid collections, inflammation, infections, and neoplastic conditions. Peritoneal carcinomatosis is the most [...] Read more.

The peritoneum is a thin membrane that lines the abdominal cavity and covers the abdominal organs. It serves as a conduit for the spread of various pathological processes, including gas and fluid collections, inflammation, infections, and neoplastic conditions. Peritoneal carcinomatosis is the most common and well-known pathology involving the peritoneum, typically resulting from the dissemination of gastrointestinal and pelvic malignancies. However, numerous benign and malignant peritoneal diseases can mimic the imaging appearance of peritoneal carcinomatosis. The aim of this review is to revisit the anatomy of peritoneal compartments and elucidate the patterns of peritoneal disease spread. Emphasis is placed on identifying the distinctive imaging features of both neoplastic and non-neoplastic peritoneal diseases that differ from peritoneal carcinomatosis. Full article

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

► Show Figures

Figure 1

15 pages, 1224 KiB

Open AccessArticle

Development of a Pulmonary Nodule Service and Clinical Pathway: A Pragmatic Approach Addressing an Unmet Need

by Georgia Hardavella, Ioannis Karampinis, Nikolaos Anastasiou, Konstantinos Stefanidis, Kyriaki Tavernaraki, Styliani Arapostathi, Nektaria Sidiropoulou, Petros Filippousis, Alexandro Patirelis, Eugenio Pompeo, Panagiotis Demertzis and Stefano Elia

Diagnostics 2025, 15(9), 1162; https://doi.org/10.3390/diagnostics15091162 - 2 May 2025

Abstract

Background/Objectives: The surveillance of patients with incidental pulmonary nodules overloads existing respiratory and lung cancer clinics, as well as multidisciplinary team meetings. In our clinical setting, until 2018, we had numerous patients with incidental pulmonary nodules inundating our outpatient clinics; therefore, the need [...] Read more.

Background/Objectives: The surveillance of patients with incidental pulmonary nodules overloads existing respiratory and lung cancer clinics, as well as multidisciplinary team meetings. In our clinical setting, until 2018, we had numerous patients with incidental pulmonary nodules inundating our outpatient clinics; therefore, the need to develop a novel service and dedicated clinical pathway arose. The aims of this study are to 1. provide (a) a model of setting up a novel pulmonary nodule service, and (b) a pragmatic clinical pathway to address the increasing need for surveillance of patients with incidental pulmonary nodules. 2. share real-world data from a dedicated pulmonary nodule service running in a tertiary setting with existing resources. Methods: A retrospective review of established processes and referral mechanisms to our tertiary pulmonary nodule service was conducted. We have also performed a retrospective collection and review of data for patients reviewed and discussed in our tertiary pulmonary nodule service between April 2018 and April 2024. Results: Our tertiary pulmonary nodule service (PNS) comprises a dedicated pulmonary nodule clinic, a nodule multidisciplinary team (MDT) meeting and a dedicated proforma referral system. Due to the current national health system legislation and relevant processes, patients are required to physically attend clinic appointments. There are various sources of referral, including other departments within the hospital, other hospitals, various specialties in primary care and self-referrals. Between 15 April 2018 and 15 April 2024, 2203 patients were reviewed in the pulmonary nodule clinic (903 females, 1300 males, mean age 64 ± 19 years). Of those patients, 65% (1432/2203) were current smokers. A total of 1365 new patients and 838 follow-up patients were reviewed in total. Emphysema was radiologically present in 72% of patients, and 75% of those (1189/1586) already had a confirmed diagnosis of chronic obstructive pulmonary disease (COPD). Coronary calcification was identified in 32% (705/2203), and 78% of those (550/705) were already known to cardiology services. Interestingly, 27% (368/1365) of the new patients were discharged following their first MDT meeting discussion, and 67% of these were discharged as the reason for their referral was an intrapulmonary lymph node which did not warrant any further action. Among all patients, 11% (246/2203) were referred to the multidisciplinary thoracic oncology service (MTOS) due to suspicious appearances/changes in their nodules that warranted further investigation, and from those, 37% were discharged (92/246) from the MTOS. The lung cancer diagnosis rate was 7% (154/2203). Conclusions: The applied pathway offers a pragmatic approach in setting up a service that addresses an increasing patient need. Its application is feasible in a tertiary care setting, and admin support is of vital importance to ensure patients are appropriately tracked and not lost to follow-up. Real-world data from pulmonary nodules services provide a clear overview and contribute to understanding patients’ characteristics and improving service provision. Full article

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

► Show Figures

Figure 1

16 pages, 1198 KiB

Open AccessReview

Circulating Cell-Free DNA as an Epigenetic Biomarker for Early Diabetic Retinopathy: A Narrative Review

by Boaz Li, Megan M. Yim, Yu Xuan Jin, Brendan K. Tao, Jim S. Xie, Michael Balas, Haaris Khan, Wai-Ching Lam, Peng Yan and Eduardo V. Navajas

Diagnostics 2025, 15(9), 1161; https://doi.org/10.3390/diagnostics15091161 - 2 May 2025

Abstract

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. [...] Read more.

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. In the early stages of DR, the retina undergoes distinct epigenetic changes, including DNA methylation and histone modifications. Recent evidence supports unique epigenetic ‘signatures’ in patients with DR compared to non-diabetic controls. These DNA ‘signature’ sequences may be specific to the retina and may circulate in peripheral blood in the form of cell-free DNA (cfDNA). In this review, we explore the literature and clinical application of cfDNA sampling as an early, non-invasive, accessible assessment tool for early DR detection. First, we summarize the known epigenetic signatures of DR. Next, we review current sequencing technologies used for cfDNA detection, such as magnetic bead-based enrichment, next-generation sequencing, and bisulfite sequencing. Finally, we outline the current research limitations and emerging areas of study which aim to improve the clinical utility of cfDNA for DR evaluation. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis and Prognosis of Eye Diseases)

► Show Figures

Figure 1

13 pages, 6991 KiB

Open AccessArticle

Ultrasonographic and Radiographic Evaluation of Osteoarthritic Changes in the Temporomandibular Joint

by Didem Dumanlı and Çiğdem Şeker

Diagnostics 2025, 15(9), 1160; https://doi.org/10.3390/diagnostics15091160 - 2 May 2025

Abstract

Background/Objectives: This study aims to determine the sensitivity, specificity, positive predictive value, and negative predictive value by comparing ultrasonography and panoramic radiography with the gold standard cone beam computed tomography in the diagnosis of osteoarthritic changes in the temporomandibular joint (TMJ) and [...] Read more.

Background/Objectives: This study aims to determine the sensitivity, specificity, positive predictive value, and negative predictive value by comparing ultrasonography and panoramic radiography with the gold standard cone beam computed tomography in the diagnosis of osteoarthritic changes in the temporomandibular joint (TMJ) and to determine the distribution of these degenerations in terms of age and gender. Methods: In the study, cone beam computed tomography (CBCT), panoramic radiography, and ultrasonography (USG) images of 143 patients who applied to the Dentomaxillofacial Radiology Department of the Faculty of Dentistry of Zonguldak Bülent Ecevit University with complaints of TMJ were retrospectively examined. Results: As a result of the analysis, the average age of the patients included in the study was found to be 50.3 ± 14.4. The incidence of degenerative changes was higher in females than in males. The most common degenerative change in both genders was found to be flattening. Of the 143 patients’ degenerative changes detected on CBCT, 135 (94.4%) were detected on panoramic radiography and 124 (86.7%) were detected on USG. Conclusions: The sensitivity rates of ultrasound and panoramic radiography were found to be lower than those of CBCT in detecting degenerative changes. Full article

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

► Show Figures

Figure 1

3 pages, 405 KiB

Open AccessInteresting Images

¹⁸F-FDG PET/CT Findings in Glandular Tularemia

by Freja Gustafsson, Karl Keigo Rasmussen, Kristina Thorsteinsson, Anne-Mette Lebech and Lasse Fjordside

Diagnostics 2025, 15(9), 1159; https://doi.org/10.3390/diagnostics15091159 - 2 May 2025

Abstract

A 47-year-old woman presented with fever, fatigue, night sweats and inguinal glandular swelling following a tick bite. Weeks of diagnostic uncertainty followed, and a lymph node biopsy was sent to be investigated for tularemia and pathology. An ¹⁸F-FDG PET/CT scan was performed [...] Read more.

A 47-year-old woman presented with fever, fatigue, night sweats and inguinal glandular swelling following a tick bite. Weeks of diagnostic uncertainty followed, and a lymph node biopsy was sent to be investigated for tularemia and pathology. An ¹⁸F-FDG PET/CT scan was performed due to a suspicion of malignant lymphoma. The scan revealed high metabolic activity in the left inguinal region, which was compatible with abscesses. The diagnosis of glandular tularemia was established on a positive PCR for Francisella tularensis (F. tularensis) and positive F. tularensis serology. This case highlights the challenges of diagnosing tularemia and illustrates the role of imaging. Full article

(This article belongs to the Collection Interesting Images)

► Show Figures

Figure 1

8 pages, 2518 KiB

Open AccessInteresting Images

Radiological and Surgery Considerations and Alternatives in Total Temporomandibular Joint Replacement in Gorlin-Goltz Syndrome

by Kamil Nelke, Klaudiusz Łuczak, Maciej Janeczek, Agata Małyszek, Piotr Kuropka and Maciej Dobrzyński

Diagnostics 2025, 15(9), 1158; https://doi.org/10.3390/diagnostics15091158 - 2 May 2025

Abstract

Gorlin-Goltz syndrome (GGS) is also known as Nevoid basal cell carcinoma syndrome (NBCCS). In the most common manifestation, GGS is diagnosed based on multiple cysts in the jaw bones, namely OKCs (odontogenic keratocysts). Other features might include major and minor clinical and radiological [...] Read more.

Gorlin-Goltz syndrome (GGS) is also known as Nevoid basal cell carcinoma syndrome (NBCCS). In the most common manifestation, GGS is diagnosed based on multiple cysts in the jaw bones, namely OKCs (odontogenic keratocysts). Other features might include major and minor clinical and radiological criteria to confirm this syndrome. Quite commonly, BCCs (basal cell carcinomas), bifid ribs, palmar and plantar pits, and ectopic calcification of the falx cerebri can be found in the majority of patients. Currently, the mutation of the PTCH1 gene seems to be responsible for GGS occurrence, while the male-to-female ratio is 1:1. The following radiological study based on OPGs and CBCT confirmed multiple cystic lesions in jaw bones, confirmed to be OKCs in the histopathological evaluation with an occurrence of numerous skin BCC lesions. In cases of most oral OKC cystic lesions, either surgical removal, curettage, or enucleation with or without any bone grafting can be used with a good amount of success. Rarely, some stable bone osteosynthesis procedures have to be carried out to avoid pathological bone fractures after cyst removal. A special consideration should include the temporomandibular joint. TMJ surgery and the replacement of the joint with an alloplastic material can be performed to improve biting, chewing, proper mouth opening, and maintain good patient occlusion. The authors want to present how effective and simple a standard dental panoramic radiograph combined with CBCT is and how it is suitable for GGS detection. They also want to underline how a standard TMJ prosthesis can be used as an alternative to a custom-made prosthesis. Full article

(This article belongs to the Collection Interesting Images)

► Show Figures

Figure 1

20 pages, 4286 KiB

Open AccessArticle

The Classification of Vestibular Schwannoma (VS) and Cerebellopontine Angle Meningioma (CPAM) Based on Multimodal Magnetic Resonance Imaging Analysis

by Lihua Yuan, Jaming Lu, Xin Shu, Kun Liang, Cheng Wang, Jiu Chen and Zhishun Wang

Diagnostics 2025, 15(9), 1157; https://doi.org/10.3390/diagnostics15091157 - 1 May 2025

Abstract

Background/Objectives: This study evaluates the diagnostic efficacy of the apparent diffusion coefficient (ADC) and T1-weighted contrast-enhanced (T1W + C) and T2-weighted (T2W) imaging modalities in differentiating vestibular schwannomas (VSs) and cerebellopontine angle meningiomas (CPAMs), aiming to optimize clinical imaging protocols for these [...] Read more.

Background/Objectives: This study evaluates the diagnostic efficacy of the apparent diffusion coefficient (ADC) and T1-weighted contrast-enhanced (T1W + C) and T2-weighted (T2W) imaging modalities in differentiating vestibular schwannomas (VSs) and cerebellopontine angle meningiomas (CPAMs), aiming to optimize clinical imaging protocols for these tumors‌. Methods: A retrospective analysis was conducted on 97 surgically and pathologically confirmed cases (65 VS, 32 CPAM) from Nanjing Drum Tower Hospital. Imaging features from ADC, T1W + C, and T2W sequences were extracted using medical imaging software. A support vector machine (SVM) model was trained to classify tumors based on these features, focusing on first-, second-, and third-order radiomic characteristics‌. Results: The ADC images‌ demonstrated the highest classification efficiency, particularly with third-order features (AUC = 0.9817). The T2W images‌ achieved the best accuracy (87.63%) using second-order features. Multimodal analysis revealed that ‌ADC alone‌ outperformed combinations with T1W + C or T2W sequences, suggesting limited added value from multi-sequence integration. Conclusions: Diffusion-weighted imaging (DWI) sequences, particularly ADC maps, exhibit superior diagnostic utility compared to T1W + C and T2W sequences in distinguishing VS and CPAM. The findings advocate prioritizing DWI in clinical imaging workflows to enhance diagnostic accuracy and streamline protocols‌. Full article

(This article belongs to the Special Issue Diagnostic Imaging in Neurological Diseases)

20 pages, 4006 KiB

Open AccessArticle

EM-DeepSD: A Deep Neural Network Model Based on Cell-Free DNA End-Motif Signal Decomposition for Cancer Diagnosis

by Zhi-Yang Zhao, Chang-Ling Huang, Tong-Min Wang, Shi-Hao Zhou, Lu Pei, Wen-Hui Jia and Wei-Hua Jia

Diagnostics 2025, 15(9), 1156; https://doi.org/10.3390/diagnostics15091156 - 1 May 2025

Abstract

Background and Objectives: The accurate discrimination between patients with and without cancer using their cell-free DNA (cfDNA) is crucial for early cancer diagnosis. The end-motifs of cfDNA serve as significant cancer biomarkers, offering compelling prospects for cancer diagnosis. This study proposes EM-DeepSD, a [...] Read more.

Background and Objectives: The accurate discrimination between patients with and without cancer using their cell-free DNA (cfDNA) is crucial for early cancer diagnosis. The end-motifs of cfDNA serve as significant cancer biomarkers, offering compelling prospects for cancer diagnosis. This study proposes EM-DeepSD, a signal decomposition deep learning framework based on cfDNA end-motifs, which is aimed at improving the accuracy of cancer diagnosis and adapting to different sequencing modalities. Materials and Methods: This study included 146 patients diagnosed with cancer and 122 non-cancer controls. EM-DeepSD comprises three core modules. Initially, it utilizes a signal decomposition module to decompose and reconstruct the input end-motif profiles, thereby generating multiple regular subsequences that optimize the subsequent modeling process. Subsequently, both a machine learning module and a deep learning module are employed to improve the accuracy of cancer diagnosis. Furthermore, this paper compares the performance of EM-DeepSD with that of existing benchmarked methods to demonstrate its superiority. Based on the EM-DeepSD framework, we developed the EM-DeepSSA model and compared it with two benchmarked methods across different cfDNA sequencing datasets. Results: In the internal validation set, EM-DeepSSA outperformed the two benchmark methods for cancer diagnosis (area under the curve (AUC), 0.920; adjusted p value < 0.05). Meanwhile, EM-DeepSSA also exhibited the best performance on two independent external testing sets that were subjected to 5-hydroxymethylcytosine sequencing (5hmCS) and broad-range cell-free DNA sequencing (BR-cfDNA-Seq), respectively (test set-1: AUC = 0.933; test set-2: AUC = 0.956; adjusted p value < 0.05). Conclusions: In summary, we present a new framework which can achieve high classification performance in cancer diagnosis and which is applicable to different sequencing modalities. Full article

(This article belongs to the Special Issue Deep Learning in Biomedical Signal Analysis)

► Show Figures

Figure 1

29 pages, 1406 KiB

Open AccessArticle

Automated Lightweight Model for Asthma Detection Using Respiratory and Cough Sound Signals

by Shuting Xu, Ravinesh C. Deo, Oliver Faust, Prabal D. Barua, Jeffrey Soar and Rajendra Acharya

Diagnostics 2025, 15(9), 1155; https://doi.org/10.3390/diagnostics15091155 - 1 May 2025

Abstract

Background and objective: Chronic respiratory diseases, such as asthma and COPD, pose significant challenges to human health and global healthcare systems. This pioneering study utilises AI analysis and modelling of cough and respiratory sound signals to classify and differentiate between asthma, COPD, [...] Read more.

Background and objective: Chronic respiratory diseases, such as asthma and COPD, pose significant challenges to human health and global healthcare systems. This pioneering study utilises AI analysis and modelling of cough and respiratory sound signals to classify and differentiate between asthma, COPD, and healthy subjects. The aim is to develop an AI-based diagnostic system capable of accurately distinguishing these conditions, thereby enhancing early detection and clinical management. Our study, therefore, presents the first AI system that leverages dual acoustic signals to enhance the diagnostic ACC of asthma using automated, lightweight deep learning models. Methods: To build an automated, lightweight model for asthma detection, tested separately with respiratory and cough sounds to assess their suitability for detecting asthma and COPD, the proposed AI models integrate the following ML algorithms: RF, SVM, DT, NN, and KNN, with an overall aim to demonstrate the efficacy of the proposed method for future clinical use. Model training and validation were performed using 5-fold cross-validation, wherein the dataset was randomly divided into five folds and the models were trained and tested iteratively to ensure robust performance. We evaluated the model outcomes with several performance metrics: ACC, precision, recall, F1 score, and area under the AUC. Additionally, a majority voting ensemble technique was employed to aggregate the predictions of the various classifiers for improved diagnostic reliability. We applied Gabor time–frequency transformation for feature extraction and NCA) for feature selection to optimise predictive accuracy. Independent comparative experiments were conducted, where cough-sound subsets were used to evaluate asthma detection capabilities, and respiratory-sound subsets were used to evaluate COPD detection capabilities, allowing for targeted model assessment. Results: The proposed ensemble approach, facilitated by a majority voting approach for model efficacy evaluation, achieved acceptable ACC values of 94.05% and 83.31% for differentiating between asthma and normal cases utilising separate respiratory sounds and cough sounds, respectively. The results highlight a substantial benefit in integrating multiple classifier models and sound modalities while demonstrating an unprecedented level of ACC and robustness for future diagnostic predictions of the disease. Conclusions: The present study sets a new benchmark in AI-based detection of respiratory diseases by integrating cough and respiratory sound signals for future diagnostics. The successful implementation of a dual-sound analysis approach promises advancements in the early detection and management of asthma and COPD. We conclude that the proposed model holds strong potential to transform asthma diagnostic practices and support clinicians in their respiratory healthcare practices. Full article

(This article belongs to the Special Issue Physiological Sound Processing for Medical Diagnostics: Innovations, Challenges, and Applications)

11 pages, 1137 KiB

Open AccessArticle

Evaluation of Adipokine Status and Leptin Receptor Gene Polymorphism in Patients with Severe Asthma

by Saule Maimysheva, Lyudmila Karazhanova, Andrey Orekhov, Assel Chinybayeva and Bolat Ashirov

Diagnostics 2025, 15(9), 1154; https://doi.org/10.3390/diagnostics15091154 - 1 May 2025

Abstract

Background: Severe and difficult-to-control asthma occurs in 3–10% of patients in developed countries. The aim of our study was to investigate the association of the prognostic role of leptin and adiponectin, as well as the leptin receptor gene polymorphism Gln223Arg, in patients [...] Read more.

Background: Severe and difficult-to-control asthma occurs in 3–10% of patients in developed countries. The aim of our study was to investigate the association of the prognostic role of leptin and adiponectin, as well as the leptin receptor gene polymorphism Gln223Arg, in patients with difficult-to-control and severe asthma. Methods: The present study included 200 patients with asthma hospitalized in the Department of Pulmonology between January 2018 and December 2021. In all patients, in addition to routine clinical investigations, adiponectin, leptin and their ratio were analyzed, as well as levels of pro-inflammatory cytokines (IL-6, IL-8 and TNF-alpha). External respiratory function was also assessed. LEPR Gln223Arg single-nucleotide polymorphisms were genotyped by real-time PCR method. Results: Patients were randomized into two groups, depending on the severity of asthma: an uncontrolled asthma group and a controlled asthma group, according to the GINA criteria. Among patients with uncontrolled asthma, 101 subjects (74.3%) had metabolic syndrome (p < 0.001). There was an inverse association of the adiponectin/leptin ratio with the eosinophil count (B = −0.305, p < 0.001), IL-6 (B = −0.026, p < 0.001), IL-8 (B = −0.062, p < 0.001) and TNF-alpha (B = −0.047, p < 0.001) and a direct correlation with the level of FEV1 (B = 0.121, p < 0.001) and FVC (B = 0.104, p < 0.001). A probable association of homozygous A/A allele with increased risk of uncontrolled asthma was shown (p = 0.007). Conclusions: Leptin receptor polymorphism with A/A genotype may be associated with a higher probability of developing severe and difficult-to-control asthma. Full article

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

► Show Figures

Figure 1

21 pages, 683 KiB

Open AccessReview

Beyond X-Rays: Unveiling the Future of Dental Diagnosis with Dental Magnetic Resonance Imaging

by Anusha Vaddi, Pranav Parasher and Sonam Khurana

Diagnostics 2025, 15(9), 1153; https://doi.org/10.3390/diagnostics15091153 - 1 May 2025

Abstract

Diagnostic imaging is fundamental in dentistry for disease detection, treatment planning, and outcome assessment. Traditional radiographic methods, such as periapical and panoramic radiographs, along with cone beam computed tomography (CBCT), utilize ionizing radiation and primarily focus on visualizing bony structures. Magnetic resonance imaging [...] Read more.

Diagnostic imaging is fundamental in dentistry for disease detection, treatment planning, and outcome assessment. Traditional radiographic methods, such as periapical and panoramic radiographs, along with cone beam computed tomography (CBCT), utilize ionizing radiation and primarily focus on visualizing bony structures. Magnetic resonance imaging (MRI) is emerging as a non-ionizing alternative that offers superior soft tissue contrast. However, standard MRI sequences face challenges visualizing mineralized tissues due to their short transverse relaxation times (T2), which results in rapid signal decay. Recent advancements exploring short T2 sequences, including Ultrashort Echo Time (UTE), Zero Echo Time (ZTE), and Sweep Imaging with Fourier Transformation (SWIFT), allow direct visualization of dental hard tissues. UTE captures signals from short T2 tissues using rapid pulse sequences, while ZTE employs encoding gradients before radiofrequency pulses to reduce signal loss. SWIFT enables near-simultaneous excitation and acquisition, improving ultrashort T2 detection. Additionally, customized intraoral and extraoral surface coils enhance the image resolution and signal-to-noise ratio (SNR), increasing MRI’s relevance in dentistry. Research highlights the potential of these short T2 sequences for early caries detection, pulp vitality assessment, and diagnosing jaw osseous pathology. While high-field MRI (3 T–7 T) improves resolution and increases susceptibility artifacts, low-field systems with specialized coils and short sequences offer promising alternatives. Despite obstacles such as cost and hardware constraints, ongoing studies refine protocols to enhance clinical applicability. Incorporating MRI in dentistry promises a safer, more comprehensive imaging methodology, potentially transforming diagnostics. This review emphasizes three types of short T2 sequences that have potential applications in the maxillofacial region. Full article

(This article belongs to the Special Issue Advances in Dental Imaging)

► Show Figures

Figure 1

19 pages, 691 KiB

Open AccessReview

Predictive Validity of Screening Tools and Role of Self-Esteem and Coping in Postpartum Depression Risk

by Nadica Motofelea, Alexandru Catalin Motofelea, Ionela Florica Tamasan, Teodora Hoinoiu, Jabri Tabrizi Madalina Ioana, Maja Vilibić, Antoniu Ionescu Cringu, Brenda Cristiana Bernad, Sorin Trinc and Dan-Bogdan Navolan

Diagnostics 2025, 15(9), 1152; https://doi.org/10.3390/diagnostics15091152 - 30 Apr 2025

Abstract

Background/Objectives: Postpartum depression (PPD) is a prevalent mental health disorder affecting women after childbirth, with significant adverse effects on both maternal and infant outcomes. Early detection and intervention are critical to improving health trajectories. Material and Methods: This narrative review compares [...] Read more.

Background/Objectives: Postpartum depression (PPD) is a prevalent mental health disorder affecting women after childbirth, with significant adverse effects on both maternal and infant outcomes. Early detection and intervention are critical to improving health trajectories. Material and Methods: This narrative review compares the predictive validity of commonly used screening instruments for PPD, including the Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 (PHQ-9), and brief tools like PHQ-2 and PHQ-4. It also examines the role of self-esteem, assessed using the Rosenberg Self-Esteem Scale (RSES), and coping mechanisms, evaluated through the COPE Inventory, in moderating PPD risk. Results: Validation studies reveal variability in the performance of screening tools across different populations, emphasizing the need for contextual calibration. Low self-esteem and maladaptive coping strategies are consistently associated with higher PPD risk, with socioeconomic status (SES) further influencing these relationships. Interventions focusing on enhancing self-esteem and promoting adaptive coping, such as cognitive–behavioral therapy and psychoeducation, show promise in reducing PPD incidence. Conclusions: This review highlights gaps in existing research, particularly regarding screening during pregnancy, and calls for integrated predictive models incorporating psychosocial variables. Early, context-sensitive screening approaches are essential for effective PPD prevention and management. Full article

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

4 pages, 1015 KiB

Open AccessInteresting Images

Visualizing Aortic Inflammation by Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression (DWIBS)

by Asuka Suzuki, Koji Hayashi, Mamiko Sato, Yuka Nakaya, Toyoaki Miura, Naoko Takaku, Toshiko Iwasaki and Yasutaka Kobayashi

Diagnostics 2025, 15(9), 1151; https://doi.org/10.3390/diagnostics15091151 - 30 Apr 2025

Abstract

A 75-year-old man, with a history of descending thoracic aortic rupture and dissection treated with aortic stenting at 73 years old, was admitted for rehabilitation following recurrent cerebral ischemic attacks. Upon admission, blood tests revealed elevated inflammatory markers, including a C-reactive protein (CRP) [...] Read more.

A 75-year-old man, with a history of descending thoracic aortic rupture and dissection treated with aortic stenting at 73 years old, was admitted for rehabilitation following recurrent cerebral ischemic attacks. Upon admission, blood tests revealed elevated inflammatory markers, including a C-reactive protein (CRP) level of 10.75 mg/dL and a D-dimer level of 4.2 µg/mL, alongside microcytic anemia. Despite thorough evaluations using computed tomography (CT) and ultrasound, the origin of these abnormalities remained unidentified. Two months later, MRI using diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) revealed hyperintensities in the thoracic aorta. He remained asymptomatic and progressed well during rehabilitation, prompting continued observation. However, three months after admission, he developed hemoptysis. Contrast-enhanced CT showed pneumonia, as well as enhanced lesions in the aortic wall, confirming aortic inflammation. Due to concerns about aortic stent ulceration, an emergency stent graft insertion extending to the superior mesenteric artery was performed. He recovered uneventfully and was discharged. DWIBS is an MRI-based tool that avoids exposure to radiation or contrast agents and is cost-effective. MRI using DWIBS demonstrated high signal accumulations in the aortic wall, indicative of inflammation. These findings suggest that DWIBS holds significant potential as a powerful imaging tool for detecting and assessing inflammation, particularly in the aorta. Full article

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

26 pages, 718 KiB

Open AccessSystematic Review

Advanced Deep Learning Approaches in Detection Technologies for Comprehensive Breast Cancer Assessment Based on WSIs: A Systematic Literature Review

by Qiaoyi Xu, Afzan Adam, Azizi Abdullah and Nurkhairul Bariyah

Diagnostics 2025, 15(9), 1150; https://doi.org/10.3390/diagnostics15091150 - 30 Apr 2025

Abstract

Background: Breast cancer is one of the leading causes of death among women worldwide. Accurate early detection of lymphocytes and molecular biomarkers is essential for improving diagnostic precision and patient prognosis. Whole slide images (WSIs) are central to digital pathology workflows in breast [...] Read more.

Background: Breast cancer is one of the leading causes of death among women worldwide. Accurate early detection of lymphocytes and molecular biomarkers is essential for improving diagnostic precision and patient prognosis. Whole slide images (WSIs) are central to digital pathology workflows in breast cancer assessment. However, applying deep learning techniques to WSIs presents persistent challenges, including variability in image quality, limited availability of high-quality annotations, poor model interpretability, high computational demands, and suboptimal processing efficiency. Methods: This systematic review, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), examines deep learning-based detection methods for breast cancer published between 2020 and 2024. The analysis includes 39 peer-reviewed studies and 20 widely used WSI datasets. Results: To enhance clinical relevance and guide model development, this study introduces a five-dimensional evaluation framework covering accuracy and performance, robustness and generalization, interpretability, computational efficiency, and annotation quality. The framework facilitates a balanced and clinically aligned assessment of both established methods and recent innovations. Conclusions: This review offers a comprehensive analysis and proposes a practical roadmap for addressing core challenges in WSI-based breast cancer detection. It fills a critical gap in the literature and provides actionable guidance for researchers, clinicians, and developers seeking to optimize and translate WSI-based technologies into clinical workflows for comprehensive breast cancer assessment. Full article

(This article belongs to the Special Issue Artificial Intelligence for Health and Medicine)

► Show Figures

Figure 1

21 pages, 764 KiB

Open AccessReview

Arrhythmic Risk Stratification in Patients with Arrhythmogenic Cardiomyopathy

by Marisa Varrenti, Eleonora Bonvicini, Leandro Fabrizio Milillo, Ilaria Garofani, Marco Carbonaro, Matteo Baroni, Lorenzo Gigli, Giulia Colombo, Federica Giordano, Raffaele Falco, Antonio Frontera, Roberto Menè, Alberto Preda, Sara Vargiu, Patrizio Mazzone and Fabrizio Guarracini

Diagnostics 2025, 15(9), 1149; https://doi.org/10.3390/diagnostics15091149 - 30 Apr 2025

Abstract

Arrhythmogenic cardiomyopathy is a heart disease in which the heart muscle is replaced by scar tissue. This is the main substrate for the development of malignant ventricular arrhythmias. Sudden cardiac death is the most common manifestation and can often be the first sign [...] Read more.

Arrhythmogenic cardiomyopathy is a heart disease in which the heart muscle is replaced by scar tissue. This is the main substrate for the development of malignant ventricular arrhythmias. Sudden cardiac death is the most common manifestation and can often be the first sign of the disease, especially in young people. Correct stratification of arrhythmic risk is essential for the management of these patients but remains a challenge for the clinical cardiologist. In this context, the aim of our work was to review the literature and to analyse the most important studies and new developments with regard to the stratification of the risk of arrhythmia in patients suffering from arrhythmogenic cardiopathy. Full article

(This article belongs to the Special Issue The Cutting Edge of Cardiac Pacing, Electrophysiology and Diagnostic Techniques)

17 pages, 923 KiB

Open AccessArticle

Clinical Significance of Rotational Thromboelastometry (ROTEM) for Detection of Early Coagulopathy in Trauma Patients: A Retrospective Study

by Mohammad Asim, Ayman El-Menyar, Ruben Peralta, Suresh Arumugam, Bianca Wahlen, Khalid Ahmed, Naushad Ahmad Khan, Amani N. Alansari, Monira Mollazehi, Muhamed Ibnas, Ammar Al-Hassani, Ashok Parchani, Talat Chughtai, Sagar Galwankar, Hassan Al-Thani and Sandro Rizoli

Diagnostics 2025, 15(9), 1148; https://doi.org/10.3390/diagnostics15091148 - 30 Apr 2025

Abstract

Background: We aimed to evaluate the clinical significance of abnormal rotational thromboelastometry (ROTEM) findings in trauma patients and investigate the relationships between FIBTEM-maximum clot firmness (MCF), fibrinogen concentration and patient outcomes. Methods: A retrospective cohort analysis was conducted on adult trauma [...] Read more.

Background: We aimed to evaluate the clinical significance of abnormal rotational thromboelastometry (ROTEM) findings in trauma patients and investigate the relationships between FIBTEM-maximum clot firmness (MCF), fibrinogen concentration and patient outcomes. Methods: A retrospective cohort analysis was conducted on adult trauma patients who underwent on-admission ROTEM testing between January 2020 and January 2021. Univariate analyses compared data based on injury severity, ROTEM findings (normal vs. abnormal), and initial fibrinogen concentration (normal vs. hypofibrinogenemia). ROC curve analysis was performed to determine the diagnostic performance of FIBTEM A10/MCF for its association with hypofibrinogenemia. Results: A total of 1488 patients were included in this study; the mean age was 36.4 ± 14.2 years and 92% were male. In total, 376 (25.3%) patients had ROTEM abnormalities. Severe injuries (ISS ≥ 16) were associated with a higher shock index, positive troponin T levels, standard coagulation abnormalities, hypofibrinogenemia, and abnormal ROTEM parameters (p < 0.05). These patients also had higher rates of massive transfusions and in-hospital mortality (p = 0.001). Coagulation alterations were significantly associated with higher injury severity score (ISS), shock index, head abbreviated injury score (AIS), hypofibrinogenemia, transfusion need, and mortality (p < 0.05). Hypofibrinogenemic patients were younger, sustained severe injuries, had higher shock indices and coagulation marker levels, required more intensive treatments, had longer hospital stays, and had higher mortality (p < 0.05). A significant positive correlation was found between plasma fibrinogen concentration and FIBTEM-MCF (r = 0.294; p = 0.001). Conclusions: Approximately one-fourth of the patients had early traumatic coagulopathy, as assessed by ROTEM. The FIBTEM A10/MCF may serves as a surrogate marker for plasma fibrinogen concentration. While prior studies have established the link between ROTEM and injury severity, our findings reinforce its relevance across varying trauma severity levels. However, prospective studies are warranted to validate its role within diverse trauma systems and evolving resuscitation protocols. Full article

(This article belongs to the Special Issue Advances in the Laboratory Diagnosis)

► Show Figures

Figure 1

Journal Description

Diagnostics

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI