Diagnostics

16 pages, 959 KB

Open AccessArticle

Integrated Exhaled VOC and Clinical Biomarker Profiling for Predicting Bronchodilator Responsiveness in Asthma and COPD Patients

by Malika Mustafina, Artemiy Silantyev, Aleksander Suvorov, Alexander Chernyak, Olga Suvorova, Anna Shmidt, Anastasia Gordeeva, Maria Vergun, Daria Gognieva, Sergey Avdeev, Vladimir Betelin and Philipp Kopylov

Diagnostics 2025, 15(21), 2738; https://doi.org/10.3390/diagnostics15212738 (registering DOI) - 28 Oct 2025

Abstract

Background. Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases with distinct inflammatory pathways but overlapping clinical features. Bronchodilator responsiveness (BDR) is a key diagnostic criterion, yet its metabolic determinants are poorly understood. Objective. This cross-sectional study investigated whether integrated [...] Read more.

Background. Asthma and chronic obstructive pulmonary disease (COPD) are prevalent obstructive lung diseases with distinct inflammatory pathways but overlapping clinical features. Bronchodilator responsiveness (BDR) is a key diagnostic criterion, yet its metabolic determinants are poorly understood. Objective. This cross-sectional study investigated whether integrated profiling of exhaled volatile organic compounds (VOCs) and clinical biomarkers can differentiate BA, COPD, and health, and predict BDR. Methods. Exhaled breath from 160 BA patients, 128 COPD patients, and 254 healthy controls was analyzed in real-time using proton-transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) during tidal and forced expiration. Clinical assessment included spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil count, and total IgE. Machine-learning (XGBoost) was employed for feature selection and model development. Results. Distinct VOC signatures effectively discriminated disease groups from controls and from each other. The model for distinguishing asthma from healthy controls achieved an AUC of 0.747 during normal quiet breathing and 0.710 during forced exhale. For discriminating COPD from healthy controls, the model performance was higher, with an AUC of 0.821 for normal quiet breathing and 0.856 for forced exhale. A model integrating VOC profiles with clinical biomarkers (FeNO, eosinophils, IgE) demonstrated very high accuracy in internal validation in predicting BDR (AUC = 1.000 for tidal breathing; AUC = 0.970 for forced expiration). Specific mass spectral features (m/z 79, m/z 101) were significantly associated with a positive BDR test. Conclusions. This study delineates disease-specific VOC signatures and underscores the profound synergy between exhaled metabolomics and clinical immunology for identifying associations treatment response, advocating for the integration of real-time breath analysis into personalized management strategies for obstructive lung diseases. Full article

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

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19 pages, 667 KB

Open AccessReview

Prostate Cancer Imaging Beyond PSMA: Applications of GRPR, AR, and Amino Acid Tracers

by Farzana Z. Ali

Diagnostics 2025, 15(21), 2737; https://doi.org/10.3390/diagnostics15212737 - 28 Oct 2025

Abstract

Prostate-specific membrane antigen (PSMA) targeting agents have been the cornerstone of advanced prostate cancer (PCa) management in theranostics due to their high sensitivity for detecting and treating metastatic disease. However, approximately one-third of metastatic castration-resistant PCa (mCRPC) lesions may exhibit low or absent [...] Read more.

Prostate-specific membrane antigen (PSMA) targeting agents have been the cornerstone of advanced prostate cancer (PCa) management in theranostics due to their high sensitivity for detecting and treating metastatic disease. However, approximately one-third of metastatic castration-resistant PCa (mCRPC) lesions may exhibit low or absent PSMA expression due to tumor heterogeneity, prior androgen deprivation therapy, or loss of androgen receptor expression, subsequently altering their response to PSMA-targeted therapy. The molecular and biological mechanisms underlying PSMA downregulation remain elusive but may include neuroendocrine differentiation or epithelial-to-mesenchymal transition (EMT). This review addresses this knowledge gap by examining recent preclinical and clinical evidence on novel radiotracers with the potential to provide alternative strategies beyond PSMA for imaging and treating PCa. The diagnostic performance and therapeutic potential of three emerging radiotracer classes are discussed, including gastrin-releasing peptide receptor (GRPR) ligands, androgen receptor (AR) ligands, and amino acid analogs. This article further highlights the complementary roles of these radiotracers along with their utility in specific patient populations, such as those with low prostate-specific antigen (PSA), biochemical recurrence (BCR), or confirmed PSMA-negative disease. For instance, GRPR-targeted radiotracers have achieved sensitivity of up to 88% and specificity of up to 90% for detecting primary tumors in PCa. The radiolabeled androgen agonist, fluorine-18 (¹⁸F)-fluoro-5α-dihydrotestosterone (FDHT), has demonstrated 98% true-positive rate in predicting lesions on positron emission tomography (PET) scans of mCRPC patients. On the other hand, the synthetic amino acid analog ¹⁸F-fluciclovine demonstrated a lesion detection rate of 84% for PSA levels at or above 5, and 62.5% for PSA levels ranging from 0.7 to less than 1. This review concludes with future directions on the paradigm of multi-tracer and dual-targeting strategies, which can effectively address challenges associated with PCa tumor heterogeneity and facilitate personalized approaches in theranostics. Full article

(This article belongs to the Special Issue Advances in Nuclear Medicine and Molecular Imaging)

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13 pages, 957 KB

Open AccessArticle

Effect of Cataracts on Hydroxychloroquine Retinopathy Screening

by Ji Soo Kang, Seong Joon Ahn and Yu Jeong Kim

Diagnostics 2025, 15(21), 2736; https://doi.org/10.3390/diagnostics15212736 - 28 Oct 2025

Abstract

Background/Objectives: To evaluate the modality-specific impact of cataracts on the detection of hydroxychloroquine retinopathy. Methods: In this retrospective cohort study, 202 eyes (101 patients) with confirmed HCQ retinopathy were included; analyses focused on 141 cataractous eyes from 72 patients. At each visit, the [...] Read more.

Background/Objectives: To evaluate the modality-specific impact of cataracts on the detection of hydroxychloroquine retinopathy. Methods: In this retrospective cohort study, 202 eyes (101 patients) with confirmed HCQ retinopathy were included; analyses focused on 141 cataractous eyes from 72 patients. At each visit, the severity of cataracts in 141 eyes was graded using the Lens Opacities Classification System III (LOCS III), with clinically significant cataracts defined as a LOCS III grade ≥ 3. Screening was performed using swept source optical coherence tomography (OCT), ultrawide field fundus autofluorescence (FAF), and Humphrey visual field (HVF) tests. The detection rates of abnormalities on OCT, FAF, and HVF were compared between minimal (at the time of diagnosis or after cataract surgery) and maximal cataract severity as well as between eyes with clinically significant cataracts and others. Multivariate logistic regression was performed to identify the factors associated with the detection of retinopathy-associated abnormalities across each screening modality. Results: Of the 141 eyes with cataracts, 52 (36.9%) developed clinically significant opacities during the monitoring period, and 23 (16.3%) underwent cataract surgery. OCT detected ellipsoid zone disruptions in 100% of cataractous eyes, while visual fields revealed characteristic paracentral scotomas with comparable sensitivity regardless of cataract severity. In contrast, FAF sensitivity was significantly lower in eyes with clinically significant cataracts (61.5%) compared to those with mild cataracts (92.1%, p < 0.001). Sensitivities were also reduced at maximal versus minimal severity in eyes with clinically significant cortical opacities and nuclear opalescence (both p < 0.05). Multivariate analysis demonstrated that higher cortical opacity (odds ratio [OR] 0.43 per grade increase, 95% CI 0.22–0.85) and nuclear opalescence (OR 0.21, 95% CI 0.07–0.66) independently decreased FAF detection, whereas greater retinopathy severity was positively associated with detection on both FAF (OR 4.85, 95% CI 1.40–16.9) and HVF (OR 3.37, 95% CI 1.17–9.71). Conclusions: Cataracts impaired the FAF-based detection of hydroxychloroquine retinopathy, while OCT and HVF remained reliable despite significant lens opacities. Therefore, clinicians should consider cataract severity when interpreting FAF results and prioritize OCT and HVF assessments in patients with clinically significant cataracts. Full article

(This article belongs to the Special Issue Innovative Diagnostic Approaches in Retinal Diseases)

19 pages, 4473 KB

Open AccessArticle

Exosomal microRNA Panels for Detecting Early-Stage Non-Small Cell Lung Cancer

by Young Jun Kim, Da Hyun Kang, Hyunmin Cho, Chaeuk Chung, Jeong Eun Lee and Yong-Beom Shin

Diagnostics 2025, 15(21), 2735; https://doi.org/10.3390/diagnostics15212735 - 28 Oct 2025

Abstract

Background: Early diagnosis of lung cancer requires lung nodule biopsies, which can lead to severe complications. This study aimed to identify optimized panels of exosomal microRNAs (miRNAs) for non-invasive diagnosis of early-stage non-small cell lung cancer (NSCLC). Materials and Methods: This [...] Read more.

Background: Early diagnosis of lung cancer requires lung nodule biopsies, which can lead to severe complications. This study aimed to identify optimized panels of exosomal microRNAs (miRNAs) for non-invasive diagnosis of early-stage non-small cell lung cancer (NSCLC). Materials and Methods: This study comprised four phases: discovery, validation, optimization, and confirmation. In the discovery phase, next-generation sequencing profiled 2656 exosomal miRNAs in serum samples (n = 76) from patients with benign lung nodules and stage-specific NSCLC. The validation phase used qPCR to analyze selected miRNAs in serum samples (n = 75). The optimization phase employed a self-devised diagnostic platform, the “up-down ratio (UDR),” to identify miRNA panels. The confirmation phase involved miRNA–target gene interaction and enrichment analyses. Results: The discovery phase identified 15 candidate miRNAs, of which six were validated by qPCR: miR-1976, miR-150-5p, miR-301b-3p, miR-369-3p, miR-497-5p, and miR-610. UDR platform identified a panel of four miRNAs optimized for early detection of NSCLC with ROC over 0.93. Bioinformatics analysis revealed 20 target genes, with VEGFA, BCL2, and PTEN showing strong interactions with the miRNAs, particularly with miR-150-5p, miR-205-5p, miR-1976, miR-301b-3p, and miR-497-5p. Conclusions: This four-phase study suggests that exosomal miRNA panels have potential diagnostic value for early-stage lung cancer. The UDR platform enabled the selection of a four-miRNA panel (miR-150-5p, miR-301b-3p, miR-369-3p, and miR-497-5p), with bioinformatics analyses providing supportive evidence. Full article

(This article belongs to the Special Issue Liquid Biopsy: Cancer Diagnostic Biomarkers of the Future)

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13 pages, 4332 KB

Open AccessArticle

Brain Perfusion Scintigraphy in the Diagnostic Toolbox for the Confirmation of Brain Death: Practical Aspects and Examination Protocol

by Albrecht Günther, Anne Gunkel, Christian Geis, Dirk Brämer, Martin Brauer, Claus Doerfel, Michael Fritzenwanger, Martin Freesmeyer, Thomas Winkens, Robert Drescher and Anke Werner

Diagnostics 2025, 15(21), 2734; https://doi.org/10.3390/diagnostics15212734 - 28 Oct 2025

Abstract

Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with [...] Read more.

Background: In addition to clinical examinations, confirmatory investigations are frequently performed to determine brain death (BD). Among other perfusion tests, brain perfusion scintigraphy (BPS) has been shown to be a reliable tool for the detection of brain circulatory arrest, particularly in cases with inconclusive clinical status or potential pharmacological interactions. Methods: Evaluation for brain death included standardized clinical examinations by two experienced neuro-intensive medicine specialists, followed by ancillary brain perfusion tests. BPS with the lipophilic tracer ^99mTc-hexamethylpropyleneamine oxime (HMPAO) was performed according to a standardized protocol. Imaging results, additional confirmatory test results, as well as clinical parameters were prospectively recorded. Results: BPS was performed in 30 patients (18 male, 12 female; median age 55.5 years, range 0.1–79.8 years). Eight patients underwent decompressive craniectomy (DC) prior to BD evaluation, three patients were supported by veno-arterial extracorporeal membrane oxygenation (vaECMO), and one patient by a left ventricular assist device (LVAD). The median interval between the initial brain-damaging event and BPS was 4.0 days (range 1–18 days). BPS demonstrated brain perfusion cessation in all patients. A concomitant single-photon emission computed tomography (SPECT) was required in one patient. There were no technical failures requiring a re-examination. Conclusions: BPS is a feasible, safe, and technically robust confirmatory test in BD diagnosis. BPS yielded unambiguous results, particularly in cases with inconclusive results of other ancillary tests, in neonates, young children and patients after DC. It is applicable to patients supported by LVAD and vaECMO. Full article

(This article belongs to the Special Issue Neurological Disorders: Diagnosis and Management)

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18 pages, 4716 KB

Open AccessReview

Role of the Ear in Meningitis: A Narrative Review of Neuroimaging

by Teresa Perillo, Raffaella Capasso, Teresa Califano, Federica Cataldo, Ludovica Fulgione, Alessandra Scaravilli, Giuseppe Vitale and Antonio Pinto

Diagnostics 2025, 15(21), 2733; https://doi.org/10.3390/diagnostics15212733 - 28 Oct 2025

Abstract

Background/Objectives: Meningitis is a life-threatening condition often associated with ear pathology. This narrative review explores the critical role of the ear in Meningitis, emphasizing neuroimaging findings. Methods: Congenital malformations of the inner ear may significantly increase the risk of recurrent Meningitis, [...] Read more.

Background/Objectives: Meningitis is a life-threatening condition often associated with ear pathology. This narrative review explores the critical role of the ear in Meningitis, emphasizing neuroimaging findings. Methods: Congenital malformations of the inner ear may significantly increase the risk of recurrent Meningitis, especially in children. Otomastoiditis, through direct extension or bony erosion, is a frequent cause of otogenic Meningitis. Cholesteatoma can erode bone and lead to severe intracranial complications, including Meningitis. Imaging is essential for early detection of bone defects, intracranial extension, and associated complications. Labyrinthitis and vestibulocochlear neuritis are usually complications of Meningitis. Less frequently, Meningitis may follow ear surgeries, such as cochlear implantation or mastoidectomy. Conclusions: Neuroradiologists must be aware of ear conditions associated with Meningitis to enable prompt diagnosis and correct management. Full article

(This article belongs to the Special Issue Advances in Diagnostic and Therapeutic Strategies for Infectious Diseases)

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23 pages, 2355 KB

Open AccessArticle

Transforming Endoscopic Image Classification with Spectrum-Aided Vision for Early and Accurate Cancer Identification

by Yu-Jen Fang, Kun-Hua Lee, Riya Karmakar, Arvind Mukundan, Yaswanth Nagisetti, Chien-Wei Huang and Hsiang-Chen Wang

Diagnostics 2025, 15(21), 2732; https://doi.org/10.3390/diagnostics15212732 - 28 Oct 2025

Abstract

Background/Objective: Esophageal cancer (EC) is a major global health issue due to its high mortality rate, as patients are often diagnosed at advanced stages. This research examines whether the Spectrum-Aided Vision Enhancer (SAVE), a hyperspectral imaging (HSI) technique, enhances endoscopic image categorization [...] Read more.

Background/Objective: Esophageal cancer (EC) is a major global health issue due to its high mortality rate, as patients are often diagnosed at advanced stages. This research examines whether the Spectrum-Aided Vision Enhancer (SAVE), a hyperspectral imaging (HSI) technique, enhances endoscopic image categorization for superior diagnostic outcomes compared to traditional White Light Imaging (WLI) and Narrow Band Imaging (NBI). Methods: A dataset including 2400 photos categorized into eight disease types from National Taiwan University Hospital Yun-Lin Branch was utilized. Multiple machine learning and deep learning models were developed, including logistic regression, VGG16, YOLOv8, and MobileNetV2. SAVE was utilized to transform WLI photos into hyperspectral representations, and band selection was executed to enhance feature extraction and improve classification outcomes. The training and evaluation of the model incorporated precision, recall, F1-score, and accuracy metrics across WLI, NBI, and SAVE modalities. Results: The research findings indicated that SAVE surpassed both NBI and WLI by achieving superior precision, recall, and F1-scores. Logistic regression and VGG16 performed with a comparable reliability to SAVE and NBI, whereas MobileNetV2 and YOLOv8 demonstrated inconsistent yet enhanced results. Overall, SAVE exhibited exceptional categorization precision and recall, showcasing impeccable performance across many models. Conclusions: This research indicates that AI hyperspectral imaging facilitates early diagnosis of esophageal diseases, hence enhancing clinical decision-making and improving patient outcomes. The amalgamation of SAVE with machine learning and deep learning models enhances diagnostic capabilities, with SAVE and NBI surpassing WLI by offering superior tissue differentiation and diagnostic accuracy. Full article

(This article belongs to the Special Issue New Insights into Gastrointestinal Endoscopy)

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14 pages, 1772 KB

Open AccessArticle

Exploring the Association Between Heart Rate Variability and Intracranial Atherosclerosis in Middle-Aged or over Community-Dwelling Adults

by Yangyang Cheng, Lihua Lai, Jieqi Luo and Michael Tin Cheung Ying

Diagnostics 2025, 15(21), 2731; https://doi.org/10.3390/diagnostics15212731 - 28 Oct 2025

Abstract

Background/Objectives: Heart rate variability (HRV) is associated with the risk of vascular events. However, the predictive value of HRV for the presence of intracranial atherosclerosis (ICAS) is unclear. This study aimed to investigate the relationship between daytime HRV measured by 3 min [...] Read more.

Background/Objectives: Heart rate variability (HRV) is associated with the risk of vascular events. However, the predictive value of HRV for the presence of intracranial atherosclerosis (ICAS) is unclear. This study aimed to investigate the relationship between daytime HRV measured by 3 min ECG monitoring and ICAS identified by high-resolution magnetic resonance imaging (HR-MRI). Methods: A total of 272 adults (mean age, 63.4 ± 6.8; 43% male) were recruited from November 2022 to December 2024. A series of cardiac function parameters is automatically generated through a 3 min analysis by the electrocardiographic dispersion mapping (ECG-DM) software, including heart rate variability and myocardial ischemic metabolic impairment. HRV was assessed as the standard deviation of normal-to-normal intervals (SDNN), which was categorized into tertiles for data analysis. Myocardial micro-alteration index (MMI, %) was used as an indicator of ischemia, reflecting myocardial abnormalities at the metabolic level. Atrial and ventricular myocardial oxygenation deficits were directly visualized in a color-coded scatter plot, with different colors indicating the severity of pathological changes. On HR-MRI intracranial artery wall scanning, the prevalence of ICAS was assessed in middle cerebral arteries (MCAs), vertebral arteries (VAs), and basilar arteries (BAs), and the associated plaque characteristics (eccentricity, thickening patterns, remodeling index, and surface morphology) were evaluated. Results: Among the subjects, 209 arterial lesions caused by ICAS were detected in 152 subjects (56%), including MCAs (105/544), VAs (68/526), and BAs (36/272). Ninety-four subjects (94/272) with significant HRV deviation had ICAS (p = 0.040). Furthermore, subjects with ICAS were more likely to present with atrial hypoxia (p = 0.030) compared to those without ICAS. In multivariate analyses, lower standard deviation of normal-to-normal intervals (SDNN, odds ratio, OR = 1.55, 95% CI 1.10–2.18, p = 0.012) and atrial deviation (OR = 1.85, 95% CI 1.10–3.14, p = 0.022) were independently associated with the presence of ICAS. Conclusions: Among middle-aged or older adults in a local community, our study suggested that lower HRV and significant atrial hypoxia were independently associated with the presence of ICAS. Full article

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

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15 pages, 943 KB

Open AccessArticle

DeepCMS: A Feature Selection-Driven Model for Cancer Molecular Subtyping with a Case Study on Testicular Germ Cell Tumors

by Mehwish Wahid Khan, Ghufran Ahmed, Muhammad Shahzad, Abdallah Namoun, Shahid Hussain and Meshari Huwaytim Alanazi

Diagnostics 2025, 15(21), 2730; https://doi.org/10.3390/diagnostics15212730 - 28 Oct 2025

Abstract

Background/Objectives: Cancer is a chronic and heterogeneous disease, possessing molecular variation within a single type, resulting in its molecular subtypes. Cancer molecular subtyping offers biological insights into cancer variability, facilitating the development of personalized medicines. Various models have been proposed for cancer molecular [...] Read more.

Background/Objectives: Cancer is a chronic and heterogeneous disease, possessing molecular variation within a single type, resulting in its molecular subtypes. Cancer molecular subtyping offers biological insights into cancer variability, facilitating the development of personalized medicines. Various models have been proposed for cancer molecular subtyping, utilizing the high-dimensional transcriptomic, genomic, or proteomic data. The issue of data scarcity, characterized by high feature dimensionality and a limited sample size, remains a persistent problem.The objective of this research is to propose a deep learning framework, DeepCMS, that leverages the capabilities of feed-forward neural networks, gene set enrichment analysis, and feature selection to construct a well-representative subset of the feature space, thereby producing promising results. Methods: The gene expression data were transformed into enrichment scores, resulting in over 22,000 features. From those, the top 2000 features were selected, and deep learning was applied to these features. The encouraging outcomes indicate the efficacy of the proposed framework in terms of defining a well-representative feature space and accurately classifying cancer molecular subtypes. Results: DeepCMS consistently outperformed state-of-the-art models in aggregated accuracy, sensitivity, specificity, and balanced accuracy. The aggregated metrics surpassed 0.90 for all efficiency measures on independent test datasets, showing the generalizability and robustness of our framework. Although developed using colon cancer’s gene expression data, this approach may be applied to any gene expression data; a case study is also devised for illustration. Conclusions: Overall, the proposed DeepCMS framework enables the accurate and robust classification of cancer molecular subtypes using a compact and informative feature set, facilitating improved precision in oncology applications. Full article

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

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15 pages, 5507 KB

Open AccessArticle

MRI-Based Morphometric Analysis of the Sacral Hiatus and Its Exploratory Value for Predicting Caudal Epidural Block Success: A Retrospective Observational Study

by Ahmet Yılmaz and Cagatay Kucukbingoz

Diagnostics 2025, 15(21), 2729; https://doi.org/10.3390/diagnostics15212729 - 28 Oct 2025

Abstract

Objectives: In this retrospective observational study, we aimed to evaluate sacral hiatus morphometry in detail using MRI and investigate whether morphometric parameters can predict the success of a caudal epidural block. We hypothesized that reduced hiatus width and altered morphometric features may increase [...] Read more.

Objectives: In this retrospective observational study, we aimed to evaluate sacral hiatus morphometry in detail using MRI and investigate whether morphometric parameters can predict the success of a caudal epidural block. We hypothesized that reduced hiatus width and altered morphometric features may increase the likelihood of block failure. Methods: MRI scans of 240 adult patients (mean age: 51 years; 50% female) were retrospectively analyzed at a single center. Hiatus height and width, canal depth, and sacrococcygeal angle were measured. Gender- and age-related differences were assessed. Multivariate regression and ROC curve analysis were used to determine predictive thresholds for block failure. Results: Hiatus height was slightly higher in women (16.97 ± 7.25 mm) than in men (15.99 ± 7.55 mm, p < 0.05, Cohen’s d = 0.25). The mean hiatus width was 9.9 ± 3.0 mm. Canal depth (5.9 ± 2.2 mm) and sacrococcygeal angle (40.8 ± 11.1°) did not differ significantly between genders (p > 0.05). A hiatus width threshold of 8 mm was identified as a predictor of block failure (AUC = 1.00, 95% CI 0.98–1.00), though this exceptionally high value should be interpreted cautiously due to the risk of overfitting in regard to a single-center cohort. Conclusions: MRI-based morphometric assessment of the sacral hiatus provides clinically relevant information. A narrow hiatus (<8 mm) is strongly associated with block failure, while other parameters showed limited predictive value. These findings are hypothesis-generating and require prospective, multicenter validation before clinical application. Full article

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

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11 pages, 5805 KB

Open AccessArticle

Distal Oblique Bundle and Membranous Thickening: Morphology and Integration with the Triangular Fibrocartilage Complex

by Yuri Seu, Seong-Kyu Choi, Jin Seo Park, Hongtae Kim and Mi-Sun Hur

Diagnostics 2025, 15(21), 2728; https://doi.org/10.3390/diagnostics15212728 - 28 Oct 2025

Abstract

Background: The distal oblique bundle (DOB) of the interosseous membrane (IOM) has been recognized as an important stabilizer of the distal radioulnar joint (DRUJ). However, its prevalence, morphology, and distal attachments—particularly its relationship to the articular disc and the extensor carpi ulnaris (ECU) [...] Read more.

Background: The distal oblique bundle (DOB) of the interosseous membrane (IOM) has been recognized as an important stabilizer of the distal radioulnar joint (DRUJ). However, its prevalence, morphology, and distal attachments—particularly its relationship to the articular disc and the extensor carpi ulnaris (ECU) tendon sheath—remain inconsistently described. Clarifying these anatomical details is essential for understanding DRUJ stability and guiding surgical reconstruction. Methods: The distal IOM was examined in 48 specimens from 24 embalmed Korean cadavers. In 46 dissected specimens, the presence, morphology, and attachment sites of distal interosseous structures were documented, and attachment levels were measured. In 38 specimens, attachment to the articular disc was assessed. In addition, serial transverse sections from one cadaver were analyzed to confirm three-dimensional relationships. Results: Two morphological patterns were identified: a distinct DOB (21/46, 45.7%) and, when absent, a membranous thickening of the distal IOM (25/46, 54.3%). The mean attachment level was 39.1 ± 9.7 mm for the DOB and 25.4 ± 4.8 mm for the membranous thickening. Both structures assumed an oblique orientation, fanning palmarly toward the capsule and articular disc and dorsally toward the ECU tendon sheath and dorsal septum. In 26 of 38 specimens (68.4%), these structures attached to the proximal palmar portion of the articular disc. Serial transverse sections confirmed this oblique configuration, linking palmar and dorsal stabilizers of the DRUJ. Conclusions: The distal IOM consistently forms specialized structures—either a DOB or a membranous thickening—that integrate with the triangular fibrocartilage complex. By bridging palmar and dorsal stabilizers, these structures contribute to joint congruency and load transfer during forearm rotation. A refined anatomical understanding of these patterns provides clinically relevant insights for surgical preservation or reconstruction, with the potential to improve outcomes in patients with chronic DRUJ instability. Full article

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

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12 pages, 810 KB

Open AccessArticle

Early Sepsis Prediction Using Publicly Available Data: High-Performance AI/ML Models with First-Hour Clinical Information

by Hao Wang, Destiny Pounds, Wenhui Zhang, Alaa Y. Mokbel, Md Niamul Kabir, Xin Yao Lin, April Highlander and Iman Dehzangi

Diagnostics 2025, 15(21), 2727; https://doi.org/10.3390/diagnostics15212727 - 28 Oct 2025

Abstract

Objectives: Early identification of sepsis is critical, as delayed diagnosis significantly increases morbidity and mortality. We aimed to develop and validate AI/ML models for early sepsis prediction using structured electronic health record (EHR) data, waveform data, and a combination of both. Methods: We [...] Read more.

Objectives: Early identification of sepsis is critical, as delayed diagnosis significantly increases morbidity and mortality. We aimed to develop and validate AI/ML models for early sepsis prediction using structured electronic health record (EHR) data, waveform data, and a combination of both. Methods: We conducted a retrospective observational study using the AIM-AHEAD60 subset of the CHoRUS dataset. Adult patients (≥18 years) with a final diagnosis of sepsis were included. Structured EHR data (demographics, initial vital signs, laboratory results) and waveform data (continuous vital signs) from the first hour of hospital arrival were extracted. Three algorithms (i.e., XGBoost, LightGBM, and HistGB) were developed with a focus on maximizing the performance metric of recall. Other performance metrics were also assessed, including accuracy, precision, F1 score, and the area under the receiver operating characteristic curve (AUROC). Results: A total of 11,312 unique patients met the inclusion criteria, among whom 2245 individuals (19.85%) were diagnosed with sepsis at least once. Using structured EHR data alone, laboratory variables such as lactate and leukocyte count were most predictive. Waveform models identified respiratory rate, systolic blood pressure, and temperature trends in the first hour as key predictors. Combined models highlighted mean temperature and mean systolic blood pressure as top features. XGBoost achieved the highest AUROC (0.922) across all data configurations, with a recall above 80%, demonstrating robust performance despite substantial missing data. Conclusions: High-performing AI/ML models for early sepsis prediction can be developed from publicly available datasets using only first-hour clinical information. XGBoost models demonstrate strong potential for real-time clinical screening. Full article

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

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5 pages, 165 KB

Open AccessEditorial

Bridging the Heart and Brain—Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases

by Sonu M. M. Bhaskar

Diagnostics 2025, 15(21), 2726; https://doi.org/10.3390/diagnostics15212726 - 28 Oct 2025

Abstract

Cardiovascular and cerebrovascular diseases (CVDs) remain the leading global causes of mortality and long-term disability [...] Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

13 pages, 1754 KB

Open AccessArticle

An ERA-CRISPR/Cas12a Method for Highly Sensitive Detection of Human Adenovirus Type 55

by Letian Zhang, Zhenghan Luo, Taiwu Wang, Yifang Han, Fuqiang Ye, Chunhui Wang, Yue Chen and Jinhai Zhang

Diagnostics 2025, 15(21), 2725; https://doi.org/10.3390/diagnostics15212725 - 27 Oct 2025

Abstract

Background/Objectives: Human adenovirus 55 (HAdV55) is a notable pathogen causing community-acquired pneumonia; outbreaks occur frequently in military camps, hospitals, and schools, thereby posing a threat to public health security. This study aimed to develop a method for detecting HAdV55 nucleic acid by targeting [...] Read more.

Background/Objectives: Human adenovirus 55 (HAdV55) is a notable pathogen causing community-acquired pneumonia; outbreaks occur frequently in military camps, hospitals, and schools, thereby posing a threat to public health security. This study aimed to develop a method for detecting HAdV55 nucleic acid by targeting the conserved region of the Hexon gene. The sequence was amplified using enzymatic recombination isothermal amplification (ERA) technology, in conjunction with CRISPR-Cas12a technology, to enhance the amplification signal. Methods: Optimized primer and crRNA sequences were selected through ERA isothermal amplification testing. The ERA-CRISPR/Cas12a detection method was completed within 30 min at a constant temperature of 42 °C. Results: Sensitivity was assessed by detecting standard plasmids and live strains at various dilution concentrations. The detection limits were determined to be 9 copies/reaction for standard plasmids and 2.5 copies/reaction for cultured HAdV55 strains. Specificity tests were conducted on positive samples for five common respiratory pathogens and five other adenovirus subtypes, all of which showed no cross-reactivity. Conclusions: A rapid ERA-CRISPR/Cas12a nucleic acid detection method for HAdV55 has been successfully developed, demonstrating high sensitivity and specificity without the need for expensive or complex instruments. This method holds promise for on-site pathogen screening and detection. Full article

(This article belongs to the Special Issue Point-of-Care Testing (POCT) for Infectious Diseases)

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9 pages, 1484 KB

Open AccessInteresting Images

Early Radiological Limitations in Bone Healing Estimation After Allogeneic Bone Grafts Used for Mandible Reconstruction

by Kamil Nelke, Klaudiusz Łuczak, Maciej Janeczek, Mikołaj Włodarczyk, Magdalena Florek, Małgorzata Tarnowska, Agata Małyszek, Cyprian Olchowy, Maciej Dobrzyński and Piotr Kuropka

Diagnostics 2025, 15(21), 2724; https://doi.org/10.3390/diagnostics15212724 - 27 Oct 2025

Abstract

Xenograft bone, autologous bone grafts or allogeneic bones from a bone bank are used for bone augmentation, reconstruction or other purposes, when the volume, shape, and size of each jawbone defect require different bone materials. In the case of some bigger and locally [...] Read more.

Xenograft bone, autologous bone grafts or allogeneic bones from a bone bank are used for bone augmentation, reconstruction or other purposes, when the volume, shape, and size of each jawbone defect require different bone materials. In the case of some bigger and locally advanced bone defects, the use of allogeneic bone can be suitable and used with great success if the wound and bone are especially carefully maintained; however, the healing period of each bone depends on good and stable wound closure followed by improved local antiseptic protocol. The individuality of each bone defect might also require additional prophylactic titanium plating in order to decrease the risk of possible mandibular fracture or to help improve bone stability, reduce bone mobility and possible inflammation or granulation tissue formation. Early radiological estimation of bone healing evaluation might be troublesome and not fully visible in radiological evaluation in the early stages of bone healing. On the other hand, possible bone inflammation, radiolucent defects, and granulation formation could be noted in cases of acute or long-lasting bone grafting material inflammation, bacterial contamination within the bone defect area, or the presence of fistula. The presented case describes a very good outcome from a dentigerous cyst removal with bone defect grafting and plating; however, because of wound dehiscence and allogeneic bone graft exposure, the patient required one additional procedure. Full article

(This article belongs to the Collection Interesting Images)

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5 pages, 1150 KB

Open AccessInteresting Images

Hyperperfusion Improvement: A Potential Therapeutic Marker in Neuromyelitis Optica Spectrum Disorder (NMOSD)

by Koichi Kimura, Koji Hayashi, Mamiko Sato, Yuka Nakaya, Asuka Suzuki, Naoko Takaku, Hiromi Hayashi, Kouji Hayashi, Toyoaki Miura and Yasutaka Kobayashi

Diagnostics 2025, 15(21), 2723; https://doi.org/10.3390/diagnostics15212723 - 27 Oct 2025

Abstract

A 70-year-old Japanese woman with longstanding hearing loss and asthma developed floating sensations, left finger numbness, and postural instability one day after influenza vaccination, leading to hospital admission. Neurological examinations showed hearing loss, hyperreflexia, left-predominant ataxia, bilateral mild bathyanesthesia, and inability to tandem [...] Read more.

A 70-year-old Japanese woman with longstanding hearing loss and asthma developed floating sensations, left finger numbness, and postural instability one day after influenza vaccination, leading to hospital admission. Neurological examinations showed hearing loss, hyperreflexia, left-predominant ataxia, bilateral mild bathyanesthesia, and inability to tandem gait. Cerebrospinal fluid (CSF) analysis showed no pleocytosis or malignant cells, but revealed positive oligoclonal bands and elevated myelin basic protein. Despite no contrast agent use due to asthma, brain magnetic resonance imaging (MRI) revealed pontine hyperintensities on diffusion-weighted imaging (DWI) and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences, along with hyperperfusion on arterial spin labeling (ASL) imaging. Serum anti-aquaporin-4 antibodies (AQP4-Ab) were negative by ELISA. Given the temporal proximity to vaccination and elevated demyelination markers, brainstem-type acute disseminated encephalomyelitis (ADEM) was initially suspected. Symptoms nearly resolved after two cycles of methylprednisolone pulse therapy. Notably, hyperperfusion gradually improved on ASL imaging. Post-discharge, a cell-based assay confirmed the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) by detecting positive anti-AQP4-Ab. She has been relapse-free for about a year without any immunosuppressants or biologics. Although contrast-enhanced MRI remains the gold standard modality for lesion evaluation due to its high sensitivity, hyperperfusion on ASL may provide a useful alternative in patients for whom contrast agents are contraindicated, such as those with asthma or impaired renal function. Full article

(This article belongs to the Special Issue Brain MRI: Current Development and Applications)

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19 pages, 2331 KB

Open AccessArticle

Advancing Prostate Cancer Assessment: A Biparametric MRI (T2WI and DWI/ADC)-Based Radiomic Approach to Predict Tumor–Stroma Ratio

by Jiangqin Ma, Xiling Gu, Zhonglin Zhang, Jun Chen, Yunfan Liu, Yang Qiu, Guangyong Ai, Xuxiang Jia, Zhenghao Li, Bo Xiang and Xiaojing He

Diagnostics 2025, 15(21), 2722; https://doi.org/10.3390/diagnostics15212722 - 27 Oct 2025

Abstract

Objectives: This study aimed to develop and validate a biparametric MRI (bpMRI)-based radiomics model for the noninvasive prediction of tumor–stroma ratio (TSR) in prostate cancer (PCa). Additionally, we sought to explore lesion distribution patterns in the peripheral zone (PZ) and transition zone (TZ) [...] Read more.

Objectives: This study aimed to develop and validate a biparametric MRI (bpMRI)-based radiomics model for the noninvasive prediction of tumor–stroma ratio (TSR) in prostate cancer (PCa). Additionally, we sought to explore lesion distribution patterns in the peripheral zone (PZ) and transition zone (TZ) to provide deeper insights into the biological behavior of PCa. Methods: This multicenter retrospective study included 223 pathologically confirmed PCa patients, with 146 for training and 39 for internal validation at Center 1, and 38 for external testing at Center 2. All patients underwent preoperative bpMRI (T2WI, DWI acquired with a b-value of 1400 s/mm², and ADC maps）, with TSR histopathologically quantified. Regions of interest (ROIs) were manually segmented on bpMRI images using ITK-SNAP software (version 4.0.1), followed by high-throughput radiomic feature extraction. Redundant features were eliminated via Spearman correlation analysis and least absolute shrinkage and selection operator (LASSO) regression. Five machine learning (ML) classifiers—Logistic Regression (LR), Support Vector Machine (SVM), BernoulliNBBayes, Ridge, and Stochastic Gradient Descent (SGD)—were trained and optimized. Model performance was rigorously evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The Ridge demonstrated superior diagnostic performance, achieving AUCs of 0.846, 0.789, and 0.745 in the training, validation, and test cohorts, respectively. Lesion distribution analysis revealed no significant differences between High-TSR and Low-TSR groups (p = 0.867), suggesting that TSR may not be strongly associated with zonal localization. Conclusions: This exploratory study suggests that a bpMRI-based radiomic model holds promise for noninvasive TSR estimation in prostate cancer and may provide complementary insights into tumor aggressiveness beyond conventional pathology. Full article

(This article belongs to the Special Issue Innovations in Medical Imaging for Precision Diagnostics)

22 pages, 2153 KB

Open AccessArticle

The Solitary Fibrous Tumor, the Chameleon of the Head and Neck Region—Clinical, Epidemiological, and Histopathological Aspects

by Marina Rakitovan, Adrian Nicoara, Raluca Maria Closca, Raluca Amalia Ceausu, Cristina Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Antonia Armega Anghelescu, Alexandru Cristian Cindrea and Flavia Zara

Diagnostics 2025, 15(21), 2721; https://doi.org/10.3390/diagnostics15212721 - 27 Oct 2025

Abstract

Background/Objectives: The solitary fibrous tumor is an uncommon benign mesenchymal neoplasm with relatively indolent and rarely metastasizing behavior. This retrospective study includes 26 cases of head and neck solitary fibrous tumors diagnosed between 2017 and 2024. Methods: The morphological examination with Hematoxylin–Eosin staining [...] Read more.

Background/Objectives: The solitary fibrous tumor is an uncommon benign mesenchymal neoplasm with relatively indolent and rarely metastasizing behavior. This retrospective study includes 26 cases of head and neck solitary fibrous tumors diagnosed between 2017 and 2024. Methods: The morphological examination with Hematoxylin–Eosin staining was completed via immunohistochemical reactions with specific antibodies. Results: The Ki-67 proliferation index had a median of 11.2%, with an interquartile range of 5% to 15%. CD20-positive B-cells had a score of 0 in 50% of cases (n = 26), while CD3 and CD5 T-cells had a score of 3 in 81% of cases (n = 21). CD4-positive T-cells had a majority score of 1 (81%, n = 21). CD8-positive T-cells had a broader distribution: 65% (n = 17) of cases presented a score of 1, 27% (n = 7) a score of 2, and 8% (n = 8) a score of 0. Antigen-presenting dendritic cells and mast cells presented a majority score of 0 in the entire cohort, being undetectable in 85% (n = 22) and 88% (n = 23) of cases, respectively. CD20-positive B-lymphocytes demonstrated moderately strong correlations with the Ki-67 cell proliferation index (r = 0.77). The time to recurrence was most strongly associated with the Ki-67 mitotic index (r = 0.81), CD4-positive (r = 0.85), and CD5-positive T-lymphocytes (r = 0.55), and CD20-positive B-lymphocyte expression (r = 0.68). Conclusions: This research illustrates our experience with head and neck solitary fibrous tumors, the surgical decisions, and the morphological and immunohistochemical features, while reviewing the cases published in English in the specialized literature. Full article

(This article belongs to the Special Issue Pathology and Diagnosis of Head and Neck Diseases)

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14 pages, 9234 KB

Open AccessArticle

Effects of Noise Stress on Neuronal Activation in Rat Auditory Pathway-Related Brain Regions

by Duygu Gök Yurtseven, Alper Vatansever, Gonca Topal, Şule Mergen, Ömer Faruk Özdemir, İlker Mustafa Kafa, Gökhan Göktalay and Özhan Eyigör

Diagnostics 2025, 15(21), 2720; https://doi.org/10.3390/diagnostics15212720 - 27 Oct 2025

Abstract

Background/Objectives: Environmental noise is a non-specific biological stressor that is becoming an escalating health concern for both industrialized and developing countries. A study by the World Health Organization identified ambient noise as the second most prevalent factor adversely affecting public health, causing high [...] Read more.

Background/Objectives: Environmental noise is a non-specific biological stressor that is becoming an escalating health concern for both industrialized and developing countries. A study by the World Health Organization identified ambient noise as the second most prevalent factor adversely affecting public health, causing high levels of stress. Extended or intense exposure to environmental noise (EN) has been linked to various alterations in auditory pathways and auditory-related central nervous system structures. We tested the hypothesis that acute exposure to intense noise could lead to such alterations. Therefore, the aim of this study is to evaluate neuronal activation in auditory-related brain regions resulting from acute noise exposure using immunohistochemistry processes. Methods: We examined a total of 12 Wistar rats (6 rats for noise exposure group; 6 rats for the control group). The noise exposure group was exposed to intense noise, while the control group experienced basal noise for thirty minutes. After scarification of the rats, tissues were collected and examined histologically using the immunohistochemical staining method. Results: Our research demonstrates that acute noise exposure markedly elevates neuronal activity in critical parts of the auditory system, such as the cochlear nuclei, inferior colliculi, trapezoid body, and primary auditory cortex. While we identified c-Fos immunoreactive neurons in the medial geniculate body of both the experiment and control groups, no statistically significant changes were found between these groups. Conclusions: These findings indicate that noise exposure-related stress could be caused primarily by the disruption of lower centers rather than the medial geniculate body. Full article

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

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