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Keywords = clinic-pathologic correlation

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18 pages, 645 KB  
Review
Thermal Ablation as a Non-Surgical Alternative for Thyroid Nodules: A Review of Current Evidence
by Andreas Antzoulas, Vasiliki Garantzioti, George S. Papadopoulos, Apostolos Panagopoulos, Vasileios Leivaditis, Dimitrios Litsas, Platon M. Dimopoulos, Levan Tchabashvili, Elias Liolis, Konstantinos Tasios, Panagiotis Leventis, Nikolaos Kornaros and Francesk Mulita
Medicina 2025, 61(11), 1910; https://doi.org/10.3390/medicina61111910 (registering DOI) - 24 Oct 2025
Viewed by 164
Abstract
Thyroid nodules, prevalent in 2% to 65% of the general population depending on diagnostic methodology, represent a significant clinical concern despite a low malignancy rate, typically 1% to 5%. A substantial proportion of thyroid cancers are small, indolent lesions, allowing for conservative management [...] Read more.
Thyroid nodules, prevalent in 2% to 65% of the general population depending on diagnostic methodology, represent a significant clinical concern despite a low malignancy rate, typically 1% to 5%. A substantial proportion of thyroid cancers are small, indolent lesions, allowing for conservative management with favorable prognoses. Nodule detection commonly occurs via palpation, clinical examination, or incidental radiological findings. Established risk factors include advanced age, female gender, obesity, metabolic syndrome, and estrogen dominance. Despite conservative management potential, a considerable number of thyroid nodules in Europe are unnecessarily referred for surgery, incurring unfavorable risk-to-benefit ratios and increased costs. Minimally invasive techniques (MITs), encompassing ethanol and thermal ablation modalities (e.g., laser, radiofrequency, microwave), offer outpatient, nonsurgical management for symptomatic or cosmetically concerning thyroid lesions. These procedures, performed under ultrasound guidance without general anesthesia, are associated with low complication rates. MITs effectively achieve substantial and sustained nodule volume reduction (57–77% at 5 years), correlating with improved local symptoms. Thermal ablation (TA) is particularly favored for solid thyroid lesions due to its precise and predictable tissue destruction. Optimal TA balances near-complete nodule eradication to prevent recurrence with careful preservation of adjacent anatomical structures to minimize complications. Radiofrequency ablation (RFA) is widely adopted, while microwave ablation (MWA) presents a promising alternative addressing RFA limitations. Percutaneous laser ablation (LA), an early image-guided thyroid ablation technique, remains a viable option for benign, hyperfunctioning, and malignant thyroid pathologies. This review comprehensively evaluates RFA, MWA, and LA for thyroid nodule treatment, assessing current evidence regarding their efficacy, safety, comparative outcomes, side effects, and outlining future research directions. Full article
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26 pages, 1535 KB  
Article
Prognostic and Predictive Significance of B7-H3 and CD155 Expression in Gastric Cancer Patients
by Ozlem Dalda, Zehra Bozdag, Sami Akbulut, Hasan Gokce, Yasin Dalda, Ayse Nur Akatli and Mustafa Huz
Diagnostics 2025, 15(21), 2695; https://doi.org/10.3390/diagnostics15212695 (registering DOI) - 24 Oct 2025
Viewed by 175
Abstract
Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included [...] Read more.
Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included 112 patients who underwent gastrectomy for gastric adenocarcinoma between 2020 and 2025, along with 30 samples of normal gastric tissue obtained from sleeve gastrectomy specimens. Histological subtype, grade of differentiation, TNM stage, and invasion parameters were re-evaluated. Immunohistochemical expression of B7-H3 and CD155 was quantified for membranous, stromal and membranous/cytoplasmic staining patterns. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed on 29 tumor and 25 normal samples to confirm mRNA expression levels, with fold change ≥2 considered biologically significant upregulation and ≤0.5 considered downregulation. Machine learning models were developed to predict metastasis and mortality based on clinical and immunohistochemical features. Results: 78.5% of tumors were at an advanced stage (T3–T4), and metastasis was present in 22.3% of patients. Perineural invasion (PNI) and lymphovascular invasion (LVI) were observed in 67.9% and 88.4% of cases, respectively. Increased B7-H3 and CD155 expression were significantly associated with advanced tumor stage, metastasis, and the presence of PNI and LVI (all p < 0.05). In metastatic tumors, median membranous B7-H3, stromal B7-H3, and CD155 scores were 60, 130, and 190, respectively, compared with 20, 90, and 120 in non-metastatic tumors. A significant positive correlation was found between stromal B7-H3 and CD155 expression (r = 0.384, p < 0.001), indicating parallel upregulation. Quantitative RT-PCR confirmed significant overexpression of both genes in tumor tissues relative to normal controls. B7-H3 was upregulated in 75.9% and CD155 in 58.6% of samples, with co-upregulation in 55.2%. Fold-change levels were markedly higher in metastatic versus non-metastatic cases (B7-H3: 7.69-fold vs. 3.04-fold; CD155: 7.44-fold vs. 1.79-fold). ML analysis using the XGBoost model achieved 91.1% accuracy for metastasis prediction (F1-score 0.800). Key variables included pathological T4b stage, perineural invasion, N3b status, T4a stage, and CD155 score. The mortality model yielded 86.7% accuracy (F1-score 0.864), with metastasis, differentiation status, nodal involvement, age, lymph node ratio, and perineural invasion emerging as principal predictors. Conclusions: Combined evaluation of B7-H3 and CD155, supported by immunohistochemical staining and RT-PCR quantification of B7-H3 and CD155 mRNA expression levels, provides meaningful prognostic insights and supports their potential as dual molecular biomarkers for aggressive gastric adenocarcinoma phenotypes. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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14 pages, 1301 KB  
Article
Tissue Factor Expression in Penile Squamous Cell Carcinoma: A Potential Marker of HPV-Independent Disease
by Jamaal C. Jackson, Andrew C. Johns, Leticia Campos Clemente, Christopher M. Manuel, Wei Qiao, Wei Lu, Khaja Khan, Luisa M. Solis Soto, Jad Chahoud, Priya Rao, Matthew T. Campbell, Curtis A. Pettaway and Niki M. Zacharias
Cancers 2025, 17(21), 3410; https://doi.org/10.3390/cancers17213410 - 23 Oct 2025
Viewed by 165
Abstract
Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human [...] Read more.
Background/Objectives: In a series of 33 patients with advanced penile squamous cell carcinoma (PSCC), we evaluated tissue factor (TF), TROP2, and nectin-4 protein expression as potential therapeutic targets. Expression levels of these proteins were also correlated to clinicopathological characteristics, including high-risk human papillomavirus (HPV), CDKN2A (p16) status, and aberrant p53 expression. Methods: A tissue microarray (TMA) was constructed with three cores per patient tumor (99 total cores). Anti-TF antibody staining was performed by immunohistochemistry, and H-scores for membrane and cytoplasm staining were assessed (range 0–300). The percentage of cores and patient tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) and H-scores were described and compared with HPV and p16 status. The association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), aberrant p53 expression, recurrence-free survival (RFS), and cancer-specific survival (CSS) was assessed. Nectin-4 and TROP2 staining and their association with clinical/pathological data were determined in a similar manner. Results: TF staining was evident in 26 (81.3%) of the cohort and was more prominent in HPV-negative tumors in both the membrane (H-score 69.6 vs. 18.8; p = 0.003) and cytoplasm (H-score 59.2 vs. 17.7, p = 0.007). Cytoplasmic (H-score 61.7 vs. 11.7, p < 0.001) and membrane TF staining (H-score 71.7 vs. 15.0, p < 0.001) favored p16-negative tumors. The p53 status was more likely to be aberrant in the higher TF staining samples (cytoplasm H-score 61.7 vs. 18.3, p = 0.012; membrane H-score 67.5 vs. 20.3, p = 0.006). We observed an association with TROP2 staining and positive p16 status (membrane H-score 120.3 vs. 85, p = 0.052; cytoplasmic H-score 135 vs. 107.5, p = 0.041). We observed an association of TROP2 staining with positive LVI (membrane H-score 136.7 vs. 66.7, p = 0.014; cytoplasmic H-score 110 vs. 93.3, p = 0.04). We found no association between TF, TROP2, or nectin-4 staining with CSS or RFS; however, we suspect that this was due to our small sample size. Conclusions: Our results indicate that TF was expressed in the majority of advanced PSCC with enhanced expression among HPV-independent, p53-aberrant tumors and may represent a novel therapy target in advanced PSCC. Full article
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15 pages, 1175 KB  
Article
The Impact of Local Ablative Therapies as Bridging Treatment on Overall Survival Following Liver Transplantation in Patients with HCC
by Laura Schwenk, Felix Dondorf, Oliver Rohland, Aladdin Ali-Deeb, Utz Settmacher and Falk Rauchfuß
Cancers 2025, 17(20), 3393; https://doi.org/10.3390/cancers17203393 - 21 Oct 2025
Viewed by 209
Abstract
Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, [...] Read more.
Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, we evaluated patients with hepatocellular carcinoma who underwent deceased donor or living donor liver transplantation at Jena University Hospital between 2019 and 2023. Comprehensive clinical and pathological variables were systematically analyzed, including correlations between neoadjuvant therapy use, tumor burden and overall survival. Survival outcomes were estimated using the Kaplan–Meier method. Results: A total of 107 patients were included in the analysis, of whom 90 received neoadjuvant therapy prior to transplantation. Treatment modalities comprised SIRT, TACE, liver resection and combined SIRT and TACE. The 1-, 3-, and 5-year OS rates following transplantation were 93.5%, 82.2%, and 79.4%, respectively. Recurrence-free survival at 1, 3, and 5 years was 91.6%, 85.0%, and 83.2%, respectively. Among the various neoadjuvant strategies, SIRT and TACE yielded the highest OS rates. Patients listed outside the transplantation criteria (Milan, UCSF, up-to-seven) at the time of initial diagnosis who underwent SIRT had significantly better OS than those outside the criteria who underwent TACE. In contrast, among patients within the Milan, UCSF and up-to-seven criteria, TACE was associated with superior OS compared with SIRT. Conclusion: The use of neoadjuvant therapies confers a significant survival benefit following liver transplantation in patients with HCC. TACE appears to be most suitable for patients listed within established transplantation criteria, who consequently have a lower tumor burden. In contrast, SIRT is more beneficial for patients with a higher tumor burden and those beyond standard transplantation criteria. A limitation of our study, however, is that the included SIRT cohort comprised only 24 patients, and TACE was preferentially performed in patients with a lower tumor burden, which means that a selection bias cannot be fully excluded. Overall, further studies are required to define the optimal bridging strategies. Full article
(This article belongs to the Special Issue Surgical Treatment of Hepatocellular Carcinoma)
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10 pages, 2921 KB  
Article
Lung Ultrasound Assessment of Lung Injury Following Acute Spinal Cord Injury in Rats
by Na Ni, Ruiliang Chu, Kai Gu and Yi Zhong
Diagnostics 2025, 15(20), 2648; https://doi.org/10.3390/diagnostics15202648 - 21 Oct 2025
Viewed by 240
Abstract
Background/Objectives: Acute spinal cord injury (ASCI) often leads to pulmonary complications, yet reliable, non-invasive assessment tools are limited. This study aimed to evaluate the utility of lung ultrasound (LUS) in assessing lung injury following ASCI in a rat model. Methods: Fifty-four female Sprague [...] Read more.
Background/Objectives: Acute spinal cord injury (ASCI) often leads to pulmonary complications, yet reliable, non-invasive assessment tools are limited. This study aimed to evaluate the utility of lung ultrasound (LUS) in assessing lung injury following ASCI in a rat model. Methods: Fifty-four female Sprague Dawley rats were randomized into sham (n = 27) or ASCI (n = 27) groups. LUS was performed at 12 h, 48 h, and 1 week post-injury, with lung injury quantified using a modified B-line score (BLS). Pulmonary function was assessed non-invasively, and histopathological evaluation and wet-to-dry (W/D) weight ratios were conducted post-mortem. Correlations between BLS and functional and pathological parameters were analyzed. Results: Histological analysis revealed progressive pulmonary hemorrhage, edema, and inflammatory infiltration peaking at 48 h post-injury, with residual hemorrhage and fibroplasia at 1 week. LUS findings evolved from narrow-based B-lines at 12 h to confluent B-lines with pleural abnormalities by 1 week. ASCI rats showed significant reductions in respiratory frequency, peak inspiratory and expiratory flow, and EF50 at all time points (p < 0.05). Tidal volume and minute volume decreased initially, with partial recovery at 1 week. BLS negatively correlated with all pulmonary function parameters and positively with the histological score and W/D ratio (p < 0.001). Conclusions: LUS reliably detects and tracks lung injury after ASCI, correlating well with physiological and pathological indicators. These findings support its potential as a non-invasive monitoring tool. Future refinement of ultrasound scoring may improve clinical applicability in ASCI-related pulmonary assessment. Full article
(This article belongs to the Special Issue Critical Ultrasound in Newborns/Children)
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18 pages, 1453 KB  
Article
Comparative Clinical and Volumetric Outcomes of Contemporary Surgical Techniques for Lumbar Foraminal Stenosis: A Retrospective Cohort Study
by Renat M. Nurmukhametov, Vladimir Klimov, Abakirov Medetbek, Stepan Anatolevich Kudryakov, Medet Dosanov, Anastasiia Alekseevna Guseva, Petr Ruslanovich Baigushev, Timur Arturovich Kerimov and Nicola Montemurro
Surgeries 2025, 6(4), 91; https://doi.org/10.3390/surgeries6040091 - 20 Oct 2025
Viewed by 216
Abstract
Background: Lumbar foraminal stenosis (LFS) is a prevalent degenerative condition associated with significant radicular pain and impaired quality of life. Advances in minimally invasive and fusion-based surgical techniques have introduced new strategies for decompressing the neural elements. However, comparative data correlating volumetric foraminal [...] Read more.
Background: Lumbar foraminal stenosis (LFS) is a prevalent degenerative condition associated with significant radicular pain and impaired quality of life. Advances in minimally invasive and fusion-based surgical techniques have introduced new strategies for decompressing the neural elements. However, comparative data correlating volumetric foraminal expansion with functional outcomes remain limited. Methods: This retrospective cohort study analyzed 256 patients treated surgically for symptomatic LFS between December 2017 and December 2023. Patients were categorized into four surgical subgroups: endoscopic decompression, anterior lumbar interbody fusion (ALIF), microsurgical decompression, and transforaminal lumbar interbody fusion (TLIF). Preoperative and postoperative assessments included magnetic resonance imaging (MRI) to calculate foraminal volume and standardized clinical scales: the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for back and leg pain, and SF-36 health-related quality-of-life scores. Statistical significance was determined using p-values, and inter-observer agreement was evaluated via κ-statistics. Results: Postoperative imaging demonstrated a significant increase in foraminal canal volume across all surgical groups: endoscopy (29.9%), ALIF (71.8%), microsurgery (48.06%), and TLIF (67.0%). ODI scores improved from a preoperative mean of 55.25 to 18.27 at 24 months post-surgery (p < 0.001). VAS scores for back pain decreased from 6.37 to 2.1 (p < 0.001), while leg pain scores declined from 6.85 to 2.05 (p < 0.001). Functional improvement reached or exceeded the minimal clinically important difference (MCID) threshold in over 66% of patients. Conclusions: Modern surgical strategies for LFS, particularly fusion-based techniques, yield significant volumetric decompression and durable clinical improvement. Volumetric gain in the foraminal canal is closely associated with pain reduction and enhanced functional outcomes. These findings support a tailored surgical approach based on anatomical pathology and segmental stability. Full article
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12 pages, 689 KB  
Article
Plasma NfL and GFAP as Candidate Biomarkers of Disease Activity in NMOSD and MOGAD
by Jarmila Szilasiová, Miriam Fedičová, Marianna Vitková, Zuzana Gdovinová, Jozef Szilasi, Pavol Mikula and Milan Maretta
Medicina 2025, 61(10), 1873; https://doi.org/10.3390/medicina61101873 - 18 Oct 2025
Viewed by 256
Abstract
Background and Objectives: Neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) are distinct autoimmune demyelinating disorders of the central nervous system, characterized by different pathological and clinical features. Reliable biomarkers are essential for accurate diagnosis and monitoring of disease activity. [...] Read more.
Background and Objectives: Neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) are distinct autoimmune demyelinating disorders of the central nervous system, characterized by different pathological and clinical features. Reliable biomarkers are essential for accurate diagnosis and monitoring of disease activity. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising candidates, reflecting astrocytic and axonal damage, respectively. Materials and Methods: To investigate the relationship between astroglial (GFAP) and neuronal (NfL) protein levels in the peripheral blood, 89 plasma samples were analyzed using Simoa immunoassays. The concentrations of pNfL and pGFAP were measured in three groups: AQP4-IgG-positive NMOSD patients (n = 18), MOGAD patients (n = 12), and healthy controls (HCs, n = 19). Statistical analyses assessed group differences, correlations, and the predictive value of biomarkers for disease activity. Results: Both NMOSD and MOGAD patients exhibited elevated pNfL compared with controls, indicating neuroaxonal injury. No significant differences in pNfL, pGFAP, or pGFAP/pNfL ratios were observed between patient groups. The pGFAP levels and the pGFAP/pNfL ratio were significantly higher in NMOSD patients, particularly during attacks, indicating prominent astrocyte damage. Correlations revealed associations between biomarker levels, disability, and disease duration. pNfL demonstrated high accuracy in predicting recent relapses (AUC = 0.906), whereas pGFAP showed moderate predictive capacity (AUC = 0.638). Elevated pNfL and pGFAP levels were associated with an increased likelihood of relapse within six months. Conclusions: Plasma NfL and GFAP are promising biomarkers for assessing tissue injury and disease activity in NMOSD and MOGAD. NfL predicts relapses, while GFAP primarily reflects astrocytic damage in NMOSD. Longitudinal studies are warranted to validate these biomarkers and establish clinical thresholds for disease management. Full article
(This article belongs to the Section Neurology)
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14 pages, 737 KB  
Article
Primary Versus Secondary Non-Urothelial Tumors Involving the Bladder: A 10-Year Analysis of Clinicopathologic Profiles and Adverse Feature Burden
by Alexei Croitor, Vlad Dema, Alin Cumpanas, Razvan Bardan, Diana Herman, Mihail Nanu and Sorin Dema
Cancers 2025, 17(20), 3369; https://doi.org/10.3390/cancers17203369 - 18 Oct 2025
Viewed by 264
Abstract
Background and Objectives: Non-urothelial bladder tumors and secondary bladder involvement from extravesical primaries are uncommon but clinically challenging. We compared clinicopathologic patterns between primary non-urothelial tumors and secondaries, and explored correlates of adverse pathologic features to inform diagnostic triage and surgical planning. Methods: [...] Read more.
Background and Objectives: Non-urothelial bladder tumors and secondary bladder involvement from extravesical primaries are uncommon but clinically challenging. We compared clinicopathologic patterns between primary non-urothelial tumors and secondaries, and explored correlates of adverse pathologic features to inform diagnostic triage and surgical planning. Methods: We performed a single-center retrospective cohort (2014–2024) of consecutive bladder lesions meeting WHO 2022 criteria and AJCC 8th staging. Eligible cases were primary non-urothelial malignancies (squamous cell carcinoma (SCC), adenocarcinoma (ADK), small-cell/neuroendocrine (NEC), sarcomatoid) or secondary bladder involvement (colorectal, prostate, cervix, ovary, uterus, breast). Outcomes included advanced pT (≥pT3), lympho–vascular invasion (LVI), perineural invasion (PNI), nodal metastasis, margin status, and composite adverse events. Results: Of 235 analyzable cases, 59 were primary and 176 were secondary. Age and sex distributions were similar. Secondaries had a higher adverse burden: advanced pT 56.8% vs. 23.7%, LVI 47.2% vs. 27.1%, PNI 40.3% vs. 22.0%, node-positive 11.9% vs. 0%, and any adverse 65.3% vs. 33.9% (all significant). Histology composition differed (p < 10−6): secondaries were ADK-dominant (59.1%), whereas primaries were enriched for SCC (38.5%), sarcomatoid (28.8%), and NEC (21.2%). Among secondaries, prostate origin showed the most ominous profile (advanced pT 97.5%, PNI 77.5%, positive margins 64.7%); colorectal cases combined high advanced pT (70.2%) with lower margin positivity (27.6%). Adverse-feature count correlated with pT (ρ = 0.586). Conclusions: Secondary bladder involvement carries substantially higher adverse-pathology rates than primary non-urothelial tumors, with origin-specific risk gradients (prostate > colorectal ≳ cervix). Rigorous origin adjudication and a margin-focused, anatomy-adapted surgical strategy may improve outcomes; prospective outcome-linked validation is warranted. Full article
(This article belongs to the Section Clinical Research of Cancer)
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15 pages, 1192 KB  
Article
Development of the Medial Longitudinal Arch of the Foot in Czech Pre- and Primary School Children—A Cross-Sectional and Longitudinal Approach
by Jakub Novák, Jan Novák, Anna Vážná and Petr Sedlak
Children 2025, 12(10), 1407; https://doi.org/10.3390/children12101407 - 17 Oct 2025
Viewed by 201
Abstract
Background/Objectives: The medial longitudinal arch (MLA) is initially masked by a fat pad that makes the foot appear flat. In preschool age, this fat pad resorbs, and the arch becomes more defined. The exact age at which the arch attains its final [...] Read more.
Background/Objectives: The medial longitudinal arch (MLA) is initially masked by a fat pad that makes the foot appear flat. In preschool age, this fat pad resorbs, and the arch becomes more defined. The exact age at which the arch attains its final form remains uncertain due to high inter-individual variability and differing assessment methods, which complicates the distinction between physiological development and potential abnormalities. Moreover, commonly used classification terms such as “flat” or “normal” do not adequately reflect the developmental progression and may be misleading in young children. This study aimed to describe the MLA developmental patterns and propose an adjusted classification terminology to improve clinical differentiation between feet undergoing normal developmental changes and cases requiring intervention. Methods: The present study employs both cross-sectional (285 children aged 4.00–8.99 years) and longitudinal (50 children measured annually between ages 4–6) designs. Foot dimensions were assessed using standard anthropometry, and the MLA was assessed via podograms using the Chippaux–Smirak index (CSI). To better reflect the developmental nature of the MLA, the arch was categorized as “formed” and “unformed”. Cross-sectional data were analyzed with ANOVA and visualized using LOESS regression, longitudinal data with linear mixed models, and relationships between CSI and foot dimensions with Spearman’s correlation. Results: MLA development showed significant changes up to age 6, with the most pronounced changes occurring between ages 4 and 5 and slowing thereafter. Children with an unformed arch at age 4 exhibited a steeper developmental trajectory than those with an already advanced arch form. Correlations between arch shape and foot dimensions were statistically significant but weak. No significant between-sex differences were observed. Conclusions: The timing of the most pronounced phase of medial longitudinal arch (MLA) development varies between individuals and is typically completed by 6 years of age, with no sex-dependent differences. Age 6 therefore represents a practical milestone for reliable clinical assessment, since earlier classifications risk misinterpreting normal developmental variation as pathology. Full article
(This article belongs to the Section Pediatric Orthopedics & Sports Medicine)
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24 pages, 661 KB  
Article
Brain Network Analysis and Recognition Algorithm for MDD Based on Class-Specific Correlation Feature Selection
by Zhengnan Zhang, Yating Hu, Jiangwen Lu and Yunyuan Gao
Information 2025, 16(10), 912; https://doi.org/10.3390/info16100912 - 17 Oct 2025
Viewed by 233
Abstract
Major Depressive Disorder (MDD) is a high-risk mental illness that severely affects individuals across all age groups. However, existing research lacks comprehensive analysis and utilization of brain topological features, making it challenging to reduce redundant connectivity while preserving depression-related biomarkers. This study proposes [...] Read more.
Major Depressive Disorder (MDD) is a high-risk mental illness that severely affects individuals across all age groups. However, existing research lacks comprehensive analysis and utilization of brain topological features, making it challenging to reduce redundant connectivity while preserving depression-related biomarkers. This study proposes a brain network analysis and recognition algorithm based on class-specific correlation feature selection. Leveraging electroencephalogram monitoring as a more objective MDD detection tool, this study employs tensor sparse representation to reduce the dimensionality of functional brain network time-series data, extracting the most representative functional connectivity matrices. To mitigate the impact of redundant connections, a feature selection algorithm combining topologically aware maximum class-specific dynamic correlation and minimum redundancy is integrated, identifying an optimal feature subset that best distinguishes MDD patients from healthy controls. The selected features are then ranked by relevance and fed into a hybrid CNN-BiLSTM classifier. Experimental results demonstrate classification accuracies of 95.96% and 94.90% on the MODMA and PRED + CT datasets, respectively, significantly outperforming conventional methods. This study not only improves the accuracy of MDD identification but also enhances the clinical interpretability of feature selection results, offering novel perspectives for pathological MDD research and clinical diagnosis. Full article
(This article belongs to the Section Artificial Intelligence)
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23 pages, 896 KB  
Review
Neoadjuvant 177Lutetium-PSMA-617 Radioligand Therapy for High-Risk Localized Prostate Cancer: Rationale, Early Clinical Evidence, and Future Directions
by Whi-An Kwon and Jae Young Joung
Cancers 2025, 17(20), 3330; https://doi.org/10.3390/cancers17203330 - 15 Oct 2025
Viewed by 599
Abstract
Men with high-risk localized prostate cancer (PCa) often have poor long-term outcomes, underscoring the need for improved neoadjuvant strategies beyond the current standard of care. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases [...] Read more.
Men with high-risk localized prostate cancer (PCa) often have poor long-term outcomes, underscoring the need for improved neoadjuvant strategies beyond the current standard of care. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases while enhancing immune-mediated clearance of the primary tumor. Initial trials have affirmed the treatment’s feasibility and safety; however, they have consistently reported a lack of pathological complete response. This absence of profound initial tumor reduction necessitates further therapeutic advancements. The underlying rationale for future strategies is clear, as 177Lu-PSMA-617 promotes immunogenic cell death, potentially sensitizing immunologically “cold” tumors to checkpoint inhibitors. However, caution is warranted. The synergy observed between these therapies in advanced, metastatic castration-resistant PCa stems from a different biological context, and similar outcomes cannot be presumed in treatment-naïve, localized disease without rigorous validation. Continued progress hinges on developing improved metrics for success and patient selection. Simple prostate-specific antigen reductions have demonstrated minimal correlation with significant pathological outcomes in this setting, underscoring the critical need for validated surrogate endpoints and predictive biomarkers. Ultimately, large-scale randomized trials are essential to determine whether this investigational approach impacts key clinical outcomes—namely, metastasis-free and overall survival. While the strategy is theoretically sound, its capacity to enhance cure rates for high-risk localized PCa remains unverified. Full article
(This article belongs to the Special Issue Novel Diagnostic and Therapeutic Approaches in Urologic Oncology)
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28 pages, 678 KB  
Systematic Review
OCTA Biomarkers Underlying Structure–Function Correlations in Idiopathic Epiretinal Membrane: A Systematic Review
by Anca Mădălina Sere, George Adrian Muntean, Andreea Petra Cristea and Simona Delia Nicoară
Diagnostics 2025, 15(20), 2596; https://doi.org/10.3390/diagnostics15202596 - 15 Oct 2025
Viewed by 341
Abstract
Background: Idiopathic epiretinal membrane (iERM) is a common retinal pathology in elderly patients, thought to originate primarily from an anomalous process of posterior vitreous detachment. The standard treatment is pars plana vitrectomy (PPV) with membrane peeling. No consensus exists regarding the optimal timing [...] Read more.
Background: Idiopathic epiretinal membrane (iERM) is a common retinal pathology in elderly patients, thought to originate primarily from an anomalous process of posterior vitreous detachment. The standard treatment is pars plana vitrectomy (PPV) with membrane peeling. No consensus exists regarding the optimal timing of surgery, nor is it clear which patients are most likely to benefit. Given that iERM profoundly affects retinal vascular morphology and function, optical coherence tomography angiography (OCTA) has emerged as a valuable tool for identifying potential biomarkers. This systematic review aimed to synthesize the available evidence on OCTA-derived biomarkers and their correlations with visual function before and/or after surgical intervention in iERM, with a particular focus on their prognostic value for postoperative outcomes. Methods: A systematic search of PubMed/MEDLINE and Scopus was conducted on the 20th of May 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with iERM undergoing vitreoretinal surgery, used OCTA for pre- and/or postoperative assessment, investigated structure–function correlations, and were designed as clinical trials, observational studies, or case series with more than 10 patients. Exclusion criteria were studies with ≤10 cases, absence of separate iERM analysis, lack of surgical intervention, or non-English language. Data extraction covered study design, demographics, surgical approach, OCTA device, follow-up, OCTA biomarkers, and structure–function outcomes. Risk of bias in observational studies was assessed using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The search yielded 1053 records, of which 71 underwent full-text review and 43 met eligibility criteria. All included studies were observational, encompassing 1958 eyes from 1953 patients. The most frequently investigated biomarkers were the foveal avascular zone (FAZ) area and related parameters, vessel density (VD), and foveal density 300 (FD-300). Additional studies evaluated average vessel length (VL), blood flow area, vessel length density (VLD), vessel tortuosity (VT), fractal dimension (FD), and perfusion capacity (PC). Conclusions: By consolidating current evidence, this systematic review provides a comprehensive overview of structure–function correlations in iERM and highlights the potential of OCTA-derived metrics as biomarkers of disease severity and surgical prognosis. These findings help clarify underlying mechanisms of visual decline and establish the context for further research. Nonetheless, interpretation is limited by the observational design of all included studies and by heterogeneity in OCTA methodology and nomenclature, underscoring the need for standardization to improve comparability and foster greater coherence across studies. No funding was provided for this review. Full article
(This article belongs to the Special Issue Optical Coherence Tomography in Diagnosis of Ophthalmology Disease)
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15 pages, 1790 KB  
Article
Rapid On-Demand Point-of-Care Monitoring of Clozapine and Its Metabolite Norclozapine Using Miniature Mass Spectrometry
by Xiaosuo Wang, Wei Yi Lew, Yang Yang, Nan Zhang, Jiexun Bu, Zhentao Li, Michael Fitzpatrick, Paul Bonnitcha, David Sullivan, Wenpeng Zhang, Yu Zheng and John F. O’Sullivan
Pharmaceuticals 2025, 18(10), 1549; https://doi.org/10.3390/ph18101549 - 14 Oct 2025
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Abstract
Background/Objectives: Clozapine remains the gold standard for treatment-resistant schizophrenia. However, its narrow therapeutic window and risk of severe side effects require close monitoring of both clozapine and its primary metabolite, norclozapine. Existing therapeutic drug monitoring (TDM) methods are limited by delays, high [...] Read more.
Background/Objectives: Clozapine remains the gold standard for treatment-resistant schizophrenia. However, its narrow therapeutic window and risk of severe side effects require close monitoring of both clozapine and its primary metabolite, norclozapine. Existing therapeutic drug monitoring (TDM) methods are limited by delays, high costs, and operational complexity. This study introduces three rapid point-of-care (POC) assays utilizing a miniature mass spectrometer (Mini-MS) to quantify clozapine and norclozapine in plasma, whole blood, and dried blood spots (DBSs), facilitating applications across diverse clinical settings. Methods: The analytical performance of the assay was evaluated for sensitivity, specificity, reproducibility, and correlation with reference methods. Clinical samples from two hospitals were analysed and validated against conventional liquid chromatography tandem mass spectrometry (LC-MS/MS) reference standards at New South Wales Health Pathology (NSWHP) and Tsinghua University laboratories. Results: The Mini-MS assay accurately quantified both analytes within therapeutic ranges across all matrices. Inter-assay coefficients of variation ranged from 7.9 to 14.1% for clozapine and from 1.6 to 14.6% for norclozapine. Accuracy fell between 85 and 117% in plasma and blood extracts. Strong linearity was demonstrated (R2 = 0.98–0.99) over the concentration range of 10–1000 ng/mL. Results from the Mini-MS analysis showed excellent correlations with LC-MS/MS results (r = 0.998). Conclusions: In this proof-of-concept study, the Mini-MS-based POC assays enable rapid, reliable quantification of clozapine and norclozapine, with performance comparable to conventional laboratory methods. This platform supports real-time TDM, facilitating timely dose adjustments, adherence monitoring, and ultimately improving patient outcomes. Full article
(This article belongs to the Section Pharmaceutical Technology)
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17 pages, 1895 KB  
Review
Diffusion Basis Restricted Fraction as a Putative Magnetic Resonance Imaging Marker of Neuroinflammation: Histological Evidence, Diagnostic Accuracy, and Translational Potential
by Szabolcs Kéri
Life 2025, 15(10), 1599; https://doi.org/10.3390/life15101599 - 14 Oct 2025
Viewed by 513
Abstract
Diffusion basis spectrum imaging–derived restricted fraction (DBSI-RF) isolates the low apparent diffusion coefficient water signal attributed to cellular crowding. It is therefore proposed as a putative magnetic resonance imaging (MRI) marker of neuroinflammation. The purpose of this narrative review is to evaluate animal [...] Read more.
Diffusion basis spectrum imaging–derived restricted fraction (DBSI-RF) isolates the low apparent diffusion coefficient water signal attributed to cellular crowding. It is therefore proposed as a putative magnetic resonance imaging (MRI) marker of neuroinflammation. The purpose of this narrative review is to evaluate animal and human studies that compared DBSI-RF with histopathological benchmarks and clinical parameters. Across inflammatory demyelination, viral encephalitis, traumatic brain injury, and neurodegenerative disorders, DBSI-RF correlated moderately to strongly with immune cell density and distinguished inflammation from demyelinating or axonal pathology. In acute multiple sclerosis, combined isotropic fractions predicted lesion evolution, clinical subtypes, and deep-learning models that included DBSI-RF classified lesion subtypes with high accuracy. DBSI-RF might also be used to track putative neuroinflammation associated with psychosocial stress, mood disorders, and anxiety disorders. The strengths of the method include sensitivity to subclinical changes and the concurrent mapping of coexisting edema, demyelination, and axon loss. Limitations include non-specific etiology features, a demanding acquisition protocol, and limited large-scale human validation. Overall, DBSI-RF may demonstrate a promising diagnostic and prognostic accuracy, warranting standardized, multicenter, prospective trials and external validation. Full article
(This article belongs to the Section Medical Research)
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14 pages, 937 KB  
Article
From Gamma Rays to Green Light: Comparative Efficacy of Indocyanine Green and Technetium-99m in Sentinel Lymph Node Biopsy for Breast Cancer
by Vlad Alexandru Gâta, Radu Alexandru Ilieș, Nicoleta Zenovia Antone, Roxana Pintican, Codruț Cosmin Nistor-Ciurba, Ștefan Țîțu, Alex Victor Orădan, Maximilian Vlad Muntean, Gheorghe Gerald Filip, Alexandru Irimie and Patriciu Andrei Achimaș-Cadariu
Med. Sci. 2025, 13(4), 231; https://doi.org/10.3390/medsci13040231 - 13 Oct 2025
Viewed by 285
Abstract
Background/Objectives: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. [...] Read more.
Background/Objectives: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. Methods: We conducted a prospective, observational study including 476 female patients diagnosed with primary invasive breast cancer who underwent SLNB at the Institute of Oncology “Prof. Dr. I. Chiricuță”, Cluj-Napoca, Romania, between January 2022 and May 2025. Clinical, surgical, and pathological variables were systematically extracted. SLNB was performed using either Tc99m or ICG, according to institutional protocols. Comparative analyses were performed to evaluate sentinel node characteristics, histopathological parameters, and positive surgical margins predictors. Results: The median age was 60 years (IQR: 52–69). Breast-conserving surgery (BCS) was performed in 77.9% of cases, while mastectomy was performed in 22.1%. Sentinel lymph node positivity was reported in 25.6% of cases, with no significant differences in the number of excised or metastatic nodes between Tc99m and ICG (mean nodes: 3.23 vs. 3.20, p = 0.860; mean positive nodes: 0.35 vs. 0.36, p = 0.897). Histologically, invasive carcinoma NST was predominant (90.1%), and surgical margins were negative in 96.8% of patients, with all margin-positive cases occurring following BCS. No pathological markers (grade, Ki67, TILs, DCIS extent) predicted margin status or nodal involvement. Notably, younger age correlated inversely with the extent of ductal carcinoma in situ (r = −0.21, p < 0.00001). Conclusions: Tc99m and ICG provided comparable diagnostic performance in performing SLNB, with equivalent rates of nodal detection and pathological yield. These findings support that ICG is a safe and effective alternative for routine axillary staging in breast cancer. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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