Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
INTRODUCTION: α-Synuclein is the hallmark pathology of Parkinson’s disease and dementia with Lewy bodies, described together as Lewy body disease (LBD).We investigated effects of α-syn biomarker positivity in clinically unimpaired (CU) individuals. METHODS: We assessed α-syn status (α-syn ±) in 269 CU individuals using a cerebrospinal fluid (CSF) seed amplification assay (SAA). Fifty-six participants with AD and 85 LBD spectrum participants were included for comparison.We compared α-syn SAA results with demographics, fluid biomarkers, cognitive performance, and clinical measures. RESULTS: α -Syn positivity was detected in 9% of CU individuals, a lower rate than in clinically impaired participants with AD (16%) and LBD diagnoses (81%). Compared to α-syn-, α-syn+ CU individuals were older, showed lower synaptic integrity, performed worse on tests of executive function and working memory, and reported more LBDrelated non-motor symptoms. DISCUSSION: Further work is needed to understand the timeline of neural and clinical changes in α-syn+ CU individuals and heterogeneity in disease progression....
Muscle-invasive bladder cancer (MIBC) presents with variable clinical and pathological features, leading to inconsistent responses to standard treatments such as neoadjuvant chemotherapy (NAC). Although transcriptome profiling has shown differences in NAC response, reliable predictors of treatment outcome remain elusive. Here this study aimed to improve NAC response prediction by integrating multicohort transcriptomic data and spatial protein expression profiles using machine learning, enabling precision diagnostics and therapeutic strategies. Transcriptome analysis from four independent cohorts (n=399) using diverse gene classifiers revealed molecular features associated with NAC response, particularly genes involved in stress responses, immunity and cell adhesion. The clinical relevance of 74 markers was validated by digital pathology for analyzing spatial protein expression. The machine learning frameworks reduced complex transcriptome and digital pathology datasets to a clinically manageable number of biomarkers, yielding an optimal antibody panel for immunohistochemistry-based clinical diagnostics. Computational pathology-driven predictions of NAC response demonstrated a strong correlation with survival outcomes in patients with MIBC, highlighting their potential clinical utility. Mechanistically, targeting the KEAP1–NRF2 axis suppressed glutathione dynamics, proliferation, stemness features and invasiveness of cisplatin-resistant MIBC cells, thereby resensitizing them to cisplatin. Combination treatment with cisplatin and inhibitors targeting the KEAP1–NRF2 pathway markedly suppressed tumor growth in an orthotopic xenograft model. Therefore, this study integrates machine learning-based transcriptome profiling and digital pathology analysis to refine gene classifiers, provide a personalized and feasible framework for treatment decision-making, and overcome chemoresistance to improve therapeutic efficacy....
Background: Current professional guidelines recommend discontinuing Papanicolaou (Pap) test screening in women aged 65 years and older who have had adequate prior negative testing. However, limited data exist on Pap test performance and histologic outcomes in this population. Methods: Searches were performed for all Pap tests from women aged 65 years and older accessioned at a women’s hospital between January 2023 and December 2024. Pap tests were performed using the liquidbased cytology ThinPrep test, and highrisk HPV testing was performed using Aptima highrisk human papillomavirus (HPV) assays. Surgical pathology followup within 6 months was recorded. A Pearson 2 test was performed to compare HPV positivity among patients who had abnormal Pap tests. Results: In total, 1536 women aged 65 years and older underwent Pap testing during the study period. The overall HPVpositivity rate was 24.2%. Abnormal Pap results (atypical squamous cells of undetermined significance or worse) comprised 939 of 1536 cases (61.1%). Histologic followup was available for 402 cases. Lesions categorized as cervical intraepithelial neoplasia grade 2 (CIN2) or more severe disease were identified in 94 cases (23.3%), including 11 squamous cell carcinomas, three endocervical carcinomas, 40 CIN2/3 lesions, and 40 endometrial carcinomas. Notably, three of 11 squamous cell carcinomas (27.3%) and 12 of 40 CIN2/3 lesions (30%) were HPVnegative. Conclusions: The abnormal Pap rate in women aged 65 years and older was high (61.1%), whereas HPV positivity remained low. CIN2 or more severe disease and endometrial lesions after negative HPV testing occurred at a substantial rate (33.8%). The rate for detecting atypical glandular cells was also elevated (3.0%), correlating with a significant number of endometrial carcinoma diagnoses. These findings underscore the need for additional research and suggest that continued screening with Pap and HPV cotesting may benefit older women....
Tissue detection is a crucial first step in most digital pathology applications. By applying image segmentation algorithms, all tissue is delineated and background discarded from further analyses, improving both computational efficiency and analytical results. Details of the segmentation algorithm are rarely reported, and there is a lack of studies investigating the downstream effects of a poor segmentation algorithm. Disregarding tissue detection quality could jeopardize patient safety if diagnostically relevant parts of the specimen are excluded from analysis in clinical applications. This study aims to determine whether performance of downstream tasks is sensitive to the tissue detection method, and to compare the performance of a classical and an AI-based tissue detection approach. To this end, we trained an AI model for Gleason grading of prostate cancer in whole slide images (WSIs) using two different tissue detection algorithms: thresholding (classical) and UNet++ (AI). A total of 33,823 WSIs scanned on seven digital pathology scanners were used to train the segmentation AI model. The downstream Gleason grading algorithm was trained and tested using 70,524 WSIs from 13 clinical sites scanned on 13 different scanners. On the slides where tissue could be detected by both algorithms, no significant difference in overall Gleason grading performance was observed. There was a decrease from 118 (0.43%) to 24 (0.09%) fully undetected tissue samples when switching from thresholding-based tissue detection to AI-based, suggesting this AI model may be more reliable than the classical model for avoiding total failures on slides with unusual appearance. Moreover, tissue detection dependent clinically significant variations in AI grading were observed in 3.5% of malignant slides, highlighting the role of tissue detection for optimal clinical performance of diagnostic AI....
Background/Objectives: Conventional chordomas are rare malignant bone tumors characterized by brachyury expression. The presence of polygonal-to-epithelioid neoplastic cells containing rich cytoplasm and relatively large nuclei in a myxoid background is a characteristic cytological feature of conventional chordomas. Physaliphorous cells, characterized by the presence of multiple well-marginated vacuoles within the cytoplasm, are also characteristic of this rare bone tumor. However, the cytological diagnosis of conventional chordomas can be challenging because of their rarity and lack of specic features. Therefore, useful immunocytochemical markers are required. Immunohistochemical staining for brachyury has been widely used for diagnosis; however, immunocytochemical staining using cytological specimens has not yet been performed. The purpose of this study was to evaluate the usefulness of the immunocytochemical staining for brachyury in cytodiagnosis of conventional chordoma. Methods: This study included patients diagnosed with conventional chordoma based on postoperative histopathological ndings who underwent intraoperative squash cytological examination. Cytological features and immunocytochemical staining for brachyury were evaluated. Results: Two patients with conventional chordoma were included. The tumor extended from the lumbar spine to the cauda equina and clivus. Cytological examination revealed the presence of small sheets and isolated polygonal neoplastic cells with rich cytoplasm and round nuclei with inconspicuous nucleoli in a myxoid background. Cellular clusters were noted in one specimen and physaliphorous cells were observed in the other. Immunocytochemical staining for brachyury revealed positive nuclear expression in both specimens. Conclusions: Immunocytochemical staining for brachyury could provide useful information for the cytodiagnosis of this rare tumor, even in cases lacking typical cytological features....
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