Laboratory Investigation最新文献

{"title":"D30 Alleviates β2-Microglobulin-Facilitated Neurotoxic Microglial Responses in Isoflurane/Surgery-Induced Cognitive Dysfunction in Aged Mice.","authors":"Ping Chen, Wan-Lan Lin, Xue-Yan Liu, Si-Jun Li, Ruo-Fan Chen, Zhi-Hui Hu, Peng-Tao Lin, Mou-Hui Lin, Meng-Yu Shi, Wei Wu, Ying Wang, Qing-Song Lin, Zu-Cheng Ye","doi":"10.1016/j.labinv.2024.102190","DOIUrl":"10.1016/j.labinv.2024.102190","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a common complication with no effective treatment in elderly patients. POCD, Alzheimer disease (AD), and many other cognitive diseases mostly involve neurotoxic microglia response, and recently, β2-microglobulin (B2M) has been suggested to play a pivotal role. A novel pyromeconic acid-styrene hybrid compound D30 was synthesized by our team and shown to be safe and effective in some neurodegenerative mouse models. In this study, we evaluated D30 on POCD and its potential mechanism. Fourteen- to 18-month-old male C57BL/6 mice were used to establish POCD through isoflurane anesthesia and surgery. The plasma of elderly patients was collected pre- and postoperatively. Primary mouse microglia were subjected to various stimulations in multiple experimental designs to imitate in vivo POCD-like conditions. Morris water maze, fear conditioning, western blot, immunofluorescent staining, and blood-brain barrier (BBB) permeability tests were conducted in this study. D30 administration significantly improved learning and memory in aged mice following POCD. Neurotoxic M1 microglia cells were dramatically increased following POCD, manifested as morphologically changing into fewer and shorter branches, enlarged somatic areas, and upregulated expression of iNOS and C1q. Notably, following POCD, B2M was significantly upregulated in the plasma and the brain. D30 treatment significantly suppressed these pathologic changes, by inhibiting the POCD-induced BBB breakdown while suppressing the surge of plasma B2M levels. D30 treatment suppressed POCD-induced surge of B2M and Aβ plaques in the brain and preserved adult hippocampal neurogenesis vulnerable to POCD. Furthermore, postoperative levels of B2M were significantly elevated over the preoperative levels in patients aged 80 years and over. In parallel with mouse plasma after POCD, the postoperative patient plasma was also much more effective at activating M1 microglia. Of note, this POCD plasma-induced activation of M1 microglia was largely prevented by D30 treatment. Taken together, by inhibiting the surge of plasma B2M, protecting BBB integrity, and reducing inflammatory response, D30 protected aged mice from B2M-facilitated POCD.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102190"},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement Component 3 Promotes Regeneration of Olfactory Receptor Neurons.","authors":"Hiroki Kuwazoe, Hideki Sakatani, Masamitsu Kono, Shizuya Saika, Norimitsu Inoue, Muneki Hotomi","doi":"10.1016/j.labinv.2024.102200","DOIUrl":"10.1016/j.labinv.2024.102200","url":null,"abstract":"<p><p>Olfactory receptor neurons (ORNs) in the olfactory epithelium are characterized by high regenerative capacity even after birth, but the molecular mechanisms involved in ORN regeneration remain unclear. Complement component 3 (C3) has been shown to promote tissue regeneration, so we hypothesized that C3 activates innate immunity and also promotes the regeneration of ORNs. In this study, we investigate the role of C3 in ORN regeneration. We used C3 knockout (KO) and wild-type C57BL/6J mice in this study to examine the olfactory regeneration process for 42 days after methimazole-induced olfactory disorder. To compare the regeneration process after ORN damage between C3 KO and wild-type mice, we conducted olfactory behavioral tests and immunohistologic analysis and examined growth factors and inflammatory cell induction. C3 KO mice showed delayed olfactory recovery with lower olfactory epithelial thickness. In C3 KO mice, ORN maturation was delayed in association with increased accumulation of immature ORNs. In the normal ORN regeneration process, undesirable immature ORNs are produced and eliminated by apoptosis. C3 deficiency reduced neutrophils induced during ORN regeneration, suggesting the involvement of C3 in ORN regeneration through neutrophil-dependent elimination of undesired ORNs. C3 is therefore suggested to have promoted ORN regeneration by preventing the accumulation of immature ORNs. In addition, C3 may assist ORN maturation by participating in ORN axon selection such as synaptic pruning. Our results indicate that C3, which is activated during pathogen infection, also promotes recovery from ORN damage. These findings may lead to new therapeutic strategies for olfactory disorder.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102200"},"PeriodicalIF":5.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Surgical Diagnostics: Artificial Intelligence-Enhanced Detection of Ganglion Cells for Hirschsprung Disease.","authors":"Derya Demir, Kutsev Bengisu Ozyoruk, Yasin Durusoy, Ezgi Cinar, Gurdeniz Serin, Kayhan Basak, Emre Cagatay Kose, Malik Ergin, Murat Sezak, G Evren Keles, Sergulen Dervisoglu, Basak Doganavsargil Yakut, Yavuz Nuri Ertas, Feras Alaqad, Mehmet Turan","doi":"10.1016/j.labinv.2024.102189","DOIUrl":"10.1016/j.labinv.2024.102189","url":null,"abstract":"<p><p>Hirschsprung disease, a congenital disease characterized by the absence of ganglion cells, presents significant surgical challenges. Addressing a critical gap in intraoperative diagnostics, we introduce transformative artificial intelligence approach that significantly enhances the detection of ganglion cells in frozen sections. The data set comprises 366 frozen and 302 formalin-fixed-paraffin-embedded hematoxylin and eosin-stained slides obtained from 164 patients from 3 centers. The ganglion cells were annotated on the whole-slide images (WSIs) using bounding boxes. Tissue regions within WSIs were segmented and split into patches of 2000 × 2000 pixels. A deep learning pipeline utilizing ResNet-50 model for feature extraction and gradient-weighted class activation mapping algorithm to generate heatmaps for ganglion cell localization was employed. The binary classification performance of the model was evaluated on independent test cohorts. In the multireader study, 10 pathologists assessed 50 frozen WSIs, with 25 slides containing ganglion cells, and 25 slides without. In the first phase of the study, pathologists evaluated the slides as a routine practice. After a 2-week washout period, pathologists re-evaluated the same WSIs along with the 4 patches with the highest probability of containing ganglion cells. The proposed deep learning approach achieved an accuracy of 91.3%, 92.8%, and 90.1% in detecting ganglion cells within WSIs in the test data set obtained from centers. In the reader study, on average, the pathologists' diagnostic accuracy increased from 77% to 85.8% with the model's heatmap support, whereas the diagnosis time decreased from an average of 139.7 to 70.5 seconds. Notably, when applied in real-world settings with a group of pathologists, our model's integration brought about substantial improvement in diagnosis precision and reduced the time required for diagnoses by half. This notable advance in artificial intelligence-driven diagnostics not only sets a new standard for surgical decision making in Hirschsprung disease but also creates opportunities for its wider implementation in various clinical settings, highlighting its pivotal role in enhancing the efficacy and accuracy of frozen sections analyses.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102189"},"PeriodicalIF":5.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD248 Cleaved Form in Human Colorectal Cancer Stroma: Implications for Tumor Behavior and Prognosis.","authors":"Elisa Pothin, Yosra Bedoui, Caroline Michault, Johanna Zemour, Emmanuel Chirpaz, Philippe Gasque, Mohamed Khettab, Franck Ah-Pine","doi":"10.1016/j.labinv.2024.102188","DOIUrl":"10.1016/j.labinv.2024.102188","url":null,"abstract":"<p><p>CD248 (endosialin/tumor endothelial marker 1) is upregulated in cancer, including colorectal cancer (CRC), but its exact role in tumor progression remains to be elucidated. Previous studies have shown that the extracellular domain of CD248 mediates the interaction between tumor cells and extracellular matrix proteins and that interfering with this interaction may reduce tumor invasion and migration activities. We have examined the expression of CD248 in 117 human CRC samples by immunohistochemistry and investigated the association with various clinicopathologic features, including the occurrence of metastasis, intratumoral immune cell density and overall survival. Of the 117 specimens analyzed, 76.1% (89/117) exhibited CD248-high stromal expression, whereas 23.9% (28/117) demonstrated CD248-low stromal expression. Interestingly, we detected the presence of a cleaved form of CD248, which appears to accumulate in the stromal extracellular matrix. A higher metastasis rate (lymph node and distant) was observed in the CD248-low group (21/28, 75.0% vs 44/89, 49.4%; P = .02). In addition, CD248-low tumors had fewer CD163-positive macrophages and FoxP3-positive regulatory T cells (P < .05) with no significant difference in CD8-positive T-cell infiltration and PD-L1 expression between the groups (P > .05). Finally, overall survival was lower in CD248-low tumors than in CD248-high tumors, with 5-year survival rates of 35.7% and 57.3%, respectively (P = .01). In a multivariate analysis, the hazard ratio of CD248-low tumors vs CD248-high tumors was 1.93 (95% CI, 1.09-3.41; P = .02). Our findings suggest that CD248 stromal expression may influence the tumor microenvironment, impacting tumor behavior and prognosis, and can serve as a promising prognostic biomarker in CRC.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102188"},"PeriodicalIF":5.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Lipidomics Reveals Myelin Defects and Protumor Macrophage Infiltration in Malignant Peripheral Nerve Sheath Tumor Adjacent Nerves.","authors":"Rick Ursem, Justus L Groen, Martijn J A Malessy, Inge Briaire-de Bruijn, Liam A McDonnell, Bram P A M Heijs, Judith V M G Bovee","doi":"10.1016/j.labinv.2024.102186","DOIUrl":"10.1016/j.labinv.2024.102186","url":null,"abstract":"<p><p>Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from peripheral nerves, accounting for 3% to 5% of soft tissue sarcomas. MPNSTs often recur locally, leading to poor survival. Achieving tumor-free surgical margins is essential to prevent recurrence, but current methods for determining tumor margins are limited, highlighting the need for improved biomarkers. In this study we investigated the degree to which MPNST extends into nerves adjacent to tumors. Alterations to the lipidome of MPNST and adjacent peripheral nerves were assessed using spatial lipidomics. Tissue samples from 5 patients with MPNST were analyzed, revealing alterations of the lipid profile extending into the peripheral nerves beyond what was expected based on macroscopic and histologic observations. Integration of spatial lipidomics and high-resolution accurate-mass profiling identified distinct lipid profiles associated with healthy nerves, connective tissue, and tumors. Notably, histologically normal nerves exhibited myelin degradation and infiltration of protumoral M2 macrophages, particularly near the tumor. Furthermore, aberrant osmium staining patterns and loss of H3K27me3 staining in the absence of atypia were observed in a case with tumor recurrence. This exploratory study thereby highlights the changes occurring in the nerves affected by MPNST beyond what is visible on hematoxylin and eosin staining and provides leads for further biomarker studies, including aberrant osmium staining, to assess resection margins in MPNST.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102186"},"PeriodicalIF":5.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switch/Sucrose Nofermentable-Deficient Tumors-Morphology, Immunophenotype, Genetics, Epigenetics, Nosology, and Therapy.","authors":"Chi Sing Ng, Jilong Qin","doi":"10.1016/j.labinv.2024.102185","DOIUrl":"10.1016/j.labinv.2024.102185","url":null,"abstract":"<p><p>About 20% of human cancers harbor mutations of genes encoding switch/sucrose nonfermentable (SWI/SNF) complex subunits. Deficiency of subunits of the complex is present in 10% of non-small-cell lung cancers (NSCLC; SMARCA4/SMARCA2 deficient), 100% thoracic SMARCA4/A2-deficient undifferentiated tumors (TSADUDT; SMARCA4/A2 deficient), malignant rhabdoid tumor, and atypical/teratoid tumor (SMARCB1-deficient), >90% of small cell carcinoma of the ovary, hypercalcemic type (SMARCA4/SMARCA2 deficient), frequently in undifferentiated/dedifferentiated endometrial carcinoma (SMARCA4, SMARCA2, SMARCB1, and ARID1A/B deficient), 100% SMARCA4 deficient undifferentiated uterine sarcoma (SMARCA4 deficient); and in various other tumors from multifarious anatomical sites. Silencing of SWI/SNF gene expression may be genomically or epigenetically driven, causing loss of tumor suppression function or facilitating other oncogenic events. The SWI/SNF-deficient tumors share the phenotype of poor or no differentiation, often with a variable component of rhabdoid tumor cells. They present at advanced stages with poor prognosis. Rhabdoid tumor cell phenotype is a useful feature to prompt investigation for this group of tumors. In the thoracic space, the overlap in morphology, immunophenotype, genetics, and epigenetics of SMARCA4/A2-deficient NSCLC and TSADUDT appears more significant. This raises a possible nosologic relationship between TSADUDT and SMARCA4/A2-deficient NSCLC. Increased understanding of the genetics, epigenetics, and mechanisms of oncogenesis in these poor prognostic tumors, which are often resistant to conventional treatment, opens a new horizon of therapy for the tumors.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102185"},"PeriodicalIF":5.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymph Node Metastasis Prediction From In Situ Lung Squamous Cell Carcinoma Histopathology Images Using Deep Learning","authors":"Lu Xia ,&nbsp;Tao Xu ,&nbsp;Yongsheng Zheng ,&nbsp;Baohua Li ,&nbsp;Yongfang Ao ,&nbsp;Xun Li ,&nbsp;Weijing Wu ,&nbsp;Jiabian Lian","doi":"10.1016/j.labinv.2024.102187","DOIUrl":"10.1016/j.labinv.2024.102187","url":null,"abstract":"<div><div>Lung squamous cell carcinoma (LUSC), a subtype of non–small cell lung cancer, represents a significant portion of lung cancer cases with distinct histologic patterns impacting prognosis and treatment. The current pathological assessment methods face limitations such as interobserver variability, necessitating more reliable techniques. This study seeks to predict lymph node metastasis in LUSC using deep learning models applied to histopathology images of primary tumors, offering a more accurate and objective method for diagnosis and prognosis. Whole slide images (WSIs) from the Outdo-LUSC and the cancer genome atlas cohorts were used to train and validate deep learning models. Multiinstance learning was applied, with patch-level predictions aggregated into WSI-level outcomes. The study employed the ResNet-18 network, transfer learning, and rigorous data preprocessing. To represent WSI features, innovative techniques like patch likelihood histogram and bag of words were used, followed by training of machine learning classifiers, including the ExtraTrees algorithm. The diagnostic model for lymph node metastasis showed strong performance, particularly using the ExtraTrees algorithm, as demonstrated by receiver operating characteristic curves and gradient-weighted class activation mapping visualizations. The signature generated by the ExtraTrees algorithm, named lymph node status-related in situ LUSC histopathology (LN_ISLUSCH), achieved an area under the curve of 0.941 (95% CI: 0.926-0.955) in the training set and 0.788 (95% CI: 0.748-0.827) in the test set. Kaplan-Meier analyses confirmed that the LN_ISLUSCH model was a significant prognostic factor (<em>P</em> = .02). This study underscores the potential of artificial intelligence in enhancing diagnostic precision in pathology. The LN_ISLUSCH model stands out as a promising tool for predicting lymph node metastasis and prognosis in LUSC. Future studies should focus on larger and more diverse cohorts and explore the integration of additional omics data to further refine predictive accuracy and clinical utility.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 1","pages":"Article 102187"},"PeriodicalIF":5.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Landscape of Superficial Malignant Peripheral Nerve Sheath Tumor.","authors":"John L McAfee, Tyler J Alban, Vladimir Makarov, Amit Rupani, Prerana B Parthasarathy, Zheng Tu, Shira Ronen, Steven D Billings, C Marcela Diaz, Timothy A Chan, Jennifer S Ko","doi":"10.1016/j.labinv.2024.102183","DOIUrl":"10.1016/j.labinv.2024.102183","url":null,"abstract":"<p><p>Superficial malignant peripheral nerve sheath tumors (SF-MPNSTs) are rare cancers and can be difficult to distinguish from spindle cell (SCM) or desmoplastic (DM) melanomas. Their biology is poorly understood. We performed whole-exome sequencing and RNA sequencing (RNA-seq) on SF-MPNST (n = 8) and compared them with cases of SCM (n = 7), DM (n = 8), and deep MPNST (D-MPNST, n = 8). Immunohistochemical staining for H3K27me3 and PRAME was also performed. SF-MPNST demonstrated intermediate features between D-MPNST and melanoma. Patients were younger than those with melanoma and older than those with D-MPNST; the outcome was worse and better, respectively. SF-MPNST tumor mutational burden (TMB) was higher than D-MPNST and lower than melanoma; differences were significant only between SF-MPNST and SCM (P = .0454) and between D-MPNST and SCM (P = .001, Dunn's Kruskal-Wallis post hoc test). Despite having an overlapping mutational profile in some common cancer-associated genes, the COSMIC mutational signatures clustered DM and SCM together with UV light exposure signatures (SBS7a, 7b), and SF- and D-MPNST together with defective DNA base excision repair (SBS30, 36). RNA-seq revealed differentially expressed genes between SF-MPNST and SCM (1670 genes), DM (831 genes), and D-MPNST (614 genes), some of which hold promise for development as immunohistochemical markers (SOX8 and PLCH1) or aids (MLPH, CALB2, SOX11, and TBX4). H3K27me3 immunoreactivity was diffusely lost in most D-MPNSTs (7/8, 88%) but showed variable and patchy loss in SF-MPNSTs (2/8, 25%). PRAME was entirely negative in the majority (0+ in 20/31, 65%), including 11/15 melanomas, and showed no significant difference between groups (P = .105, Kruskal-Wallis test). Expression of immune cell transcripts was upregulated in melanomas relative to MPNSTs. Next-generation sequencing revealed multiple differential features between SF- MPNST, D-MPNST, SCM, and DM, including tumor mutation burden, mutational signatures, and differentially expressed genes. These findings help advance our understanding of disease pathogenesis and improve diagnostic modalities.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102183"},"PeriodicalIF":5.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Segmentation With Globally Optimized Boundaries (CSGO): A Deep Learning Pipeline for Whole-Cell Segmentation in Hematoxylin-and-Eosin-Stained Tissues.","authors":"Zifan Gu, Shidan Wang, Ruichen Rong, Zhuo Zhao, Fangjiang Wu, Qin Zhou, Zhuoyu Wen, Zhikai Chi, Yisheng Fang, Yan Peng, Liwei Jia, Mingyi Chen, Donghan M Yang, Yujin Hoshida, Yang Xie, Guanghua Xiao","doi":"10.1016/j.labinv.2024.102184","DOIUrl":"10.1016/j.labinv.2024.102184","url":null,"abstract":"<p><p>Accurate whole-cell segmentation is essential in various biomedical applications, particularly in studying the tumor microenvironment. Despite advancements in machine learning for nuclei segmentation in hematoxylin and eosin (H&E)-stained images, there remains a need for effective whole-cell segmentation methods. This study aimed to develop a deep learning-based pipeline to automatically segment cells in H&E-stained tissues, thereby advancing the capabilities of pathological image analysis. The Cell Segmentation with Globally Optimized boundaries (CSGO) framework integrates nuclei and membrane segmentation algorithms, followed by postprocessing using an energy-based watershed method. Specifically, we used the You Only Look Once (YOLO) object detection algorithm for nuclei segmentation and U-Net for membrane segmentation. The membrane detection model was trained on a data set of 7 hepatocellular carcinomas and 11 normal liver tissue patches. The cell segmentation performance was extensively evaluated on 5 external data sets, including liver, lung, and oral disease cases. CSGO demonstrated superior performance over the state-of-the-art method Cellpose, achieving higher F1 scores ranging from 0.37 to 0.53 at an intersection over union threshold of 0.5 in 4 of the 5 external datasets, compared to that of Cellpose from 0.21 to 0.36. These results underscore the robustness and accuracy of our approach in various tissue types. A web-based application is available at https://ai.swmed.edu/projects/csgo, providing a user-friendly platform for researchers to apply our method to their own data sets. Our method exhibits remarkable versatility in whole-cell segmentation across diverse cancer subtypes, serving as an accurate and reliable tool to facilitate tumor microenvironment studies. The advancements presented in this study have the potential to significantly enhance the precision and efficiency of pathologic image analysis, contributing to better understanding and treatment of cancer.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102184"},"PeriodicalIF":5.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Cellular Dynamics of Germinal Center Reaction in Coronavirus Disease 2019 Lung-Draining Lymph Node Based on Imaging-Based Spatial Transcriptomics","authors":"Taehwan Oh ,&nbsp;YoungMin Woo ,&nbsp;Green Kim ,&nbsp;Bon-Sang Koo ,&nbsp;Seung Ho Baek ,&nbsp;Eun-Ha Hwang ,&nbsp;You Jung An ,&nbsp;Yujin Kim ,&nbsp;Dong-Yeon Kim ,&nbsp;Jung Joo Hong","doi":"10.1016/j.labinv.2024.102180","DOIUrl":"10.1016/j.labinv.2024.102180","url":null,"abstract":"<div><div>Although lymph node structures may be compromised in severe SARS-CoV-2 infection, the extent and parameters of recovery in convalescing patients remain unclear. Therefore, this study aimed to elucidate the nuances of lymphoid structural recovery and their implications for immunologic memory in nonhuman primates infected with SARS-CoV-2. To do so, we utilized imaging-based spatial transcriptomics to delineate immune cell composition and tissue architecture formation in the lung-draining lymph nodes during primary infection, convalescence, and reinfection from COVID-19. We noted the establishment of a germinal center with memory B cell differentiation within lymphoid follicles during convalescence accompanied by contrasting transcriptome patterns indicative of the acquisition of follicular helper T cells versus the loss of regulatory T cells. Additionally, repopulation of germinal center-like B cells was observed in the medullary niche with accumulating plasma cells along with enhanced transcriptional expression of B cell-activating factor receptor over the course of reinfection. The spatial transcriptome atlas produced herein enhances our understanding of germinal center formation with immune cell dynamics during COVID-19 convalescence and lymphoid structural recovery with transcriptome dynamics following reinfection. These findings have the potential to inform the optimization of vaccine strategies and the development of precise therapeutic interventions in the spatial context.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 1","pages":"Article 102180"},"PeriodicalIF":5.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}