Laboratory Investigation最新文献

{"title":"Age and Hypertension Synergize With Dehydration to Cause Renal Frailty in Rats and Predispose Them to Intrinsic Acute Kidney Injury","authors":"Noelia Díaz-Morales ,&nbsp;Sandra M. Sancho-Martínez ,&nbsp;Eva M. Baranda-Alonso ,&nbsp;Isabel Fuentes-Calvo ,&nbsp;Rebeca S. Sidhu-Muñoz ,&nbsp;Nuria Martín-Fernández ,&nbsp;Francisco J. López-Hernández ,&nbsp;Carlos Martínez-Salgado","doi":"10.1016/j.labinv.2024.102211","DOIUrl":"10.1016/j.labinv.2024.102211","url":null,"abstract":"<div><div>Acute kidney frailty (AKF) is a condition of increased susceptibility to acute kidney injury (AKI), an abrupt impairment of renal excretory function potentially leading to severe complications. Prevention of AKI relies on the recognition of risk factors contributing to AKF. At the population level, dehydration constitutes a predisposing factor for AKI. However, renal frailty may be context-specific, with variations among patients in the types of damage and the distinct pathological mechanisms. In this regard, we studied the combined effect of dehydration with other factors on renal homeostasis, such as increasing age and hypertension. AKF status was studied in rats bearing risk factors individually and in combination and was evaluated as the level of AKI induced by a triggering dose of cisplatin, which is known to be mildly nephrotoxic for young, healthy rats. AKI was assessed through parameters of renal function (including creatinine, urea, creatinine clearance, proteinuria, and fractional excretion of sodium) and histopathology of renal tissue specimens. The hydration status was measured by bioelectric impedance and other techniques. Water deprivation induces a dehydration state characterized by reductions in body weight and urinary flow and increases in hematocrit and plasma and urine osmolality. Bioelectric impedance showed a net loss of body water after water deprivation with no relevant changes in body mass distribution. Dehydration is not sufficient to predispose young control rats to intrinsic AKI. However, the combination of dehydration with advanced age or hypertension induces AKF evidenced by a magnified response of renal dysfunction (reduced filtration and tubular function) and tubular necrosis caused by low-dose cisplatin treatment. This study highlights the relevance of addressing AKF as a premorbid condition providing prophylactic opportunities and shows that dehydration differentially predisposes to prerenal and intrinsic AKI.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102211"},"PeriodicalIF":5.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of MHC-I on Melanoma Cells and Decreased CD8+ T-Cell Infiltration Are Associated With Metastatic Spread and Resistance to Immunotherapy","authors":"Miriam Mengoni ,&nbsp;Felix O. Mahlo ,&nbsp;Evelyn Gaffal ,&nbsp;Thomas Tüting ,&nbsp;Andreas D. Braun","doi":"10.1016/j.labinv.2024.102209","DOIUrl":"10.1016/j.labinv.2024.102209","url":null,"abstract":"<div><div>The success of immune checkpoint inhibitors (ICI) in melanoma therapy has catalyzed the introduction of ICI in increasingly early stages of the disease. This exposes many patients with a lower risk of relapse to the risk of protracted adverse events, highlighting the need for biomarkers guiding the use of ICI. Already many years ago, brisk infiltration of primary melanomas by lymphocytes has been linked to improved patient outcome, but controversial findings due to a high variability in classification systems have been described CD8+ T cells have been identified as a primary mediator of antitumor immunity in patients treated with ICI. As CD8+ T cells require the presentation of antigens via MHC-I on target cells, downregulation and loss of MHC-I have been observed as resistance mechanisms to ICI. In this study, we revisit the role of MHC-I expression and CD8+ T-cell infiltration in melanoma evolution using a cohort of advanced primary and matched metastatic melanomas by using an automated immunohistochemistry and digital pathology workflow. Our results show that downregulation of MHC-I expression is a frequent event in advanced primary melanomas that is associated with decreased CD8+ T-cell infiltration and an early metastatic spread to sentinel lymph nodes. Furthermore, MHC-I downregulation and decreased infiltration with CD8+ T cells are also associated with resistance to ICI. Our results suggest that analyses of MHC-I expression and CD8+ T-cell infiltration patterns could serve as future biomarkers to guide the decision to treat patients in early stages of melanoma with ICI.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102209"},"PeriodicalIF":5.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of Fibrotic Interstitial Lung Diseases Based on the Combination of Label-Free Quantitative Multiphoton Fiber Histology and Machine Learning","authors":"Wenzhuo Qiu ,&nbsp;Qingyang Wang ,&nbsp;Ying Zhang ,&nbsp;Xiuxue Cao ,&nbsp;Ling Zhao ,&nbsp;Longhao Cao ,&nbsp;Yuxuan Sun ,&nbsp;Feili Yang ,&nbsp;Yuanyuan Guo ,&nbsp;Yuming Sui ,&nbsp;Ziyi Chang ,&nbsp;Congcong Wang ,&nbsp;Lifang Cui ,&nbsp;Yun Niu ,&nbsp;Pingping Liu ,&nbsp;Jie Lin ,&nbsp;Shixuan Liu ,&nbsp;Jia Guo ,&nbsp;Bei Wang ,&nbsp;Ruiqi Zhong ,&nbsp;Dingrong Zhong","doi":"10.1016/j.labinv.2024.102210","DOIUrl":"10.1016/j.labinv.2024.102210","url":null,"abstract":"<div><div>Interstitial lung disease (ILD), characterized by inflammation and fibrosis, often suffers from low diagnostic accuracy and consistency. Traditional hematoxylin and eosin (H&amp;E) staining primarily reveals cellular inflammation with limited detail on fibrosis. To address these issues, we introduce a pioneering label-free quantitative multiphoton fiber histology (MPFH) technique that delineates the intricate characteristics of collagen and elastin fibers for ILD diagnosis. We acquired colocated multiphoton and H&amp;E-stained images from a single tissue slice. Multiphoton imaging was performed on the deparaffinized section to obtain fibrotic tissue information, followed by H&amp;E staining to capture cellular information. This approach was tested in a blinded diagnostic trial among 7 pathologists involving 14 patients with relatively normal lung and 31 patients with ILD (11 idiopathic pulmonary fibrosis/usual interstitial pneumonia, 14 nonspecific interstitial pneumonia, and 6 pleuroparenchymal fibroelastosis). A customized algorithm extracted quantitative fiber indicators from multiphoton images. These indicators, combined with clinical and radiologic features, were used to develop an automatic multiclass ILD classifier. Using MPFH, we can acquire high-quality, colocalized images of collagen fibers, elastin fibers, and cells. We found that the type, distribution, and degree of fibrotic proliferation can effectively distinguish between different subtypes. The blind study showed that MPFH enhanced diagnostic consistency (κ values from 0.56 to 0.72) and accuracy (from 73.0% to 82.5%, <em>P</em> = .0090). The combination of quantitative fiber indicators effectively distinguished between different tissues, with areas under the receiver operating characteristic curves exceeding 0.92. The automatic classifier achieved 93.8% accuracy, closely paralleling the 92.2% accuracy of expert pathologists. The outcomes of our research underscore the transformative potential of MPFH in the field of fibrotic-ILD diagnostics. By integrating quantitative analysis of fiber characteristics with advanced machine learning algorithms, MPFH facilitates the automatic and accurate identification of various fibrotic disease subtypes, showcasing a significant leap forward in precision diagnostics.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102210"},"PeriodicalIF":5.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829285","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 Molecular Landscape of 227 Adult Granulosa Cell Tumors of the Ovary: Insights into the Progression from Primary to Recurrence","authors":"Romana Michálková ,&nbsp;Adam Šafanda ,&nbsp;Nikola Hájková ,&nbsp;Jan Hojný ,&nbsp;Eva Krkavcová ,&nbsp;Michaela Kendall Bártů ,&nbsp;Marián Švajdler ,&nbsp;Tetiana Shatokhina ,&nbsp;Jan Laco ,&nbsp;Radoslav Matěj ,&nbsp;Gábor Méhes ,&nbsp;Jitka Hausnerová ,&nbsp;Jozef Škarda ,&nbsp;Mária Hácová ,&nbsp;Monika Náležinská ,&nbsp;Tomáš Zima ,&nbsp;Pavel Dundr ,&nbsp;Kristýna Němejcová","doi":"10.1016/j.labinv.2024.102201","DOIUrl":"10.1016/j.labinv.2024.102201","url":null,"abstract":"<div><div>Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The <em>FOXL2</em> p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and <em>TERT</em> promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of <em>FOXO1</em> mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases.</div><div>Our findings confirmed the high prevalence (99%) of the <em>FOXL2</em> p.C134W mutation in AGCTs. Secondary truncating <em>FOXL2</em> mutations were observed in 5% of cases. Two cases with typical AGCT morphology were <em>FOXL2</em> wild-type, harboring mutations in <em>KRAS</em> or <em>KMT2D</em> instead, suggesting alternative genetic pathways. <em>TERT</em> promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included <em>KMT2D</em> (10%), <em>FOXO1</em> (7%), <em>CHEK2</em> (5%), <em>TP53</em> (3.5%), <em>PIK3CA</em> (3.5%), and <em>AKT1</em> (3%). Two recurrent, <em>FOXL2</em>-mutated cases also carried <em>DICER1</em> mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of <em>FOXO1</em> as a potential prognostic marker in AGCTs.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102201"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770094","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":"NKX3.1 Helps Distinguish Hyalinizing Clear Cell Carcinoma From Other Clear Cell Salivary Gland Neoplasms","authors":"Airi Sakyo ,&nbsp;Eijitsu Ryo ,&nbsp;Shogo Nishino ,&nbsp;Kenya Kobayashi ,&nbsp;Seiichi Yoshimoto ,&nbsp;Go Omura ,&nbsp;Chihiro Fushimi ,&nbsp;Toshihiko Sakai ,&nbsp;Azusa Sakai ,&nbsp;Kohtaro Eguchi ,&nbsp;Hideaki Takahashi ,&nbsp;Kazuki Yokoyama ,&nbsp;Yoshitaka Honma ,&nbsp;Akiko Mori ,&nbsp;Hiroko Kato ,&nbsp;Toshiyuki Hatano ,&nbsp;Akihiko Yoshida ,&nbsp;Fumihiko Matsumoto ,&nbsp;Yasushi Yatabe ,&nbsp;Taisuke Mori","doi":"10.1016/j.labinv.2024.102205","DOIUrl":"10.1016/j.labinv.2024.102205","url":null,"abstract":"<div><div>Hyalinized clear cell carcinoma (HCCC) is a rare tumor of the minor salivary gland, characterized by pale cytoplasm and EWSR1::ATF1 fusion. Recently, new fusions, such as EWSR1::LARP4 and SMARCA2::CREM, have also been identified. Histologically, HCCC closely resembles other salivary gland tumors like mucoepidermoid carcinoma and myoepithelial carcinoma, and there are no specific immunohistological markers for its identification. In this study, we investigated potential markers for HCCC based on the characteristics of minor salivary gland acini, from which these tumors may originate. SOX10 is a known marker for serous gland clusters and NKX3.1 for mucus gland clusters. Fluorescence intensity analysis of double staining, objectively evaluated by artificial intelligence, revealed variations in the positive intensity of cells single positive for NKX3.1 and SOX10, as well as cells positive for both markers, which are commonly observed in normal minor salivary glands. We evaluated NKX3.1 expression by immunohistochemistry in 12 HCCC cases (including 9 EWSR1::ATF1, 1 EWSR1::LARP4, and 1 SMARCA2::CREM), 12 myoepithelial carcinoma cases, and tissue microarray containing 88 cases of multiple salivary gland tumors using immunohistochemistry. NKX3.1 was expressed in all 12 HCCC cases (100%), with NKX3.1-positive cells ≧90% in 3 cases, ≧60% 1 case, ≧30% 4 cases, and &lt;30% 4 cases, respectively. SOX10 was negative in 10 cases and weakly positive in 2 cases. This finding mimics the pattern of expression in minor salivary glands and may explain the occurrence of weak NKX3.1 staining and SOX10-positive cases in HCCC. Additionally, in the tissue microarray analysis, NKX3.1 staining was observed in only 1 HCCC case. These findings indicate that NKX3.1 is a useful marker for distinguishing HCCC from other clear cell salivary gland neoplasms. This study suggests that NKX3.1, along with SOX10 and CK7, can be utilized to improve the accuracy of HCCC diagnosis.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102205"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770136","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":"Annotation Practices in Computational Pathology: A European Society of Digital and Integrative Pathology (ESDIP) Survey Study","authors":"Diana Montezuma ,&nbsp;Sara P. Oliveira ,&nbsp;Yuri Tolkach ,&nbsp;Peter Boor ,&nbsp;Alex Haragan ,&nbsp;Rita Carvalho ,&nbsp;Vincenzo Della Mea ,&nbsp;Tim-Rasmus Kiehl ,&nbsp;Sabine Leh ,&nbsp;Mustafa Yousif ,&nbsp;David Ameisen ,&nbsp;Mircea-Sebastian Șerbănescu ,&nbsp;Norman Zerbe ,&nbsp;Vincenzo L’Imperio","doi":"10.1016/j.labinv.2024.102203","DOIUrl":"10.1016/j.labinv.2024.102203","url":null,"abstract":"<div><div>Integrating digital pathology and artificial intelligence (AI) algorithms can potentially improve diagnostic practice and precision medicine. Developing reliable, generalizable, and comparable AI algorithms depends on access to meticulously annotated data. However, achieving this requires robust collaboration among pathologists, computer scientists, and other researchers to ensure data quality and consistency. The lack of standardization and scalability is a significant challenge when generating annotations and annotated data sets. Recognizing these limitations, the Scientific Committee of the European Society of Digital and Integrative Pathology (ESDIP) performed a comprehensive international survey to understand the current state of annotation practices and identify actionable areas to address critical needs in the annotation process. The analysis and summary of the survey results provide several insights for all stakeholders involved in data preparation and ground truthing, ultimately contributing to the advancement of AI in computational pathology.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102203"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive RNA Sequencing Analysis Identifies Network Hub Genes and Biomarkers Differentiating Desmoid-type Fibromatosis From Reactive Fibrosis","authors":"Eunjin Jeong ,&nbsp;Jamin Ku ,&nbsp;Ji Min Na ,&nbsp;Wonkyung Kim ,&nbsp;Chang Ohk Sung ,&nbsp;Seok-Hyung Kim","doi":"10.1016/j.labinv.2024.102204","DOIUrl":"10.1016/j.labinv.2024.102204","url":null,"abstract":"<div><div>Desmoid-type fibromatosis (DTF) is a benign but locally aggressive neoplasm characterized by persistent fibroblast activation, unlike reactive fibrosis (RF), where fibroblast activation is transient. Although the Wnt/β-catenin signaling pathway is known to play a role in DTF pathogenesis, the specific genetic drivers contributing to this abnormal fibroblast activation are not fully understood. To identify additional driver genes that underlie the persistent activation of fibroblasts in DTF, we conducted a comparative transcriptome analysis between 29 DTF and 14 RF tissue samples, identifying 4267 differentially expressed genes (DEGs) specific to DTF. These DTF-specific DEGs were significantly associated with pathways involved in embryonic limb morphogenesis and muscle contraction, whereas RF-specific DEGs were linked to immune response and apoptosis. Using weighted gene coexpression network analysis to further elucidate the key regulatory circuits associated with persistent activation of DTF fibroblasts, we identified a highly DTF-specific gene module comprising 120 genes. This module was also significantly enriched in other fibroproliferative conditions showing persistent fibroblast activation, such as keloid disease and idiopathic pulmonary fibrosis. Subsequent analyses identified 7 driver transcription factors (<em>ZNF536, IRX5, TWIST2, NKD2, PAX9, SHOX2,</em> and <em>SALL4</em>) within this DTF-specific module that may contribute to the sustained activation of DTF fibroblasts. We further assessed the utility of 5 key genes from this module (TWIST2, LRRC15, CTHRC1, SHOX2, and SALL4) as potential biomarkers to distinguish DTF from RF using immunohistochemistry. All markers demonstrated excellent diagnostic performance, with TWIST2 showing exceptionally high sensitivity and specificity, surpassing β-catenin, the current standard biomarker for DTF. In conclusion, our study identifies gene modules and driver transcription factors that are highly specific to DTF, offering new insights into the genetic underpinnings of abnormal fibroblast activation in DTF. We also propose novel biomarkers that could improve the diagnostic accuracy and clinical management of DTF.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 3","pages":"Article 102204"},"PeriodicalIF":5.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770130","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":"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}

{"title":"Quantifying Cardiac Tissue Composition Using QuPath and Cellpose: An Accessible Approach to Postmortem Diagnosis","authors":"Pernille Heimdal Holm ,&nbsp;Kristine Boisen Olsen ,&nbsp;Richard Denis Maxime De Mets ,&nbsp;Jytte Banner","doi":"10.1016/j.labinv.2024.102181","DOIUrl":"10.1016/j.labinv.2024.102181","url":null,"abstract":"<div><div>Sudden death can be the first symptom of cardiac disease, and establishing a precise postmortem diagnosis is crucial for genetic testing and follow-up of relatives. Arrhythmogenic cardiomyopathy is a structural cardiomyopathy that can be challenging to diagnose postmortem because of differences in structural findings and propagation of the disease at the time of death. Cases can have minimal or no structural findings and later be diagnosed according to genotype, known as concealed cardiomyopathy. Postmortem diagnosis often lacks clinical information, whereas antemortem diagnosis is based on paraclinical investigations that cannot be performed after death. However, the entire substrate is available, which is unique to postmortem diagnosis and research and can provide valuable insights when adding new methods. Reactive changes in the heart, such as myocardial fibrosis and fat, are significant findings. The patterns of these changes in various diseases are not yet fully understood and may be limited by sampling material and conventional microscopic diagnostics. We demonstrate an automated pipeline in QuPath for quantifying postmortem picrosirius red cardiac tissue for collagen, residual myocardium, and adipocytes by integrating Cellpose into a versatile pipeline. This method was developed and tested using cardiac tissues from autopsied individuals. Cases diagnosed with arrhythmogenic cardiomyopathy and age-matched controls were used for validation and testing. This approach is free and easy to implement by other research groups using this paper as a template. This can potentially lead to the development of quantitative diagnostic criteria for postmortem cardiac diseases, eliminating the need to rely on diagnostic criteria from endomyocardial biopsies that are not applicable to postmortem specimens. We propose that this approach serves as a template for creating a more efficient process for evaluating postmortem cardiac measurements in an unbiased manner, particularly for rare cardiac diseases.</div></div>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":"105 1","pages":"Article 102181"},"PeriodicalIF":5.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623193","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}