Applied Immunohistochemistry & Molecular Morphology最新文献

{"title":"Telomerase Immunocytochemistry in Lymphocytes From Chronic Lymphocytic Leukemia.","authors":"Mirna Sučić, Nives Ljubić, Dubravka Županić Krmek","doi":"10.1097/PAI.0000000000001263","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001263","url":null,"abstract":"<p><p>Human telomerase reverse transcriptase (hTERT) is detectable in normal progenitor cells, tumor cells, and B-cell chronic lymphocytic leukemia (B-CLL) cells. hTERT expression, in addition to other prognostic factors, is reportedly associated with a poor prognosis in B-CLL. In this study, we aimed to analyze and compare hTERT immunoexpression in B-CLL bone marrow (BM) lymphocytes and benign pleural effusion lymphocytes. Standard cytologic analysis and immunocytochemical assessment of hTERT immunoexpression were performed in BM lymphocytes from 25 patients with B-CLL and pleural effusion lymphocytes from 18 patients with pneumonia and effusion-reactive lymphocytosis. The percentages and score values of hTERT nucleus (TN)-immunopositive BM lymphocytes in patients with CLL were significantly higher than those for reactive effusion lymphocytes with no or few TN-immunopositive lymphocytes. The appearance of TN immunopositivity in CLL lymphocytes showed mainly numerous prominent or large dots, and diffused TN immunopositivity was detected; in contrast, TN-immunopositive benign effusion lymphocytes had one or few immunopositive nuclear dots. Further investigations are needed to clarify whether lymphocyte TN immunopositivity can reveal subgroups of patients with CLL with a worse prognosis and whether there is a reliable difference in TN immunopositivity between CLL and benign effusion lymphocytes.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of MammaPrint to Histopathologic Variables and Comparison to Magee Equations in Adjuvant and Neoadjuvant Cohorts of Estrogen-Receptor Positive HER2-Negative Breast Carcinoma.","authors":"Mariel Bedell, Tatiana M Villatoro, Stephanie N David, Beth Z Clark, Jeffrey L Fine, Jing Yu, Rohit Bhargava","doi":"10.1097/PAI.0000000000001262","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001262","url":null,"abstract":"<p><p>MammaPrint (MP) is a multigene assay utilized for prognostic and predictive use in early stage ER+/HER2-negative breast cancer (BC). There is limited data on MP correlation to histopathologic variables, including multivariable model Magee Equations (MEs). We compared pathologic variables to MP on 365 ER+/HER2-negative BCs in the adjuvant setting. Further, we analyzed MP and ME results in 26 core biopsy-proven ER+/HER2-negative BCs subjected to neoadjuvant chemotherapy (NACT). Post-NACT response was assessed by residual cancer burden (RCB) score. In the adjuvant cohort (n=365), high-risk (HR) MP correlated with high Nottingham score, low progesterone receptor H-score, ductal morphology, high Ki-67 index, and high ME score. In the neoadjuvant cohort (n=26), 24 were MP-HR and 2 were MP low-risk (MP-LR). The 2 MP-LR cases correlated with average ME scores of ≤25 and showed RCB scores of 2 or 3. Of the 24 MP-HR, 2 showed RCB-0 or RCB-1. Average ME>25 was seen in both of these cases and 7 others corresponding to an RCB-0 and RCB-1 rate of 22% (2 of 9) with ME>25 compared with 8% (2 of 24) with MP-HR. Lack of significant benefit from NACT (RCB-2 or RCB-3) was accurately predicted by average ME≤25 in 17 of 26 cases (65%) compared with only 2 of 26 cases (8%) with MP-LR. MP correlates with aggressive histopathologic features. While both MP and ME identified cases with robust chemotherapeutic response, MP overpredicted cases that would benefit. Therefore, MEs may more accurately predict response to NACT.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Expression Patterns of Bcl-2, D2-40, β-Katenin, and E-Cadherin in Thymomas: Correlation With Clinical Stages and Subtypes.","authors":"Busra Yaprak Bayrak, Aysegul U Kefeli, Cigdem Vural, Isa Cam, Ekin Y Calcali, Aykut Elicora, Huseyin F Sezer, Salih Topcu","doi":"10.1097/PAI.0000000000001264","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001264","url":null,"abstract":"<p><p>Thymomas are rare mediastinal tumors exhibiting heterogeneous behavior. Although histologic subtypes and stages serve as prognostic factors, the molecular mechanisms of thymoma progression are unclear. Immunohistochemical markers like Bcl-2, D2-40, β-catenin, and E-cadherin offer insights into thymoma biology, but their predictive value for clinical outcomes remains uncertain. This study evaluated the expression of these markers across thymoma subtypes and stages, aiming to assess their prognostic significance. A retrospective analysis was conducted on 66 thymoma cases resected at a single center between 2005 and 2023. Immunohistochemical staining was performed to assess the expression of Bcl-2, D2-40, β-catenin, and E-cadherin. Clinicopathological characteristics were correlated with immunohistochemical findings using statistical analysis. Differential expression patterns of Bcl-2, D2-40, β-catenin, and E-cadherin were observed across thymoma subtypes and clinical stages. Bcl-2 displayed cytoplasmic positivity predominantly in type A and B thymomas, while E-cadherin showed membranous staining in type B thymomas and cytoplasmic staining in type A and AB thymomas. β-catenin demonstrated membranous staining in type B thymomas and cytoplasmic staining in type A and AB thymomas. D2-40 expression was localized to peripheral regions and invasive nests of thymomas, with higher expression in type B2 thymomas and early-stage tumors. Our findings indicate that immunohistochemical markers may provide valuable insights into thymoma biology and prognosis. Further validation in larger, multicenter cohorts is warranted to confirm the prognostic significance of these markers and their potential utility in guiding clinical management.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":""},"PeriodicalIF":1.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prevention of Fatal Tauopathy in a Mouse Model of Alzheimer Disease by Blocking BCL2.","authors":"Gerard J Nuovo, Madison Rice, Nicola Zanesi, Dwitiya Sawant, Candice Crilly, Esmerina Tili","doi":"10.1097/PAI.0000000000001251","DOIUrl":"10.1097/PAI.0000000000001251","url":null,"abstract":"<p><p>A major goal in Alzheimer disease (AD) research is the reduction of the abnormal tau burden. Using multispectral analyses on brain tissues from humans who died of AD it was documented that neurons with hyperphosphorylated tau protein accumulate many proteins of the BCL2 family, including those that block cell turnover (eg, BCL2, MCL1, BCLXL) and those that promote cell turnover (eg, NOXA, PUMA, BAK, BAX). A mouse model of AD with the humanized hyperphosphorylated tau protein was used to test the hypothesis that shifting this balance to a pro-cell turnover milieu would reduce the tau burden with concomitant clinical improvement. Here, we show that a mouse model of AD with death at 11 to 15 months due to CNS tauopathy had a marked reduction in the tau burden after treatment with the FDA-approved drug venetoclax, which blocks BCL2. The reduction of the number of target neurons positive for hyperphosphorylated tau protein after venetoclax treatment in the brain and spinal cord neurons was 94.5% as determined by immunohistochemistry and 98.1% as documented with the modified Bielchowsky stain. The venetoclax treatment began after documented neurofibrillary tangles (NFTs) were evident and there was a concomitant reduction in neuroinflammation. The treated mice were robust until sacrificed at 13 months as compared with the untreated mice that showed unequivocal evidence of brain and spinal cord damage both clinically and at autopsy. We conclude that otherwise inexorable abnormal tau protein deposition, even after initiation, can be prevented by a drug that blocks one anti-cell turnover protein abundant in the NFTs of human AD.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"142-151"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Accurate Deep Learning-Based Prediction of Ki67, ER, PR, and HER2 Status From H&E-Stained Breast Cancer Images.","authors":"Amir Akbarnejad, Nilanjan Ray, Penny J Barnes, Gilbert Bigras","doi":"10.1097/PAI.0000000000001258","DOIUrl":"10.1097/PAI.0000000000001258","url":null,"abstract":"<p><p>Despite improvements in machine learning algorithms applied to digital pathology, only moderate accuracy, to predict molecular information from histology alone, has been achieved so far. One of the obstacles is the lack of large data sets to properly train machine learning models. We therefore built a data set of 185,538 breast cancer (BC) including hematoxylin and eosin (H&E) and associated immunohistochemistry (IHC) images of the proliferative marker Ki67, estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Optimal registration of H&E and IHC pairs was achieved. Ki67, ER, and PR IHC labels, to be predicted, were extracted from IHC assays using image analysis. These labels were ordinaly classified with incremental thresholds (cumulative logit models with balanced and partial proportional odds). HER2 label was determined as follows: positive if tumor IHC 3+ pattern is identified and otherwise negative. Cases with IHC equivocal score (2+) were excluded. A vision transformer (ViT)-based pipeline, trained with this data set, achieved prediction performance of 90% in terms of area under the curve (AUC) of the receiver operating characteristic (ROC) curves. ViT outperformed the weakly supervised clustering-constrained attention multiple instance learning (CLAM) which was developed to automatically identify subregions of high diagnostic value in whole slide. As a first step to \"explain\" artificial intelligence (AI), we evaluated the ability of both classifiers to localize these high diagnostic value subregions by inspecting their respective \"attention\" heat-maps. Despite high ViT AUC-ROC results, heat-maps do not obviously match areas of high diagnostic value subregions; it might however provide direction for future work to improve AI attention within whole slide images. Our proposed data set is publicly available.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"131-141"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and Epigenetic Changes in Melanoma Progression: A TCGA-based Study.","authors":"Yasemin Cakir, Banu Lebe, M Hasan Toper, Sulen Sarioglu","doi":"10.1097/PAI.0000000000001257","DOIUrl":"10.1097/PAI.0000000000001257","url":null,"abstract":"<p><p>We aimed to investigate molecular mechanisms affecting melanoma progression by comparing genetic/epigenetic features between melanomas of different Breslow thickness and stage using TCGA (The Cancer Genome Atlas) data. The TCGA, Firehose Legacy, melanoma data set was utilized on the cBioPortal website. The cases were compared in terms of mRNA expression and DNA methylation. Gene Ontology (GO) and KEGG pathways enrichment analysis were performed using the online WebGestalt tool. STRING and Cytoscape software were used to construct a protein-protein interaction network and identify hub genes. P and q <0.05, FDR< 0.05 were considered statistically significant. 1001 differentially expressed genes were identified between thin (≤1 mm) and thick (>1 mm) melanomas. Pathway analyses revealed that genes enriched in thin melanomas were associated with adaptive immune response, T-cell activation, immune response regulation, leukocyte, and cytokine-related pathways, whereas genes enriched in thick melanomas were related to epidermis development. Ten hub genes were identified ( CD4, IFNG, PTPRC, CD8A, CTLA4, CD69, ICOS, CD27, CD28, CD19 ). All of these genes are involved in crucial immunological processes. Understanding the complex changes in melanoma progression is essential for accurate diagnosis and prediction of prognosis. Our results may shed light on subsequent studies to identify the steps in melanoma progression.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"170-179"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classifying Pulmonary and Urinary High-grade Neuroendocrine Carcinoma by CK7 Immunohistochemistry: Erratum.","authors":"","doi":"10.1097/PAI.0000000000001255","DOIUrl":"10.1097/PAI.0000000000001255","url":null,"abstract":"","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"193"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membranous Staining of CD10 Is Related to Steatosis Changes in Hepatocellular Carcinoma: An Investigation of CD10 Stainning in Hepatocellular Carcinoma, Focal Nodular Hyperplasia, and Intrahepatic Cholangiocarcinoma.","authors":"Caiyan Wen, Chuqiang Huang, Shouguo Chen, Xia Liu, Weihua Yin, Lili Tao","doi":"10.1097/PAI.0000000000001249","DOIUrl":"10.1097/PAI.0000000000001249","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the staining patterns of CD10 in hepatocellular carcinoma (HCC), focal nodular hyperplasia (FNH), and intrahepatic cholangiocarcinoma (ICC).</p><p><strong>Methods: </strong>The expression pattern of CD10 was analyzed using immunohistochemistry in HCC cases. Focal nodular hyperplasia (FNH) and intrahepatic cholangiocarcinoma (ICC) cases were also examined. CD10 staining pattern in relationship with histologic subtypes and growth patterns of HCC was also analyzed.</p><p><strong>Results: </strong>CD10 expression was observed in 61% (64/105) of HCC cases, 100% (12/12) of FNH cases, and 31.6% (6/19) of ICC cases. Different expression patterns were noted, including cell membrane (13/64; 20.3%), luminal (9/64; 14.0%), cytoplasmic puncta (15/64; 23.4%), and canalicular (27/64; 42.3%) patterns of CD10 expression in HCC. Interestingly, CD10 membranous expression was found to be associated with steatosis changes. The observed pattern rates of CD10-positive ICC cases were 16.6% (1/6) for cell membrane, 50% (3/6) for cytoplasmic, and 33.3% (2/6) for luminal patterns; with 2 samples having a 1+ score (33.3%), 1 having a 2+ score (16.7%), and 3 having a 3+ score (50%).</p><p><strong>Conclusions: </strong>Different CD10 expression patterns were observed in HCC, FNH, and ICC. A canalicular CD10 expression pattern does not distinguish between benign and malignant lesions in the HCC, but reduced CD10 expression or no canalicular pattern suggests that a tumor is more likely to be HCC. Contrary to previous understanding, we found that CD10 is also expressed in ICC cases.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"180-185"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of EZH2 and Fatty Acid Synthase in Breast Tissues From Healthy Women With Breast Cancer Risk Factors.","authors":"Katelyn Zebrowski, Kaleb June, Dafydd Thomas, Zora Djuric, Tarah Ballinger, Celina G Kleer","doi":"10.1097/PAI.0000000000001250","DOIUrl":"10.1097/PAI.0000000000001250","url":null,"abstract":"<p><p>Tissue-based biomarkers that identify women with increased breast cancer risk are needed for cancer prevention. Enhancer of zeste 2 (EZH2) and fatty acid synthase (FASN) are associated with breast cancer aggressiveness, but their expression in normal breast tissues and association with breast cancer risk factors are unclear. Further, there is a need to characterize healthy breast tissue cohorts for unbiased biomarker evaluation. In this study, we employed the Susan G. Komen healthy volunteer tissue bank to evaluate EZH2 and FASN expression and their relationship to breast cancer risk factors. Normal breast core biopsies from 40 healthy donors with low or high Gail scores (<11 or >20, respectively) and normal or obese body mass index (BMI, <25 kg/m 2 or >30 kg/m 2 , respectively) were stained for H&E, EZH2, and FASN and scored independently and blindly using the Allred method. We analyzed the associations between EZH2 and FASN with Gail score, BMI, menopausal status, hormone replacement therapy (HRT), and family history of breast cancer. None of the donors had BRCA1/2 mutations or developed breast cancer after 5 to 9 years. We found that premenopausal women had significantly higher expression of FASN and that EZH2 was higher with increasing Gail risk scores, compared with postmenopausal women. In postmenopausal women, increased EZH2 expression was associated with >5 years of HRT compared with <1 year or no HRT. No associations were found with BMI. This study provides validation of a healthy breast tissue cohort and initial characterization of EZH2 and FASN and their associations with breast cancer risk factors.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"186-192"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Cytokeratin 7 (CK7) Expression Can be Seen in Significant Proportion of Solid Papillary Carcinoma of Breast and Associated Invasive Component.","authors":"Fahad Sheikh, Susan Fineberg, Javier Laurini, Sonali Lanjewar","doi":"10.1097/PAI.0000000000001256","DOIUrl":"10.1097/PAI.0000000000001256","url":null,"abstract":"<p><strong>Abstract: </strong>Cytokeratin 7 (CK7) is a marker of epithelial differentiation and is positive in >90% of breast carcinomas. In the right clinical setting, coexpression of CK7 and GATA3 is considered as strong evidence of breast origin, which can be further confirmed by positive expression of estrogen and progesterone receptors. Pathologists use CK7 in the breast to confirm epithelial differentiation and highlight foci of invasion, and outside the breast it is often used as a marker to support breast origin of metastatic tumors. Few studies have reported loss of CK7 in invasive breast carcinoma, however, association of CK7 loss with any histopathologic subtype has not been well documented in the literature. We stained a series of solid papillary carcinoma of the breast (SPC) and associated invasive ductal carcinoma (IDC) with CK7 to document that CK7 loss can occur in both SPC and associated IDC. Archived breast tumor tissue specimens with a diagnosis of SPC with IDC were identified from our Department of Pathology database from January 2019 to January 2023. Blocks with tumors were initially evaluated on Hematoxylin and Eosin (H&E) slides, and subsequently with CK7, synaptophysin, and chromogranin immunostains. The results of these immunohistochemical markers were tabulated in an Excel sheet. Expression of CK7 was entered as negative, marked loss of CK7 (weak positive staining in <1% of tumor), and positive (diffuse expression >1% to 100% of tumor cells). Out of 26 tumors of SPC, 15 showed negative to a marked loss of expression for CK7 in both in-situ and invasive components (57.7%), while 11 were diffusely positive (42.3%). Neuroendocrine differentiation was present in 57.7% of tumors of which 60% were CK7 negative. However, there was no significant association between neuroendocrine differentiation in SPC and associated IDC with CK7 loss ( P =1). In addition, histologic parameters, biomarkers expression, Ki-67 expression, and clinical follow-up were studied in detail.</p><p><strong>Conclusion: </strong>A significant proportion of solid papillary carcinoma of the breast and the associated invasive component can show loss of CK7.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"152-159"},"PeriodicalIF":1.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}