American Journal of Pathology最新文献

{"title":"Histopathologic Differential Diagnosis and Estrogen Receptor/Progesterone Receptor Immunohistochemical Evaluation of Breast Carcinoma Using a Deep Learning-Based Artificial Intelligence Architecture.","authors":"Zhi Han, Shihong Ding, Baichen Liu, Yandong Tang, Xueshan Qiu, Enhua Wang, Huanyu Zhao","doi":"10.1016/j.ajpath.2024.08.011","DOIUrl":"10.1016/j.ajpath.2024.08.011","url":null,"abstract":"<p><p>In breast carcinoma, invasive ductal carcinoma (IDC) is the most common histopathologic subtype, and ductal carcinoma in situ (DCIS) is a precursor of IDC. They are often concomitant. The immunohistochemical staining of estrogen receptor (ER)/progesterone receptor (PR) in IDC/DCIS on whole slide histopathologic images (WSIs) can predict the prognosis of patients. However, the interobserver variability among pathologists in reading WSIs is inevitable. Thus, artificial intelligence (AI) technology is crucial. Herein, IDC/DCIS detection was conducted by a deep learning approach, including faster region-based convolutional neural network (Faster R-CNN), RetinaNet, single-shot multibox detector 300 (SSD300), you only look once (YOLO) v3, YOLOv5, YOLOv7, YOLOv8, and Swin transformer. Their performance was estimated by mean average precision (mAP) values. Cell recognition and counting were performed using AI technology to evaluate the intensity and proportion of ER/PR-immunostained cancer cells in IDC/DCIS. A three-round ring study (RS) was conducted to assess WSIs. A database for modelling the underlying probability distribution of a data set with labels was established. YOLOv8 exhibits the highest detection performance with an mAP at 0.5 of 0.944 and an mAP at 0.5 to 0.95 of 0.790. With the assistance of YOLOv8, the scoring concordance across all pathologists was boosted to excellent in RS3 (0.970) from moderate in RS1 (0.724) and good in RS2 (0.812). Deep learning detection can be applied in the clinicopathologic field. To facilitate the histopathologic diagnosis of IDC/DCIS and immunostaining scoring of ER/PR, a novel AI architecture and well-organized data set were developed.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144953","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":"Tumor-Derived Immunoglobulin-Like Transcript 4 Promotes Postoperative Relapse via Inducing Vasculogenic Mimicry through MAPK/ERK Signaling in Hepatocellular Carcinoma.","authors":"Jiayan Li, Xiaofeng Ding, Wanping Yan, Ke Liu, Wei Ye, Huali Wang, Lili Wang","doi":"10.1016/j.ajpath.2024.08.010","DOIUrl":"10.1016/j.ajpath.2024.08.010","url":null,"abstract":"<p><p>Conventional anti-angiogenesis drugs are usually unsatisfactory in hepatocellular carcinoma (HCC) treatment. Therefore, it is urgent to find new precise therapeutic targets and to further develop more effective drugs for the treatment of HCC. Vasculogenic mimicry (VM) is different from classic endothelium-dependent angiogenesis and is associated with a poor prognosis in patients with malignant tumor. However, the mechanism underlying VM is complex and not fully defined. Ig-like transcript (ILT)-4, as a negative regulator of immune response, was recently found to be expressed in many solid tumors. However, whether and how ILT4 regulates VM remains unclear. This study found VM enriched in HCC tissues, especially in tissues from patients with relapse within 5 years after surgery. Similarly, ILT4 expression level was also higher in HCC tissues from patients with relapse within 5 years after surgery. Linear regression analysis revealed a positive correlation between the expression of ILT4 and VM density. Furthermore, Overexpression/knockdown of ILT4 expression upregulated/down-regulated VM-related marker, three-dimensional tube formation, and migration and invasion in HCC cell lines in vitro. In mechanistic studies, ILT4 promoted VM formation via MAPK/ERK signaling. This study provides a rationale and mechanism for ILT4-mediated postoperative relapse via inducing VM in HCC. The related molecular pathways can be used as novel therapeutic targets for the inhibition of HCC angiogenesis and postoperative relapse.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131618","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 Transcriptomics Reveals the Transcriptomic Signatures in a Mouse Model of Pediatric Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Lu Jiang, Qing-Yang Xu, Yong-Chang Zhou, Juan Xu, Jian-Gao Fan","doi":"10.1016/j.ajpath.2024.08.008","DOIUrl":"10.1016/j.ajpath.2024.08.008","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, we developed a mouse model of pediatric MASH and characterized the hepatic transcriptomic profile using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl₄) from the age of 3 to 8 weeks. After 5 weeks of feeding, WD + CCl₄-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl₄ induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Through spatial transcriptomics analysis of liver tissues, we identified that cluster 0 in the mouse from the WD + CCl₄ group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl₄ group. These findings suggest that our mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118820","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":"Glucose-Regulated Protein 78, via Releasing β-Catenin from Adherens Junctions, Facilitates Its Interaction with STAT3 in Mediating Retinal Neovascularization.","authors":"Raj Kumar, Gadiparthi N Rao","doi":"10.1016/j.ajpath.2024.08.005","DOIUrl":"10.1016/j.ajpath.2024.08.005","url":null,"abstract":"<p><p>Retinopathy due to neovascularization is one of the major causes of vision loss. To understand the mechanisms underlying retinal neovascularization, using the oxygen-induced retinopathy (OIR) model, we performed two-dimensional gel matrix-assisted laser desorption/ionization time-of-flight/time-of-flight analysis of normoxic and 24-hour post-OIR mice pups' retinas. Two-dimensional gel analysis revealed that glucose-regulated protein 78 (GRP78) is one of the several molecules induced by OIR in the retinal endothelial cells (ECs). Vascular endothelial growth factor A (VEGFA) also induced GRP78 expression independent of endoplasmic reticulum stress response in human retinal microvascular endothelial cells, and depletion of its levels reduced VEGFA-induced EC angiogenic responses. Consistent with these observations, EC-specific deletion of GRP78 inhibited OIR-induced retinal neovascularization. In exploring the mechanisms, we found that GRP78 binds with vascular endothelial-cadherin and releases adherens junction- but not Wnt-mediated β-catenin and that β-catenin, in turn, via interacting with STAT3, triggers cyclin D1 expression. Furthermore, depletion of β-catenin or cyclin D1 levels negated VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. EC-specific deletion of GRP78 also suppressed OIR-induced vascular leakage. In elucidating the upstream signaling, we found that activating transcription factor 6 mediates GRP78 induction in the modulation of VEGFA-induced EC angiogenic responses and OIR-induced retinal neovascularization. Together, these observations reveal that GRP78, independent of its response to endoplasmic reticulum stress, is involved in mediating EC angiogenic responses by VEGFA and retinal neovascularization by OIR. In view of these findings, it appears that GRP78 could be a desirable target for drug development against diabetic retinopathy.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118817","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":"Lipopolysaccharide Triggers Luminal Acidification to Promote Defense Against Bacterial Infection in Vaginal Epithelium.","authors":"Yi-Lin Zhang, Yu-Yun Zhou, Li-Jiao Ke, Jie Sheng, Dan-Yang Zou, Ting-Ting Tang, Zi-Ying Yang, Lei Chen, Xiao-Chun Hou, Jie Zhu, Jian-Bang Xu, Yun-Xin Zhu, Wen-Liang Zhou","doi":"10.1016/j.ajpath.2024.08.009","DOIUrl":"10.1016/j.ajpath.2024.08.009","url":null,"abstract":"<p><p>The vaginal epithelium plays pivotal roles in host defense against pathogen invasion, contributing to the maintenance of an acidic microenvironment within the vaginal lumen through the activity of acid-base transport proteins. However, the precise defense mechanisms of the vaginal epithelium after a bacterial infection remain incompletely understood. This study showed that bacterial lipopolysaccharide (LPS) potentiated net proton efflux by up-regulating the expression of Na⁺-H⁺ exchanger 1 (NHE1) without affecting other acid-base transport proteins in vaginal epithelial cells. Pharmacologic inhibition or genetic knockdown of Toll-like receptor-4 and the extracellular signal-regulated protein kinase signaling pathway effectively counteracted the up-regulation of NHE1 and the enhanced proton efflux triggered by LPS in vaginal epithelial cells. In vivo studies revealed that LPS administration led to luminal acidification through the up-regulation of NHE1 expression in the rat vagina. Moreover, inhibition of NHE exhibited an impaired defense against acute bacterial infection in the rat vagina. These findings collectively indicate the active involvement of vaginal epithelial cells in facilitating luminal acidification during acute bacterial infection, offering potential insights into the treatment of bacterial vaginosis.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118818","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":"Methyltransferase-Like 3-Driven N6-Methyladenosine Modification of RBPJ Promotes Vascular Remodeling in Pulmonary Hypertension.","authors":"Qiang Du, Chun Zhang, Tianyu Qu, Xiao Zhou, Yingying Liu, Zhixuan Chen, Zilin Shen, Pingsheng Chen, Ruifeng Zhang","doi":"10.1016/j.ajpath.2024.08.007","DOIUrl":"10.1016/j.ajpath.2024.08.007","url":null,"abstract":"<p><p>The dysregulation of N6-methyladenosine (m6A) RNA modification is widely recognized for its crucial roles in various diseases, including pulmonary hypertension (PH). Prior studies have highlighted the significant role of methyltransferase-like 3 (METTL3) in the pathogenesis of PH. Nevertheless, the potential and underlying mechanisms of METTL3 and its inhibitors as targets for PH treatment require further elucidation. In this study, we observed increased levels of METTL3 in various rodent models of PH. In vitro studies revealed that METTL3 silencing or treatment with STM2457, a specific METTL3 inhibitor, attenuated the proliferation and migration of pulmonary artery smooth muscle cells stimulated by platelet-derived growth factor-BB or hypoxia. Moreover, in vivo experiments using adeno-associated virus 9-mediated METTL3 silencing or STM2457 inhibition demonstrated improvement in SU5416/hypoxia-induced PH in mice. Additionally, m6A RNA immunoprecipitation analysis identified RBPJ as a gene regulated by METTL3 in rodent models of PH. Loss-of-function studies showed that silencing RBPJ could attenuate the changes in the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB or hypoxia. Further studies indicated that METTL3 and YTHDF1 regulate RBPJ mRNA expression in an m6A-dependent manner. These findings indicated that targeting METTL3 may be a promising therapeutic strategy for treating PH, and modulation of RBPJ could offer a potential intervention mechanism.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118819","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":"A Deep Learning Approach for the Identification of the Molecular Subtypes of Pancreatic Ductal Adenocarcinoma Based on Whole Slide Pathology Images.","authors":"Pouya Ahmadvand, Hossein Farahani, David Farnell, Amirali Darbandsari, James Topham, Joanna Karasinska, Jessica Nelson, Julia Naso, Steven J M Jones, Daniel Renouf, David F Schaeffer, Ali Bashashati","doi":"10.1016/j.ajpath.2024.08.006","DOIUrl":"10.1016/j.ajpath.2024.08.006","url":null,"abstract":"<p><p>Delayed diagnosis and treatment resistance make pancreatic ductal adenocarcinoma (PDAC) mortality rates high. Identifying molecular subtypes can improve treatment, but current methods are costly and time-consuming. In this study, deep learning models were used to identify histologic features that classify PDAC molecular subtypes based on routine hematoxylin-eosin-stained histopathologic slides. A total of 97 histopathology slides associated with resectable PDAC from The Cancer Genome Atlas project were used to train a deep learning model and tested the performance on 44 needle biopsy material (110 slides) from a local annotated patient cohort. The model achieved balanced accuracy of 96.19% and 83.03% in identifying the classical and basal subtypes of PDAC in The Cancer Genome Atlas and the local cohort, respectively. This study provides a promising method to cost-effectively and rapidly classifying PDAC molecular subtypes based on routine hematoxylin-eosin-stained slides, potentially leading to more effective clinical management of this disease.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118816","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":"Sex Differences in Impacts of Early Gestational and Peri-Adolescent Ozone Exposure on Lung Development in Rats","authors":"Janice A. Dye ,&nbsp;Helen H. Nguyen ,&nbsp;Erica J. Stewart ,&nbsp;Mette C.J. Schladweiler ,&nbsp;Colette N. Miller","doi":"10.1016/j.ajpath.2024.05.013","DOIUrl":"10.1016/j.ajpath.2024.05.013","url":null,"abstract":"<div><p>Air pollution exposure during pregnancy may affect fetal growth. Fetal growth restriction (FGR) is associated with reduced lung function in children that can persist into adulthood. Using an established model of asymmetrical FGR in Long-Evans rats, this study investigated sex differences in effects of early life ozone exposure on lung development and maturation. Adverse health effects for i) gestational exposure (with impacts on primary alveolarization), ii) peri-adolescent exposure (with impacts on secondary alveolarization), and iii) cumulative exposure across both periods were evaluated. Notably, female offspring were most affected by gestational ozone exposure, likely because of impaired angiogenesis and corresponding decreases in primary alveolarization. Females had diminished lung capacity, fewer mature alveoli, and medial hypertrophy of small and large pulmonary arteries. Males, especially FGR-prone offspring, were more affected by peri-adolescent ozone exposure. Males had increased ductal areas, likely due to disrupted secondary alveolarization. Altered lung development may increase risk of developing diseases, such as pulmonary arterial hypertension or chronic obstructive pulmonary disease. Pulmonary arterial hypertension disproportionately affects women. In the United States, chronic obstructive pulmonary disease prevalence is increasing, especially in women; and prevalence for both men and women is highest in urbanized areas. This investigation underlines the importance of evaluating results separately by sex, and provides biologic plausibility for later consequences of early-life exposure to ozone, a ubiquitous urban air pollutant.</p></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Pages 1636-1663"},"PeriodicalIF":4.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054695","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":"Retraction notice to “Pharmacologic Blockade of 5-Lipoxygenase Improves the Amyloidotic Phenotype of an Alzheimer's Disease Transgenic Mouse Model: Involvement of γ-Secretase” [Am J Pathol 178 (2011) 1762–1769]","authors":"Jin Chu,&nbsp;Domenico Praticò","doi":"10.1016/j.ajpath.2024.07.006","DOIUrl":"10.1016/j.ajpath.2024.07.006","url":null,"abstract":"","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 9","pages":"Page 1799"},"PeriodicalIF":4.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002944024002487/pdfft?md5=aa082668392dc040e86274c51430baca&pid=1-s2.0-S0002944024002487-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054694","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":"Hepatocyte-Specific Casein Kinase 1 Epsilon Ablation Ameliorates Metabolic Dysfunction–Associated Steatohepatitis by Up-Regulating Tumor Necrosis Factor Receptor–Associated Factor 3 in Mice","authors":"Mwense Leya ,&nbsp;Hyuneui Jeong ,&nbsp;Daram Yang ,&nbsp;Tien Huyen Ton Nu Bao ,&nbsp;Prakash Raj Pandeya ,&nbsp;Sang-Ik Oh ,&nbsp;Yoon-Seok Roh ,&nbsp;Jong-Won Kim ,&nbsp;Bumseok Kim","doi":"10.1016/j.ajpath.2024.08.003","DOIUrl":"10.1016/j.ajpath.2024.08.003","url":null,"abstract":"<div><div>Casein kinase 1 epsilon (CK1ε), a member of the serine/threonine protein kinase family, phosphorylates a broad range of substrates. However, its role in the development of chronic liver diseases remains elusive. This study aimed to investigate the role of CK1ε in the development and progression of metabolic dysfunction–associated steatohepatitis (MASH). Hepatocyte-specific CK1ε knockout (CK1ε^ΔHEP) mice were generated by crossbreeding mice with floxed CK1ε alleles (CK1ε^fl/fl) and <em>Cre-</em>expressing albumin mice. Mice were fed either a Western diet (WD) or a methionine- and choline-deficient diet to induce MASH. CK1ε^ΔHEP was associated with a decreased severity of WD- or methionine- and choline-deficient diet–induced MASH, as confirmed by reduced incidence of hepatic lesions and significantly lower levels of alanine aminotransferase, aspartate aminotransferase, and proinflammatory cytokine tumor necrosis factor (TNF)-α. CK1ε^ΔHEP WD-fed mice exhibited significant amelioration of total cholesterol, triglycerides, and <em>de novo</em> lipogenic genes, indicating that CK1ε could influence lipid metabolism. CK1ε^ΔHEP WD-fed mice showed significantly down-regulated TNF receptor–associated factor (TRAF) 3, phosphorylated (p) transforming growth factor-β–activated kinase 1, p–TRAF-associated NF-κB activator (TANK)-binding kinase 1 (TBK1), and p-AKT levels, thereby affecting downstream mitogen-activated protein kinase signaling, indicating a potential mechanism for the observed rescue. Finally, pharmacologic inhibition of CK1ε with PF670462 improved palmitic acid–induced steatohepatitis <em>in vitro</em> and attenuated WD-induced metabolic profile <em>in vivo</em>. In conclusion, CK1ε up-regulates TNF receptor–associated factor 3, which, in turn, causes transforming growth factor-β–activated kinase 1–dependent signaling, amplifies downstream mitogen-activated protein kinase signaling, modifies p-c-Jun levels, and exacerbates inflammation, all of which are factors in WD-induced metabolic dysfunction–associated steatotic liver disease.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"194 11","pages":"Pages 2106-2127"},"PeriodicalIF":4.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046120","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}