Applied Immunohistochemistry & Molecular Morphology最新文献

{"title":"Characterization of BCL-X L , MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer.","authors":"Tareq Saleh, Sofian Al Shboul, Heyam Awad, Mohammed El-Sadoni, Ahmad Alhesa, Elham Alsharaiah, Nisreen Abu Shahin, Moureq R Alotaibi, AbdelKader Battah, Bilal Azab","doi":"10.1097/PAI.0000000000001189","DOIUrl":"10.1097/PAI.0000000000001189","url":null,"abstract":"<p><p>The use of chemotherapy has improved the overall treatment of breast cancer, which is frequently administered in the form of neoadjuvant chemotherapy (NAC). Apoptosis is an established cell stress response to NAC in preclinical models; however, there is limited understanding of its role in clinical cancer, specifically, its contribution to favorable pathologic responses in breast cancer therapy. Here, we aimed to characterize the change in protein expression of 3 apoptosis-associated biomarkers, namely, BCL-X L , MCL-1, and BAX in breast cancer in response to NAC. For this, we utilized a set of 68 matched invasive breast cancer FFPE samples that were collected before (pre) and after (post) the exposure to NAC therapy that were characterized by incomplete pathologic response. Immunohistochemistry (IHC) analysis suggested that most of the samples show a decrease in the protein expression of all 3 markers following exposure to NAC as 90%, 69%, and 76% of the matched samples exhibited a decrease in expression for BCL-X L , MCL-1, and BAX, respectively. The median H-score of BCL-X L post-NAC was 150/300 compared with 225/300 pre-NAC ( P value <0.0001). The median H-score of MCL-1 declined from 200 pre-NAC to 160 post-NAC ( P value <0.0001). The median H-score of BAX protein expression decreased from 260 pre-NAC to 190 post-NAC ( P value <0.0001). There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"189-199"},"PeriodicalIF":1.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997939","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":"Programmed Cell Death Ligand 1 Expression in CD163 + Tumor-associated Macrophages in Cancer Gland Rupture Microenvironment.","authors":"Yilmaz Baş, Bayram Yilmaz, Serhat Furkan Acar, İbrahim Karadağ","doi":"10.1097/PAI.0000000000001186","DOIUrl":"10.1097/PAI.0000000000001186","url":null,"abstract":"<p><p>In this study, we aimed to examine the relationship among cancer gland rupture microenvironment, programmed cell death ligand 1 (PD-L1) expression in CD163 + tumor-associated macrophages (TAMs), and prognosis in colon adenocarcinoma. A total of 122 patients were diagnosed with colon adenocarcinoma between 2010 and 2019. PD-L1 + (clone 22C3) \"macrophage scores\" in the microenvironment of cancer gland rupture were calculated. The effects of these variables on prognosis were statistically analyzed. CD163 + TAMs were denser in the cancer gland rupture microenvironment. PD-L1 + TAMs were observed in the tumor periphery, and there was a significant difference between the rates of PD-L1 expression in TAMs and survival time (log-rank = 10.46, P = 0.015), clinical stage 2 ( P = 0.038), and primary tumor 3 and primary tumor 4 cases ( P = 0.004, P = 0.013). The risk of mortality was 4.070 times higher in patients with a PD-L1 expression rate of ≥1% in CD163 + TAMs. High PD-L1 expression in CD163 + TAMs is associated with poor overall survival. Therefore, blocking PD-L1 in CD163 + TAMs can be used as a target for immunotherapy.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"176-182"},"PeriodicalIF":1.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693271","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 Between miR-497-5p Expression With Clinicopathological Characteristics and Prognosis in Patients With Breast Cancer.","authors":"Zhiying Zhang, Ying Zhou, Shujing Liang","doi":"10.1097/PAI.0000000000001190","DOIUrl":"10.1097/PAI.0000000000001190","url":null,"abstract":"<p><p>Breast cancer (BC) comprises multiple biological and histologic properties. MicroRNAs show key functions in cancer prognosis. This paper explored the relationship between miR-497-5p with clinicopathological characteristics and prognosis in BC. Cancer tissues and normal adjacent tissues (NATs) were collected from 140 included patients with BC. The clinical baseline data, including age, tumor size, pathologic grade, clinical stage, modified Scraff-Bloom-Richardson grade, and lymph node metastasis, were recorded. miR-497-5p expression in cancer tissues and NAT was determined by reverse transcription-quantitative polymerase chain reaction. Patients with BC were followed up for 5 years to record their survival. Patients were divided into the miR-497-5p low expression and high expression groups to assess the correlation between miR-497-5p expression with clinicopathological characteristics and overall survival of patients. The role of miR-497-5p as an independent risk factor for death was further analyzed by a multivariate Cox regression model. miR-497-5p was downregulated in BC tissues than NAT. Tumor size, clinical stage, and lymph node metastasis showed significant differences among patients with high and low miR-497-5p expression levels. Patients with BC with low miR-497-5p expression presented decreased survival. Lowly-expressed miR-497-5p was an independent risk factor for death in patients. Collectively, cancer tissue miR-497-5p low expression increases the risk of death and serves as an independent risk factor for death in patients with BC.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"200-205"},"PeriodicalIF":1.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144378","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":"Diminution of Primary Cilia in the Stromal Cells at the Tumor-stromal Interface Correlates With an Aggressive Tumor Biology in the Urothelial Carcinoma of the Urinary Bladder.","authors":"Vamsi K Kapaganti, Suvendu Purkait, Prasant Nayak, Dipanwita Biswas, Rasheeda Mohamedali, Amit K Adhya, Suvradeep Mitra","doi":"10.1097/PAI.0000000000001187","DOIUrl":"10.1097/PAI.0000000000001187","url":null,"abstract":"<p><strong>Background and aims: </strong>Primary cilia (PC) are cellular organelles that regulate the cellular homeostasis. They are the seats of many oncogenic pathways and indirectly regulate the epithelial-mesenchymal transition (EMT) and extracellular matrix, both critical for the tumor microenvironment (TME). Though there are a few studies highlighting the alteration of PC in the tumor cells of various malignancies, none depict the PC in the stromal cells in the urothelial carcinoma of the urinary bladder (UC), the stromal cells being an essential component of TME. Therefore, we intend to evaluate the PC in the stromal cells at the tumor-stromal interface in UC.</p><p><strong>Methods: </strong>Immunohistochemistry for acetylated-α-tubulin (for PC), Ki67, E-cadherin, and SNAI1 was performed in 141 cases of UC and 5 normal controls, and primary cilium: nucleus (C:N) ratio was counted in the stromal cells at the tumor-stromal interface. The C:N ratio was correlated with various clinical and histopathological parameters.</p><p><strong>Results: </strong>The C:N ratio showed significant diminution from normal control (mean=0.75) to low-grade UC (mean=0.24) ( P =0.001) to high-grade UC (mean value=0.17) ( P =0.001). There was a significant diminution of the C:N ratio from the noninvasive to invasive UC ( P =0.025). The C:N ratio did not show any correlation with EMT although negatively correlated with the Ki67 index ( r =-0.32; P =0.001), and a higher ratio showed a trend with a higher recurrence-free survival ( P =0.07).</p><p><strong>Conclusions: </strong>The diminution of the PC in the stromal cells at the tumor-stromal interface is an early event and correlates with an aggressive tumor biology of UC.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"130-136"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906740","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":"Rapid Immunohistochemistry Based on Ultrasonic Thermal Steam Heating for Improvement of Intraoperative Diagnosis.","authors":"Guangyin Yu, Lili Tao, Mengying Liao, ChuQiang Huang, Cuimin Chen, Xiaomin Yin","doi":"10.1097/PAI.0000000000001178","DOIUrl":"10.1097/PAI.0000000000001178","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the role of rapid immunohistochemistry (RIHC) based on ultrasonic thermal steam heating in improving diagnostic accuracy of intraoperative frozen section diagnosis and to recommend RIHC antibody panels for pathologic differential diagnosis.</p><p><strong>Materials and methods: </strong>RIHC based on ultrasonic thermal steam heating was tested for intraoperative frozen diagnosis with difficulty in diagnosis, and all slides were reviewed and compared with the final diagnosis. Ninety-three cases of surgical specimens involving RIHC examination were studied. Discordance rates with paraffin immunohistochemistry were calculated.</p><p><strong>Results: </strong>In 93 cases where RIHC was performed, 85 cases (91%) were proven to be helpful for the diagnosis. A total of 58 antibodies were used for RIHC 276 times, of which 19 antibodies were not effective 25 times. Fifteen RIHC antibody panels are recommended based on staining stability and utilization frequency.</p><p><strong>Conclusion: </strong>After improving the staining method, ultrasonic thermal steam heating RIHC is practical, convenient, and cost-effective, making it suitable for use in any pathology department with routine immunohistochemistry reagents. It plays an important auxiliary role in improving the accuracy of intraoperative rapid pathologic diagnosis.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"137-142"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808279","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":"Immunohistochemical Expression of CK14 and Bcl-2 in Odontogenic Keratocyst and Its Variants.","authors":"Reshma Poothakulath Krishnan, Deepak Pandiar, Sandra Sagar","doi":"10.1097/PAI.0000000000001182","DOIUrl":"10.1097/PAI.0000000000001182","url":null,"abstract":"<p><p>Odontogenic keratocysts (OKCs) are aggressive cystic jaw lesions with a high epithelial turnover rate and increased propensity for recurrence. Sometimes, the characteristic histopathological features of OKCs are either completely lost or seen focally due to previous marsupialization or inflammation. This research aimed to determine whether specific patterns of CK14 and Bcl-2 staining could assist in diagnosing OKCs with altered epithelial features and provide clues in elucidating their aggressive nature. CK14 expression was restricted to basal and suprabasal layers near satellite cysts and in areas showing subepithelial split. The entire epithelial lining showed CK14 expression in areas of inflammation and after marsupialization. The typical basal/suprabasal staining of Bcl-2 was lost in areas of inflammation and intensity is decreased in OKCs after marsupialization. These new findings could offer a hint into the biological nature and pathogenesis of OKCs. Because of its therapeutic consequences and high recurrence rate, proper recognition and diagnosis are essential for treatment planning.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"151-156"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038058","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":"Immunohistochemical Expression of Epidermal Growth Factor Receptor (EGFR) in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.","authors":"Razia Aamir, Fozia Rauf, Fatima Iqbal, Sarah Yousuf, Asif Rehman, Ahmareen K Sheikh, Sardar Muhammad","doi":"10.1097/PAI.0000000000001185","DOIUrl":"10.1097/PAI.0000000000001185","url":null,"abstract":"<p><strong>Background: </strong>Increased epidermal growth factor receptor (EGFR) expression has been implicated in several tumors and is associated with increased tumor advancement as well as a potential drug target. The objective of the study was to compare the immunohistochemical expression of EGFR in oral squamous cell carcinoma (OSCC) with oral potentially malignant disorders (OPMDs) and their demographic and pathologic parameters.</p><p><strong>Methods: </strong>This study was a comparative cross-sectional analytical study. It was conducted at the Department of Pathology, Peshawar Medical College, Riphah International University, Islamabad, Pakistan, from March 2021 to February 2022. The sample size was calculated through G Power. Thirty-eight cases of oral squamous cell carcinoma and 38 cases of oral potentially malignant disorders (OPMDs) were included in the study. Statistical analysis was performed using the Statistical Package for Social Sciences version 20.0. χ 2 tests and Fisher exact tests were applied to compare categorical variables.</p><p><strong>Results: </strong>Mean age of OSCC was 61.6±13.9, with age range from 26 to 90 years. The male-to-female ratio for OSCC was 2.16:1. Buccal mucosa was the most common site involved (34.2%). The most common histologic type was well-differentiated OSCC (71.05%) followed by poorly differentiated (16%) and moderately differentiated (13.15%). The mean age of OPMDs cases was 59.16 ± 10.81 with a male-to-female ratio of 1:1.2. Buccal mucosa was the common site (55.3%), followed by the tongue (18.4%). The OPMDs with dysplasia were 55.2%, and without dysplasia were 44.8%. A total of 55.7% of cases of OSCC showed positive EGFR expression as compared with 36.9% OPMDs cases. A higher number of low-grade OSCC cases showed increased EGFR positivity (59.3%) as compared with high grade (45.45%). EGFR positivity in OPMD cases without dysplasia was 41.2% as compared with cases with dysplasia (33.3%). The EGFR expression in OPMD cases was higher in the ≤50 age group ( P =0.001) and in females ( P =0.032), which was statistically significant.</p><p><strong>Conclusions: </strong>EGFR expression by Immunohistochemistry may not be a helpful prognostic marker to determine the risk of OPMDs progressing to higher grades of dysplasia or invasive cancer. However, further studies relating this tumor marker to stage, lymph node metastasis, hematogenous metastasis, survival outcomes, and treatment response may give useful information regarding the utility of this marker.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"157-162"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546827","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":"Diagnostic Value of CD34 and CD117 Immunohistochemistry and Megakaryocyte Morphology in Myelodysplastic Syndromes: A Retrospective Case-control Study.","authors":"Ying Zhang, Wenhua Li, Yuanchu Liang, Youli Liu, Wenbin Dai","doi":"10.1097/PAI.0000000000001177","DOIUrl":"10.1097/PAI.0000000000001177","url":null,"abstract":"<p><p>This study evaluated the diagnostic value of CD34 and CD117 immunohistochemistry(IHC) and megakaryocyte morphology in Myelodysplastic syndromes (MDS). In this study, CD34-positive individual cells (Type I) and small clusters (Type II) were observed in most cases (91.2%). Type II CD34-positive was seen in 24 (49%) MDS cases, and positive percentage was higher than in acute myelogenous leukemia (AML) or aplastic anemia (AA). Type II CD117-positive were observed in 44 (89.8%) MDS cases and Type I were observed in 5 (10.2%) MDS. Type II CD117-positive percentage was higher than in AML or AA. Megakaryocyte counts were normal or increased in most MDS cases except one. Although megakaryocyte counts of AML and AA were predominantly decreased, Most MDS patients (81.6%) had abnormal megakaryocyte, whereas almost none of megakaryocyte abnormality was found in AML and AA. In conclusion, combined detection of CD34 and CD117 and observation of megakaryocyte count and morphology are useful for the diagnosis of MDS.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"125-129"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488835","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":"Mast Cell Concentrations in Pancreatic Disease Processes.","authors":"Lindsey Wynn, Victoria Hodges, Sheila Criswell","doi":"10.1097/PAI.0000000000001174","DOIUrl":"10.1097/PAI.0000000000001174","url":null,"abstract":"<p><p>Mast cells enumeration has been performed using various histologic staining techniques with the goal of elucidating the influence mast cells exert on pathologic processes. In this study, 77 human pancreatic tissues evidencing morphologically normal pancreas, benign fibrotic changes, endocrine tumors, and adenocarcinoma were evaluated using Wright stain and immunohistochemistry markers for tryptase and CD117. Mast cell counts were similar with tryptase and CD117 but were both significantly higher than counts obtained with the Wright stain. Furthermore, all analyses demonstrated that endocrine tumors and morphologically normal pancreatic tissues had significantly lower mast cell counts as compared with benign fibrosis and adenocarcinoma suggesting that the highly fibrotic nature of both pancreatitis and adenocarcinoma are related to increased mast cell concentrations.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":" ","pages":"163-168"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138048277","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":"Ki-67 Testing in Breast Cancer: Assessing Variability With Scoring Methods and Specimen Types and the Potential Subsequent Impact on Therapy Eligibility.","authors":"Therese Bocklage, Virgilius Cornea, Caylin Hickey, Justin Miller, Jessica Moss, Mara Chambers, S Emily Bachert","doi":"10.1097/PAI.0000000000001188","DOIUrl":"10.1097/PAI.0000000000001188","url":null,"abstract":"<p><p>Abemaciclib was originally FDA approved for patients with ER-positive/HER2-negative breast cancer with Ki-67 expression ≥20%. However, there were no guidelines provided on which specimen to test or which scoring method to use. We performed a comprehensive study evaluating the variation in Ki-67 expression in breast specimens from 50 consecutive patients who could have been eligible for abemaciclib therapy. Three pathologists with breast expertise each performed a blinded review with 3 different manual scoring methods [estimated (EST), unweighted (UNW), and weighted (WT) (WT recommended by the International Ki-67 in Breast Cancer Working Group)]. Quantitative image analysis (QIA) using the HALO platform was also performed. Three different specimen types [core needle biopsy (CNB) (n=63), resection (RES) (n=52), and axillary lymph node metastasis (ALN) (n=50)] were evaluated for each patient. The average Ki-67 for all specimens was 14.68% for EST, 14.46% for UNW, 14.15% for WT, and 11.15% for QIA. For the manual methods, the range between the lowest and highest Ki-67 for each specimen between the 3 pathologists was 8.44 for EST, 5.94 for WT, and 5.93 for UNW. The WT method limited interobserver variability with ICC1=0.959 (EST ICC1=0.922 and UNW=0.949). Using the aforementioned cutoff of Ki-67 ≥20% versus <20% to determine treatment eligibility, the averaged EST method yields 20 of 50 patients (40%) who would have been treatment-eligible, versus 15 (30%) for the UNW, 17 (34%) for the WT, and 12 (24%) for the QIA. There was no statistically significant difference in Ki-67 among the 3 specimen types. The average Ki-67 difference was 4.36 for CNB vs RES, 6.95 for CNB versus ALN, and RES versus ALN (P=0.93, 0.99, and 0.94, respectively). Our study concludes that further refinement in Ki-67 scoring is advisable to reduce clinically significant variation.</p>","PeriodicalId":48952,"journal":{"name":"Applied Immunohistochemistry & Molecular Morphology","volume":"32 3","pages":"119-124"},"PeriodicalIF":1.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050770","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}