Molecular Oncology最新文献

{"title":"Simultaneous detection of eight cancer types using a multiplex droplet digital PCR assay.","authors":"Isabelle Neefs, Nele De Meulenaere, Thomas Vanpoucke, Janah Vandenhoeck, Dieter Peeters, Marc Peeters, Guy Van Camp, Ken Op de Beeck","doi":"10.1002/1878-0261.13708","DOIUrl":"10.1002/1878-0261.13708","url":null,"abstract":"<p><p>DNA methylation biomarkers have emerged as promising tools for cancer detection. Common methylation patterns across tumor types allow multi-cancer detection. Droplet digital PCR (ddPCR) has gained considerable attention for methylation detection. However, multi-cancer detection using multiple targets in ddPCR has never been performed before. Therefore, we developed a multiplex ddPCR assay for multi-cancer detection. Based on previous data analyses using The Cancer Genome Atlas (TCGA), we selected differentially methylated targets for eight frequent tumor types (lung, breast, colorectal, prostate, pancreatic, head and neck, liver, and esophageal cancer). Three targets were validated using ddPCR in 103 tumor and 109 normal adjacent fresh frozen samples. Two distinct ddPCR assays were successfully developed. Output data from both assays is combined to obtain a read-out from the three targets together. Our overall ddPCR assay has a cross-validated area under the curve (cvAUC) of 0.948. Performance between distinct cancer types varies, with sensitivities ranging from 53.8% to 100% and specificities ranging from 80% to 100%. Compared to previously published single-target parameters, we show that combining targets can drastically increase sensitivity and specificity, while lowering DNA input. In conclusion, we are the first to report a multi-cancer methylation ddPCR assay, which allows for highly accurate tumor predictions.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"188-203"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140469","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":"ENL mutation and AML: a new model that reveals oncogenic condensate's function in leukemogenesis.","authors":"Zhong Fan, Yanan Jiang, Xiaotian Zhang","doi":"10.1002/1878-0261.13731","DOIUrl":"10.1002/1878-0261.13731","url":null,"abstract":"<p><p>Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y et al. (2023) Nat Chem Biol 19, 1223-1234; Chandra B et al. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation \"reader\" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations drive tumorigenesis and whether it is correlated with their condensate formation property. Liu et al. now show, using a conditional knock-in mouse model, that ENL YEATS domain mutation is a bona fide oncogenic driver for AML. This mutant ENL forms condensates in hematopoietic stem/progenitor cells at the genomic loci of key leukemogenic genes, including Meis1 and Hoxa cluster genes, and disrupting condensate formation via mutagenesis impairs its chromatin and oncogenic function. Furthermore, they show that small-molecule inhibition of the acetyl-binding activity displaces ENL mutant condensates from oncogenic target loci, and this inhibitor significantly impairs the onset and progression of AML driven by mutant ENL in vivo.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"7-10"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350334","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":"RETRACTION: Long Noncoding RNA ZNF667-AS1 Reduces Tumor Invasion and Metastasis in Cervical Cancer by Counteracting Microrna-93-3p-Dependent PEG3 Downregulation.","authors":"","doi":"10.1002/1878-0261.13777","DOIUrl":"10.1002/1878-0261.13777","url":null,"abstract":"<p><strong>Retraction: </strong>Y.-J. Li, Z. Yang, Y.-Y. Wang, and Y. Wang, \"Long Noncoding RNA ZNF667-AS1 Reduces Tumor Invasion and Metastasis in Cervical Cancer by Counteracting Microrna-93-3p-Dependent PEG3 Downregulation,\" Molecular Oncology 13, no. 11 (2019): 2375-2392, https://doi.org/10.1002/1878-0261.12565. The above article, published online on 17 October 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin Ryan; FEBS Press; and John Wiley & Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed implausible Western blot data (Figures 5B, L, G and Q), and an image duplication in Figure 6B. The authors' failure to respond with the original raw data has led the editors to lose confidence in the data presented. Therefore, the editors consider the conclusions substantially compromised and are retracting the paper.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"263"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739908","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":"APOBEC3C-mediated NF-κB activation enhances clear cell renal cell carcinoma progression.","authors":"Nora Hase, Danny Misiak, Helge Taubert, Stefan Hüttelmaier, Michael Gekle, Marcel Köhn","doi":"10.1002/1878-0261.13721","DOIUrl":"10.1002/1878-0261.13721","url":null,"abstract":"<p><p>Renowned as the predominant form of kidney cancer, clear cell renal cell carcinoma (ccRCC) exhibits susceptibility to immunotherapies due to its specific expression profile as well as notable immune cell infiltration. Despite this, effectively treating metastatic ccRCC remains a significant challenge, necessitating a more profound comprehension of the underlying molecular mechanisms governing its progression. Here, we unveil that the enhanced expression of the RNA-binding protein DNA dC → dU-editing enzyme APOBEC-3C (APOBEC3C; also known as A3C) in ccRCC tissue and ccRCC-derived cell lines serves as a catalyst for tumor growth by amplifying nuclear factor-kappa B (NF-κB) activity. By employing RNA-sequencing and cell-based assays in ccRCC-derived cell lines, we determined that A3C is a stress-responsive factor and crucial for cell survival. Furthermore, we identified that A3C binds and potentially stabilizes messenger RNAs (mRNAs) encoding positive regulators of the NF-κB pathway. Upon A3C depletion, essential subunits of the NF-κB family are abnormally restrained in the cytoplasm, leading to deregulation of NF-κB target genes. Our study illuminates the pivotal role of A3C in promoting ccRCC tumor development, positioning it as a prospective target for future therapeutic strategies.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"114-132"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056096","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":"Nongenetic evolution of the tumor: from challenges to new therapeutic opportunities.","authors":"Elisa Oricchio","doi":"10.1002/1878-0261.13753","DOIUrl":"10.1002/1878-0261.13753","url":null,"abstract":"<p><p>The ability of cancer cells to change and adapt poses a critical challenge to identifying curative solutions. Tumor evolution has been extensively studied from a genetic perspective, to guide clinicians in selecting the most appropriate therapeutic option based on a patient's mutational profile. However, several studies reported that tumors can evolve toward more aggressive stages or become resistant to therapies without changing their genetic makeup. Indeed, several cell-intrinsic and cell-extrinsic mechanisms contribute to tumor evolution. In this viewpoint, I focus on how chromatin, epigenetic, and transcriptional changes contribute to tumor evolution, allowing cancer cells to transition to different cell states and bypass response to therapies. Although tumor nongenetic evolution is harder to trace and predict, understanding its principles might open new therapeutic opportunities.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"3-6"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470167","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":"Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway.","authors":"Adrish Sen, Salmaan Khan, Stefano Rossetti, Aaron Broege, Ian MacNeil, Ann DeLaForest, Jhomary Molden, Laura Davis, Charles Iversrud, Megan Seibel, Ross Kopher, Stephen Schulz, Lance Laing","doi":"10.1002/1878-0261.13703","DOIUrl":"10.1002/1878-0261.13703","url":null,"abstract":"<p><p>Metastatic castration-resistant prostate cancer (mCRPC) is characterized by loss of androgen receptor (AR) sensitivity and oncogenic activation of the PI3K/AKT/mTOR (PAM) pathway. Loss of the PI3K regulator PTEN is frequent during prostate cancer (PC) initiation, progression, and therapeutic resistance. Co-targeting the PAM/AR pathways is a promising mCRPC treatment strategy but is hampered by reciprocal negative feedback inhibition or feedback relief. Most PAM inhibitors selectively spare (or weakly inhibit) one or more key nodes of the PAM pathway, potentiating drug resistance depending on the PAM pathway mutation status of patients. We posited that gedatolisib, a uniformly potent inhibitor of all class I PI3K isoforms, as well as mTORC1 and mTORC2, would be more effective than inhibitors targeting single PAM pathway nodes in PC cells. Using a combination of functional and metabolic assays, we evaluated a panel of PC cell lines with different PTEN/PIK3CA status for their sensitivity to multi-node PAM inhibitors (PI3K/mTOR: gedatolisib, samotolisib) and single-node PAM inhibitors (PI3Kα: alpelisib; AKT: capivasertib; mTOR: everolimus). Gedatolisib induced anti-proliferative and cytotoxic effects with greater potency and efficacy relative to the other PAM inhibitors, independent of PTEN/PIK3CA status. The superior effects of gedatolisib were likely associated with more effective inhibition of critical PAM-controlled cell functions, including cell cycle, survival, protein synthesis, oxygen consumption rate, and glycolysis. Our results indicate that potent and simultaneous blockade of all class I PI3K isoforms, mTORC1, and mTORC2 could circumvent PTEN-dependent resistance. Gedatolisib, as a single agent and in combination with other therapies, reported promising preliminary efficacy and safety in various solid tumor types. Gedatolisib is currently being evaluated in a Phase 1/2 clinical trial in combination with darolutamide in patients with mCRPC previously treated with an AR inhibitor, and in a Phase 3 clinical trial in combination with palbociclib and fulvestrant in patients with HR+/HER2- advanced breast cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"225-247"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875292","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":"Dynamic methylation and expression of alternative promoters for oestrogen receptor alpha in cell line models of fulvestrant resistance.","authors":"Juliane Albrecht, Mirjam Müller, Völundur Hafstað, Kamila Kaminska, Johan Vallon-Christersson, Gabriella Honeth, Helena Persson","doi":"10.1002/1878-0261.13713","DOIUrl":"10.1002/1878-0261.13713","url":null,"abstract":"<p><p>Oestrogen receptor alpha (ER; gene symbol ESR1) is the most important prognostic and treatment-predictive biomarker in breast cancer. Drugs targeting oestrogen and ER for endocrine therapy of breast cancer include aromatase inhibitors, the selective ER modulator tamoxifen and the selective ER degrader fulvestrant. Tumours can develop resistance to endocrine therapy through several mechanisms, which is often linked to altered expression of ER. To investigate the role of promoter methylation in the regulation of ESR1 expression, we used bisulfite sequencing to measure methylation at CpG sites in alternative ER promoter regions for six cell line models of fulvestrant resistance. Both CpG methylation and expression of alternative first exons changed dynamically, with striking differences between cell lines that had stable or unstable resistance upon fulvestrant withdrawal. Methylation at some CpG sites was strongly negatively correlated with expression of specific first exons. In a breast tumour cohort, higher relative expression of upstream alternative first exons was associated with worse prognosis in post-menopausal women with ER-positive tumours who received endocrine therapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"204-224"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897827","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":"RETRACTION: Frequent Alterations of LOH11CR2A, PIG8 and CHEK1 Genes at Chromosomal 11q24.1-24.2 Region in Breast Carcinoma: Clinical and Prognostic Implications.","authors":"","doi":"10.1002/1878-0261.13774","DOIUrl":"10.1002/1878-0261.13774","url":null,"abstract":"<p><strong>Retraction: </strong>S. Sinha, R.K. Singh, N. Bhattacharya, N. Mukherjee, S. Ghosh, N. Alam, A. Roy, S. Roychoudhury, and C.K. Panda, \"Frequent Alterations of LOH11CR2A, PIG8 and CHEK1 Genes at Chromosomal 11q24.1-24.2 Region in Breast Carcinoma: Clinical and Prognostic Implications,\" Molecular Oncology 5, no. 5 (2011): 454-464, https://doi.org/10.1016/j.molonc.2011.06.005. The above article, published online on 7 July 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Kevin M. Ryan; the Federation of European Biochemical Societies (FEBS); and John Wiley & Sons Ltd. Following publication, concerns were raised by a third party that portions of Figure 2 were duplicated, and Figures 5A and 5D were duplicated from an earlier publication by this research group. Internal investigation confirmed the duplications in these figures. The retraction has been agreed because of concerns that the images were manipulated, affecting the interpretation of the data and results presented.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"260"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770556","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":"The genetic duet of concurrent RASAL1 and PTEN alterations promotes cancer aggressiveness by cooperatively activating the PI3K-AKT pathway.","authors":"Xiaopei Shen, Jie Tan, Rengyun Liu, Guangwu Zhu, Lisa Rooper, Mingzhao Xing","doi":"10.1002/1878-0261.13701","DOIUrl":"10.1002/1878-0261.13701","url":null,"abstract":"<p><p>The significance of the prominent tumor suppressor gene for RAS protein activator-like 1 (RASAL1) could be better understood by combined genetic, clinical, and functional studies. Here, we investigated the oncogenic and clinical impacts of genetic alterations of RASAL1, particularly when coexisting with genetic alterations of the gene for phosphatase and tensin homolog (PTEN), in 9924 cancers of 33 types in the TCGA database. We found common concurrent genetic alterations of the two genes, which were cooperatively associated with activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, with cancer progression and mortality rates being 46.36% and 31.72% with concurrent gene alterations, versus 29.80% and 16.93% with neither gene alteration (HR 1.64, 95% CI 1.46-1.84 and 1.77, 95% CI 1.53-2.05), respectively. This was enhanced by additional tumor protein p53 (TP53) gene alterations, with cancer progression and mortality rates being 47.65% and 34.46% with coexisting RASAL1, PTEN, and TP53 alterations versus 25.30% and 13.11% with no alteration (HR 2.21, 95% CI 1.92-2.56 and 2.76, 95% CI 2.31-3.30), respectively. In the case of breast cancer, this genetic trio was associated with a triple-negative risk of 68.75% versus 3.83% with no genetic alteration (RR 17.94, 95% CI 9.60-33.51), consistent with the aggressive nature of triple-negative breast cancer. Mice with double knockouts of Rasal1 and Pten displayed robust Pi3k pathway activation, with the development of metastasizing malignancies, while single gene knockout resulted in only benign neoplasma. These results suggest that RASAL1, like PTEN, is a critical player in negatively regulating the PI3K-AKT pathway; defect in RASAL1 causes RAS activation, thus initiating the PI3K-AKT pathway signaling, which cannot terminate with concurrent PTEN defects. Thus, the unique concurrent RASAL1 and PTEN defects drive oncogenesis and cancer aggressiveness by cooperatively activating the PI3K-AKT pathway. This represents a robust genetic mechanism to promote human cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"248-259"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731273","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":"Importin subunit beta-1 mediates ERK5 nuclear translocation, and its inhibition synergizes with ERK5 kinase inhibitors in reducing cancer cell proliferation.","authors":"Zoe Lombardi, Lucia Gardini, Anatolii V Kashchuk, Alessio Menconi, Matteo Lulli, Ignazia Tusa, Alessandro Tubita, Luisa Maresca, Barbara Stecca, Marco Capitanio, Elisabetta Rovida","doi":"10.1002/1878-0261.13674","DOIUrl":"10.1002/1878-0261.13674","url":null,"abstract":"<p><p>The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5) is emerging as a promising target in cancer. Indeed, alterations of the MEK5/ERK5 pathway are present in many types of cancer, including melanoma. One of the key events in MAPK signalling is MAPK nuclear translocation and its subsequent regulation of gene expression. Likewise, the effects of ERK5 in supporting cancer cell proliferation have been linked to its nuclear localization. Despite many processes regulating ERK5 nuclear translocation having been determined, the nuclear transporters involved have not yet been identified. Here, we investigated the role of importin subunit alpha (α importin) and importin subunit beta-1 (importin β1) in ERK5 nuclear shuttling to identify additional targets for cancer treatment. Either importin β1 knockdown or the α/β1 importin inhibitor ivermectin reduced the nuclear amount of overexpressed and endogenous ERK5 in HEK293T and A375 melanoma cells, respectively. These results were confirmed in single-molecule microscopy in HeLa cells. Moreover, immunofluorescence analysis showed that ivermectin impairs epidermal growth factor (EGF)-induced ERK5 nuclear shuttling in HeLa cells. Both co-immunoprecipitation experiments and proximity ligation assay provided evidence that ERK5 and importin β1 interact and that this interaction is further induced by EGF administration and prevented by ivermectin treatment. The combination of ivermectin and the ERK5 inhibitor AX15836 synergistically reduced cell viability and colony formation ability in A375 and HeLa cells and was more effective than single treatments in preventing the growth of A375 and HeLa spheroids. The increased reduction of cell viability upon the same combination was also observed in patient-derived metastatic melanoma cells. The combination of ivermectin and ERK5 inhibitors other than AX15836 provided similar effects on cell viability. The identification of importin β1 as the nuclear transporter of ERK5 may be exploited for additional ERK5-inhibiting strategies for cancer therapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"99-113"},"PeriodicalIF":6.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534838","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}