Molecular Oncology最新文献

{"title":"Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.","authors":"Giulia Schiavoni, Antonella Palmese, Stefano Scalera, Laura Cipriani, Davide Mascolo, Patrizia Vici, Teresa Arcuri, Lorena Filomeno, Eriseld Krasniqi, Giovanni Blandino, Giulia Bon, Marcello Maugeri-Saccà","doi":"10.1002/1878-0261.70232","DOIUrl":"10.1002/1878-0261.70232","url":null,"abstract":"<p><p>Breast cancer, the most frequently diagnosed cancer in women globally, is a heterogeneous disease with distinct subtypes requiring distinct therapeutic approaches. Regardless of molecular subtyping, breast cancer stem cells significantly contribute to tumor heterogeneity, distant dissemination, and therapeutic resistance. The Hippo pathway is a key regulator of organogenesis and tissue development, and its deregulation is common in breast cancer and linked to cancer stem cell features across several cancer types. Dysfunctional pathway activity leads to the aberrant activation of Hippo downstream effectors, the Yes-associated protein (YAP) and its paralog transcriptional co-activator with PDZ-binding motif (TAZ), which promote epithelial-to-mesenchymal transition, growth factor-independent proliferation, and maintenance of the breast cancer stem cells' niche. This review summarizes the regulation of the Hippo pathway, emphasizing its significant role in coordinating stemness-related mechanisms in breast cancer. An overview of how the Hippo pathway fuels stemness in triple-negative breast cancer, the most aggressive BC subtype, is then provided. We also discuss how the activation of stem cell-like properties, driven by dysregulation of the Hippo pathway, contributes to the development of resistance to current therapies across the spectrum of breast cancer subtypes.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1667-1693"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521466","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":"Interrogating the immune landscape of microsatellite stable RAS-mutated colon cancer.","authors":"Rodrigo Dienstmann, Eduardo García-Galea, Alice O'Farrell, Zak Kinsella, Maxime Meylan, Florent Petitprez, Ingrid Arijs, Tom Venken, Hari Ps, Adrian Lärkeryd, Ian Miller, Janick Selves, Nadja Meindl-Beinker, Fiorella Ruiz-Pace, Elena Élez, Raquel Comas-Navarro, Frank Lincoln, Dirk Fey, Gift Nyamundanda, Aoife Nolan, Joern Lewin, Raquel Perez-Lopez, Jonathan Briody, Kathleen Bennett, Walter Kolch, David Matallanas, Alexander Kel, Enrique Arenas, Joaquín Arribas, Bart Ghesquière, Josep Tabernero, Julie Meilleroux, Deborah McNamara, Ray McDermott, Marvin Lim, Mary O'Reilly, Brian Bird, Lisa Stack, Lucia Moloney, Patrick Morris, Keith Egan, Maciej Milewski, Lars Scheuer, Joachim Behringer, Georg Bolz, Ramon Salazar, Cristina Santos, Andrea Ruiz, Orla Casey, Verena Murphy, Matthias Ebert, Livio Trusolino, Diether Lambrechts, Anguraj Sadanandam, Catherine Sautès-Fridman, Jochen Prehn, Paolo Nuciforo, Jacques Fieschi, Florence Monville, Darran O'Connor, Wolf Fridman, Annette Byrne","doi":"10.1002/1878-0261.70225","DOIUrl":"10.1002/1878-0261.70225","url":null,"abstract":"<p><p>To explore the immune microenvironment of RAS-mutated (RASmt) microsatellite stable (MSS) colon cancer (CC), we retrospectively performed whole exome sequencing, RNA sequencing, and robust digital pathology analyses and studied immune markers in a cohort of 161 patients treated with standard-of-care therapies with early stage disease (both fresh frozen and formalin-fixed paraffin-embedded [FFPE] samples) or 121 patients with metastatic setting (primary tumor FFPE samples). Only a small proportion of cases exhibited a highly infiltrated immune microenvironment, with a strong association between Immunoscore^® (IS)-high (13% of the samples) and Tumor Lymphocytes Infiltrating Score (TuLIS)-high scores (25% of the samples). Immunoscore Immune-Checkpoint (ISIC)-high tumors (52% of the samples) shared a similar microenvironment composition to IS-high and TuLIS-like high tumors and displayed higher mutational burdens than ISIC-low tumors. In conclusion, a substantial proportion of MSS RASmt CCs exhibit high ISIC scores, meriting evaluation in prospective trials of immunotherapy-based combination regimens.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1713-1725"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284518","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":"COMP-PMEPA1 axis promotes epithelial-to-mesenchymal transition in breast cancer cells.","authors":"Konstantinos S Papadakos, Gilar Gorji-Bahri, Lejla Gradjan, Julia Zajac, Kacper Gil, Yvonne Thokozile Nduku, Anna M Blom","doi":"10.1002/1878-0261.70221","DOIUrl":"10.1002/1878-0261.70221","url":null,"abstract":"<p><p>Epithelial-to-mesenchymal transition (EMT), driven by cues from the tumor microenvironment, is a critical initiator of metastatic progression. In breast cancer patients, elevated expression of cartilage oligomeric matrix protein (COMP) is associated with shorter survival and increased metastatic risk. Here, we investigated the role of COMP in regulating EMT in breast cancer. Breast cancer cells treated with recombinant COMP or engineered to overexpress COMP exhibited a marked decrease in the epithelial marker CDH1 and an increase in mesenchymal markers such as VIM and VCAN. Consistent with these in vitro findings, COMP-expressing xenograft tumor tissues showed enhanced EMT characteristics. Functionally, COMP promoted increased migration and invasion of breast cancer cells in both autocrine and paracrine manners, dependent on its thrombospondin (TSP) and C-terminal domains. We further identified protein TMEPAI (encoded by gene PMEPA1) as a functional COMP-binding partner that mediates COMP-induced EMT, primarily through interaction with the TSP domain of COMP. Mechanistically, COMP shifted transforming growth factor beta (TGFβ) signaling from canonical phosphorylated mothers against decapentaplegic homolog 2/3 (pSMAD2/3) activation toward pSMAD1/5, likely through its interaction with PMEPA1. This study suggests the COMP-PMEPA1 axis as a new driver of EMT in breast cancer models.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1780-1799"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194992","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":"Cell-cycle-specific lesion evolution rather than inhibition of double-strand-break repair underpins cisplatin radiosensitization.","authors":"Ye Qiu, Xixi Lin, Emil Mladenov, Veronika Mladenova, Jürgen Thomale, Ali Sak, Yao Wang, Yunxuan Deng, Eleni Gkika, Martin Stuschke, George Iliakis","doi":"10.1002/1878-0261.70240","DOIUrl":"10.1002/1878-0261.70240","url":null,"abstract":"<p><p>DNA double-strand breaks (DSBs) generated from collisions of DNA replication forks with cisplatin-induced interstrand crosslinks underpin cisplatin cytotoxicity. Yet, the impact of cell-cycle-dependent cisplatin-DNA adduct (CDA) formation on cell cycle progression and interactions with DNA replication remain incompletely characterized. Also, although cisplatin enhances tumor response to ionizing radiation (IR), the underpinning radiosensitizing mechanisms remain unresolved. Here, we close this void and analyze CDAs (GpG crosslinks) and DSB (γH2AX foci) induction and repair in a strictly cell-cycle-dependent manner. We report for the first time that CDAs form in a dose- and time-dependent manner in all cell cycle phases, whereas DSBs emerge only in S-phase. Repair of IR-induced DSBs remains largely unaffected by CDAs in G₁, S, and G₂ phases, but is inhibited when S-phase-treated cells progressed to G₂. Radiosensitization occurs after prolonged cisplatin exposure, likely owing to G₂-phase accumulation and lesion evolution from S-phase, thus impairing repair of IR-induced DSBs. Cisplatin fails to radiosensitize quiescent (G₀) cells. In summary, CDA formation is similar across the cell cycle, but DSBs form only in S-phase. Whereas CDAs fail to interfere with repair of IR-induced DSBs, progression-dependent repair disruptions cause radiosensitization. Elucidation of the underpinning mechanisms may help to design improved cisplatin-radiation schedules for more efficacious therapies.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1814-1834"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486501","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":"Weakening the nuclear envelope: Lamin B receptor in melanoma metastasis.","authors":"Francesca Lorenzini, Maria Caterina Mione","doi":"10.1002/1878-0261.70281","DOIUrl":"10.1002/1878-0261.70281","url":null,"abstract":"<p><p>Nuclear envelope fragility has been identified as a hallmark of the metastatic process. Indeed, cancer cells undertake a challenging journey through diverse environments during metastasis, notably squeezing through narrow spaces and dense collagen matrices. In their report, Baird et al. identify a key player in nuclear fragility in confined cancer cell migration: the Lamin B receptor. Its overexpression and clustering in specific regions of the nuclear envelope increase nuclear distortion and fragility, rendering nuclei more susceptible to rupture with consequent chromatin extrusion and genomic instability. Elucidating the mechanisms underlying this process, particularly the receptor's sterol reductase activity, represents a promising step towards the identification of novel therapeutic targets.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1663-1666"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199361","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":"Pre-analytical optimization of cell-free DNA and extracellular vesicle-derived DNA for mutation detection in liquid biopsies.","authors":"Jonas Dohmen, Lucrezia De Santis, Bret M Stephens, Vincent Bernard, Jörg C Kalff, Lara Braun, Phillipp Leyendecker, Johannes Röttgen, Daniel Weissinger, Anirban Maitra, Paola A Guerrero, Alexander Semaan","doi":"10.1002/1878-0261.70222","DOIUrl":"10.1002/1878-0261.70222","url":null,"abstract":"<p><p>Liquid biopsies enable noninvasive tumor profiling and longitudinal disease monitoring. Their analytical performance is strongly influenced by pre-analytical factors, yet direct comparisons between cell-free DNA (cfDNA) and extracellular vesicle-derived DNA (evDNA) remain scarce. We prospectively evaluated four pre-analytical variables: processing delay, storage temperature, tube type, and plasma input volume, on cfDNA and evDNA from cancer patient plasma (n = 244) using ddPCR, Qubit, and TapeStation. Key findings were validated in archived plasma samples (n = 723). In the prospective cohort, cfDNA concentrations increased after 24 h and evDNA after 48 h at room temperature, while retrospective analysis revealed earlier changes (cfDNA: 6 h; evDNA: 24 h). Storage conditions influenced both analytes, as short-term refrigeration (4 °C) better preserved DNA quality than -80 °C freezing, while extracted DNA remained stable at -80 °C. Acid citrate dextrose (ACD) and K₂EDTA tubes performed similarly under prompt processing. Higher plasma volumes improved evDNA, but not cfDNA, for mutation detection. evDNA demonstrates greater resilience than cfDNA under suboptimal conditions. Standardized workflows and prompt processing are essential to ensure reliable mutation detection in clinical liquid biopsy applications.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1762-1779"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271547","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":"Correction to \"Human papillomavirus (HPV)-18 E6 oncoprotein interferes with the epithelial cell polarity Par3 protein\".","authors":"","doi":"10.1002/1878-0261.70278","DOIUrl":"10.1002/1878-0261.70278","url":null,"abstract":"","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1890"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150448","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":"E2A selectively regulates TGF-β-induced apoptosis in KRAS-mutant non-small cell lung cancer.","authors":"Sergei Chuikov, Shiva Krishna Katkam, Zhefan Wang, Venkateshwar G Keshamouni","doi":"10.1002/1878-0261.70236","DOIUrl":"10.1002/1878-0261.70236","url":null,"abstract":"<p><p>Transforming growth factor-β (TGF-β) regulates epithelial homeostasis by inducing growth arrest and apoptosis during early carcinogenesis; however, these tumor-suppressive functions are frequently lost in advanced nonsmall cell lung cancer (NSCLC) despite intact signaling. We identify the transcription factor E2A as a critical mediator of resistance to TGF-β-induced apoptosis in mutant KRAS-driven NSCLC. TGF-β induces E2A expression in a SMAD3-dependent manner in NSCLC cells harboring mutant KRAS, but not in those with wild-type KRAS. Silencing E2A restores TGF-β-induced apoptosis in mutant KRAS cell lines without affecting epithelial-mesenchymal transition. E2A depletion promotes mitochondrial apoptosis through mitochondrial outer membrane permeabilization, caspase-3 activation, and regulation of BCL-2 family and inhibitor-of-apoptosis proteins. In contrast, wild-type KRAS NSCLC cells fail to upregulate E2A in response to TGF-β and remain resistant to apoptosis following E2A silencing. Knockdown of mutant KRAS abrogates the pro-apoptotic effects of E2A silencing, establishing KRAS dependency. E2A silencing enhances radiation-induced growth inhibition, likely through increased sensitivity to TGF-β signaling. E2A is overexpressed in lung adenocarcinoma and is significantly elevated in tumors harboring mutant KRAS. These findings identify E2A as a context-specific suppressor of TGF-β-mediated apoptosis and a potential therapeutic target in mutant KRAS NSCLC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1877-1888"},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499443","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":"Inhibition of cyclin-dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation.","authors":"Wylie K Watlington, Divya L Dayanidhi, Mohammad Zokaasadi, John B Mantyh, Pelumi D Olawuni, Gabrielle Rupprecht, Jeremy M Force, Shannon McCall, Ashwani K Bahl, David S Hsu, Jason A Somarelli","doi":"10.1002/1878-0261.70290","DOIUrl":"10.1002/1878-0261.70290","url":null,"abstract":"<p><p>Cyclin-dependent kinase (CDK) 12 and its paralog, CDK13, phosphorylate RNA polymerase II, enabling transcriptional elongation. In solid tumors, CDK12 loss promotes progression by inducing replication-transcription conflict and fueling genomic instability. However, we have uncovered upregulation of CDK12 and CDK13 in ~5% of colorectal cancer (CRC) specimens, suggesting a role in cancer cell survival. Based on this, we postulated that CDK12/13 inhibition in CRC may represent a useful therapeutic strategy. To test this, we screened CDK12 and CDK12/13 inhibitors across multiple cancer cell lines and patient-derived organoids (PDO) from a range of solid tumors, demonstrating potent activity in CRC PDO. Using siRNA-mediated knockdown, we identified CDK13 as a potential mechanism of resistance to CDK12-specific inhibition. Mechanistically, CDK12/13 inhibition led to a decreased abundance of BRCA1 long transcripts, rendering cells susceptible to combination therapy with PARP inhibitors. To further assess the clinical utility of CDK12/13 inhibition, we focused on CRC, for which there is an urgent need for additional therapies. We tested the efficacy of CT7439, a novel CDK12/13 inhibitor and cyclin K degrader, which showed cytotoxicity in the low nanomolar range, reduced BRCA1 expression, and concomitant DNA damage. Together, our data support further clinical development of CDK12/13 inhibition in CRC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352539","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":"In vitro and in silico modelling of ROS1-positive non-small cell lung cancer reveals fusion-dependent tyrosine kinase inhibitor responses.","authors":"Farhan Ul Haq, Marc Terrones, Felicia Rodrigues Fortes, Anne Schepers, Alessia Denis, Christophe Deben, Ken Op de Beeck, Guy Van Camp, Geert Vandeweyer","doi":"10.1002/1878-0261.70291","DOIUrl":"10.1002/1878-0261.70291","url":null,"abstract":"<p><p>The emergence of drug resistance in ROS1-rearranged non-small cell lung cancer (NSCLC) represents a major therapeutic challenge. Although several resistance mutations have been described in patients, preclinical models derived from patient material remain limited, thereby hindering mechanistic insight into this malignancy. In this study, we investigated three clinically relevant ROS1 variants (G2032R, L2026M, and S1986Y) using CRISPR/Cas9-edited patient-derived cell lines and complemented these analyses with molecular docking and molecular dynamics simulations. The efficacy of tyrosine kinase inhibitors (TKIs) crizotinib, ceritinib, lorlatinib, entrectinib, and repotrectinib was systematically evaluated. Dose-response assays with CUTO-28 (TPM3-ROS1) and CUTO-37 (CD74-ROS1) lines reproduced clinical drug responses, revealing fusion-dependent differences in resistance. The G2032R mutation led to reduced sensitivity to entrectinib and lorlatinib, with lower area-over-the-curve values compared with ROS1 wild-type (WT) cells. Similar reductions were observed for L2026M and S1986Y, while complete resistance was only seen in CUTO-37 G2032R. Immunoblotting confirmed impaired inhibition of p-ROS1 (Tyr2274) in resistant models. Structural modelling revealed alterations in kinase active site pocket volume, activation helix rotation, and activation loop dynamics in ROS1 mutants, providing a mechanistic basis for the observed drug responses. Molecular dynamics simulations validated the type I inhibitor binding mode across ROS1 WT and mutant complexes, while highlighting conformational effects extending beyond direct ligand interactions. Our findings underscore that although G2032R and L2026M mutations reside within the kinase active site, their impact extends far beyond steric hindrance, altering overall kinase domain dynamics. Collectively, these data establish a robust panel of patient-derived ROS1 cell lines that recapitulate clinical resistance patterns and, together with complementary computational modeling, provide a valuable framework to dissect ROS1 tumor biology and support rational design of next-generation inhibitors.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308400","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}