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Tumor-Derived Exosomes and the Role of Liquid Biopsy in Human Papillomavirus Oropharyngeal Squamous Cell Carcinoma. 肿瘤来源的外泌体和液体活检在人乳头瘤病毒口咽鳞状细胞癌中的作用。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-07-01 DOI: 10.1097/PPO.0000000000000671
Michael M Allevato, Joshua D Smith, Michael J Brenner, Steven B Chinn

Abstract: The global incidence of human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has surged in recent decades, with HPV+ HNSCC accounting for >70% of oropharynx cancers in the United States. Its incidence in men has surpassed that of HPV+ cervical cancer in women, and reliable assays are needed for early detection and to monitor response to therapy. Human papillomavirus-positive OPSCC has a more favorable response to therapy and prognosis than HPV-negative (HPV-) HNSCC, motivating regimens to deintensify curative surgery or chemoradiotherapy protocols. A barrier to deintensifying and personalizing therapy is lack of reliable predictive biomarkers. Furthermore, HPV- HNSCC survival rates are static without reliable surveillance biomarkers available. The emergence of circulating plasma-based biomarkers reflecting the tumor-immune microenvironment heralds a new era in HNSCC diagnosis and therapy. We review evidence on tumor-derived extracellular vesicles (exosomes) as biomarkers for diagnosis, prognostication, and treatment in HPV+ and HPV- HNSCC.

摘要:近几十年来,全球人乳头瘤病毒阳性(HPV+)头颈部鳞状细胞癌(HNSCC)的发病率激增,其中HPV+HNSCC占美国口咽癌的70%以上。它在男性中的发病率已经超过了在女性中的HPV+宫颈癌症,需要可靠的检测来早期检测和监测对治疗的反应。与HPV阴性(HPV-)HNSCC相比,人乳头瘤病毒阳性的OPSCC对治疗和预后有更有利的反应,促使治疗方案去强化治疗性手术或放化疗方案。去紧张化和个性化治疗的一个障碍是缺乏可靠的预测性生物标志物。此外,HPV-HNSCC的存活率是静态的,没有可靠的监测生物标志物可用。反映肿瘤免疫微环境的循环血浆生物标志物的出现预示着HNSCC诊断和治疗的新时代。我们综述了肿瘤衍生的细胞外囊泡(外泌体)作为HPV+和HPV-HNSCC诊断、预测和治疗的生物标志物的证据。
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引用次数: 0
Circulating Tumor DNA in Human Papillomavirus-Mediated Oropharynx Cancer: Leveraging Early Data to Inform Future Directions. 人类乳头瘤病毒介导的口咽癌症中的循环肿瘤DNA:利用早期数据为未来方向提供信息。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-07-01 DOI: 10.1097/PPO.0000000000000670
Molly E Heft Neal, Heather M Walline, Catherine T Haring

Abstract: Circulating tumor DNA (ctDNA) has become an area of intense study in many solid malignancies including head and neck cancer. This is of particular interest for human papillomavirus-mediated oropharyngeal squamous cell carcinoma as this cohort of patients has excellent survival and is undergoing current clinical trials aimed at treatment de-escalation. Recent studies have demonstrated the prognostic implications of pretreatment ctDNA and the utility of monitoring ctDNA during and posttreatment; however, there is a need for a more critical understanding of ctDNA as it is beginning to be incorporated into clinical trials. This review discusses the current state of ctDNA in oropharynx cancer focusing on ctDNA kinetics and minimal residual disease detection and ends with a discussion of future applications.

摘要:循环肿瘤DNA(ctDNA)已成为包括头颈部癌症在内的许多实体恶性肿瘤的一个研究热点。这对人乳头瘤病毒介导的口咽鳞状细胞癌特别感兴趣,因为这组患者具有良好的生存率,目前正在进行旨在降低治疗效果的临床试验。最近的研究已经证明了预处理ctDNA的预后影响以及在治疗期间和治疗后监测ctDNA的效用;然而,随着ctDNA开始被纳入临床试验,需要对其进行更批判性的理解。本文综述了口咽癌症ctDNA的研究现状,重点讨论了ctDNA动力学和最小残留疾病检测,并对未来的应用进行了讨论。
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引用次数: 0
Novel Approaches and Future Directions in Myelodysplastic Syndrome Treatment. 骨髓增生异常综合征治疗的新方法和未来方向。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000658
Jan Philipp Bewersdorf, Zhuoer Xie, Amer M Zeidan

Abstract: Myelodysplastic syndromes/neoplasms (MDSs) constitute a heterogeneous group of clonal disorders that are clinically characterized by dysplastic changes in multiple hematopoietic lineages, cytopenias, and a variable risk of progression to acute myeloid leukemia. Patients with MDS are classified as either lower- or higher-risk based on risk stratification tools such as the International Prognostic Scoring System and its revised version, which continue to be the basis for prognosis and treatment selection. Although anemic patients with lower-risk MDS are currently treated with an erythropoiesis-stimulating agent, luspatercept, and transfusions, the telomerase inhibitor imetelstat and the hypoxia-inducible factor α inhibitor roxadustat have shown encouraging early results and are now in phase III clinical trials. For higher-risk MDS patients, hypomethylating agent monotherapy continues to be the standard of care. However, with various novel hypomethylating agent-based combination therapies in advanced clinical testing and an increased emphasis on individualized biomarker-driven treatment decisions, the standard therapy paradigms might change in the future.

骨髓增生异常综合征/肿瘤(mds)是一组异质性克隆性疾病,其临床特征是多种造血谱系的增生异常改变、细胞减少和发展为急性髓系白血病的可变风险。根据风险分层工具,如国际预后评分系统及其修订版本,MDS患者被分为低风险或高风险,这仍然是预后和治疗选择的基础。虽然低风险MDS的贫血患者目前使用促红细胞生成剂luspatercept和输血治疗,但端粒酶抑制剂伊美司他和缺氧诱导因子α抑制剂罗沙司他已经显示出令人鼓舞的早期结果,目前正在进行III期临床试验。对于高风险MDS患者,低甲基化药物单药治疗仍然是标准治疗。然而,随着各种新型的基于低甲基化药物的联合疗法在高级临床试验中的应用,以及对个体化生物标志物驱动的治疗决策的日益重视,标准治疗模式可能在未来发生变化。
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引用次数: 0
Updates in Classification of Myelodysplastic Syndrome. 骨髓增生异常综合征分类的最新进展。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000659
Mina L Xu, Robert P Hasserjian

Abstract: Myelodysplastic syndrome includes a broad range of myeloid neoplasms characterized by cytopenia and morphologic dysplasia. Recently, 2 new classification systems emerged to further define how these diseases are diagnosed and risk stratified. This review compares these models, provides detailed approaches, and reveals practical ways to move forward in clinical practice of myelodysplastic syndrome diagnosis.

摘要:骨髓增生异常综合征包括以细胞减少和形态异常增生为特征的多种髓系肿瘤。最近,出现了两种新的分类系统,以进一步确定如何诊断这些疾病并对其进行风险分层。这篇综述比较了这些模型,提供了详细的方法,并揭示了在骨髓增生异常综合征诊断的临床实践中前进的实用方法。
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引用次数: 0
Epidemiology and Pathogenesis of Myelodysplastic Syndrome. 骨髓增生异常综合征的流行病学和发病机制。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000665
Lara K Rotter, Shai Shimony, Kelly Ling, Evan Chen, Rory M Shallis, Amer M Zeidan, Maximilian Stahl
Abstract Myelodysplastic syndrome (MDS) is a clonal disorder characterized by ineffective hematopoiesis and variable cytopenias with a considerable risk of progression to acute myeloid leukemia. Epidemiological assessment of MDS remains challenging because of evolving classification systems, but the overall incidence in the United States is estimated to be approximately 4 per 100,000 and increases with age. The sequential accumulation of mutations drives disease evolution from asymptomatic clonal hematopoiesis (CH) to CH of indeterminate potential, clonal cytopenia of unknown significance, to frank MDS. The molecular heterogeneity seen in MDS is highly complex and includes mutations of genes involved in splicing machinery, epigenetic regulation, differentiation, and cell signaling. Recent advances in the understanding of the molecular landscape of MDS have led to the development of improved risk assessment tools and novel therapies. Therapies targeting the underlying pathophysiology will hopefully further expand the armamentarium of MDS therapeutics, bringing us closer to a more individualized therapeutic approach based on the unique molecular profile of each patient and eventually improving the outcomes of patients with MDS. We review the epidemiology of MDS and the newly described MDS precursor conditions CH, CH of indeterminate potential, and CCUS. We then discuss central aspects of MDS pathophysiology and outline specific strategies targeting hallmarks of MDS pathophysiology, including ongoing clinical trials examining the efficacy of these therapeutic modalities.
摘要:骨髓增生异常综合征(MDS)是一种以造血功能低下和变胞减少为特征的克隆性疾病,有相当大的发展为急性髓系白血病的风险。由于分类系统的发展,MDS的流行病学评估仍然具有挑战性,但美国的总体发病率估计约为每10万人中有4人,并且随着年龄的增长而增加。突变的顺序积累驱动疾病从无症状克隆造血(CH)到潜力不确定的CH、意义未知的克隆性细胞减少,再到MDS。MDS的分子异质性非常复杂,包括参与剪接机制、表观遗传调控、分化和细胞信号传导的基因突变。最近对MDS分子结构的理解取得了进展,导致了改进的风险评估工具和新疗法的发展。针对潜在病理生理的治疗有望进一步扩大MDS治疗的范围,使我们更接近基于每个患者独特的分子特征的更个性化的治疗方法,并最终改善MDS患者的预后。我们回顾了MDS的流行病学和新描述的MDS前体条件CH,不确定电位的CH和CCUS。然后,我们讨论了MDS病理生理的核心方面,并概述了针对MDS病理生理特征的具体策略,包括正在进行的检查这些治疗方式有效性的临床试验。
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引用次数: 0
Spectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms. 从克隆造血到骨髓增生异常肿瘤/综合征和其他髓系肿瘤的频谱。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000656
Zhuoer Xie, Evan C Chen, Lourdes M Mendez, Rami Komrokji, Amer M Zeidan

Abstract: Clonal hematopoiesis (CH) confers a high risk of aging-related diseases and hematologic malignancy. There are still significant knowledge gaps in identifying high-risk patients with CH and managing such patients. In this review, we focus on 3 areas: (1) the natural history of CH; (2) the risks of progression of CH, including CH of indeterminate potential, clonal cytopenia of undetermined significance, and therapy-related CH, to myeloid malignancy; and (3) the challenges and unmet needs of CH management and research.

摘要:克隆造血(CH)是衰老相关疾病和血液恶性肿瘤的高风险因素。在识别高危CH患者和管理此类患者方面仍存在显著的知识空白。本文主要从3个方面进行综述:(1)植物的自然历史;(2) CH进展的风险,包括潜力不确定的CH、意义不确定的克隆性细胞减少症和治疗相关的CH向髓系恶性肿瘤发展的风险;(3)卫生管理和研究面临的挑战和未满足的需求。
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引用次数: 0
Supportive Care for Patients With Myelodysplastic Syndromes. 骨髓增生异常综合征患者的支持治疗。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000661
Jessica M Stempel, Nikolai A Podoltsev, Talib Dosani

Abstract: Myelodysplastic syndromes are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis, progressive cytopenias, and an innate capability of progressing to acute myeloid leukemia. The most common causes of morbidity and mortality are complications related to myelodysplastic syndromes rather than progression to acute myeloid leukemia. Although supportive care measures are applicable to all patients with myelodysplastic syndromes, they are especially essential in patients with lower-risk disease who have a better prognosis compared with their higher-risk counterparts and require longer-term monitoring of disease and treatment-related complications. In this review, we will address the most frequent complications and supportive care interventions used in patients with myelodysplastic syndromes, including transfusion support, management of iron overload, antimicrobial prophylaxis, important considerations in the era of COVID-19 (coronavirus infectious disease 2019), role of routine immunizations, and palliative care in the myelodysplastic syndrome population.

骨髓增生异常综合征是一组异质性的骨髓疾病,其特征是造血功能低下、进行性细胞减少和先天发展为急性髓性白血病的能力。发病和死亡的最常见原因是与骨髓增生异常综合征相关的并发症,而不是进展为急性髓性白血病。虽然支持治疗措施适用于所有骨髓增生异常综合征患者,但对于低风险患者尤其必要,因为与高风险患者相比,低风险患者预后更好,需要长期监测疾病和治疗相关并发症。在这篇综述中,我们将讨论骨髓增生异常综合征患者最常见的并发症和支持性护理干预措施,包括输血支持、铁超载管理、抗菌预防、COVID-19(冠状病毒传染病2019)时代的重要考虑因素、常规免疫的作用以及骨髓增生异常综合征人群的姑息治疗。
{"title":"Supportive Care for Patients With Myelodysplastic Syndromes.","authors":"Jessica M Stempel, Nikolai A Podoltsev, Talib Dosani","doi":"10.1097/PPO.0000000000000661","DOIUrl":"10.1097/PPO.0000000000000661","url":null,"abstract":"<p><strong>Abstract: </strong>Myelodysplastic syndromes are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis, progressive cytopenias, and an innate capability of progressing to acute myeloid leukemia. The most common causes of morbidity and mortality are complications related to myelodysplastic syndromes rather than progression to acute myeloid leukemia. Although supportive care measures are applicable to all patients with myelodysplastic syndromes, they are especially essential in patients with lower-risk disease who have a better prognosis compared with their higher-risk counterparts and require longer-term monitoring of disease and treatment-related complications. In this review, we will address the most frequent complications and supportive care interventions used in patients with myelodysplastic syndromes, including transfusion support, management of iron overload, antimicrobial prophylaxis, important considerations in the era of COVID-19 (coronavirus infectious disease 2019), role of routine immunizations, and palliative care in the myelodysplastic syndrome population.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"29 3","pages":"168-178"},"PeriodicalIF":2.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9500765","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}
引用次数: 0
Myelodysplastic Syndromes/Neoplasms-Insights Into Pathogenesis Leading to Improved Classification, Risk Stratification, and Treatments. 骨髓增生异常综合征/肿瘤-导致改进分类,风险分层和治疗的发病机制的见解。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000663
Michal G Rose, Amer M Zeidan
{"title":"Myelodysplastic Syndromes/Neoplasms-Insights Into Pathogenesis Leading to Improved Classification, Risk Stratification, and Treatments.","authors":"Michal G Rose,&nbsp;Amer M Zeidan","doi":"10.1097/PPO.0000000000000663","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000663","url":null,"abstract":"","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"29 3","pages":"109-110"},"PeriodicalIF":2.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498185","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}
引用次数: 0
Germline Predisposition to Myelodysplastic Syndromes. 骨髓增生异常综合征的种系易感性。
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000660
Georgina Gener-Ricos, Yoheved S Gerstein, Danielle Hammond, Courtney D DiNardo

Abstract: While germline predisposition to myelodysplastic syndromes is well-established, knowledge has advanced rapidly resulting in more cases of inherited hematologic malignancies being identified. Understanding the biological features and main clinical manifestations of hereditary hematologic malignancies is essential to recognizing and referring patients with myelodysplastic syndrome, who may underlie inherited predisposition, for appropriate genetic evaluation. Importance lies in individualized genetic counseling along with informed treatment decisions, especially with regard to hematopoietic stem cell transplant-related donor selection. Future studies will improve comprehension of these disorders, enabling better management of affected patients and their families.

摘要:虽然骨髓增生异常综合征的种系易感性已经确立,但随着知识的迅速发展,越来越多的遗传性血液系统恶性肿瘤病例被发现。了解遗传性血液系统恶性肿瘤的生物学特征和主要临床表现对于识别和推荐骨髓增生异常综合征患者至关重要,这些患者可能存在遗传易感性,并进行适当的遗传评估。重要的是个性化的遗传咨询以及知情的治疗决定,特别是关于造血干细胞移植相关供体的选择。未来的研究将提高对这些疾病的理解,从而更好地管理受影响的患者及其家属。
{"title":"Germline Predisposition to Myelodysplastic Syndromes.","authors":"Georgina Gener-Ricos,&nbsp;Yoheved S Gerstein,&nbsp;Danielle Hammond,&nbsp;Courtney D DiNardo","doi":"10.1097/PPO.0000000000000660","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000660","url":null,"abstract":"<p><strong>Abstract: </strong>While germline predisposition to myelodysplastic syndromes is well-established, knowledge has advanced rapidly resulting in more cases of inherited hematologic malignancies being identified. Understanding the biological features and main clinical manifestations of hereditary hematologic malignancies is essential to recognizing and referring patients with myelodysplastic syndrome, who may underlie inherited predisposition, for appropriate genetic evaluation. Importance lies in individualized genetic counseling along with informed treatment decisions, especially with regard to hematopoietic stem cell transplant-related donor selection. Future studies will improve comprehension of these disorders, enabling better management of affected patients and their families.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"29 3","pages":"143-151"},"PeriodicalIF":2.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498189","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}
引用次数: 0
Novel Therapies in Myelodysplastic Syndrome: Where Do Venetoclax and Isocitrate Dehydrogenase Inhibitors Fit in? 骨髓增生异常综合征的新疗法:Venetoclax和异柠檬酸脱氢酶抑制剂适用于哪里?
IF 2.2 4区 医学 Q3 ONCOLOGY Pub Date : 2023-05-01 DOI: 10.1097/PPO.0000000000000657
Yasmin Abaza, Anand Ashwin Patel

Abstract: Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders with treatment approaches tailored to the presence of cytopenias, disease risk, and molecular mutation profile. In higher-risk MDSs, the standard of care are DNA methyltransferase inhibitors, otherwise referred to as hypomethylating agents (HMAs), with consideration for allogeneic hematopoietic stem cell transplantation in appropriate candidates. Given modest complete remission rates (15%-20%) with HMA monotherapy and median overall survival of approximately 18 months, there is much interest in the investigation of combination and targeted treatment approaches. Furthermore, there is no standard treatment approach in patients with progression of disease after HMA therapy. In this review, we aim to summarize the current evidence for the B-cell lymphoma-2 inhibitor, venetoclax, and a variety of isocitrate dehydrogenase inhibitors in the treatment of MDSs along with discussing their potential role in the treatment paradigm of this disease.

骨髓增生异常综合征(mds)是一组异质性克隆造血干细胞疾病,其治疗方法针对细胞减少、疾病风险和分子突变谱的存在量身定制。在高风险mds中,护理标准是DNA甲基转移酶抑制剂,或者称为低甲基化剂(HMAs),并考虑在适当的候选者中进行同种异体造血干细胞移植。考虑到HMA单药治疗的适度完全缓解率(15%-20%)和中位总生存期约为18个月,人们对联合治疗和靶向治疗方法的研究非常感兴趣。此外,HMA治疗后疾病进展的患者没有标准的治疗方法。在这篇综述中,我们旨在总结目前b细胞淋巴瘤-2抑制剂venetoclax和各种异柠檬酸脱氢酶抑制剂治疗mds的证据,并讨论它们在这种疾病的治疗模式中的潜在作用。
{"title":"Novel Therapies in Myelodysplastic Syndrome: Where Do Venetoclax and Isocitrate Dehydrogenase Inhibitors Fit in?","authors":"Yasmin Abaza,&nbsp;Anand Ashwin Patel","doi":"10.1097/PPO.0000000000000657","DOIUrl":"https://doi.org/10.1097/PPO.0000000000000657","url":null,"abstract":"<p><strong>Abstract: </strong>Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders with treatment approaches tailored to the presence of cytopenias, disease risk, and molecular mutation profile. In higher-risk MDSs, the standard of care are DNA methyltransferase inhibitors, otherwise referred to as hypomethylating agents (HMAs), with consideration for allogeneic hematopoietic stem cell transplantation in appropriate candidates. Given modest complete remission rates (15%-20%) with HMA monotherapy and median overall survival of approximately 18 months, there is much interest in the investigation of combination and targeted treatment approaches. Furthermore, there is no standard treatment approach in patients with progression of disease after HMA therapy. In this review, we aim to summarize the current evidence for the B-cell lymphoma-2 inhibitor, venetoclax, and a variety of isocitrate dehydrogenase inhibitors in the treatment of MDSs along with discussing their potential role in the treatment paradigm of this disease.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"29 3","pages":"188-194"},"PeriodicalIF":2.2,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9500762","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}
引用次数: 0
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