Aging and cancer最新文献

{"title":"Cancer in old population: We need more practice","authors":"Siyi Zou,&nbsp;Baiyong Shen","doi":"10.1002/aac2.12034","DOIUrl":"10.1002/aac2.12034","url":null,"abstract":"<p>The world's population is rapidly aging, and health problems of the elderly are a major focus of the medical system. According to the latest epidemiological report, cancer has surpassed heart disease as the leading cause of death for people over 60 years old. In 2018, a total of 498,963 people over 60 years old died of cancer in the United States. It is estimated that by 2030, 70% of cancers and 85% of cancer-related deaths will occur in the elderly over 65 years old.<span>¹</span> The elderly population will undoubtedly comprise a major part of cancer cases in the future. Previous research has revealed the intimate association between aging and cancer.<span>^1-3</span> The development of cancer is a time-dependent process with increased incidence in later phases of life. Environmental carcinogens are more likely to impact older tissues and carcinogenesis is also promoted by the aging-related changes in body environments like chronic inflammation and immunosenescence. These factors contribute to the increased incidence of cancers with age. Currently, more than 50% of newly diagnosed cancer patients are over 60 years old and about one-third older than 70 years. Take lung cancer and pancreatic cancer for example—the incidence of lung cancer is only 0.7% in patients younger than 60 years old, while the incidence is up to 14.3% in those over 60 years old. Among newly diagnosed pancreatic cancer patients, only 13% of all pancreatic cancer cases were diagnosed below the age of 60.<span>⁴</span></p><p>In clinical practice, surgery and chemotherapy still remain the primary options for most cancers, and a comprehensive assessment for physical condition is required before decision making to determine whether the patient is sufficiently tolerant of treatment.<span>⁵</span> The treatment strategies for elderly cancer patients are less aggressive based on various considerations, medical and socioeconomic, thereby leading to detrimental effects on life expectancy for these patients. Although elderly patients often present with additional chronic diseases (e.g., heart diseases, chronic lower respiratory diseases, and cerebrovascular diseases), and decline of multiple organ functions, aging is still a highly individualized process that cannot be evaluated merely by chronological age.<span>⁶</span> Comprehensive geriatric assessment (CGA) is a concept proposed in geriatric oncology to serve as a multidimensional tool for integrating therapeutic decision making in older adults based on their biological age. Prior studies have confirmed the capability of CGA to predict the risk of morbidity and mortality among elderly cancer patients, suggesting that evaluation systems of high sensitivity and specificity for treatment strategies of old patients with cancer are clearly needed.<span>⁷</span></p><p>Anesthesia and surgery are both challenging for older patients requiring tumor resections. Many elderly ","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 1-2","pages":"4-5"},"PeriodicalIF":0.0,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41361588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging","authors":"Zachary S. Clayton,&nbsp;David A. Hutton,&nbsp;Sophia A. Mahoney,&nbsp;Douglas R. Seals","doi":"10.1002/aac2.12033","DOIUrl":"10.1002/aac2.12033","url":null,"abstract":"<p>Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can “accelerate” these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents, and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in midlife (50–64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to age-matched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induces a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps, and make recommendations for future research.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 1-2","pages":"45-69"},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39142236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of cord blood to replenish young immune cells against cancer","authors":"Xiaoyang Li,&nbsp;Lin Cheng,&nbsp;Junmin Li,&nbsp;Ruibao Ren","doi":"10.1002/aac2.12032","DOIUrl":"10.1002/aac2.12032","url":null,"abstract":"<p>The immune system of elderly individuals behaves differently from young adults, leading to a general assumption that the decline of immune system function increases the susceptibility to infectious and noninfectious diseases. This age-related internal immune function failure, termed \"immune senescence,\" contributes to the increment of morbidity and mortality associated with diseases in elderly populations. Cord blood is considered as a source of “young” immune cells for anti-infectious immunity and adoptive cancer immunotherapy. In this review, we describe immune aging and the application of cord blood for replenishing aging immune cells against neoplastic diseases.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 1-2","pages":"36-44"},"PeriodicalIF":0.0,"publicationDate":"2021-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46451291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle and childhood cancer: Where are we now and where we go from here","authors":"Chelsea G. Goodenough,&nbsp;Robyn E. Partin,&nbsp;Kirsten K. Ness","doi":"10.1002/aac2.12027","DOIUrl":"10.1002/aac2.12027","url":null,"abstract":"<p>Skeletal muscle (muscle) is essential for physical health and for metabolic integrity, with sarcopenia (progressive muscle mass loss and weakness), a precursor of aging and chronic disease. Loss of lean mass and muscle quality (force generation per unit of muscle) in the general population are associated with fatigue, weakness, and slowed walking speed, eventually interfering with the ability to maintain physical independence, and impacting participation in social roles and quality of life. Muscle mass and strength impairments are also documented during childhood cancer treatment, which often persist into adult survivorship, and contribute to an aging phenotype in this vulnerable population. Although several treatment exposures appear to confer increased risk for loss of mass and strength that persists after therapy, the pathophysiology responsible for poor muscle quantity and quality is not well understood in the childhood cancer survivor population. This is partly due to limited access to both pediatric and adult survivor muscle tissue samples, and to difficulties surrounding noninvasive investigative approaches for muscle assessment. Because muscle accounts for just under half of the body's mass and is essential for movement, metabolism, and metabolic health, understanding mechanisms of injury responsible for both initial and persistent dysfunction is important and will provide a foundation for intervention. The purpose of this review is to provide an overview of the available evidence describing associations between childhood cancer, its treatment, and muscle outcomes, identifying gaps in current knowledge.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 1-2","pages":"13-35"},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39434364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case for improving frail patient outcomes in multiple myeloma with phenotype-driven personalized medicine","authors":"Lauren T. Reiman,&nbsp;Zachary J. Walker,&nbsp;Lyndsey R. Babcock,&nbsp;Peter A. Forsberg,&nbsp;Tomer M. Mark,&nbsp;Daniel W. Sherbenou","doi":"10.1002/aac2.12022","DOIUrl":"10.1002/aac2.12022","url":null,"abstract":"<p>The treatment of older persons with cancer is fraught by a delicate balance of targeting the disease while avoiding treatment-related complications. “Personalized,” or “precision” medicine approaches can ease this problem through more efficacious and less toxic treatments. Multiple myeloma epitomizes the struggle to balance treatment options and their complications, for it is an incurable disease afflicting a predominantly aged population, and treatment is administered on a continuous schedule with little or no breaks. Over the last two decades, advances in drug development have improved outcomes for younger, fit patients, but older, frail patients have not realized the same benefit. This could be related to the benefits of three drug combinations, when frail patients can often tolerate only two drugs at a time. In myeloma, personalized approaches have lagged behind some other malignancies due to its genetic complexity and a paucity of abnormalities with associated targeted therapies. In contrast, the disease is managed with an array of drugs that target phenotypic characteristics common in malignant plasma cells. To address the unmet need for personalized medicine in myeloma, we developed a functional approach by profiling the sensitivity of patients’ myeloma to clinically available drugs. Through this, we observed that receiving at least two effective drugs portended better outcomes, leaving those patients who can only tolerate two drug regimens without room for error. We now describe a frail patient's case and their drug sensitivity profile to illustrate how personalized treatment could have led to an improved disease course. Personalized treatment could provide the greatest survival improvements to older adults with cancers, such as multiple myeloma, through avoiding undertreatment, limiting attrition through subsequent lines of therapy, reducing exposure to ineffective drugs and streamlining the management of relapses. Exploring these avenues is imperative to closing the gap of cancer-related mortality in older and frail persons.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 1-2","pages":"6-12"},"PeriodicalIF":0.0,"publicationDate":"2021-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44139558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary patterns and the neoplastic-prone tissue landscape of old age","authors":"Fabio Marongiu,&nbsp;Ezio Laconi","doi":"10.1002/aac2.12021","DOIUrl":"10.1002/aac2.12021","url":null,"abstract":"<p>There is now sufficient evidence to indicate that aging is associated with the emergence of a clonogenic and neoplastic-prone tissue landscape, which fuels early stages of cancer development and helps explaining the rise in cancer incidence and mortality in older individuals. Dietary interventions are among the most effective approaches to delay aging and age-related diseases, including cancer. Reduced caloric intake has been, historically, the most intensely investigated strategy. Recent findings point to a critical role of a long fasting interval in mediating some of the beneficial effects of caloric restriction. Time-restricted feeding, intermittent fasting, and fasting mimicking diets are being proposed for their potential to prolong healthy life span and to delay late-onset diseases such as neoplasia. Evidence will be discussed suggesting that the effects of these dietary regimens are mediated, at least in part, through retardation of age-related functional changes at cell and tissue level, including a delay in the emergence of the neoplastic-prone tissue microenvironment.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"1 1-4","pages":"45-57"},"PeriodicalIF":0.0,"publicationDate":"2020-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46186837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leukocyte telomere length associated with glioma risk and survival","authors":"Jie Shen,&nbsp;Renduo Song,&nbsp;Yuanqing Ye,&nbsp;Ye Gong,&nbsp;Hua Zhao","doi":"10.1002/aac2.12020","DOIUrl":"10.1002/aac2.12020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Relative telomere length (RTL) in leukocytes has been linked to risks of many cancers, although how leukocyte RTL contributes to adult glioma has rarely been studied</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We performed a case-control study to evaluate the association between RTL in leukocytes and glioma risk in 565 glioma patients and 1130 healthy controls</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Overall, mean leukocyte RTL was significantly higher in cases than controls (<i>P</i> &lt; .001). Longer RTL was associated with a 1.32-fold increased risk of glioma (odds ratio [OR] = 1.32, 95% confidence internal [CI] = 1.13-1.64). In quartile analysis, a significant dose-response relationship was noted (<i>P</i> &lt; .001). Compared to the first quartile with shortest RTL, the fourth quartile with longest RTL was associated with 1.51-fold elevated risk of glioma (OR = 1.51, 95% CI = 1.10-2.18). In further stratified analysis by clinical characteristics at baseline, the significant relationship was observed among cases with aggressive tumor characteristics, including glioblastoma multiforme (GBM), high tumor grade, and absence of <i>IDH</i> mutation and 1p/19q co-deletion. Finally, we evaluated leukocyte RTL in GBM prognosis. We found that longer RTL was associated with increased probability of overall survival (hazard ratio [HR] = 0.88, 95% CI = 0.70-0.98), and progression/recurrence-free survival (HR = 0.81, 95% CI = 0.60-0.93) in patients with primary GBM</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that longer RTL is significantly associated with glioma risk, and the association differs by tumor aggressiveness. Also, RTL in leukocyte could be a prognostic predictor of survival and progression in patients with GBM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"1 1-4","pages":"71-78"},"PeriodicalIF":0.0,"publicationDate":"2020-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43924483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A glitch in the matrix: Age-dependent changes in the extracellular matrix facilitate common sites of metastasis","authors":"Gloria E. Marino,&nbsp;Ashani T. Weeraratna","doi":"10.1002/aac2.12013","DOIUrl":"10.1002/aac2.12013","url":null,"abstract":"<p>People over 55 years old represent the majority of cancer patients and suffer from increased metastatic burden compared to the younger patient population. As the aging population increases globally, it is prudent to understand how the intrinsic aging process contributes to cancer progression. As we age, we incur aberrant changes in the extracellular matrix (ECM) of our organs, which contribute to numerous pathologies, including cancer. Notably, the lung, liver, and bone represent the most common sites of distal metastasis for all cancer types. In this review, we describe how age-dependent changes in the ECM of these organs influence cancer progression. Further, we outline how these alterations prime the premetastatic niche and why these may help explain the disparity in outcome for older cancer patients.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"1 1-4","pages":"19-29"},"PeriodicalIF":0.0,"publicationDate":"2020-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44750650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and immunotherapies: New horizons for the golden ages","authors":"Jamie A.G. Hamilton,&nbsp;Curtis J. Henry","doi":"10.1002/aac2.12014","DOIUrl":"10.1002/aac2.12014","url":null,"abstract":"<p>The life expectancy of the world's elderly population (65 and older) continues to reach new milestones with older individuals currently comprising greater than 8.5% (617 million) of the world's population. This percentage is predicted to approach 20% of the world's population by 2050 (representing 1.6 billion people). Despite this amazing feat, many healthcare systems are not equipped to handle the multitude of diseases that commonly manifest with age, including most types of cancers. As the world's aging population grows, cancer treatments continue to evolve. Immunotherapies are a new drug class that has revolutionized our ability to treat previously intractable cancers; however, their efficacy in patients with compromised immune systems remains unclear. In this review, we will discuss how aging-associated losses in immune homeostasis impact the efficacy and safety of immunotherapy treatment in preclinical models of aging. We will also discuss how these findings translate to elderly patients receiving immunotherapy treatment for refractory and relapsed cancers, as well as, strategies that could be explored to improve the efficacy of immunotherapies in aged patients.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"1 1-4","pages":"30-44"},"PeriodicalIF":0.0,"publicationDate":"2020-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40535507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of age-related T-cell dynamics on the identification of biomarkers predictive of immunotherapy discontinuation: A prospective cohort study","authors":"Jason E. Galloway,&nbsp;Andrea M. Holderbaum,&nbsp;Namrata Arya,&nbsp;Suohui Zhang,&nbsp;Michael S. Bodnar,&nbsp;Ruthann Norman,&nbsp;William E. Carson,&nbsp;Lianbo Yu,&nbsp;Kari L. Kendra,&nbsp;Christin E. Burd","doi":"10.1002/aac2.12012","DOIUrl":"10.1002/aac2.12012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of biologic aging on immune checkpoint inhibitor (ICI) toxicity and efficacy is underexplored in metastatic melanoma (MM). In peripheral blood T lymphocytes (PBTLs), biologic aging is characterized by changes in T-cell composition and cellular senescence. Whether indicators of PBTL biologic aging vary in MM patients or can be used to predict premature ICI discontinuation (pID) is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively collected PBTLs from 117 cancer-free controls and 46 MM patients scheduled to begin pembrolizumab or nivolumab monotherapy. Seventy-four mRNAs indicative of T-cell subset, activation, costimulation/inhibition, and cellular senescence were measured by Nanostring. Relationships between each mRNA and chronologic age were assessed in patients and controls. Candidate biomarkers were identified by calculating the hazard ratio (HR) for pID in patients divided into low and high groups based on log-transformed mRNA levels or the magnitude by which each mRNA measurement deviated from the control trend (Δage). Area under the curve (AUC) analyses explored the ability of each biomarker to discriminate between patients with and without pID at 6 months and 1 year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifteen mRNAs correlated with chronologic age in controls, including markers of T-cell subset, differentiation, cytokine production, and costimulation/inhibition. None of these mRNAs remained correlated with age in patients. Median follow-up was 94.8 (1.6-195.7) weeks and 35 of 46 patients discontinued therapy (23 progression, seven toxicity, and five comorbidity/patient preference). Elevated pretherapy <i>CD8A</i> (HR = 2.2 [1.1-4.9]), <i>CD45RB</i> (HR = 2.9 [1.4-5.8]), and <i>TNFRSF14</i> (HR = 2.2 [1.1-4.5]) levels predicted pID independent of Δage-correction. <i>CD3ε</i>, <i>CD27</i>, and <i>FOXO1</i> predicted pID only after Δage-correction (HR = 2.5 [1.3-5.1]; 3.7 [1.8-7.8]; 2.1 [1.1-4.3]). AUC analysis identified Δage-<i>CD3ε</i> and Δage<i>-CD27</i> as candidate predictors of pID (AUC = .73 and .75).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Correlations between transcriptional markers of PBTL composition and chronologic age are disrupted in MM. Correcting for normal, age-related trends in biomarker expression unveils new biomarker candidates predictive of ICI outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"1 1-4","pages":"58-70"},"PeriodicalIF":0.0,"publicationDate":"2020-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/aac2.12012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39266853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}