Mutation Research-Reviews in Mutation Research最新文献

{"title":"Recommendations and quality criteria for micronucleus studies with humans","authors":"A. Nersesyan ,&nbsp;M. Kundi ,&nbsp;M. Fenech ,&nbsp;H. Stopper ,&nbsp;J. da Silva ,&nbsp;C. Bolognesi ,&nbsp;M. Mišík ,&nbsp;S. Knasmueller","doi":"10.1016/j.mrrev.2021.108410","DOIUrl":"10.1016/j.mrrev.2021.108410","url":null,"abstract":"<div><p>Micronucleus (MN) analyses in peripheral blood lymphocytes and exfoliated cells from different organs (mouth, nose, bladder and cervix) are at present the most widely used approaches to detect damage of genetic material in humans. MN are extranuclear DNA-containing bodies, which can be identified microscopically. They reflect structural and numerical chromosomal aberrations and are formed as a consequence of exposure to occupational, environmental and lifestyle genotoxins. They are also induced as a consequence of inadequate intake of certain trace elements and vitamins. High MN rates are associated with increased risk of cancer and a range of non-cancer diseases in humans. Furthermore, evidence is accumulating that measurements of MN could be a useful tool for the diagnosis and prognosis of different forms of cancer and other diseases (inflammation, infections, metabolic disorders) and for the assessment of the therapeutic success of medical treatments. Recent reviews of the current state of knowledge suggest that many clinical studies have methodological shortcomings. This could lead to controversial findings and limits their usefulness in defining the impact of exposure concentrations of hazardous chemicals, for the judgment of remediation strategies, for the diagnosis of diseases and for the identification of protective or harmful dietary constituents. This article describes important quality criteria for human MN studies and contains recommendations for acceptable study designs. Important parameters that need more attention include sufficiently large group sizes, adequate duration of intervention studies, the exclusion of confounding factors which may affect the results (sex, age, body mass index, nutrition, etc.), the evaluation of appropriate cell numbers per sample according to established scoring criteria as well as the use of proper stains and adequate statistical analyses.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108410"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46162972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review","authors":"Samantha Goodman ,&nbsp;Grace Chappell ,&nbsp;Kathryn Z. Guyton ,&nbsp;Igor P. Pogribny ,&nbsp;Ivan Rusyn","doi":"10.1016/j.mrrev.2021.108408","DOIUrl":"10.1016/j.mrrev.2021.108408","url":null,"abstract":"<div><p><span><span><span>Epigenetic alterations, such as changes in DNA </span>methylation, histones/chromatin structure, </span>nucleosome positioning<span>, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, </span></span><em>in vivo</em> exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108408"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent driver mutations in benign tumors","authors":"Carolina Cavalieri Gomes","doi":"10.1016/j.mrrev.2022.108412","DOIUrl":"10.1016/j.mrrev.2022.108412","url":null,"abstract":"<div><p><span>The understanding of the molecular pathogenesis<span><span> of benign tumors<span> may bring essential information to clarify the process of tumorigenesis, and ultimately improve the understanding of events such as malignant transformation<span>. The definition of benign neoplasia is not always straightforward and herein the issues surrounding this concept are discussed. Benign neoplasms share all cancer hallmarks with malignancies, except for metastatic potential<span>. Recently, next-generation sequencing has provided unprecedented opportunities to unravel the genetic basis of benign neoplasms and, so far, we have learned that benign neoplasms are indeed characterized by the presence of </span></span></span></span>genetic mutations<span>, including genes rearrangements. Driver mutations in advanced cancer are those that confer growth advantage, and which have been positively selected during cancer evolution. Herein, some discussion will be brought about this concept in the context of cancer prevention, involving precursor lesions and benign neoplasms. When considering early detection and cancer prevention, a driver mutation should not only be advantageous (</span></span></span><em>i.e.,</em> confer survival advantage), but predisposing (<em>i.e.,</em> promoting a cancer phenotype). By including the benign counterparts of malignant neoplasms in tumor biology studies, it is possible to evaluate the risk posed by a given mutation and to differentiate advantageous from predisposing mutations, further refining the concept of driver mutations. Therefore, the study of benign neoplasms should be encouraged because it provides valuable information on tumorigenesis central for understanding the progression from initiation to malignant transformation.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108412"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42229217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the structural features of the xeroderma pigmentosum proteins: Focus on mutations and knowledge gaps","authors":"Bruno César Feltes","doi":"10.1016/j.mrrev.2022.108416","DOIUrl":"10.1016/j.mrrev.2022.108416","url":null,"abstract":"<div><p><span>The nucleotide excision repair pathway is a broadly studied DNA repair mechanism because impairments of its key players, the </span>xeroderma pigmentosum proteins (XPA to XPG), are associated with multiple hereditary diseases. Due to the massive number of novel mutations reported for these proteins and new structural data published every year, proper categorization and discussion of relevant observations is needed to organize this extensive inflow of knowledge. This review aims to revisit the structural data of all XP proteins while updating it with the information developed in of the past six years. Discussions and interpretations of mutation outcomes, mechanisms of action, and knowledge gaps regarding their structures are provided, as well as new perspectives based on recent research.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108416"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42401128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA damage, DNA repair and carcinogenicity: Tobacco smoke versus electronic cigarette aerosol","authors":"Moon-shong Tang ,&nbsp;Hyun-Wook Lee ,&nbsp;Mao-wen Weng ,&nbsp;Hsiang-Tsui Wang ,&nbsp;Yu Hu ,&nbsp;Lung-Chi Chen ,&nbsp;Sung-Hyun Park ,&nbsp;Huei-wei Chan ,&nbsp;Jiheng Xu ,&nbsp;Xue-Ru Wu ,&nbsp;He Wang ,&nbsp;Rui Yang ,&nbsp;Karen Galdane ,&nbsp;Kathryn Jackson ,&nbsp;Annie Chu ,&nbsp;Elizabeth Halzack","doi":"10.1016/j.mrrev.2021.108409","DOIUrl":"10.1016/j.mrrev.2021.108409","url":null,"abstract":"<div><p>The allure of tobacco smoking is linked to the instant gratification provided by inhaled nicotine. Unfortunately, tobacco curing and burning generates many mutagens including more than 70 carcinogens. There are two types of mutagens and carcinogens in tobacco smoke (TS): direct DNA damaging carcinogens and procarcinogens, which require metabolic activation to become DNA damaging. Recent studies provide three new insights on TS-induced DNA damage. First, two major types of TS DNA damage are induced by direct carcinogen aldehydes, cyclic-1,<em>N²</em>-hydroxy-deoxyguanosine (γ-OH-PdG) and α-methyl-1, <em>N²</em>-γ-OH-PdG, rather than by the procarcinogens, polycyclic aromatic hydrocarbons and aromatic amines. Second, TS reduces DNA repair proteins and activity levels. TS aldehydes also prevent procarcinogen activation. Based on these findings, we propose that aldehydes are major sources of TS induce DNA damage and a driving force for carcinogenesis. E-cigarettes (E-cigs) are designed to deliver nicotine in an aerosol state, without burning tobacco. E-cigarette aerosols (ECAs) contain nicotine, propylene glycol and vegetable glycerin. ECAs induce O⁶-methyl-deoxyguanosines (O⁶-medG) and cyclic γ-hydroxy-1,<em>N²</em><span>--propano-dG (γ-OH-PdG) in mouse lung, heart and bladder tissues and causes a reduction of DNA repair proteins and activity in lungs. Nicotine and nicotine-derived nitrosamine ketone (NNK) induce the same types of DNA adducts and cause DNA repair inhibition in human cells. After long-term exposure, ECAs induce lung adenocarcinoma and bladder urothelial hyperplasia in mice. We propose that E-cig nicotine can be nitrosated in mouse and human cells becoming nitrosamines, thereby causing two carcinogenic effects, induction of DNA damage and inhibition of DNA repair, and that ECA is carcinogenic in mice. Thus, this article reviews the newest literature on DNA adducts and DNA repair inhibition induced by nicotine and ECAs in mice and cultured human cells, and provides insights into ECA carcinogenicity in mice.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108409"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of mentoring in the careers of geneticists","authors":"Elof Axel Carlson","doi":"10.1016/j.mrrev.2022.108417","DOIUrl":"10.1016/j.mrrev.2022.108417","url":null,"abstract":"<div><p>This commentary reflects on the importance of mentoring in science education. It is written from the perspective of a geneticist and historian of science, but its implications extend to many other fields. A lineage of mentoring is traced from the author's educational experience back through several centuries in the form of an intellectual pedigree.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108417"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49430184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation","authors":"Olivia Solomon ,&nbsp;Karen Huen ,&nbsp;Paul Yousefi ,&nbsp;Leanne K. Küpers ,&nbsp;Juan R. González ,&nbsp;Matthew Suderman ,&nbsp;Sarah E. Reese ,&nbsp;Christian M. Page ,&nbsp;Olena Gruzieva ,&nbsp;Peter Rzehak ,&nbsp;Lu Gao ,&nbsp;Kelly M. Bakulski ,&nbsp;Alexei Novoloaca ,&nbsp;Catherine Allard ,&nbsp;Irene Pappa ,&nbsp;Maria Llambrich ,&nbsp;Marta Vives ,&nbsp;Dereje D. Jima ,&nbsp;Tuomas Kvist ,&nbsp;Andrea Baccarelli ,&nbsp;Nina Holland","doi":"10.1016/j.mrrev.2022.108415","DOIUrl":"10.1016/j.mrrev.2022.108415","url":null,"abstract":"<div><h3>Background</h3><p>Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.</p></div><div><h3>Methods</h3><p>We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268).</p></div><div><h3>Results</h3><p>In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (<em>p</em> &lt; 1.3 × 10⁻⁷) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (<em>p</em> &lt; 1.1 × 10⁻⁶) in older children and had methylation differences in the same direction.</p></div><div><h3>Conclusions</h3><p>This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108415"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623595/pdf/nihms-1829703.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9150913","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":"Genotoxicity evaluation of medical devices: A regulatory perspective","authors":"Tirukalikundram S. Kumaravel ,&nbsp;Tiruvathipuram N. Sathya ,&nbsp;Ramalingam Balaje ,&nbsp;Pitchaipillai Pradeepa ,&nbsp;Desikan Yogaraj ,&nbsp;Malliga R. Murali ,&nbsp;K.R. Navaneethakrishnan ,&nbsp;Sivasubramanian Murugan ,&nbsp;Awadhesh N. Jha","doi":"10.1016/j.mrrev.2021.108407","DOIUrl":"10.1016/j.mrrev.2021.108407","url":null,"abstract":"<div><p><span>This review critically evaluates our current regulatory understanding of genotoxicity testing and risk assessment of medical devices. Genotoxicity risk assessment of these devices begins with the evaluation of materials of construction, manufacturing additives and all residual materials for potential to induce DNA damage. This is followed by extractable and/or leachable (E&amp;L) studies to understand the worst case and/or clinical exposures, coupled with risk assessment of extractables or leachables. The TTC (Threshold of Toxicological Concern) approach is used to define acceptable levels of genotoxic chemicals, when identified. Where appropriate, </span><em>in silico</em> predictions may be used to evaluate the genotoxic potentials of identifiable chemicals with limited toxicological data and above the levels defined by TTC. Devices that could not be supported by E&amp;L studies are evaluated by <em>in vitro</em><span> genotoxicity studies conducted in accordance with ISO10993-3 and 33. Certain endpoints such as ‘site of contact genotoxicity’ that are specific for certain classes of medical devices are currently not addressed in the current standards. The review also illustrates the potential uses of recent advances to achieve the goal of robust genotoxicity assessment of medical devices which are being increasingly used for health benefits. The review also highlights the gaps for genotoxicity risk assessment of medical devices and suggests possible approaches to address them taking into consideration the recent advances in genotoxicity testing including their potential uses in biocompatibility assessment.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108407"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42533687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of hypoxanthine guanine phosphoribosyltransferase mutant T cells in human blood: The concept of surrogate selection for immunologically relevant cells","authors":"Noah A. Kaitz ,&nbsp;Cindy L. Zuleger ,&nbsp;Peng Yu ,&nbsp;Michael A. Newton ,&nbsp;Richard J. Albertini ,&nbsp;Mark R. Albertini","doi":"10.1016/j.mrrev.2022.108414","DOIUrl":"10.1016/j.mrrev.2022.108414","url":null,"abstract":"<div><p><span><span>Somatic cell </span>gene mutations<span><span><span> arise in vivo due to replication errors during DNA synthesis<span> occurring spontaneously during normal DNA synthesis or as a result of replication on a DNA template damaged by endogenous or exogenous </span></span>mutagens<span>. In principle, changes in the frequencies of mutant cells in vivo in humans reflect changes in exposures to exogenous or endogenous DNA damaging insults, other factors being equal. It is becoming increasingly evident however, that </span></span>somatic mutations<span><span> in humans have a far greater range of interpretations. For example, mutations in lymphocytes provide invaluable probes for in vivo cellular and molecular processes, providing identification of clonal amplifications of these cells in autoimmune and infectious diseases, transplantation recipients, paroxysmal nocturnal hemoglobinuria (PNH), and cancer. The assay for mutations of the X-chromosomal hypoxanthine </span>guanine phosphoribosyltransferase (</span></span></span><em>HPRT</em>) gene has gained popular acceptance for this purpose since viable mutant cells can be recovered for molecular and other analyses. Although the major application of the <em>HPRT</em><span> T cell assay remains human population monitoring, the enrichment of activated T cells in the mutant fraction in individuals with ongoing immunological processes has demonstrated the utility of surrogate selection, a method that uses somatic mutation as a surrogate marker for the in vivo T cell proliferation that underlies immunological processes to investigate clinical disorders with immunological features. Studies encompassing a wide range of clinical conditions are reviewed. Despite the historical importance of the </span><em>HPRT</em> mutation system in validating surrogate selection, there are now additional mutational and other methods for identifying immunologically active T cells. These methods are reviewed and provide insights for strategies to extend surrogate selection in future studies.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108414"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9454872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of COVID-19 in the induction of DNA damage","authors":"Pablo Pánico,&nbsp;Patricia Ostrosky-Wegman,&nbsp;Ana María Salazar","doi":"10.1016/j.mrrev.2022.108411","DOIUrl":"10.1016/j.mrrev.2022.108411","url":null,"abstract":"<div><p>The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is challenging global health and economic systems. In some individuals, COVID-19 can cause a wide array of symptoms, affecting several organs, such as the lungs, heart, bowels, kidneys and brain, causing multiorgan failure, sepsis and death. These effects are related in part to direct viral infection of these organs, immunological deregulation, a hypercoagulatory state and the potential for development of cytokine storm syndrome. Since the appearance of COVID-19 is recent, the long-term effects on the health of recovered patients remain unknown. In this review, we focused on current evidence of the mechanisms of DNA damage mediated by coronaviruses. Data supports that these viruses can induce DNA damage, genomic instability, and cell cycle deregulation during their replication in mammalian cells. Since the induction of DNA damage and aberrant DNA repair mechanisms are related to the development of chronic diseases such as cancer, diabetes, neurodegenerative disorders, and atherosclerosis, it will be important to address similar effects and outcomes in recovered COVID-19 patients.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108411"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10811554","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}