Progress in Retinal and Eye Research最新文献

{"title":"Cellular component transfer between photoreceptor cells of the retina.","authors":"Joyce Wang, Patrick O Nnoromele, Ying V Liu, Robert J Johnston, Mandeep S Singh","doi":"10.1016/j.preteyeres.2024.101317","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101317","url":null,"abstract":"<p><p>Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as \"cell replacement\" in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections. The discovery of CCT in the transplantation context triggered a re-interpretation of prior transplantation studies that generally did not include specific CCT assays and thereby broadly emphasized the cell replacement model, reflecting the prevailing understanding of retinal transplantation biology at that time. In addition to clarifying our understanding of photoreceptor biology, CCT has raised the possibility of developing treatments to replenish molecular deficiencies in diseased photoreceptor cells. As the CCT field evolves, investigators have used diverse terminology, and implemented different CCT assays following transplantation in animal models. The non-standardized terminology of CCT and absent minimal assay standards for detection can hinder communication between investigators and comparison between studies. In this review, we discuss the current understanding of CCT, provide an overview of transplantation and regeneration studies in small and large animals, and propose terminology and a minimal assay standard for CCT. Further research on CCT may eventually provide new avenues to treat a range of hereditary and acquired retinopathies while illuminating mechanisms of cell-cell interaction in the retina.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":" ","pages":"101317"},"PeriodicalIF":18.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of epigenetics in corneal health and disease.","authors":"Swati Sood, Anil Tiwari, Jyoti Sangwan, Mehak Vohra, Nishant R Sinha, Ratnakar Tripathi, Virender S Sangwan, Rajiv R Mohan","doi":"10.1016/j.preteyeres.2024.101318","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101318","url":null,"abstract":"<p><p>Epigenetics plays a vital role in corneal health and diseases. Epigenetic changes regulate the expression of genes by altering the accessibility of chromatin via histone modifications, DNA methylation and miRNAs without altering DNA sequence. Ocular trauma and infections are common causes of corneal damage, vision impairment, and mono/bilateral blindness worldwide. Mounting literature shows that epigenetic modifications can modulate corneal clarity, function, and pathogenesis including inflammation, wound healing, fibrosis, and neovascularization. Additionally, epigenetic modifications can be targeted to reverse corneal pathologies and develop interventional therapies. However, current understanding on how epigenetic modifications lead to corneal abnormalities and diseases is limited. This review provides in-depth knowledge and mechanistic understanding of epigenetics alterations in corneal pathogenesis, and information on potential epigenetic targets for treatment of corneal diseases.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":" ","pages":"101318"},"PeriodicalIF":18.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual inheritance patterns: A spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms","authors":"Lara K. Holtes,&nbsp;Suzanne E. de Bruijn,&nbsp;Frans P.M. Cremers,&nbsp;Susanne Roosing","doi":"10.1016/j.preteyeres.2024.101308","DOIUrl":"10.1016/j.preteyeres.2024.101308","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs) encompass a variety of disease phenotypes and are known to display both clinical and genetic heterogeneity. A further complexity is that for several IRD-associated genes, pathogenic variants have been reported to cause either autosomal dominant (AD) or autosomal recessive (AR) diseases. The possibility of dual inheritance can create a challenge for variant interpretation as well as the genetic counselling of patients. This review aims to determine whether the molecular mechanisms behind the dual inheritance of each IRD-associated gene is well established, not yet properly understood, or if the association is questionable. Each gene is discussed individually in detail due to different protein structures and functions, but there are overlapping characteristics. For example, eight genes only have a limited number of reported pathogenic variants or a hotspot region implicated in the second inheritance pattern. Whereas <em>CRX</em> and <em>RP1</em> display distinct spatial patterns for AR and AD pathogenic variants based on the variant type and/or location. The genes with a questionable dual inheritance, namely <em>AIPL1</em>, <em>CRB1,</em> and <em>RCBTB1</em> highlight the importance of carefully considering allele frequency data. Finally, the crucial role relevant functional studies in animal and cell models play in validating a variant's biochemical or molecular effect is emphasised.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101308"},"PeriodicalIF":18.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eye on the horizon: The metabolic landscape of the RPE in aging and disease","authors":"David S. Hansman ,&nbsp;Jianhai Du ,&nbsp;Robert J. Casson ,&nbsp;Daniel J. Peet","doi":"10.1016/j.preteyeres.2024.101306","DOIUrl":"10.1016/j.preteyeres.2024.101306","url":null,"abstract":"<div><div>To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress – all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101306"},"PeriodicalIF":18.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standard automated perimetry for glaucoma and diseases of the retina and visual pathways: current and future perspectives.","authors":"Jack Phu, Sieu K Khuu, Lisa Nivison-Smith, Michael Kalloniatis","doi":"10.1016/j.preteyeres.2024.101307","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101307","url":null,"abstract":"<p><p>Static automated perimetry (SAP) remains a mainstay of functional assessment of the visual field in diseases of the visual pathway, such as glaucoma and age-related macular degeneration. The fundamental psychophysical task of responding to stimuli of different levels of contrast has remained minimally changed since its inception in the 1980s, and this is potentially the root of several unresolved issues involving the technique. Enduring issues include the optimisation of SAP parameters for maximising defect detection, the influence of subjective behaviour on the response, structure-function discordance, and ageing- and disease-related changes of the visual pathway. Addressing these issues has been a focus of our research program and is the subject of this manuscript. We will review some of the basic psychophysical principles and methods that have contributed to the development of SAP and their contributions to its output measurements. Parameters that are interrogated include stimulus size and background luminance and their modification to improve defect defection in glaucoma and age-related macular degeneration. We propose frameworks for optimising testing parameters and leveraging the results for changing clinical care. In our pursuit of optimising the structure-function relationship in the eye, several areas of research have been developed and explored, including: the reconciliation of subjective responses in perimetry; by minimising sources of biases, such as Method of Limits we have been able to equate static and kinetic perimetry outputs in relation to underlying structural loci. This also formed the basis for our clustering framework, which groups together statistically similar structural and functional test locations to maximise structure-function concordance. Throughout the manuscript, we review the scientific underpinnings of clinical measurements, framing application into real-world patients to improve clinical practice.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":" ","pages":"101307"},"PeriodicalIF":18.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathobiology of the crystalline lens in Stickler syndrome","authors":"Martin P. Snead ,&nbsp;Frank J. Lovicu ,&nbsp;Thomas RW. Nixon ,&nbsp;Allan J. Richards ,&nbsp;Howard Martin","doi":"10.1016/j.preteyeres.2024.101304","DOIUrl":"10.1016/j.preteyeres.2024.101304","url":null,"abstract":"<div><h3>Purpose</h3><div>The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract.</div></div><div><h3>Methods</h3><div>Author observations drawn from a cohort of over 1800 patients with genetically confirmed Stickler syndrome.</div></div><div><h3>Results</h3><div>3 distinct lens pathologies were identified. Firstly, a congenital quadrantic lamellar opacity. This can be present in both type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome. Secondly, early onset Pantone 557 C blue-green nuclear cataract. Thirdly, congenital lens coloboma associated with localised zonule deficiency.</div></div><div><h3>Conclusions</h3><div>The characteristic quadrantic lamellar lens opacity can be helpful in alerting to the possible diagnosis, particularly in sub-groups with an ocular-only phenotype.</div><div>Temporal and spatial signalling pathways shared embryologically by both the developing vitreous body and crystalline lens suggest an ancillary role of the fibrillar collagens in cell signalling beyond their basic structural function. A common pathway of TGFβ/BMP super-family dysregulation may be shared with allied disorders associated with both retinal detachment and cataract as well as the pathobiology linking retinal detachment and cataract in the population at large.</div><div>Congenital lens coloboma associated with localised zonule deficiency can increase the difficulty and risks of cataract surgery. Strategies to mitigate such risks are presented.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101304"},"PeriodicalIF":18.6,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI in the clinical management of GA: A novel therapeutic universe requires novel tools","authors":"Gregor S. Reiter,&nbsp;Julia Mai,&nbsp;Sophie Riedl,&nbsp;Klaudia Birner,&nbsp;Sophie Frank,&nbsp;Hrvoje Bogunovic,&nbsp;Ursula Schmidt-Erfurth","doi":"10.1016/j.preteyeres.2024.101305","DOIUrl":"10.1016/j.preteyeres.2024.101305","url":null,"abstract":"<div><div>Regulatory approval of the first two therapeutic substances for the management of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a major breakthrough following failure of numerous previous trials. However, in the absence of therapeutic standards, diagnostic tools are a key challenge as functional parameters in GA are hard to provide. The majority of anatomical biomarkers are subclinical, necessitating advanced and sensitive image analyses. In contrast to fundus autofluorescence (FAF), optical coherence tomography (OCT) provides high-resolution visualization of neurosensory layers, including photoreceptors, and other features that are beyond the scope of human expert assessment. Artificial intelligence (AI)-based methodology strongly enhances identification and quantification of clinically relevant GA-related sub-phenotypes. Introduction of OCT-based biomarker analysis provides novel insight into the pathomechanisms of disease progression and therapeutic, moving beyond the limitations of conventional descriptive assessment. Accordingly, the Food and Drug Administration (FDA) has provided a paradigm-shift in recognizing ellipsoid zone (EZ) attenuation as a primary outcome measure in GA clinical trials. In this review, the transition from previous to future GA classification and management is described. With the advent of AI tools, diagnostic and therapeutic concepts have changed substantially in monitoring and screening of GA disease. Novel technology combined with pathophysiological knowledge and understanding of the therapeutic response to GA treatments, is currently opening the path for an automated, efficient and individualized patient care with great potential to improve access to timely treatment and reduce health disparities.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101305"},"PeriodicalIF":18.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between intraocular pressure and glaucoma: An evolving concept","authors":"Sanjay G. Asrani ,&nbsp;Elyse J. McGlumphy ,&nbsp;Lama A. Al-Aswad ,&nbsp;Craig J. Chaya ,&nbsp;Shan Lin ,&nbsp;David C. Musch ,&nbsp;Ian Pitha ,&nbsp;Alan L. Robin ,&nbsp;Barbara Wirostko ,&nbsp;Thomas V. Johnson","doi":"10.1016/j.preteyeres.2024.101303","DOIUrl":"10.1016/j.preteyeres.2024.101303","url":null,"abstract":"<div><div>Intraocular pressure (IOP) is the most important modifiable risk factor for glaucoma and fluctuates considerably within patients over short and long time periods. Our field's understanding of IOP has evolved considerably in recent years, driven by tonometric technologies with increasing accuracy, reproducibility, and temporal resolution that have refined our knowledge regarding the relationship between IOP and glaucoma risk and pathogenesis. The goal of this article is to review the published literature pertinent to the following points: 1) the factors that determine IOP in physiologic and pathologic states; 2) technologies for measuring IOP; 3) scientific and clinical rationale for measuring diverse IOP metrics in patients with glaucoma; 4) the impact and shortcomings of current standard-of-care IOP monitoring approaches; 5) recommendations for approaches to IOP monitoring that could improve patient outcomes; and 6) research questions that must be answered to improve our understanding of how IOP contributes to disease progression. Retrospective and prospective data, including that from landmark clinical trials, document greater IOP fluctuations in glaucomatous than healthy eyes, tendencies for maximal daily IOP to occur outside of office hours, and, in addition to mean and maximal IOP, an association between IOP fluctuation and glaucoma progression that is independent of mean in-office IOP. Ambulatory IOP monitoring, measuring IOP outside of office hours and at different times of day and night, provides clinicians with discrete data that could improve patient outcomes. Eye care clinicians treating glaucoma based on isolated in-office IOP measurements may make treatment decisions without fully capturing the entire IOP profile of an individual. Data linking home blood pressure monitors and home glucose sensors to dramatically improved outcomes for patients with systemic hypertension and diabetes and will be reviewed as they pertain to the question of whether ambulatory tonometry is positioned to do the same for glaucoma management. Prospective randomized controlled studies are warranted to determine whether remote tonometry-based glaucoma management might reduce vision loss and improve patient outcomes.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101303"},"PeriodicalIF":18.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocular adverse events associated with antibody-drug conjugates used in cancer: Focus on pathophysiology and management strategies","authors":"Eric E. Gabison ,&nbsp;Antoine Rousseau ,&nbsp;Marc Labetoulle ,&nbsp;Anas Gazzah ,&nbsp;Benjamin Besse","doi":"10.1016/j.preteyeres.2024.101302","DOIUrl":"10.1016/j.preteyeres.2024.101302","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) are designed to maximize cancer cell death with lower cytotoxicity toward noncancerous cells and are an increasingly valuable option for targeted cancer therapies. However, anticancer treatment with ADCs may be associated with ocular adverse events (AEs) such as dry eye, conjunctivitis, photophobia, blurred vision, and corneal abnormalities. While the pathophysiology of ADC-related ocular AEs has not been fully elucidated, most ocular AEs are attributed to off-target effects. Product labelling for approved ADCs includes drug-specific guidance for dose modification and management of ocular AEs; however, limited data are available regarding effective strategies to minimize and mitigate ocular AEs. Overall, the majority of ocular AEs are reversible through dose modification or supportive care. Eye care providers play key roles in monitoring patients receiving ADC therapy for ocular signs and symptoms to allow for the early detection of ADC-related ocular AEs and to ensure the timely administration of appropriate treatment. Therefore, awareness is needed to help ophthalmologists to identify treatment-related ocular AEs and provide effective management in collaboration with oncologists as part of the patient's cancer care team. This review provides an overview of ocular AEs that may occur with approved and investigational ADC anticancer treatments, including potential underlying mechanisms for ADC-related ocular AEs. It also discusses clinical management practices relevant to ophthalmologists for prevention, monitoring, and management of ADC-related ocular AEs. In collaboration with oncologists, ophthalmologists play a vital role in caring for patients with cancer by assisting with the prompt recognition, mitigation, and management of treatment-related ocular AEs.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101302"},"PeriodicalIF":18.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health","authors":"Elena K. Schneider-Futschik ,&nbsp;Yimin Zhu ,&nbsp;Danni Li ,&nbsp;Mark D. Habgood ,&nbsp;Bao N. Nguyen ,&nbsp;Ines Pankonien ,&nbsp;Margarida D. Amaral ,&nbsp;Laura E. Downie ,&nbsp;Holly R. Chinnery","doi":"10.1016/j.preteyeres.2024.101299","DOIUrl":"10.1016/j.preteyeres.2024.101299","url":null,"abstract":"<div><div>Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that plays a crucial role in various human organs, including the respiratory and digestive systems. Dysfunctional CFTR is the key variant of the lethal genetic disorder, cystic fibrosis (CF). In the past decade, highly effective CFTR modulator therapies, including elexacaftor-tezacaftor-ivacaftor, have revolutionised CF management by correcting the underlying molecular defect to improve patient outcomes and life expectancy. Despite demonstrating multiorgan efficacy, clinical studies have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of crystalline lens pathologies in young children on CFTR modulators, and in breastfed infants born to individuals who were on CFTR modulator treatment during pregnancy. CFTR is present in multiple tissues during embryonic development, including the eye, and its expression can be influenced by genetic and environmental factors. This review summarises the role of CFTR in the eye, and the potential impact of CFTR on eye function and vision later in life. This information provides a framework for understanding the use and possible effects of CFTR-modulating therapeutics in the context of eye health, including the potential to leverage the eye for non-invasive and accessible diagnostic and monitoring capabilities in patients with CF.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101299"},"PeriodicalIF":18.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}