Ocular Surface最新文献

{"title":"Culture- and non-culture-based approaches reveal unique features of the ocular microbiome in dry eye patients","authors":"Maria Naqvi ,&nbsp;Fredrik Fineide ,&nbsp;Tor Paaske Utheim ,&nbsp;Colin Charnock","doi":"10.1016/j.jtos.2024.02.002","DOIUrl":"10.1016/j.jtos.2024.02.002","url":null,"abstract":"<div><h3>Purpose</h3><p>The purpose of this study was to investigate the ocular microbiome in individuals with dry eye disease and to identify features of their ocular microbiome of possible health and diagnostic significance.</p></div><div><h3>Methods</h3><p>Conjunctival samples were collected from both eyes in duplicate from 91 individuals (61 dry eye, 30 healthy) and used for both culture-dependent and culture-independent analyses. Samples were either analysed using next generation sequencing (V3-V4 16S rDNA) or inoculated on a wide range of agar types and grown under a broad range of conditions to maximize recovery. Isolates were identified by partial sequencing of the 16S rDNA and rpoB genes and tested for antibiotic susceptibility. We applied a L2-regularized logistic regression model on the next generation sequencing data to investigate any potential association between severe dry eye disease and the ocular microbiome.</p></div><div><h3>Results</h3><p>Culture-dependent analysis showed the highest number of colony forming units in healthy individuals. The majority of isolates recovered from the samples were <em>Corynebacterium, Micrococcus</em> sp., <em>Staphylococcus epidermidis</em>, and <em>Cutibacterium acnes</em>. Culture independent analysis revealed 24 phyla, of which <em>Actinobacteria, Firmicutes</em> and <em>Proteobacteria</em> were the most abundant. Over 405 genera were detected of which <em>Corynebacterium</em> was the most dominant, followed by <em>Staphylococcus</em> and <em>Cutibacterium.</em> The L2-regularized logistic regression model indicated that <em>Blautia</em> and <em>Corynebacterium</em> sp. may be associated with severe DED.</p></div><div><h3>Conclusions</h3><p>Our study indicates that the ocular microbiome has characteristic features in severe DED patients. Certain <em>Corynebacterium</em> species and <em>Blautia</em> are of particular interest for future studies.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 123-129"},"PeriodicalIF":6.4,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000247/pdfft?md5=a9fb9fc2dbc9e7ff1129a0b6b02b10e5&pid=1-s2.0-S1542012424000247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139737020","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":"Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study","authors":"Michelle Guo ,&nbsp;Gabriela M. Diaz ,&nbsp;Yinxi Yu ,&nbsp;Chandani A. Patel ,&nbsp;John T. Farrar ,&nbsp;Penny A. Asbell ,&nbsp;Gui-Shuang Ying ,&nbsp;Dry Eye Assessment and Management Study Research Group","doi":"10.1016/j.jtos.2024.01.009","DOIUrl":"10.1016/j.jtos.2024.01.009","url":null,"abstract":"<div><h3>Purpose</h3><p>Some systemic medications are reported to be associated with dry eye disease (DED), yet their associations with the severity of DED signs and symptoms are not well studied. To evaluate these associations, we performed a secondary analysis of data from the DRy Eye Assessment and Management (DREAM) Study.</p></div><div><h3>Methods</h3><p>Participants (N = 535) were assessed for DED signs using tear break-up time (TBUT), Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, meibomian gland dysfunction (MGD), and tear osmolarity and DED symptoms using the Ocular Surface Disease Index (OSDI). We derived a composite signs severity score from the 6 DED signs and categorized participant-reported systemic medications into antidepressants, antihistamines, aspirin, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, statins, vitamin D3, and medications for diabetes mellitus, hypertension, hypothyroidism, migraine, and seizure. Generalized linear models were used to compare DED symptom and sign scores between medication users and non-users, with adjustment for factors associated with DED severity.</p></div><div><h3>Results</h3><p>Compared to non-users, antihistamine users had lower TBUT (p = 0.01) and higher OSDI score (p = 0.02); aspirin users had lower TBUT (p = 0.02); corticosteroid users had lower TBUT (p = 0.02), lower Schirmer test scores (p = 0.03), higher cornea fluorescein staining (p = 0.01), higher composite severity score (p = 0.01), and higher OSDI score (p = 0.03); seizure medication users had higher composite severity score (p = 0.02); vitamin D3 users had lower TBUT (p = 0.001) and greater MGD (p = 0.03); and diuretic users had less MGD (p = 0.03).</p></div><div><h3>Conclusions</h3><p>Certain systemic medications may be associated with more severe DED. This may guide prescription practices in patients with DED.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 112-119"},"PeriodicalIF":6.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139670482","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 epidemiology of pediatric dry eye disease in the United States: An IRIS® registry (Intelligent Research in Sight) analysis","authors":"Vivian Paraskevi Douglas,&nbsp;Nathan Hall ,&nbsp;Connor Ross,&nbsp;Konstantinos A.A. Douglas,&nbsp;Tobias Elze,&nbsp;Joan W. Miller ,&nbsp;Alice C. Lorch ,&nbsp;Aisha S. Traish","doi":"10.1016/j.jtos.2024.01.012","DOIUrl":"10.1016/j.jtos.2024.01.012","url":null,"abstract":"<div><h3>Purpose</h3><p>Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology's IRIS® Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients &lt;18 years old) and the demographic differences of DED between pediatric and adult patients (ADED).</p></div><div><h3>Methods</h3><p>Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N = 4,795,979) were included. Descriptive statistics, Pearson's chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts.</p></div><div><h3>Results</h3><p>The average age at onset for ADED patients was 61.06 (±14.75) years and for PDED patients was 12.51 (±3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p &lt; 0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08 % vs. 50.60 %), male sex (41.58 % vs. 48.78 %) and Asian race (6.02 % vs. 3.11 %) respectively. Within the PDED cohort, females were at higher risk of PDED (58 % vs. 42 %). PDED was more prevalent in children with refractive errors (76 %) and eyelid/conjunctival disorders (41 %). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 % vs. 68.12 %), male sex (41.58 % vs. 31.55 %) and Caucasian race (50.24 % vs. 67.06 %) respectively.</p></div><div><h3>Conclusions</h3><p>Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 106-111"},"PeriodicalIF":6.4,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568706","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":"Corrigendum to “Topical formulations of aprepitant are safe and effective in relieving pain and inflammation, and drive neural regeneration” [Ocul Surf 30 (2023) 92–103]","authors":"Filippo Bonelli ,&nbsp;Ibrahim Demirsoy ,&nbsp;Romina Mayra Lasagni Vitar ,&nbsp;Philippe Fonteyne ,&nbsp;Giulio Ferrari","doi":"10.1016/j.jtos.2024.01.011","DOIUrl":"10.1016/j.jtos.2024.01.011","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Page 105"},"PeriodicalIF":6.4,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S154201242400020X/pdfft?md5=ef5ae642640a46ba8846d06d27f75cbf&pid=1-s2.0-S154201242400020X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568415","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":"Single-cell RNA sequencing reveals the complex cellular niche of pterygium","authors":"Xueling Zhang ,&nbsp;Peizhen Han ,&nbsp;Jini Qiu ,&nbsp;Feifei Huang ,&nbsp;Qiting Luo ,&nbsp;Jingyi Cheng ,&nbsp;Kun Shan ,&nbsp;Yujing Yang ,&nbsp;Chaoran Zhang","doi":"10.1016/j.jtos.2024.01.013","DOIUrl":"10.1016/j.jtos.2024.01.013","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Pterygium is a vision-threatening conjunctival fibrovascular degenerated disease with a high global prevalence up to 12 %, while no absolute pharmacotherapy has been applied in clinics. In virtue of single-cell </span>RNA sequencing (scRNA-seq) technique, our study investigated underlying pathogeneses and potential therapeutic targets of pterygium from the cellular transcriptional level.</p></div><div><h3>Methods</h3><p><span>A total of 45605 cells from pterygium of patients and conjunctiva of normal controls (NC) were conducted with scRNA-seq, and then analyzed via integrated analysis, pathway enrichment, pseudotime trajectory, and cell-cell communications. Besides, immunofluorescence and </span>western blot were performed in vivo and in vitro to verify our findings.</p></div><div><h3>Results</h3><p><span><span>In brief, 9 major cellular types were defined, according to canonical markers. Subsequently, we further determined the subgroups of each major cell lineages<span>. Several newly identified cell sub-clusters could promote pterygium, including immuno-fibroblasts, epithelial mesenchymal transition (EMT)-epithelial cells, and activated </span></span>vascular endothelial cells<span> (activated-vEndo). Besides, we also probed the enrichment of immune cells<span> in pterygium. Particularly, macrophages, recruited by ACKR1</span></span></span>⁺<span>activated-vEndo, might play an important role in the development of pterygium by promoting angiogenesis<span>, immune suppression, and inflammation.</span></span></p></div><div><h3>Conclusion</h3><p>An intricate cellular niche was revealed in pterygium via scRNA-seq analysis and the interactions between macrophages and ACKR1⁺ activated-vEndo might be the key part in the development of pterygia.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 91-103"},"PeriodicalIF":6.4,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139568527","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":"Corrigendum to “TFOS lifestyle: Impact of lifestyle challenges on the ocular surface” [Ocul Surf 28 (2023) 262–303]","authors":"Anat Galor ,&nbsp;Alexis Ceecee Britten-Jones ,&nbsp;Yun Feng ,&nbsp;Giulio Ferrari ,&nbsp;David Goldblum ,&nbsp;Preeya K. Gupta ,&nbsp;Jesus Merayo-Lloves ,&nbsp;Kyung-Sun Na ,&nbsp;Shehzad A. Naroo ,&nbsp;Kelly K. Nichols ,&nbsp;Eduardo M. Rocha ,&nbsp;Louis Tong ,&nbsp;Michael T.M. Wang ,&nbsp;Jennifer P. Craig","doi":"10.1016/j.jtos.2024.01.010","DOIUrl":"10.1016/j.jtos.2024.01.010","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Page 104"},"PeriodicalIF":6.4,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1542012424000193/pdfft?md5=bb650bd212273a9a869d13248efa3ee8&pid=1-s2.0-S1542012424000193-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562528","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":"Corneal acetylcholine regulates sensory nerve activity via nicotinic receptors","authors":"Takayoshi Masuoka ,&nbsp;Takeshi Kiyoi ,&nbsp;Shijie Zheng ,&nbsp;Qiang He ,&nbsp;Li Liu ,&nbsp;Junsuke Uwada ,&nbsp;Ikunobu Muramatsu","doi":"10.1016/j.jtos.2024.01.006","DOIUrl":"10.1016/j.jtos.2024.01.006","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Sensory nerve terminals are highly distributed in the cornea, and regulate ocular surface sensation and </span>homeostasis<span> in response to various endogenous and exogenous stimuli. However, little is known about mediators regulating the physiological and pathophysiological activities of corneal sensory nerves. The aim of this study was to investigate the presence of cholinergic regulation in sensory nerves in the cornea.</span></p></div><div><h3>Methods</h3><p><span>Localization of choline<span> acetyltransferase (ChAT) and vesicular acetylcholine<span> transporter (vAChT) was evaluated using western blotting and immunohistochemical analysis. The synthesis and liberation of acetylcholine from the cornea were assessed using corneal segments pre-incubated with [</span></span></span>³<span><span>H]choline. The responsiveness of corneal neurons and nerves to cholinergic drugs was explored using calcium imaging with primary cultures of trigeminal </span>ganglion neurons and extracellular recording from corneal preparations in guinea pigs.</span></p></div><div><h3>Results</h3><p><span>ChAT, but not vAChT, was highly distributed in the corneal epithelium. In corneal segments, [</span>³H] acetylcholine was synthesized from [³<span><span>H]choline, and was also released in response to electrical stimuli. In cultured corneal neurons, the population sensitive to a transient receptor potential melastatin 8 (TRPM8) agonist exhibited high probability of responding to nicotine in a calcium imaging experiment. The firing frequency of cold-sensitive </span>corneal nerves<span> was increased by the application of nicotine, but diminished by an α4 nicotinic acetylcholine receptor antagonist.</span></span></p></div><div><h3>Conclusions</h3><p>The corneal epithelium can synthesize and release acetylcholine. Corneal acetylcholine can excite sensory nerves via nicotinic receptors containing the α4 subunit. Therefore, corneal acetylcholine may be one of the important regulators of corneal nerve activity arranging ocular surface condition and sensation.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 60-70"},"PeriodicalIF":6.4,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489212","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":"Readership awareness series – Paper 8: Research ethics and ‘editorial expressions of concern’","authors":"Mohammad Javed Ali,&nbsp;Ali Djalilian","doi":"10.1016/j.jtos.2024.01.007","DOIUrl":"10.1016/j.jtos.2024.01.007","url":null,"abstract":"","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 58-59"},"PeriodicalIF":6.4,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489358","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 Yin and Yang of non-immune and immune responses in meibomian gland dysfunction","authors":"Cole J. Beatty ,&nbsp;Raul E. Ruiz-Lozano M.D. ,&nbsp;Manuel E. Quiroga-Garza M.D. ,&nbsp;Victor L. Perez M.D. ,&nbsp;James V. Jester PhD ,&nbsp;Daniel R. Saban PhD","doi":"10.1016/j.jtos.2024.01.004","DOIUrl":"10.1016/j.jtos.2024.01.004","url":null,"abstract":"<div><p><span>Meibomian gland dysfunction<span> (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation – functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and </span></span>atopy<span>, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.</span></p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 81-90"},"PeriodicalIF":6.4,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436761","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":"Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43","authors":"Jun Wu ,&nbsp;Nu Chen ,&nbsp;Elizabeth Grau ,&nbsp;Luke Johnson ,&nbsp;Yongqing Liu ,&nbsp;Chi Li ,&nbsp;Patrick A. Scott ,&nbsp;Chang Kim ,&nbsp;Deming Sun ,&nbsp;Henry J. Kaplan ,&nbsp;Hui Shao","doi":"10.1016/j.jtos.2024.01.005","DOIUrl":"10.1016/j.jtos.2024.01.005","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>Short chain fatty acids (SCFAs) produced by </span>gut microbiota<span> are known to play primary roles in gut homeostasis<span><span> by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of </span>TLR ligand induced </span></span></span>keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye.</p></div><div><h3>Methods</h3><p>Both human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope<span><span>. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal </span>fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount.</span></p></div><div><h3>Results</h3><p>GPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells.</p></div><div><h3>Conclusions</h3><p>This is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.</p></div>","PeriodicalId":54691,"journal":{"name":"Ocular Surface","volume":"32 ","pages":"Pages 48-57"},"PeriodicalIF":6.4,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436744","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}