ERJ Open ResearchPub Date : 2024-07-18DOI: 10.1183/23120541.00312-2024
S. Law, G. Hardisty, J. Gillan, Nicola J Robinson, Donald J Davidson, Moira KB Whyte, Ian Dransfield, Robert D Gray
{"title":"Neutrophil extracellular traps are associated with airways inflammation and increased severity of lung disease in Cystic Fibrosis","authors":"S. Law, G. Hardisty, J. Gillan, Nicola J Robinson, Donald J Davidson, Moira KB Whyte, Ian Dransfield, Robert D Gray","doi":"10.1183/23120541.00312-2024","DOIUrl":"https://doi.org/10.1183/23120541.00312-2024","url":null,"abstract":"Cystic Fibrosis (CF) is characterised by inflammatory lung disease and large numbers of airways neutrophils. In health, neutrophils undergo apoptosis and removal from the airway. Since CF neutrophils are known to engage in apoptosis less efficiently, we wanted to assess whether alternative forms of neutrophil clearance such as NETosis were prominent in the CF airway.Sputum and blood were collected from 45 CF and 15 healthy control (HC) participants. Neutrophil morphology and biochemical properties were assessed in CF and HC sputum. Neutrophil Extracellular Traps (NETs) were measured by a novel histone-calprotectin ELISA. NET levels were compared to established measurements of airway inflammation. CF participants were followed up for one year and number of exacerbations recorded. Neutrophil and macrophage co-culture experiments were undertaken with cells from CF and HC.Neutrophil numbers were significantly higher in CF and associated with abnormal morphology. Several inflammatory mediators were elevated in CF sputum, as was cell-free DNA. This was highly correlated with sputum calprotectin, a known NET associated protein. Using a Histone/Calprotectin NETs ELISA, we demonstrated higher levels of NETs in the CF airway. CF participants treated with DNase had less sputum NETs, and in neutrophil/macrophage co-culture experiments, DNase effectively attenuated the pro-inflammatory potential of NETs, suggesting a previously unrecognised anti-inflammatory role for this treatment.NETs in the CF airway are associated with increased levels of inflammatory mediators and more severe lung disease. NETs effects on macrophages can be blocked by DNase, suggesting an anti-inflammatory role for this treatment in CF.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-18DOI: 10.1183/23120541.00314-2024
Yoann Guirriec, D. Luque-Paz, Gontran Bernard, Axelle Mabo, M. Kerjouan, Cédric Ménard, Delphine Monnier, Hilario Nunes, Yurdagul Uzunhan, M. Reynaud-Gaubert, J. Bermudez, Raphaël Borie, B. Crestani, J. Traclet, L. Wémeau-Stervinou, Cécile Chenivesse, E. Gomez, G. Prévôt, Arnaud Bourdin, B. Bondue, Anne Bergeron, Vincent Cottin, Mathieu Lederlin, S. Jouneau
{"title":"Pulmonary fibrosis in patients with auto-immune pulmonary alveolar proteinosis: a retrospective nationwide cohort study","authors":"Yoann Guirriec, D. Luque-Paz, Gontran Bernard, Axelle Mabo, M. Kerjouan, Cédric Ménard, Delphine Monnier, Hilario Nunes, Yurdagul Uzunhan, M. Reynaud-Gaubert, J. Bermudez, Raphaël Borie, B. Crestani, J. Traclet, L. Wémeau-Stervinou, Cécile Chenivesse, E. Gomez, G. Prévôt, Arnaud Bourdin, B. Bondue, Anne Bergeron, Vincent Cottin, Mathieu Lederlin, S. Jouneau","doi":"10.1183/23120541.00314-2024","DOIUrl":"https://doi.org/10.1183/23120541.00314-2024","url":null,"abstract":"Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease that may progress toward pulmonary fibrosis. Data about fibrosis prevalence and risk factors are lacking.In this retrospective multicentric nationwide cohort, we included patients newly diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected from medical record, using a standardized questionnaire.Sixty-one patients were included in the final analysis. We identified 5 patients (8%) with fibrosis on initial CT and 16 patients (26%) with fibrosis on final CT after a median time of 3.6 years. Dust exposure was associated with pulmonary fibrosis occurrence (OR=4.3; p=0.038).aPAP patients treated with whole lung lavage (WLL), rituximab, or GM-CSF therapy did not have more fibrotic evolution than patients who did not receive these treatments (n=25/45, 57%versusn=10/16, 62%, p=0.69). All-cause mortality was significantly higher in fibrotic than in non-fibrotic cases: n=4/16, 25%versusn=2/45, 4.4%, p=0.036 respectively.In our population, a quarter of aPAP patients progressed toward pulmonary fibrosis. Dust exposure seems to be an important factor associated with this complication. More studies are needed to analyse precisely the impact of dust exposure impact, especially silica, in patients with aPAP.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-18DOI: 10.1183/23120541.00248-2024
Min-Seok Chang, Hyun-Jung Kim, Ji-Ho Lee
{"title":"The prevalence and implications of depression and anxiety in patients with bronchiectasis: a systematic review and meta-analysis","authors":"Min-Seok Chang, Hyun-Jung Kim, Ji-Ho Lee","doi":"10.1183/23120541.00248-2024","DOIUrl":"https://doi.org/10.1183/23120541.00248-2024","url":null,"abstract":"Comorbidities significantly affect bronchiectasis prognosis. Depression and anxiety are frequently encountered psychological comorbidities that have the greatest impact on bronchiectasis. This review aimed to identify the prevalence of depression and anxiety and describe their implications on bronchiectasis.Three databases were searched from inception to October 2023 for studies reporting the prevalence and/or clinical implications of depression and anxiety in patients with bronchiectasis. Two independent reviewers rated the quality of the evidence presented in the studies using the risk of bias tool for prevalence studies.Of the 50 studies identified, 17 studies with 2637 patients were included. The overall risk of bias was classified as low (10 studies) or moderate (seven studies). The pooled prevalence of depression and anxiety was 31% (95% CI: 24%–38%) and 34% (95% CI: 28%–40%), respectively. Depression was significantly higher in female compared to male patients (risk difference: 10%; 95% CI: 0%–21%) and associated with bronchiectasis exacerbation (adjusted odds ratio: 1.72; 95% CI: 1.28–2.15). Depression and anxiety are closely associated with poor health-related quality of life (HRQOL). However, clinical outcomes including dyspnea symptoms, severity index, computed tomography score, lung function, and physical activity were not associated with depression or anxiety.This study revealed a high prevalence of depression and anxiety among patients with bronchiectasis. Depression was more prevalent in females and is significantly associated with bronchiectasis exacerbation. Depression and anxiety were associated with poor HRQOL.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-18DOI: 10.1183/23120541.00188-2024
Michael E. Wechsler, L. Rogers, G. Canonica, Arnaud Bourdin, A. Altincatal, Megan Hardin, X. Soler, Paul J. Rowe, Y. Deniz, H. Sacks, J. Jacob-Nara
{"title":"Long-term dupilumab efficacy in type 2 asthma regardless of baseline characteristics","authors":"Michael E. Wechsler, L. Rogers, G. Canonica, Arnaud Bourdin, A. Altincatal, Megan Hardin, X. Soler, Paul J. Rowe, Y. Deniz, H. Sacks, J. Jacob-Nara","doi":"10.1183/23120541.00188-2024","DOIUrl":"https://doi.org/10.1183/23120541.00188-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-11DOI: 10.1183/23120541.00216-2024
Beatriz Valeiro, Esther Rodríguez, Jaume Ferrer, A. Pasarín, Jordi Ibañez, M. Ramon
{"title":"Barriers and enablers of physical activity and its association with daily steps after hospitalisation for a COPD exacerbation: what patients say matters","authors":"Beatriz Valeiro, Esther Rodríguez, Jaume Ferrer, A. Pasarín, Jordi Ibañez, M. Ramon","doi":"10.1183/23120541.00216-2024","DOIUrl":"https://doi.org/10.1183/23120541.00216-2024","url":null,"abstract":"Exacerbations of chronic obstructive pulmonary disease (COPD) decrease physical activity (PA). PA interventions after these events are desirable but have had mixed results. Understanding the barriers and enablers of PA may help to improve their results. We aimed to assess the barriers and enablers of PA after COPD exacerbation and its association with daily steps.Cross-sectional analysis of patients with COPD enrolled during a hospitalisation for an exacerbation. PA was measured with an accelerometer for 7 days after discharge. Patients completed an ad-hoc 6-point Likert-scale questionnaire about 13 barriers and 9 enablers of PA. We analysed the association between each item and patients’ daily step counts.46 patients with FEV1%pred (mean (sd)) of 48.6 (15.9) completed the assessments. They were 65 (10) years old, spent 8 (2) days hospitalised, and walked 5633 (3314) steps·day−1after discharge. The patients who reported “breathlessness” (median (p25-p75)) (3813 (2664–5639)versus5549 (3692–9984), p 0.034) and “low mood” (3813 (2456–5471)versus5426 (3612–8942), p 0.047) as barriers(yes (≥2/6) versus no (<2/6) responders, respectively)took statistically fewer daily steps; whereas if they considered “PA as healthy” as an enabler walked statically more (5085 (3538–8703)versus2760 (2271–5298), p 0.031).some barriers and enablers of PA reported by patients after a COPD exacerbation relate to daily steps. Assessing PA barriers and enablers could be useful to improve future PA interventions after these events.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-11DOI: 10.1183/23120541.00547-2024
E. Ben-Meir, Lina Antounians, Shafinaz Eisha, F. Ratjen, Augusto Zani, Hartmut Grasemann
{"title":"Extracellular vesicles in sputum of children with cystic fibrosis pulmonary exacerbations","authors":"E. Ben-Meir, Lina Antounians, Shafinaz Eisha, F. Ratjen, Augusto Zani, Hartmut Grasemann","doi":"10.1183/23120541.00547-2024","DOIUrl":"https://doi.org/10.1183/23120541.00547-2024","url":null,"abstract":"The aim of this study was to quantify mediators of neutrophilic inflammation within airway extracellular vesicles (EVs) of children treated for a cystic fibrosis (CF) pulmonary exacerbation (PEx).EVs were isolated from stored sputum samples collected before and after antibiotic therapy for PEx between 2011–2013, and characterised by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Western blot analysis of EV protein extracts was used for EV canonical protein markers CD63, CD9, and flotillin-1 (FLOT1), as well as neutrophil elastase (NE), myeloperoxidase (MPO) and interleukin-8. EV content of NE and MPO was expressed as ratios of NE/FLOT1 and MPO/FLOT1 protein band densities.Sputum samples from 21 children aged 13.3 (range 8.0–17.0) years were analysed. NTA showed high concentrations of particles at the size of small EVs (50–200 nm), and typical EV morphology was confirmed by TEM. CD63, CD9 and FLOT1 was detectable in all samples. Median (IQR) NE/FLOT1 increased from 2.46 (1.68–5.25) before to 6.83 (3.89–8.89, p<0.001) after PEx therapy and MPO/FLOT1 from 2.30 (1.38–4.44) to 5.76 (3.45–6.94, p<0.01), while EV size remained unchanged. Improvement in lung function (ppFEV1) with PEx therapy correlated with NE EV content (r=0.657, p=0.001).Airways of children with CF contain EVs that carry NE and MPO as cargo. The lower NE and MPO content at the time of PEx compared to after therapy and the correlation with pulmonary function suggest both a functional role of EVs in CF airway inflammation and potential as a biomarker to monitor CF lung disease.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-11DOI: 10.1183/23120541.00266-2024
I. Buendía-Roldán, L. Chávez-Galán, H. Aguilar-Duran, Andy Ruiz, R. Falfán-Valencia, G. Pérez-Rubio, A. Pardo, M. Selman
{"title":"Matrix metalloprotease-7 is associated with post-COVID persistent lung abnormalities.","authors":"I. Buendía-Roldán, L. Chávez-Galán, H. Aguilar-Duran, Andy Ruiz, R. Falfán-Valencia, G. Pérez-Rubio, A. Pardo, M. Selman","doi":"10.1183/23120541.00266-2024","DOIUrl":"https://doi.org/10.1183/23120541.00266-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-11DOI: 10.1183/23120541.00416-2024
Jordan Jeffery, A. Vertigan, Sarah L. Bone, Peter G Gibson
{"title":"Abnormal breathing pattern features in chronic refractory cough","authors":"Jordan Jeffery, A. Vertigan, Sarah L. Bone, Peter G Gibson","doi":"10.1183/23120541.00416-2024","DOIUrl":"https://doi.org/10.1183/23120541.00416-2024","url":null,"abstract":"Chronic refractory cough (CRC) is a challenging condition that responds to speech pathology intervention. Clinical observation suggests abnormal breathing patterns occur in CRC and may be indirectly addressed as part of behavioural treatment, yet breathing pattern changes in CRC are poorly understood. The aims of this study were to (1) describe breathing patterns in patients with CRC, (2) compare breathing pattern features between patients with CRC and inducible laryngeal obstruction (ILO), and (3) estimate the effect of breathing pattern features on clinical measures of laryngeal sensory and motor dysfunction.This retrospective cross sectional observational study included 634 patients with CRC or ILO. A file audit of speech pathology assessment data was undertaken. Analysis of self-reported laryngeal symptoms (viaquestionnaires) and clinical assessment of voice and breathing of those with CRC and ILO was conducted.Most participants with CRC (73%) demonstrated at least one abnormal breathing pattern feature. The most common feature was thoracic breathing (69%) followed by oral breathing (33%). The type and prevalence of abnormal breathing patterns were similar between CRC and ILO. Abnormal breathing patterns were associated with reduced maximum phonation time (MPT), however there was no association between these features and laryngeal hypersensitivity questionnaire scores.Abnormal breathing features are common in patients with CRC and are not significantly different from those occurring in ILO. There is some association between abnormal breathing features and MPT, suggesting impairment of laryngeal motor function. Conversely, there is no association between abnormal breathing features and laryngeal hypersensitivity.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141657583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-11DOI: 10.1183/23120541.00288-2024
Esl Pedersen, M. Goutaki, L. Schreck, B. Rindlisbacher, L. Dixon, Jane S Lucas, C. Kuehni
{"title":"Questionnaire assessed genotypes and associations with symptoms in primary ciliary dyskinesia","authors":"Esl Pedersen, M. Goutaki, L. Schreck, B. Rindlisbacher, L. Dixon, Jane S Lucas, C. Kuehni","doi":"10.1183/23120541.00288-2024","DOIUrl":"https://doi.org/10.1183/23120541.00288-2024","url":null,"abstract":"","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141655579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ERJ Open ResearchPub Date : 2024-07-04DOI: 10.1183/23120541.00154-2024
A. Ramírez-Venegas, F. Montiel-Lopez, R. Robles-Hernández, Bartolome R Celli, R. Sansores, Maricruz Cassou-Martínez, J. L. P. Lara-Albisua, Claudia González-González, M. E. Mayar-Maya, Aloisa P. Hernández-Morales, R. Hernández-Zenteno, R. Falfán-Valencia, Ireri Thirión-Romero, Oliver Pérez-Bautista, Rogelio Pérez-Padilla
{"title":"Effectiveness of ICS/LABA and LAMA/LABA in COPD due to Biomass","authors":"A. Ramírez-Venegas, F. Montiel-Lopez, R. Robles-Hernández, Bartolome R Celli, R. Sansores, Maricruz Cassou-Martínez, J. L. P. Lara-Albisua, Claudia González-González, M. E. Mayar-Maya, Aloisa P. Hernández-Morales, R. Hernández-Zenteno, R. Falfán-Valencia, Ireri Thirión-Romero, Oliver Pérez-Bautista, Rogelio Pérez-Padilla","doi":"10.1183/23120541.00154-2024","DOIUrl":"https://doi.org/10.1183/23120541.00154-2024","url":null,"abstract":"Chronic obstructive pulmonary disease due to biomass exposure (COPD-B) is highly prevalent in low-and middle-income countries, and there are no clinical trials designed to evaluate the effectiveness of the treatments currently recommended for patients with COPD due to cigarette smoking (COPD-C). The purpose of the study was to compare the efficacy of Fluticasone Furoate/Vilanterol (FF/V) 100/25 μg and Umeclidinium/Vilanterol (U/V) 62.5/25 μg on the rate of exacerbations, the time to first exacerbation, on dyspnea, health-related quality of life (HRQL) and forced expiratory volume during the first second (FEV1) and inspiratory capacity (IC) during six months in patients with COPD-B and COPD-C, at a third level referral center in Mexico City.A pilot, single-center, open-label, parallel-group study included 132 patients with a history of at least two exacerbations. They were randomised to receive one of four treatment groups: 33 COPD-B patients received FF/VI 100/25 μg, 31 COPD-B patients received UMEC/VI 62.5/25 μg, 34 COPD-C patients received FF/V, and 34 received UMEC/VI.There were no differences in exacerbation rates between patients receiving FF/VI or UMEC/VI in either the COPD-B [0.07 (CI 95%, 0.03–0.13), 0.06 (CI 95%, 0.03–0.12] or COPD-C group [0.06 (CI 95%, 0.04–0.11); 0.08 (CI 95%, 0.05–0.13)], nor in the time of first exacerbation, nor FEV1and IC. All groups showed improvement in dyspnea and HRQL, independently of medication used.Among patients with COPD-B and COPD-C with a history of exacerbation, FF/VI was equally effective as UMEC/VI in preventing exacerbations and improving dyspnea and HRQL.","PeriodicalId":504874,"journal":{"name":"ERJ Open Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141680725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}