Marianne Baastrup Soendergaard, Frederikke Hjortdahl, Susanne Hansen, Anne-Sofie Bjerrum, Anna von Bülow, Ole Hilberg, Barbara Bonnesen Bertelsen, Claus Rikard Johnsen, Sofie Lock-Johansson, Roxana Vijdea, Linda Makowska Rasmussen, Johannes Martin Schmid, Charlotte Suppli Ulrik, Celeste Porsbjerg, Kjell Erik Julius Håkansson
{"title":"Pre-biologic disease trajectories are associated with morbidity burden and biologic treatment response in severe asthma.","authors":"Marianne Baastrup Soendergaard, Frederikke Hjortdahl, Susanne Hansen, Anne-Sofie Bjerrum, Anna von Bülow, Ole Hilberg, Barbara Bonnesen Bertelsen, Claus Rikard Johnsen, Sofie Lock-Johansson, Roxana Vijdea, Linda Makowska Rasmussen, Johannes Martin Schmid, Charlotte Suppli Ulrik, Celeste Porsbjerg, Kjell Erik Julius Håkansson","doi":"10.1183/13993003.01497-2024","DOIUrl":"10.1183/13993003.01497-2024","url":null,"abstract":"<p><strong>Background: </strong>Biologics can induce remission in some patients with severe asthma, however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.</p><p><strong>Methods: </strong>Patients in the Danish Severe Asthma Registry initiating biologic therapy between 2016-2022 were included and followed retrospectively in prescription databases starting 1995. We performed sequence analysis for inhaled corticosteroid (ICS) treatment intensity over time combined with unsupervised trajectory clustering.</p><p><strong>Results: </strong>In total, 755 patients were included and three pre-biologic disease trajectories were identified: Chronic severe asthma (26%), Gradual onset severe asthma (35%), Recent, sudden onset severe asthma (39%). Chronic severe asthma patients were older, had the longest disease duration (35 years), the most impaired pulmonary function, the highest comorbidity prevalence and the lowest employment rate. <b><i>Recent, sudden onset severe asthma</i></b> patients were younger, had shorter disease duration (5 years), more tobacco exposure and the least impaired lung function. <b><i>Gradual onset severe asthma</i></b> had an intermediate burden of disease. The <b><i>Chronic severe asthma</i></b> cluster demonstrated the lowest prevalence of remission (17%) compared to the <b><i>Gradual onset severe asthma</i></b> (29%) and <b><i>Recent onset severe asthma</i></b> (32%) clusters.</p><p><strong>Conclusions: </strong>Three pre-biologic disease trajectories were identified, with increased disease duration and activity associating with asthma- and comorbidity burden. Early intervention may be key to prevent irreversible adverse outcomes for patients with severe asthma.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947050","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 <i>European Respiratory Journal</i>: our drive to thrive in '25!","authors":"James D Chalmers, Neil J Bullen, Don D Sin","doi":"10.1183/13993003.00047-2025","DOIUrl":"https://doi.org/10.1183/13993003.00047-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064837","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":"Real-world health data potential for economic insights in COPD.","authors":"Pierrick Bedouch, Sébastien Chanoine","doi":"10.1183/13993003.02188-2024","DOIUrl":"https://doi.org/10.1183/13993003.02188-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064833","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":"Trajectories of responses to mepolizumab in severe asthma.","authors":"Santi Nolasco, Manali Mukherjee, Parameswaran Nair","doi":"10.1183/13993003.02023-2024","DOIUrl":"https://doi.org/10.1183/13993003.02023-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064839","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}
Marius M Hoeper, Mardi Gomberg-Maitland, David B Badesch, J Simon R Gibbs, Ekkehard Grünig, Grzegorz Kopeć, Vallerie V McLaughlin, Gisela Meyer, Karen M Olsson, Ioana R Preston, Stephan Rosenkranz, Rogerio Souza, Aaron B Waxman, Loïc Perchenet, James Strait, Aiwen Xing, Solaiappan Manimaran, Xuelong Wang, Barry Miller, Alexandra G Cornell, Janethe de Oliveira Pena, H Ardeschir Ghofrani, Marc Humbert
{"title":"Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies.","authors":"Marius M Hoeper, Mardi Gomberg-Maitland, David B Badesch, J Simon R Gibbs, Ekkehard Grünig, Grzegorz Kopeć, Vallerie V McLaughlin, Gisela Meyer, Karen M Olsson, Ioana R Preston, Stephan Rosenkranz, Rogerio Souza, Aaron B Waxman, Loïc Perchenet, James Strait, Aiwen Xing, Solaiappan Manimaran, Xuelong Wang, Barry Miller, Alexandra G Cornell, Janethe de Oliveira Pena, H Ardeschir Ghofrani, Marc Humbert","doi":"10.1183/13993003.01424-2024","DOIUrl":"https://doi.org/10.1183/13993003.01424-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.</p><p><strong>Methods: </strong>This post-hoc, exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies. Both studies were international, multicentre, randomised, double-blind, placebo-controlled trials in patients with PAH. Efficacy and safety parameters common to both studies were analysed.</p><p><strong>Results: </strong>A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo. Adding sotatercept to background PAH therapy for 24 weeks improved exercise capacity (as assessed by 6-min walk distance), pulmonary vascular resistance, World Health Organization functional class, and delayed time to first occurrence of death or clinical worsening event. There were clinically important reductions in both pulmonary and right heart pressures; improvements in right ventricle (RV) size during both systole and diastole; and enhancements in RV contractility and RV-pulmonary artery coupling. The number of patients who experienced at least one adverse event of interest or special interest (increased haemoglobin, thrombocytopenia, bleeding events [mostly epistaxis], increased blood pressure, and telangiectasia) was higher in the sotatercept group than the placebo group.</p><p><strong>Discussion: </strong>This pooled analysis confirms that sotatercept delivers therapeutic benefit across a range of efficacy endpoints and has favourable safety in patients with PAH. Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with PAH.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064847","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}
Athénaïs Boucly, David Montani, Fabrice Bauer, Elise Artaud-Macari, Emmanuel Bergot, Clément Boissin, Ari Chaouat, Vincent Cottin, Claire Dauphin, Bruno Degano, Pascal De Groote, Camille du Roure, Nicolas Favrolt, Delphine Horeau-Langlard, Xavier Jaïs, Mitja Jevnikar, Thomas Lacoste-Palasset, François Picard, Grégoire Prévôt, Martine Reynaud-Gaubert, Anne Roche, Ségolène Turquier, Marc Humbert, Olivier Sitbon, Laurent Savale
{"title":"Initial therapy in patients with pulmonary arterial hypertension and cardiovascular comorbidities.","authors":"Athénaïs Boucly, David Montani, Fabrice Bauer, Elise Artaud-Macari, Emmanuel Bergot, Clément Boissin, Ari Chaouat, Vincent Cottin, Claire Dauphin, Bruno Degano, Pascal De Groote, Camille du Roure, Nicolas Favrolt, Delphine Horeau-Langlard, Xavier Jaïs, Mitja Jevnikar, Thomas Lacoste-Palasset, François Picard, Grégoire Prévôt, Martine Reynaud-Gaubert, Anne Roche, Ségolène Turquier, Marc Humbert, Olivier Sitbon, Laurent Savale","doi":"10.1183/13993003.00895-2024","DOIUrl":"https://doi.org/10.1183/13993003.00895-2024","url":null,"abstract":"<p><strong>Background: </strong>European guidelines recommend initial monotherapy in PAH patients with cardiovascular (CV) comorbidities based on the limited of evidence for combination therapy in this growing population.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on incident PAH patients enrolled in the French Pulmonary Hypertension Registry between 2009 and 2020. Propensity score matching was used to investigate initial dual oral combination therapy <i>versus</i> oral monotherapy in patients with at least one CV comorbidity (<i>i.e.</i>, hypertension, obesity, diabetes and coronary artery disease).</p><p><strong>Results: </strong>Of the 1784 patients identified, 1088 had ≥1 CV comorbidity, including 20% with ≥3 comorbidities. In the propensity score matched population (N=708), the majority of patients were female, with idiopathic/heritable/drug-induced PAH, at intermediate 1-year mortality risk. At first follow-up, initial dual therapy led to larger improvements in symptoms, exercise capacity, hemodynamics, and risk status than initial monotherapy, with no differences in long-term survival. Treatment discontinuations were observed in 23% of patients initiated on dual therapy and 24% of those initiated on monotherapy.</p><p><strong>Conclusions: </strong>Initial dual oral combination therapy may be beneficial and well tolerated in most PAH patients with CV comorbidities.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064848","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}
Alena Moiseenko, Anthony Sinadinos, Ana Sergijenko, Kyriel Pineault, Aarash Saleh, Konradin Nekola, Nathalie Strang, Anastasia Eleftheraki, A Christopher Boyd, Jane C Davies, Deborah R Gill, Stephen C Hyde, Gerry McLachlan, Tim Rath, Michael Rothe, Axel Schambach, Silke Hobbie, Michael Schuler, Udo Maier, Matthew J Thomas, Detlev Mennerich, Manfred Schmidt, Uta Griesenbach, Eric W F W Alton, Sebastian Kreuz
{"title":"Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.","authors":"Alena Moiseenko, Anthony Sinadinos, Ana Sergijenko, Kyriel Pineault, Aarash Saleh, Konradin Nekola, Nathalie Strang, Anastasia Eleftheraki, A Christopher Boyd, Jane C Davies, Deborah R Gill, Stephen C Hyde, Gerry McLachlan, Tim Rath, Michael Rothe, Axel Schambach, Silke Hobbie, Michael Schuler, Udo Maier, Matthew J Thomas, Detlev Mennerich, Manfred Schmidt, Uta Griesenbach, Eric W F W Alton, Sebastian Kreuz","doi":"10.1183/13993003.01683-2023","DOIUrl":"10.1183/13993003.01683-2023","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR modulators offer significant improvements, but ∼10% of patients remain nonresponsive or are intolerant. This study provides an analysis of rSIV.F/HN, a lentiviral vector optimised for lung delivery, including CFTR protein expression, functional correction of CFTR defects and genomic integration site analysis in preparation for a first-in-human clinical trial.</p><p><strong>Methods: </strong>Air-liquid interface cultures of primary human bronchial epithelial cells (HBECs) from CF patients (F508del/F508del), as well as a CFTR-deficient immortalised human lung epithelial cell line mimicking class I (CFTR-null) homozygous mutations, were used to assess transduction efficiency. Quantification methods included a novel proximity ligation assay for CFTR protein expression. For assessment of CFTR channel activity, Ussing chamber studies were conducted. The safety profile was assessed using integration site analysis and <i>in vitro</i> insertional mutagenesis studies.</p><p><strong>Results: </strong>rSIV.F/HN expressed CFTR and restored CFTR-mediated chloride currents to physiological levels in primary F508del/F508del HBECs as well as in a class I cells. In contrast, the latter could not be achieved by small-molecule CFTR modulators, underscoring the potential of gene therapy for this mutation class. Combination of rSIV.F/HN-CFTR with the potentiator ivacaftor showed a greater than additive effect. The genomic integration pattern showed no site predominance (frequency of occurrence ≤10%), and a low risk of insertional mutagenesis was observed in an <i>in vitro</i> immortalisation assay.</p><p><strong>Conclusions: </strong>The results underscore rSIV.F/HN as a promising gene therapy vector for CF, providing a mutation-agnostic treatment option.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035602","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}
Annemie Deiteren, Emmanuel Krupka, Lieselot Bontinck, Karine Imberdis, Griet Conickx, Selcuk Bas, Naimish Patel, Heribert W Staudinger, Benjamin T Suratt
{"title":"A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule.","authors":"Annemie Deiteren, Emmanuel Krupka, Lieselot Bontinck, Karine Imberdis, Griet Conickx, Selcuk Bas, Naimish Patel, Heribert W Staudinger, Benjamin T Suratt","doi":"10.1183/13993003.01461-2024","DOIUrl":"https://doi.org/10.1183/13993003.01461-2024","url":null,"abstract":"<p><strong>Background: </strong>Monovalent biologics blocking thymic stromal lymphopoietin or interleukin-13 have been shown to elicit pharmacodynamic responses in asthma following a single dose. Therefore, dual blockade of these cytokines may result in an enhanced response compared to single targeting and has the potential to break efficacy ceilings in asthma. This study assessed the safety and tolerability of lunsekimig, a bispecific NANOBODY<b>®</b> molecule that blocks thymic stromal lymphopoietin and interleukin-13, and its effect on Type 2 inflammatory biomarkers and lung function in asthma.</p><p><strong>Methods: </strong>This was a Phase 1b, single-dose (subcutaneous lunsekimig 400 mg or placebo), randomised (2:1), double-blind, proof-of-mechanism study in 36 participants with mild-to-moderate asthma and elevated fractional exhaled nitric oxide (≥25 ppb), a marker of airway inflammation. The primary endpoint was safety and tolerability through Day 71. The main pharmacodynamic secondary endpoint was change from baseline in fractional exhaled nitric oxide at Day 29.</p><p><strong>Results: </strong>Lunsekimig was well tolerated, with no serious treatment-emergent adverse events. Fractional exhaled nitric oxide was significantly reduced from Day 8 through Day 29 after a single dose, with change from baseline of -40.9 ppb (90% CI: -55.43 to -26.39; p<0.0001) <i>versus</i> placebo at Day 29. Blood-based Type 2 biomarkers at Day 29 were significantly reduced from baseline. Lung function, particularly small airway dysfunction, was numerically improved at Day 29, most notably in participants with impaired lung function at baseline.</p><p><strong>Conclusions: </strong>A single dose of lunsekimig was well tolerated, significantly suppressed Type 2 inflammation, and improved lung function in mild-to-moderate asthma.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064843","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":"<i>ERJ</i> Podcast January 2025: Treatment response to mepolizumab in severe eosinophilic asthma.","authors":"","doi":"10.1183/13993003.E6501-2025","DOIUrl":"10.1183/13993003.E6501-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064773","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}
Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake
{"title":"Protein biomarkers of interstitial lung abnormalities in relatives of patients with pulmonary fibrosis.","authors":"Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake","doi":"10.1183/13993003.01349-2024","DOIUrl":"10.1183/13993003.01349-2024","url":null,"abstract":"<p><strong>Rationale: </strong>First-degree relatives of patients with pulmonary fibrosis (relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.</p><p><strong>Methods: </strong>Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA was assessed with CT scans per Fleischner Society recommendations. Protein associations with ILA were assessed using regression, and significant proteins were used with clinical variables to detect ILA.</p><p><strong>Results: </strong>Of 237 relatives from two independent cohorts, 26% had ILA. Seven proteins were associated with ILA in the discovery cohort after FDR-adjustment, and all remained significant after adjusting for age, gender, and smoking status. Six of seven were significant in the validation cohort including GDF15, SFTPD, and SFTPB. In a multivariable model, six proteins combined with basic demographics in the discovery cohort had AUC=0.92 (0.88 in validation cohort). LASSO modelling identified three proteins and age as predictors with an AUC=0.89. When applied to the combined cohorts, this simple model would reduce the need for CT imaging in one of every three relatives screened.</p><p><strong>Conclusion: </strong>Peripheral blood proteins are associated with ILA in relatives of patients with pulmonary fibrosis and can be used to detect ILA. Our findings demonstrate the potential utility of blood biomarkers in this high-risk group and suggests molecular targets for future investigation.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064850","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}