Amyloid-Journal of Protein Folding Disorders最新文献

{"title":"Patient-reported outcome measures for transthyretin cardiac amyloidosis: the ITALY study.","authors":"Alberto Aimo, Lucio Teresi, Vincenzo Castiglione, Anna Lisa Picerni, Martina Niccolai, Silvia Severino, Assunta Agazio, Anna Carnevale Baraglia, Laura Obici, Giovanni Palladini, Lucia Ponti, Alessia Argirò, Francesco Cappelli, Federico Perfetto, Matteo Serenelli, Giancarlo Trimarchi, Roberto Licordari, Gianluca Di Bella, Olena Chubuchna, Filippo Quattrone, Sabina Nuti, Sabina De Rosis, Claudio Passino, Claudio Rapezzi, Giampaolo Merlini, Michele Emdin, Giuseppe Vergaro","doi":"10.1080/13506129.2023.2254451","DOIUrl":"10.1080/13506129.2023.2254451","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin cardiac amyloidosis (ATTR-CA) has a deep impact on the quality of life (QoL), yet no specific patient-reported outcome measures (PROMs) for ATTR-CA exist.</p><p><strong>Methods: </strong>The ITALY study involved 5 Italian referral centres (Pisa, Pavia, Ferrara, Florence, Messina) enrolling consecutive outpatients with ATTR-CA.</p><p><strong>Results: </strong>Two 30-item questionnaires were created for wild-type (wt) and variant (v) ATTR-CA. Scores ranged from 100 (best condition) to 0 (worst condition). Out of 140 patients enrolled (77% with ATTRwt-CA), 115 repeated the re-evaluation at 6 months. At baseline, only 30% of patients needed help to fill out the questionnaires. Among baseline variables, all KCCQ and SF-36 domains were univariate predictors of ITALY scores in ATTRwt-CA patients, with the KCCQ Symptom Summary score (beta coefficient 0.759), Social Limitations (0.781), and Overall summary score (0.786) being the strongest predictors. The SF-36 Emotional well-being score (0.608), the KCCQ Overall summary score (0.656), and the SF-36 Energy/fatigue score (0.669) were the strongest univariate predictors of ITALY scores in ATTRv-CA. Similar results were found at 6 months.</p><p><strong>Conclusions: </strong>The ITALY questionnaires are the first specific PROMs for ATTRwt- and ATTRv-CA. Questionnaire completion is feasible. ITALY scores display close relationships with non-ATTR-specific measures of QoL.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"52-61"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction in ^99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.","authors":"René Rettl, Raffaella Calabretta, Franz Duca, Christina Binder, Christina Kronberger, Robin Willixhofer, Michael Poledniczek, Carolina Donà, Christian Nitsche, Dietrich Beitzke, Christian Loewe, Michaela Auer-Grumbach, Diana Bonderman, Stefan Kastl, Christian Hengstenberg, Roza Badr Eslam, Johannes Kastner, Jutta Bergler-Klein, Marcus Hacker, Andreas Kammerlander","doi":"10.1080/13506129.2023.2247136","DOIUrl":"10.1080/13506129.2023.2247136","url":null,"abstract":"<p><p><b>Aims:</b> Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.<b>Methods and results:</b> ATTRv-CM patients underwent [^99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: <i>n</i> = 5, inotersen: <i>n</i> = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, <i>p</i> = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, <i>p</i> < .001) in ATTRwt-CM patients (historical control cohort: <i>n</i> = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.<b>Conclusions:</b> RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial ^99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"42-51"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10088979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.","authors":"Guillaume Fargeot, Andoni Echaniz-Laguna, Céline Labeyrie, Juliette Svahn, Jean-Philippe Camdessanché, Pascal Cintas, Jean-Baptiste Chanson, Florence Esselin, Céline Piedvache, Céline Verstuyft, Steeve Genestet, Emmeline Lagrange, Laurent Magy, Yann Péréon, Sabrina Sacconi, Aissatou Signate, Aleksandra Nadaj-Pakleza, Frédéric Taithe, Karine Viala, Céline Tard, Vianney Poinsignon, Cécile Cauquil, Shahram Attarian, David Adams","doi":"10.1080/13506129.2023.2270661","DOIUrl":"10.1080/13506129.2023.2270661","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from <i>TTR</i> gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available.</p><p><strong>Methods: </strong>In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the <i>TTR</i> gene in French patients with age >50 years with a progressive idiopathic polyneuropathy.</p><p><strong>Results: </strong>553 patients (70% males) with a mean age of 70 years were included. A <i>TTR</i> gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met <i>TTR</i> variation in 10 cases. In comparison with patients with no <i>TTR</i> gene pathogenic variants (<i>n</i> = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, <i>p</i> = .007), significant weight loss (33 vs 11%, <i>p</i> = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, <i>p</i> = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives.</p><p><strong>Conclusion: </strong>In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"62-69"},"PeriodicalIF":5.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of cardiac involvement, extracardiac manifestations and outcomes between homozygote and heterozygote transthyretin p.Val142Ile (V122I) variant in patients with hereditary transthyretin amyloidosis: a cohort study.","authors":"Grégoire Albenque, Mélanie Bézard, Mounira Kharoubi, Shirley Odouard, Ariane Lunati, Elsa Poullot, Amira Zaroui, Emmanuel Teiger, Luc Hittinger, Vincent Audard, Khalil El Karoui, Benoît Funalot, Pascale Fanen, Thibaud Damy, Silvia Oghina","doi":"10.1080/13506129.2023.2227322","DOIUrl":"10.1080/13506129.2023.2227322","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) p.Val142Ile (V122I) mutation is the most common inherited cause of cardiac amyloidosis and little is known about the phenotype and outcome of the rare homozygotic genotype. This study aimed to compare phenotypic characteristics and outcomes between heterozygous and homozygous patients with ATTRv V122I amyloidosis.</p><p><strong>Material and methods: </strong>This monocentric, observational, retrospective study conducted at the French National Referral Centre for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil), described clinical, electrocardiographic, cardiac imaging features and prognostic data for patients with ATTRv V122I amyloidosis.</p><p><strong>Results: </strong>Among 185 ATTRv V122I patients identified, 161 were heterozygous and 24 were homozygous. The homozygous frequency was 13%. Onset occured significantly earlier in the homozygotes compared to heterozygotes with earlier median age at diagnosis (67[63-71] years vs 76[70-79] years, <i>p</i> < .001), age at first cardiac symptom (66[61-71] years vs 74[68-78] years, <i>p</i> < .001) and age at first extracardiac symptom (59[52-70] years vs 69[62-75] years, <i>p</i> = .003). Homozygous ATTRv V122I was also associated with greater disease burden with earlier events (death, transplant or hospitalisation for acute heart failure) compared with heterozygotes (71[67-74] vs 78[76-79] years, <i>p</i> = .018).</p><p><strong>Conclusion: </strong>This rare, homozygous V122I cohort confirmed the earlier age of onset, death and cardiac events in this population.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"407-415"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How well does liver span as part of the consensus criteria for liver involvement in AL amyloidosis perform?","authors":"Anne F Brunger, Ronald van Rheenen, Reinold O B Gans, Bouke P C Hazenberg, Hans L A Nienhuis","doi":"10.1080/13506129.2023.2222878","DOIUrl":"10.1080/13506129.2023.2222878","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"437-439"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human lysozyme inhibits the fibrillation of serum amyloid a protein from systemic AA amyloidosis.","authors":"Tim Moderer, Ioana Puşcalău-Gîrţu, Christian Haupt, Julian Baur, Armando Rodríguez-Alfonso, Sebastian Wiese, Christoph Q Schmidt, Miroslav Malešević, Wolf-Georg Forssmann, Ludger Ständker, Marcus Fändrich","doi":"10.1080/13506129.2023.2232518","DOIUrl":"10.1080/13506129.2023.2232518","url":null,"abstract":"<p><strong>Background: </strong>Systemic AA amyloidosis is a world-wide occurring protein misfolding disease in humans and animals that arises from the formation of amyloid fibrils from serum amyloid A (SAA) protein and their deposition in multiple organs.</p><p><strong>Objective: </strong>To identify new agents that prevent fibril formation from SAA protein and to determine their mode of action.</p><p><strong>Materials and methods: </strong>We used a cell model for the formation of amyloid deposits from SAA protein to screen a library of peptides and small proteins, which were purified from human hemofiltrate. To clarify the inhibitory mechanism the obtained inhibitors were characterised in cell-free fibril formation assays and other biochemical methods.</p><p><strong>Results: </strong>We identified lysozyme as an inhibitor of SAA fibril formation. Lysozyme antagonised fibril formation both in the cell model as well as in cell-free fibril formation assays. The protein binds SAA with a dissociation constant of 16.5 ± 0.6 µM, while the binding site on SAA is formed by segments of positively charged amino acids.</p><p><strong>Conclusion: </strong>Our data imply that lysozyme acts in a chaperone-like fashion and prevents the aggregation of SAA protein through direct, physical interactions.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"424-433"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hereditary gelsolin amyloidosis: a rare cause of cranial, peripheral and autonomic neuropathies linked to D187N and Y447H substitutions.","authors":"Lisa Mendelson, Tatiana Prokaeva, K H Vincent Lau, Vaishali Sanchorawala, Kristen McCausland, Brian Spencer, Surendra Dasari, Ellen D McPhail, Michelle C Kaku","doi":"10.1080/13506129.2023.2204999","DOIUrl":"10.1080/13506129.2023.2204999","url":null,"abstract":"<p><strong>Introduction: </strong>Hereditary gelsolin (AGel) amyloidosis is a systemic disease that is characterised by neurologic, ophthalmologic, dermatologic, and other organ involvements. We describe the clinical features with a focus on neurological manifestations in a cohort of patients with AGel amyloidosis referred to the Amyloidosis Centre in the United States.</p><p><strong>Methods: </strong>Fifteen patients with AGel amyloidosis were included in the study between 2005 and 2022 with the permission of the Institutional Review Board. Data were collected from the prospectively maintained clinical database, electronic medical records and telephone interviews.</p><p><strong>Results: </strong>Neurologic manifestations were featured in 15 patients: cranial neuropathy in 93%, peripheral and autonomic neuropathy in 57% and bilateral carpal tunnel syndrome in 73% of cases. A novel p.Y474H gelsolin variant featured a unique clinical phenotype that differed from the one associated with the most common variant of AGel amyloidosis.</p><p><strong>Discussion: </strong>We report high rates of cranial and peripheral neuropathy, carpal tunnel syndrome and autonomic dysfunction in patients with systemic AGel amyloidosis. The awareness of these features will enable earlier diagnosis and timely screening for end-organ dysfunction. The characterisation of pathophysiology will assist the development of therapeutic options in AGel amyloidosis.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"357-363"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9397959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iatrogenic cerebral amyloid angiopathy rather than sporadic CAA in younger adults with lobar intracerebral haemorrhage.","authors":"J C Purrucker, C Röcken, D Reuss","doi":"10.1080/13506129.2023.2212394","DOIUrl":"10.1080/13506129.2023.2212394","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"434-436"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger.","authors":"Christian Treitz, Neelis Müller-Marienburg, Rolf Rüdiger Meliß, Peter Urban, Hans-Detlef Axmann, Frank Siebert, Karsten Becker, Klaus Martens, Hans-Michael Behrens, Eva Gericke, Andreas Tholey, Christoph Röcken","doi":"10.1080/13506129.2023.2226298","DOIUrl":"10.1080/13506129.2023.2226298","url":null,"abstract":"<p><strong>Introduction: </strong>Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics.</p><p><strong>Methods: </strong>205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics.</p><p><strong>Results: </strong>Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament.</p><p><strong>Conclusion: </strong>Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"394-406"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of amyloid in ligamentum flavum of patients with lumbar spinal stenosis.","authors":"Francesco Marchi, Chiara Kessler, Daniela Distefano, Lodovico Terzi di Bergamo, Luca Fumagalli, Manuela Averaimo, Emanuele Crupi, Fabio Bergamini, Giorgia Melli, Georg Stussi, Davide Rossi, Claudio Gobbi, Paolo Ripellino, Emanuele Pravatà, Dominique E Kuhlen, Christoph Röcken, Pietro Scarone, Bernhard Gerber, Adalgisa Condoluci","doi":"10.1080/13506129.2023.2230516","DOIUrl":"10.1080/13506129.2023.2230516","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin (ATTR) amyloidosis is often diagnosed in an advanced stage, when irreversible cardiac damage has occurred. Lumbar spinal stenosis (LSS) may precede cardiac ATTR amyloidosis by many years, offering the opportunity to detect ATTR already at the time of LSS surgery. We prospectively assessed the prevalence of ATTR in the ligamentum flavum by tissue biopsy in patients aged >50 years undergoing surgery for LSS.</p><p><strong>Methods: </strong>Ligamentum flavum thickness was assessed pre-operatively on axial T2 magnetic resonance imaging (MRI) slices. Tissue samples from ligamentum flavum were screened centrally by Congo red staining and immunohistochemistry (IHC).</p><p><strong>Results: </strong>Amyloid in the ligamentum flavum was detected in 74/94 patients (78.7%). IHC revealed ATTR in 61 (64.9%), whereas amyloid subtyping was inconclusive in 13 (13.8%). Mean thickness of ligamentum flavum was significantly higher at all levels in patients with amyloid (<i>p</i> < .05). Patients with amyloid deposits were older (73.1 ± 9.2 vs. 64.6 ± 10.1 years, <i>p</i> = .01). No differences in sex, comorbidities, previous surgery for carpal tunnel syndrome or LSS were observed.</p><p><strong>Conclusions: </strong>Amyloid, mostly of the ATTR subtype, was found in four out of five patients with LSS and is associated with age and ligamentum flavum thickness. Histopathological work-up of ligamentum flavum might inform future decision making.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"416-423"},"PeriodicalIF":5.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}