Clinical Reviews in Allergy & Immunology最新文献

{"title":"Autoimmune Hepatitis: Serum Autoantibodies in Clinical Practice.","authors":"Benedetta Terziroli Beretta-Piccoli,&nbsp;Giorgina Mieli-Vergani,&nbsp;Diego Vergani","doi":"10.1007/s12016-021-08888-9","DOIUrl":"https://doi.org/10.1007/s12016-021-08888-9","url":null,"abstract":"<p><p>Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued by the International Autoimmune Hepatitis Group. They also allow the distinction between type 1 AIH, characterized by positive anti-nuclear and/or anti-smooth muscle antibody, and type 2 AIH, characterized by positive anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. Anti-soluble liver antigen is the only AIH-specific autoantibody, and is found in 20-30% of both type 1 and type 2 AIH. Anti-neutrophil cytoplasmic antibody is frequently positive in type 1 AIH, being associated also with inflammatory bowel disease and with primary/autoimmune sclerosing cholangitis. The reference method for autoantibody testing remains indirect immunofluorescence on triple tissue (rodent liver, kidney and stomach), allowing both the detection of the majority of liver-relevant reactivities, including those autoantibodies whose molecular target antigens are unknown. Of note, the current knowledge of the clinical significance of autoantibodies relies on studies based on this technique. However, immunofluorescence requires trained laboratory personnel, is observer-dependent, and lacks standardization, leading to ongoing attempts at replacing this method with automated assays, the sensitivity, and specificity of which, however, require further studies before they can be used as a reliable alternative to immunofluorescence; currently, they may be used as complementary to immunofluorescence.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"124-137"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10506789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Italian Multicenter Study on Anti-NXP2 Antibodies: Clinical and Serological Associations.","authors":"Micaela Fredi,&nbsp;Ilaria Cavazzana,&nbsp;Angela Ceribelli,&nbsp;Lorenzo Cavagna,&nbsp;Simone Barsotti,&nbsp;Elena Bartoloni,&nbsp;Maurizio Benucci,&nbsp;Ludovico De Stefano,&nbsp;Andrea Doria,&nbsp;Giacomo Emmi,&nbsp;Martina Fabris,&nbsp;Marco Fornaro,&nbsp;Federica Furini,&nbsp;Maria Grazia Giudizi,&nbsp;Marcello Govoni,&nbsp;Anna Ghirardello,&nbsp;Luca Iaccarino,&nbsp;Fiorenzo Iannone,&nbsp;Maria Infantino,&nbsp;Natasa Isailovic,&nbsp;Maria Grazia Lazzaroni,&nbsp;Mariangela Manfredi,&nbsp;Alessandro Mathieu,&nbsp;Emiliano Marasco,&nbsp;Paola Migliorini,&nbsp;Carlomaurizio Montecucco,&nbsp;Boaz Palterer,&nbsp;Paola Parronchi,&nbsp;Matteo Piga,&nbsp;Federico Pratesi,&nbsp;Valeria Riccieri,&nbsp;Carlo Selmi,&nbsp;Marilina Tampoia,&nbsp;Alessandra Tripoli,&nbsp;Giovanni Zanframundo,&nbsp;Antonella Radice,&nbsp;Roberto Gerli,&nbsp;Franco Franceschini","doi":"10.1007/s12016-021-08920-y","DOIUrl":"https://doi.org/10.1007/s12016-021-08920-y","url":null,"abstract":"<p><p>The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p < 0.0001). As for clinical features, NXP2+ more frequently develop specific skin manifestations and less frequently features related with overlap myositis and anti-synthetase syndrome. IP confirmed NXP2 positivity in 31 of 52 available sera (62%). Most clinical associations were confirmed comparing NXP2 LB+/IP+ versus NXP2-negative myositis, with the following exceptions: inclusion-body myositis diagnosis was not detected, whilst dysphagia and myositis were found more frequently in NXP2 LB+/IP+ patients. The 21 LB+ /IP-myositis patients did not show differences in clinical features when compared with the NXP2-myositis patients and more frequently displayed multiple positivity at LB. Risk of developing cancer-associated myositis was similar between NXP2-positive and NXP2-negative myositis patients, either when detected by LB or IP. Protein-IP confirmed NXP2 antibodies in nearly 60% of sera positive for the same specificity with commercial assay. Double-positive cases rarely occurred in myositis patients with a clinical diagnosis other than dermatomyositis. Patients only positive by LB (LB+/IP-) did not display clinical features typical of NXP2. NXP2 positivity by LB should be confirmed by other methods in order to correctly diagnose and characterize patients affected by idiopathic inflammatory myositis.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"240-250"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings.","authors":"Maria V Sokolova,&nbsp;Georg Schett,&nbsp;Ulrike Steffen","doi":"10.1007/s12016-021-08890-1","DOIUrl":"https://doi.org/10.1007/s12016-021-08890-1","url":null,"abstract":"<p><p>Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA (\"seropositive\") in general display a different etiology and disease course compared to so-called \"seronegative\" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"138-151"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis.","authors":"Marco Folci,&nbsp;Giacomo Ramponi,&nbsp;Virginia Solitano,&nbsp;Enrico Brunetta","doi":"10.1007/s12016-021-08887-w","DOIUrl":"https://doi.org/10.1007/s12016-021-08887-w","url":null,"abstract":"<p><p>Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"107-123"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10520703","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":"Anti-Ro52 Autoantibody Is Common in Systemic Autoimmune Rheumatic Diseases and Correlating with Worse Outcome when Associated with interstitial lung disease in Systemic Sclerosis and Autoimmune Myositis.","authors":"Edward K L Chan","doi":"10.1007/s12016-021-08911-z","DOIUrl":"https://doi.org/10.1007/s12016-021-08911-z","url":null,"abstract":"<p><p>This review highlights the 30 plus years research progress since the discovery of autoantibody to Ro52/TRIM21 in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SjS). After the initial expression cloning of the Ro52 cDNA, it has taken many years to the current understanding in the interesting biological function of Ro52 as an E3 ubiquitin ligase and its role in innate immune clearance of intracellular IgG-bound complex. Early observations show that anti-Ro52, mostly associated with anti-SS-A/Ro60 and/or anti-SS-B/La, is commonly found in SLE (40-70%), SjS (70-90%), neonatal lupus erythematosus (NLE, 75-90%), and subacute cutaneous lupus erythematosus (50-60%). Anti-Ro52 has long been postulated to play a direct pathogenic role in congenital heart block in NLE as well as in the QT interval prolongation in some adults. The widespread availability of the anti-Ro52 assay has led to the detection of anti-Ro52 in other diseases including autoimmune hepatitis (20-40%), systemic sclerosis (10-30%), and autoimmune myositis (20-40%). More than ten studies have pointed to an association of anti-Ro52 with interstitial lung disease and, more importantly, correlating with poor outcome and worse survival. Other studies are implicating an interesting role for anti-Ro52 in the diagnosis of certain cancers. Future studies are needed to examine the mechanism in the pathogenesis of anti-Ro52 and carefully documenting its causal relationships in different disease conditions.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 2","pages":"178-193"},"PeriodicalIF":9.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9079755","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":"Agammaglobulinemia: from X-linked to Autosomal Forms of Disease.","authors":"Melissa Cardenas-Morales,&nbsp;Vivian P Hernandez-Trujillo","doi":"10.1007/s12016-021-08870-5","DOIUrl":"https://doi.org/10.1007/s12016-021-08870-5","url":null,"abstract":"<p><p>Interruptions or alterations in the B cell development pathway can lead to primary B cell immunodeficiency with resultant absence or diminished immunoglobulin production. While the most common cause of congenital agammaglobulinemia is X-linked agammaglobulinemia (XLA), accounting for approximately 85% of cases, other genetic forms of agammaglobulinemia have been identified. Early recognition and diagnosis of these conditions are pivotal for improved outcomes and prevention of sequelae and complications. The diagnosis of XLA is often delayed, and can be missed if patient has a mild phenotype. The lack of correlation between phenotype and genotype in this condition makes management and predicting outcomes quite difficult. In contrast, while less common, autosomal recessive forms of agammaglobulinemia present at younger ages and with typically more severe clinical features resulting in an earlier diagnosis. Some diagnostic innovations, such as KREC level measurements and serum BCMA measurements, may aid in facilitating an earlier identification of agammaglobulinemia leading to prompt treatment. Earlier diagnosis may improve the overall health of patients with XLA.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 1","pages":"22-35"},"PeriodicalIF":9.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12016-021-08870-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Genetic Discoveries in Primary Immunodeficiency Disorders.","authors":"Margaret T Redmond,&nbsp;Rebecca Scherzer,&nbsp;Benjamin T Prince","doi":"10.1007/s12016-021-08881-2","DOIUrl":"https://doi.org/10.1007/s12016-021-08881-2","url":null,"abstract":"<p><p>The field of Immunology is one that has undergone great expansion in recent years. With the advent of new diagnostic modalities including a variety of genetic tests (discussed elsewhere in this journal), the ability to diagnose a patient with a primary immunodeficiency disorder (PIDD) has become a more streamlined process. With increased availability of genetic testing for those with suspected or known PIDD, there has been a significant increase in the number of genes associated with this group of disorders. This is of great importance as a misdiagnosis of these rare diseases can lead to a delay in what can be critical treatment options. At times, those options can include life-saving medications or procedures. Presentation of patients with PIDD can vary greatly based on the specific genetic defect and the part(s) of the immune system that is affected by the variation. PIDD disorders lead to varying levels of increased risk of infection ranging from a mild increase such as with selective IgA deficiency to a profound risk with severe combined immunodeficiency. These diseases can also cause a variety of other clinical findings including autoimmunity and gastrointestinal disease.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 1","pages":"55-74"},"PeriodicalIF":9.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10859989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newborn Screening in the Diagnosis of Primary Immunodeficiency.","authors":"Lisa J Kobrynski","doi":"10.1007/s12016-021-08876-z","DOIUrl":"https://doi.org/10.1007/s12016-021-08876-z","url":null,"abstract":"<p><p>Newborn screening for severe combined immune deficiency (SCID) is the first inborn error of immunity (IEI) to be detected through population screening. It also represents the first newborn screening test to utilize molecular testing on DNA from newborn dried blood spots. Newborn screening for SCID has provided opportunities to measure the population prevalence of this disorder and evaluate the effect of early interventions on the overall outcomes in affected infants. The success of SCID newborn screening has increased interest in developing and implementing molecular testing for other clinically significant inborn errors of immunity. This methodology has been adapted to screen for another monogenic inborn defect, spinal muscle atrophy. Advances in the clinical care and new therapeutics for many inborn errors of immunity support the need for early diagnosis and prompt institution of therapies to reduce morbidity and mortality. Early diagnosis may also improve the quality of life for affected patients. This article provides an overview of newborn screening for SCID, recommended steps for follow-up testing and early intervention as well as long-term follow-up. Numerous challenges remain, including the development of clinical consensus regarding confirmatory and diagnostic testing, early interventions, and best practices for immune reconstitution in affected infants.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 1","pages":"9-21"},"PeriodicalIF":9.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12016-021-08876-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501061","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":"Spectrum of Genetic T-Cell Disorders from 22q11.2DS to CHARGE.","authors":"Daniel Urschel,&nbsp;Vivian P Hernandez-Trujillo","doi":"10.1007/s12016-022-08927-z","DOIUrl":"https://doi.org/10.1007/s12016-022-08927-z","url":null,"abstract":"<p><p>Improved genetic testing has led to recognition of a diverse group of disorders of inborn errors of immunity that present as primarily T-cell defects. These disorders present with variable degrees of immunodeficiency, autoimmunity, multiple organ system dysfunction, and neurocognitive defects. 22q11.2 deletion syndrome, commonly known as DiGeorge syndrome, represents the most common disorder on this spectrum. In most individuals, a 3 Mb deletion of 22q11 results in haploinsufficiency of 90 known genes and clinical complications of varying severity. These include cardiac, endocrine, gastrointestinal, renal, palatal, genitourinary, and neurocognitive anomalies. Multidisciplinary treatment also includes pediatrics/general practitioners, genetic counseling, surgery, interventional therapy, and psychology/psychiatry. Chromosome 10p deletion, TBX1 mutation, CHD7 mutation, Jacobsen syndrome, and FOXN1 deficiency manifest with similar overlapping clinical presentations and T-cell defects. Recognition of the underlying disorder and pathogenesis is essential for improved outcomes. Diagnosing and treating these heterogenous conditions are a challenge and rapidly improving with new diagnostic tools. Collectively, these disorders are an example of the complex penetrance and severity of genetic disorders, importance of translational diagnostics, and a guide for multidisciplinary treatment.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 1","pages":"99-105"},"PeriodicalIF":9.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511080","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":"Diagnostic Modalities in Primary Immunodeficiency.","authors":"Loveita S Raymond,&nbsp;Jennifer Leiding,&nbsp;Lisa R Forbes-Satter","doi":"10.1007/s12016-022-08933-1","DOIUrl":"https://doi.org/10.1007/s12016-022-08933-1","url":null,"abstract":"<p><p>As the field of inborn errors of immunity expands, providers continually update and fine-tune their diagnostic approach and selection of testing modalities to increase diagnostic accuracy. Here, we first describe a mechanistic consideration of laboratory testing, highlighting both benefits and drawbacks of currently clinically available testing modalities. Next, we provide methods in evaluation of patients presenting with concern for inborn errors of immunity as defined by the International Union of Immunological Societies 2019 phenotypic categories: primary antibody deficiencies, cellular and humoral immune deficiency, disorders of the innate immune system, and syndrome-associated and primary immune regulation disorders (PIRDs). Using the suggested approach in this paper as a roadmap highlights the importance of thorough history taking and physical examination as the foundation to guide further diagnostic tests. This is followed by enumeration and functional testing. Finally, to determine the underlying molecular etiology-specific genetic panels, chromosomal microarrays, and broad genetic testing (whole exome sequencing or whole genome sequencing) are available.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"63 1","pages":"90-98"},"PeriodicalIF":9.1,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073277","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}