Neuromuscular Disorders最新文献

{"title":"Two novel deep intronic variants cause Duchenne muscular dystrophy by splice-altering mechanism","authors":"Lei Zhao ,&nbsp;Chaoping Hu ,&nbsp;Shirang Pan ,&nbsp;Depeng Wang ,&nbsp;Yi Wang ,&nbsp;Xihua Li","doi":"10.1016/j.nmd.2024.104470","DOIUrl":"10.1016/j.nmd.2024.104470","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness, due to mutations in the DMD gene, which encodes the dystrophin protein. While mutations within the coding regions of DMD have been extensively studied, recent focus has shifted to deep intronic variants for their potential impact on disease severity. Here, we characterize two deep intronic variants, c.8669-19_8669-24del and c.6439-1016_6439-3376del, in unrelated DMD patients. These variants were identified using targeted long-read sequencing on patients' DNA. RNA sequencing/reverse transcription polymerase chain reaction on RNA extracted from muscle biopsies revealed the presence of a pseudoexon or retention of part of the intron in the transcript, resulting in the introduction of premature termination codons. This study enhances our understanding of pseudoexon activation mechanisms in DMD and underscores the diverse genetic abnormalities contributing to the disease's complexity.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 104470"},"PeriodicalIF":2.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9–11 February 2024, Hoofddorp, the Netherlands","authors":"Amelia Evoli ,&nbsp;Jacqueline Palace ,&nbsp;Gregorio Spagni ,&nbsp;Marta Cheli ,&nbsp;Annabel Ruiter ,&nbsp;Jan Verschuuren ,&nbsp;Lorenzo Maggi","doi":"10.1016/j.nmd.2024.104468","DOIUrl":"10.1016/j.nmd.2024.104468","url":null,"abstract":"<div><div>The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9–11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs. The workshop has highlighted considerable challenges in the SNMG diagnostic work-up. To date, SNMG confirmation is often controversial, given the absence of specific diagnostic tests; no recommendations from international panels of experts are available in literature; myopathies, congenital myasthenic syndromes and functional disorders are the commonest misdiagnoses. Improving the disease diagnosis is crucial to avoid long delays in receiving appropriate treatment. To this purpose, a comprehensive diagnostic algorithm achieved consensus. Moreover, a remarkable variability in SNMG response to therapy and long-term prognosis has also been highlighted.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"44 ","pages":"Article 104468"},"PeriodicalIF":2.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent nodular lymphocytic myositis and myasthenia gravis. A case report","authors":"Eleonora S D'Ambrosio ,&nbsp;Matti D Allen ,&nbsp;Burcak Ozes ,&nbsp;Zarife Sahenk","doi":"10.1016/j.nmd.2024.105211","DOIUrl":"10.1016/j.nmd.2024.105211","url":null,"abstract":"<div><div>Localized painful nodules associated with focal myositis have been previously documented, either as isolated occurrences or in conjunction with systemic illnesses, such as polymyositis [<span><span>[1]</span></span>, <span><span>[2]</span></span>, <span><span>[3]</span></span>, <span><span>[4]</span></span>]. These nodules typically manifest over the course of 2-8 weeks and exhibit histological features consistent with inflammatory myositis. Here we present a unique case of a patient with a history of myasthenia gravis, who experienced exacerbation of myasthenic symptoms, accompanied by the development of palpable, tender nodules on her thighs and proximal weakness. Muscle biopsy revealed circumscribed mononuclear infiltrates predominantly composed of CD3+ and CD4+ lymphocytes. Furthermore, we detail the patient's rapid and sustained response to treatment with steroids (both intravenous pulse and maintenance therapy) and methotrexate. To the best of our knowledge, this represents the first documented case of nodular lymphocytic myositis concurrent with an exacerbation of myasthenia gravis, in a patient with no prior history of significant immunosuppression or chronic infection.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 105211"},"PeriodicalIF":2.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards harmonization of clinical tools for assessing Brain Involvement in Dystrophinopathies (BIND); report of four expert workshops: Newcastle, Leiden, Rome, Paris","authors":"Jos Hendriksen ,&nbsp;Pien Weerkamp ,&nbsp;Ruben Miranda ,&nbsp;Anna Kolesnik ,&nbsp;Daniela Chieffo ,&nbsp;David Skuse ,&nbsp;Elizabeth Vroom ,&nbsp;Chloe Geagan ,&nbsp;Francesco Muntoni ,&nbsp;Eugenio Mercuri ,&nbsp;BIND WP5 working group","doi":"10.1016/j.nmd.2024.104452","DOIUrl":"10.1016/j.nmd.2024.104452","url":null,"abstract":"<div><div>As part of an international project aimed at improving the characterization of brain involvement in Duchenne and Becker Muscular Dystrophies, a group of clinicians, researchers and family associations held multiple meetings between March 2021 and March 2024 to identify and reach a consensus on the possible tools that could assess the spectrum of neurocognitive and neurobehavioral brain comorbidities in dystrophinopathies. Consensus was achieved on which of these tools should be used across different settings, ranging from screening to clinical practice and scientific research. Screening questionnaires were found to be valuable not only for providing epidemiological data but also for raising awareness among the Duchenne community and professionals. More standardised and detailed online questionnaires, combined with in-depth clinical assessments can help better identify the profile of brain comorbidities and plan appropriate interventions. Additionally, the information gathered from assessing multiple features of brain involvement can be used to explore correlations with other aspects, such as the regional expression of the different dystrophin isoforms, brain imaging, and the animal models deficient in these isoforms.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"44 ","pages":"Article 104452"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"273rd ENMC International workshop: Clinico-Sero-morphological classification of the Antisynthetase syndrome. Amsterdam, The Netherlands, 27-29 October 2023","authors":"Werner Stenzel ,&nbsp;Andrew L Mammen ,&nbsp;Laure Gallay ,&nbsp;Marie-Therese Holzer ,&nbsp;Felix Kleefeld ,&nbsp;Olivier Benveniste ,&nbsp;Yves Allenbach","doi":"10.1016/j.nmd.2024.104453","DOIUrl":"10.1016/j.nmd.2024.104453","url":null,"abstract":"<div><div>Among the idiopathic inflammatory myopathies, patients harbouring an Antisynthetase syndrome exhibit a unique clinical picture, with characteristic signs such as myositis, interstitial lung disease, arthritis, rash, and/or fever. Characteristic morphological features on skeletal muscle biopsies differentiate Antisynthetase syndrome from other forms of myositis. Autoantibodies typically recognizing one of the members of the aminoacyl-tRNA synthetase family of proteins can be detected in the serum of such patients, with anti-Jo1 being most frequent. Until now, an international consensus definition of the Antisynthetase syndrome is lacking, hence this workshop has undertaken the task to inform about the clinical, morphological and autoantibody profiles of Antisynthetase syndrome. The authors also expand their aims by giving management and therapeutic strategies, and finally provide precise classification criteria for Antisynthetase syndrome.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 104453"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnosis of Duchenne muscular dystrophy - A Treat-NMD international workshop","authors":"M. Lorentzos ,&nbsp;JA. Parsons ,&nbsp;KJ. Jones ,&nbsp;L. Servais ,&nbsp;The Treat NMD Early Diagnosis Workshop Participants","doi":"10.1016/j.nmd.2024.104467","DOIUrl":"10.1016/j.nmd.2024.104467","url":null,"abstract":"<div><div>The diagnosis of Duchenne muscular dystrophy (DMD) is significant at any stage, however an early diagnosis in a presymptomatic or very early phase of DMD, offers unique opportunities and challenges for families and health care providers. Currently, there is limited evidence as to the optimal models of care during this stage of the condition.. To address this, in 2023, Treat-NMD facilitated the Early Diagnosis for DMD project; bringing together 42 experts from across Europe, the US and Australasia, including health care professionals, researchers, and people with lived experience to discuss the complexities of an early or newborn diagnosis of DMD, and provide recommendations regarding approaches to multidisciplinary care. A series of virtual meetings followed by a hybrid workshop resulted in broad recommendations to support clinicians in caring for children and families following an early diagnosis of DMD. The workshop did not define a cut-off for early diagnosis, however much of the discussion focused on diagnoses that occurred prior to 2 years. There is recognition that boys may first present with non-motor symptoms, such as speech delay or neurodevelopmental issues that are secondary to their dystrophinopathy, and therefore this report refers reflects that infants with DMD may be presymptomatic or early symptomatic.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"45 ","pages":"Article 104467"},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"271P Exploring the effects of the epi-drug Remodelin on murine myoblasts differentiation","authors":"V. Sian ,&nbsp;J. Sarparanta ,&nbsp;A. Hentschel ,&nbsp;P. Jonson ,&nbsp;A. Roos ,&nbsp;S. Natraj Gayathri ,&nbsp;B. Udd ,&nbsp;M. Savarese ,&nbsp;A. Nebbioso","doi":"10.1016/j.nmd.2024.07.089","DOIUrl":"10.1016/j.nmd.2024.07.089","url":null,"abstract":"<div><div>Skeletal muscle differentiation is a tightly controlled and elaborated process, that consists of alignment and fusion of myoblasts to form mature myotubes. A growing interest for epigenetics involvement in guiding muscle differentiation raised the attention on epi-modulators as pivotal regulators in this process. Our in vitro study aimed to investigate the potential effects of Remodelin in muscle differentiation. Remodelin is the inhibitor of N-acetyltransferase 10, the key-player of RNA acetylation. We used the well-consolidated model of murine C2C12 cells cultivated on ultra-compliant gelatin hydrogels for long-term studies. The newly developed hydrogel scaffold promotes myotube alignment and maturation, mimicking the skeletal muscle biology observed in vivo. We differentiated C2C12 cells in low-serum conditions up to 16 days and treated them with the epi-drug Remodelin. At day 7 of differentiation, confocal images revealed that Remodelin prompted a lack of organization, proper morphology, and maturation of myotubes compared to the control. Marked twitching was neither visible upon Remodelin treatment, even in the late stage of differentiation. Remodelin downregulated the expression of protein markers of differentiation, but without any significant epi-modulation. Both transcriptomics and proteomics analyses confirmed that Remodelin effectively slowed down the process of myotube formation. RNAseq analysis revealed that the epi-drug down-regulated 749 genes, predominantly encoding proteins involved in muscle contraction, sarcomere organization, muscle structure development, and calcium ion binding. Proteomics analysis further unveiled that 37 significantly down-regulated proteins were related to extracellular matrix, cell-matrix adhesion, positive regulation of muscle cell differentiation, and calcium ion binding. Taken together, these results suggest that Remodelin exerts a broad effect on the regulatory networks of skeletal muscle differentiation.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.80"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"145P Efficacy of SMA NBS: 4-year comparative study with control group","authors":"T. Dangouloff ,&nbsp;L. De Waele ,&nbsp;D. Beysen ,&nbsp;N. Smeets ,&nbsp;A. Vanlander ,&nbsp;N. Benmhammed ,&nbsp;C. Tychon ,&nbsp;A. Daron ,&nbsp;N. Deconinck ,&nbsp;P. Dontaine ,&nbsp;L. Servais","doi":"10.1016/j.nmd.2024.07.052","DOIUrl":"10.1016/j.nmd.2024.07.052","url":null,"abstract":"<div><div>Several newborn screening (NBS) programs for Spinal Muscular Atrophy (SMA) have demonstrated feasibility-reliability and short-term efficacy of PCR-based universal SMA NBS, but longer-term data are needed to precise the benefit of this intervention. In addition, the comparison with external control groups can reinforce the level of evidence and support robust health economic assessment. The aim of this study is to compare the medical, quality of life and economic data for SMA patients diagnosed by NBS and those identified by symptoms, in the same country, during the same time period. We collected data on all SMA patients born in Flanders and the Wallonia-Brussels Federation (FWB) between January 1, 2019 (the date on which the entire FWB began screening for SMA) and 30 November 2022 (the date on which Flanders began screening). We compared the median age of diagnosis and initiation of treatment, the treatment, scores on motor development scales, and the age of acquisition of sitting and walking. We also collected quality of life data for parents, utility data for children, and costs associated with the disease. A total of 30 patients were included in the analysis: 16 patients in FWB (7 with 2 SMN2 copies, 4 with 3 copies and 5 with 4 copies) and 13 in Flanders. One patient with a point mutation was not identified by NBS in FWB. Patients in FWB were initially treated by nusinersen (n = 5) risdiplam (n = 3) and onasemnogene abeparvovec (n = 7) at 36 days of life on average (29, 37, and 44 days respectively for patients with 2, 3 and 4 SMN2 copies of SMN2). Two patients shifted from nusinersen to risdiplam, one from nusinersen to onasemnogene abeparvovec and one from risdiplam to onasemnogene abeparvovec. One patient with 4 SMN2 copies was still untreated at 26 months. Median follow up was 32 months (9-54 months). All patients over 18 months with 3 and 4 SMN2 copies acquired ambulation (median age: 17 months, 13-24 months). Of the 7 patients with 2 SMN2 copies, 2 are not yet 18 months old, 4 are walking, and one aged 24 months is not yet walking. One child with 2 SMN2 copies have non-invasive nocturnal ventilation. None of the children needed nutritional support at the time of the last follow-up. Data in Flanders, where NBS was not implemented in the studied time, are currently collected, and will be presented during the congress. Our data shows that middle term outcome of patients identified by NBS is very good so far. Estimation of health care cost saving will be presented.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.43"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"136P Medical treatment of children with spinal muscular atrophy - An investigation of parents' experiences of hopes, worries and need for rehabilitation for their child","authors":"C. Handberg ,&nbsp;U. Werlauff ,&nbsp;P. Drivsholm ,&nbsp;S. Lorenzen ,&nbsp;A. Mahoney","doi":"10.1016/j.nmd.2024.07.043","DOIUrl":"10.1016/j.nmd.2024.07.043","url":null,"abstract":"<div><div>In Denmark, newborn screening was introduced at the beginning of 2023, and per July 2023 the Medical Council recommended medical treatment of SMA for children, young people, and adults up to and including 25 years of age who meet the inclusion criteria in the treatment guidelines. The medical advances give both children, parents and health professionals hope for a new life with SMA. The children receive treatment at the pediatric departments at university hospitals in Denmark and most of them are referred to the Danish National Rehabilitation Centre for Neuromuscular Diseases (RCFM) where they and their families receive guidance and advice from rehabilitation specialists. There is currently scant knowledge about how parents of a child with SMA type 1, 2 or 3 experience their child's illness, their contact with health professionals, and their needs for information and advice on the medical treatments and its effect. The aim of the project is to gain knowledge about how Danish parents whose children with SMA have been offered medical treatment handle hopes and worries in relation to disease progression. And to investigate the families’ needs for information, advice, and rehabilitation initiatives. The study was designed as a qualitative interview study guided by the interpretive description methodology and Joyce Travelbee's theory of interpersonal aspects such as suffering, meaning, hope and communication. The method was semi-structured couple interviews with parents of children with SMA type 1, 2 and 3 aged 14 and younger. In all, 41 couples with children registered at RCFM were invited to participate. Nineteen couples (38 parents) accepted the invitation. The analysis is ongoing, and the results will be presented on the conference poster.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.34"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"143P Swallowing physiology and function in untreated patients with Spinal Muscular Atrophy type 1: establishing natural history reference values","authors":"K. McGrattan ,&nbsp;R. Graham ,&nbsp;A. Miles ,&nbsp;J. Allen ,&nbsp;A. Hofelich Mohr ,&nbsp;V. Rao ,&nbsp;L. Alfano ,&nbsp;L. Smith ,&nbsp;J. Brandesma ,&nbsp;C. Leon Astudillo ,&nbsp;D. Levy ,&nbsp;W. Tang ,&nbsp;A. Brown ,&nbsp;A. Spoden ,&nbsp;G. Schenck ,&nbsp;B. Darras","doi":"10.1016/j.nmd.2024.07.050","DOIUrl":"10.1016/j.nmd.2024.07.050","url":null,"abstract":"<div><div>Dysphagia has been a leading source of morbidity in patients with spinal muscular atrophy type 1 (SMA 1). The paucity of investigations has impeded the ability to judge the effect of disease modifying therapies (DMT). We report a natural history dataset characterizing swallowing biomechanics and function in untreated children with SMA 1. Infants with SMA 1 who had not received DMT and underwent a videofluoroscopic swallow study (VFSS) were retrospectively identified from 13 international children's hospitals. Charts were reviewed for oral intake and secretion management. VFSS’ were prospectively evaluated for biomechanics. Differences in swallowing between patients referred for VFSS due to swallowing concerns vs. those referred as part of a routine high-risk referral were tested using paired t-tests. Of the 77 children included, 30% of required suctioning, and 39% received alternative nutrition. Profound deficits were observed in sucking, with the inability to extract a bolus in 25% of children. Impairments in bolus clearance were common, with severe reductions in tongue base retraction (49%), absent pharyngeal stripping wave (23%), and minimal to no upper esophageal segment opening (50%) resulting in a majority-no clearance of the bolus from the pharynx in 40% of children. Pharyngeal constriction ratio (0.41 ± 0.28) and upper esophageal segment opening (0.12 ± 0.09) were consistent with these results. More than trace aspiration (56%) on &gt;1 occurrence was seen in 52% of children. Deficits were significant worse in patients referred due to symptoms than asymptomatic (p &lt; 0.05). Without pharmaceuticals patients with type 1 SMA exhibit profound deficits in swallowing. Although the presence of clinical signs of swallowing impairment may identify those children with the most profound deficits, they are not reliable for identifying a magnitude of other clinically significant impairments.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"43 ","pages":"Article 104441.41"},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}