Therapeutic advances in rare disease最新文献

{"title":"Access to drugs for rare diseases (DRD) in Canada: a comprehensive review of the provincial DRD-specific programs.","authors":"Nahya Awada","doi":"10.1177/26330040251335660","DOIUrl":"https://doi.org/10.1177/26330040251335660","url":null,"abstract":"<p><p>Access to drugs for rare diseases (DRDs) in Canada depends largely on the province of living and the specific disease. The federal government and each of the ten provincial governments have their own drug review processes to determine DRD coverage, resulting in a fragmented system. This fragmentation leads to disparities in coverage, delays in treatment access, and exacerbates the challenges faced by patients with rare diseases (RDs) seeking lifesaving treatments. Canada lags behind many developed countries in adopting a national strategy for DRDs. In 2019, the Canadian government announced a plan to develop such a strategy to improve access, affordability, and consistency. A plan was launched in March 2023, though details were sparse. Although a pilot strategy involving two DRDs began in July 2024 through a bilateral agreement between the federal government and British Columbia, there remains an opportunity for Canada to learn from both domestic and international approaches. By examining these strategies, Canada is well-positioned to develop a robust, evidence-based national policy. Employing a qualitative document review approach, this study examined and compared the specific programs that target DRDs, which have been implemented in five provinces-Ontario (ON), Alberta (AB), New Brunswick (NB), British Columbia (BC), and Saskatchewan (SK)-to facilitate access to DRDs. The study, conducted between February 2019 and April 2022, reviewed policy documents related to these programs (referred to as DRD-SPs), as these programs have not been formally evaluated. The review revealed that AB and NB have active DRD-SPs, while ON's DRD-SP framework has been terminated. Despite reliable sources indicating otherwise, SK does not have a DRD-SP. The status of BC's DRD-SP, if one exists, remained unclear. The investigation into DRD-SPs demonstrated the creation of an uncoordinated, inefficient, patchwork of programs that often neither covered all DRDs, nor provided clear guidelines for accessing them. These policies lacked defined objectives and performance measures for periodic review. A unified, evidence-based national DRD policy is needed to ensure consistent and timely access, incorporating insights from both domestic and international approaches.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251335660"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating gynaecological challenges in Gaucher's disease: insights from five European countries.","authors":"Ljubas Dominik, Krstulović Opara Anđela, Wagner Jasenka, Duraković Nadira","doi":"10.1177/26330040251335665","DOIUrl":"https://doi.org/10.1177/26330040251335665","url":null,"abstract":"<p><strong>Background: </strong>Gaucher's disease (GD), a rare lysosomal storage disorder, primarily affects haematopoietic tissue. Emerging evidence suggests that GD also has an impact on gynaecological well-being, with documented pregnancy-related complications. However, substantial evidence is still lacking, indicating the need for better surveillance of GD-associated gynaecological complications.</p><p><strong>Objectives: </strong>To assess the frequency of gynaecological ailments, pregnancies and pregnancy-related complications and outcomes in women diagnosed with GD in Central and Southeastern Europe.</p><p><strong>Design: </strong>An online questionnaire was developed to gather data on gynaecological and reproductive health among female patients aged 18 years or older from five countries (Croatia, Slovenia, Serbia, Northern Macedonia, Bosnia and Herzegovina). The questionnaire was translated to native language of participating countries and distributed by the Croatian Gaucher Association. The study was conducted from December 2021 to March 2022.</p><p><strong>Methods: </strong>The variables assessed were treatment type, age at diagnosis, reproductive history, frequency of haematological disorders, infertility issues and pregnancy outcomes, as well as comparison of these variables between treated and untreated patients. Descriptive statistics were employed to calculate proportions, and mean values were computed for continuous variables. Fisher's exact test was used to compare categorical variables.</p><p><strong>Results: </strong>The study involved 26 participants. At the time of the study, four of the participants were undergoing substrate reduction therapy (SRT), and the remainder were receiving enzyme replacement therapy (ERT). Patients who received treatment during pregnancy reported a higher frequency of pregnancy-associated bleeding (71.3% vs 22.2%, <i>p</i> = 0.030). In total, there were 25 pregnancies and 20 births reported, while 11 (42.3%) respondents did not have children. All women conceived naturally, yet three reported difficulties with conception. Women who reported bleeding during pregnancy were more likely to experience issues with conception (<i>p</i> = 0.036) and bleeding during childbirth (<i>p</i> = 0.018). However, no significant difference was observed in relation to bleeding prior to pregnancy (<i>p</i> = 0.529).</p><p><strong>Conclusion: </strong>GD does not hinder pregnancy or motherhood, nor does it affect fertility, although it does require proper medical oversight and care. ERT alone may not be sufficient to prevent bleeding events, and detailed studies concerning coagulation might be necessary in pregnant women with GD.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251335665"},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilomatricomas in a patient with Rubinstein-Taybi syndrome: diagnostic and therapeutic clues.","authors":"Laura Battaglia, Corrado Ini', Manuela Lo Bianco, Roberta Leonardi, Eleonora Ini', Pietro Valerio Foti, Stefano Palmucci, Marco Fichera, Martino Ruggieri, Antonio Basile","doi":"10.1177/26330040251330316","DOIUrl":"https://doi.org/10.1177/26330040251330316","url":null,"abstract":"<p><p>Pilomatricoma is a rare benign neoplasm originating from hair cortex cells and typically manifests in children as a slow-growing bluish-red, superficial and firm mass. Multiple pilomatricomas can be associated with genetic mutations and syndromic disorders, most commonly with Rubinstein-Taybi syndrome, Gardner syndrome, myotonic dystrophy, Turner syndrome, and Sotos syndrome. Ultrasound examination allows this tumor to be characterized, to assess the involvement of deeper structures and to plan treatment. Pilomatricoma shows some distinctive ultrasonographic features that aid in its diagnosis and it may be seen on ultrasound as an ovoid complex mass. Complications and malignant transformation of pilomatricomas have been described as a possible tumor evolution, and surgical resection is recommended. We present a rare case of a 17-year-old female patient with intellectual disability and microcephaly, and with the evidence of multiple pilomatricomas in the head-neck region on ultrasound examination. The syndromic features of the patient and genetic tests led to a diagnosis of Rubinstein-Taybi syndrome. We also focused on the association between pilomatricomas and genetic mutations in patients with Rubinstein-Taybi syndrome.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251330316"},"PeriodicalIF":0.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging need to manage patient expectations of haemophilia gene therapy amidst media hype in the UK.","authors":"Laurence Woollard, Richard Gorman","doi":"10.1177/26330040251330317","DOIUrl":"10.1177/26330040251330317","url":null,"abstract":"","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251330317"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequent report of vitamin deficiencies and use of supplements and complementary/alternative treatment approaches in patients with eosinophilic gastrointestinal diseases.","authors":"Brenderia A Cameron, Elizabeth T Jensen, Xiangfeng Dai, Chelsea Anderson, Ellyn Kodroff, Mary Jo Strobel, Amy Zicarelli, Sarah Gray, Amanda Cordell, Girish Hiremath, Evan S Dellon","doi":"10.1177/26330040251326928","DOIUrl":"https://doi.org/10.1177/26330040251326928","url":null,"abstract":"<p><strong>Background: </strong>Eosinophilic gastrointestinal diseases (EGIDs) impact nutrition.</p><p><strong>Objectives: </strong>To assess the frequency of vitamin deficiencies, supplement use, and complementary/alternative-medication (CAM) use in EoE and non-EoE EGID patients.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>We surveyed members of EGID Partners (egidpartners.org), a patient-centered research network, to assess physician-diagnosed vitamin deficiencies, supplement use, and use of CAM in patients with EoE versus non-EoE EGIDs.</p><p><strong>Results: </strong>Of 81 EGID patients (58 EoE and 23 non-EoE EGID), self-reported frequency of vitamin deficiencies were higher in non-EoE EGIDs compared to EoE (61% vs 50%; <i>p</i> = 0.38; Table 1). Most patients (77%) indicated taking vitamins or supplements, with higher frequency in non-EoE EGID cases (87% vs 72%; <i>p</i> = 0.16). Use of >30 different supplements was reported. For CAM, herbal approaches were more frequent in non-EoE EGIDs compared to EoE (26% vs 5%; <i>p</i> = 0.008).</p><p><strong>Conclusion: </strong>Vitamin deficiencies and supplement/CAM use are frequent in EGIDs, highlighting the need for additional EGID treatment.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251326928"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient leadership and partnerships accelerate therapies for SCN8A and other developmental and epileptic encephalopathies.","authors":"Gabrielle Conecker, JayEtta Hecker, Michael F Hammer","doi":"10.1177/26330040241252449","DOIUrl":"10.1177/26330040241252449","url":null,"abstract":"<p><p>Families are a driving force in accelerating the understanding and science of SCN8A. The urgency felt by families facing the absence of treatments for their children makes them uniquely positioned to advance therapies through advocacy, data sharing, and partnerships. The International SCN8A Alliance (Alliance) brings families together to collaborate on advancing the science of SCN8A. The Alliance hosts SCN8A <i>scientific meetings -</i> facilitating coordination and collaboration among clinicians, researchers, industry, and the SCN8A community; funds early investigators to <i>support research</i> - building a new generation of investigators; builds and maintains a robust and dedicated International <i>SCN8A Registry</i> (Registry) providing longitudinal data on the natural history of the disorder and leading to over two dozen publications; cultivates <i>partnerships</i> with key stakeholders to accelerate innovation and progress including a Research Consortium, Global Clinicians Network, and the first global Consensus on the Diagnosis and Treatment of SCN8A; coordinates global <i>community engagement</i> by hosting families in virtual meetings in multiple languages and uniting advocates from across all epilepsies to call for more strategic and expanded investment in the epilepsies; builds and hosts the <i>Global SCN8A Leaders Alliance</i> (<i>Leaders Alliance</i>) promoting coordination and collaboration among leaders of SCN8A organizations worldwide; and advances a <i>Global SCN8A Research Roadmap</i> (<i>Research Roadmap</i>) - convening leading stakeholders in the SCN8A community to identify research priorities and accelerate progress toward better care, treatments, and outcomes. The outsized impact of small family advocacy organizations demonstrates that patient advocates can be effective agents in accelerating new therapeutics through maximizing their power to convene diverse stakeholders around a shared vision grounded in patient/caregiver priorities, maintaining a core focus on improving outcomes that are most important to families, and recognizing the importance of being bold, thinking big, and collaborating across disease areas.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040241252449"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paving the way toward treatment solutions for CTNNB1 syndrome: a patient organization perspective.","authors":"Špela Miroševič, Shivang Khandelwal, Emily Amerson, Effie Parks, Mariana Parks, Lauren Cochran, Ana González Hernández, Mirela Ferraro, Leszek Lisowski, Andrea Perez-Iturralde, Wendy Chung, Michele H Jacob, Nina Žakelj, Duško Lainšček, Vida Forstnerič, Petra Sušjan, Matea Maruna, Roman Jerala, Damjan Osredkar","doi":"10.1177/26330040251318355","DOIUrl":"10.1177/26330040251318355","url":null,"abstract":"<p><p>The CTNNB1 Connect & Cure and CTNNB1 Foundation, alongside Asociación CTNNB1, CTNNB1 Italia, Association CTNNB1 France, and researchers and clinicians globally are dedicated to finding effective treatments and cures for CTNNB1 syndrome. The syndrome is also characterized by progressive spasticity, which can in some cases cause loss of already achieved motor milestones. Since 2019, they have brought together researchers from different fields and invested in various research efforts to advance the search for treatment solutions for patients with CTNNB1 syndrome. Simons Searchlight serves as an important platform by remotely collecting high-quality, standardized data on the natural history of the disease and making it available to researchers around the world. Conducting genotype-phenotype correlation study and biochemically characterizing the mutations were critical to understand the effects of the patients' mutations and related molecular function to symptoms. Several induced pluripotent stem cells were generated from patient cells, and preclinical mouse models have provided new insights into the molecular downstream effects of CTNNB1 haploinsufficiency. Multiple therapeutic approaches are in the developing, including small molecule treatments, RNA- and DNA-based therapies, AAV9 gene replacement therapy, which entered the manufacturing phase in November 2023. In this article, we summarize the journey of the CTNNB1 community and its organizations, highlight ongoing and future research projects, and outline the available research resources. The vision for the CTNNB1 community is that in the future several therapeutic options will be available that can be customized to every CTNNB1 patient's needs.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251318355"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nirogacestat-the pathway to approval of the first treatment for desmoid tumors, a rare disease.","authors":"Shivaani Kummar, Nam Bui, Wells A Messersmith, Jeanne Whiting, Marlene Portnoy, Allison Lim, L Mary","doi":"10.1177/26330040251317546","DOIUrl":"10.1177/26330040251317546","url":null,"abstract":"<p><p>Drug development for rare diseases can be long, complex, and costly. Desmoid tumors (DT), a rare type of soft-tissue tumor, are associated with substantial and debilitating burden, including disease-specific symptoms (e.g., pain, impaired mobility), reduce functioning for daily activities, and worsen quality of life for patients with this condition. These tumors can be potentially life-threatening when they invade surrounding tissues, affect vital structures, or interfere with the body's functions. Until recently, there were no approved treatments specific to DT and little alignment on disease management. However, on November 27, 2023, the US Food and Drug Administration approved nirogacestat, an oral, targeted, and selective gamma secretase inhibitor, indicated for adult patients with progressing DT who require systemic treatment. This development milestone ascribes to nirogacestat the first approval of a gamma secretase inhibitor for human clinical use and the first therapy specifically indicated for treating patients with DT, thus addressing a long-term unmet need in this patient population. In the DeFi phase III trial of nirogacestat in adults with DT (NCT03785964), nirogacestat demonstrated statistically significant and clinically meaningful improvement in progression-free survival, objective response rate, DT-specific symptom burden (including pain), physical functioning, role functioning, and overall quality of life. This review chronicles the clinical development journey of nirogacestat from 2009 to the present day. Motivated to improve patient outcomes-and navigating considerable skepticism and uncertainty-the dedicated efforts of individuals within academic and medical institutions, industry, and patient advocacy groups shepherded nirogacestat through the development process, including those times when development stalled and might otherwise have been abandoned. Nirogacestat's pathway to becoming a treatment for DT demonstrates how critically important collaboration and coordination are for identifying unique, creative solutions to overcome challenges in rare disease drug development.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251317546"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behcet's disease in a tertiary eye hospital in Pakistan.","authors":"Tabish Ali Shalwani, Alishan Khowaja, Narmeen Punjwani","doi":"10.1177/26330040251314126","DOIUrl":"10.1177/26330040251314126","url":null,"abstract":"<p><p>Behçet's disease is a kind of variable vessel vasculitis (VVV) and inflammatory systematic disease affecting various organs of the body. The cause of the disease is idiopathic but is most commonly genetic in origin. A positive skin prick test (dermatographia), genital sores, eye irritation, skin sores, and at least three episodes of mouth sores in a year confirm the diagnosis. Treatment may include immunosuppressive agents, immune modulators, and biological markers such as corticosteroids, immunosuppressants, and antibodies. We report a case of a 23-year-old male patient, presented in an outpatient clinic in a tertiary care eye hospital located in Pakistan. The patient reported sudden loss of vision in one eye and graduate loss of vision in the other eye. Ocular and systemic investigations were performed to correlate with clinical findings to reach a diagnosis. The patient was managed symptomatically and was put on corticosteroids. Our hospital is a research and postgraduate educational institution that deals with complex eye diseases. The range of investigations and clinical exams helped clinical decision-makers in evaluating the patient's diagnosis.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040251314126"},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roadmap to advance therapeutics for <i>SYNGAP1</i>-related disorder: a patient organization perspective from SynGAP Research Fund.","authors":"J Michael Graglia, Aaron J Harding, Kathryn A Helde","doi":"10.1177/26330040241308285","DOIUrl":"10.1177/26330040241308285","url":null,"abstract":"<p><p><i>SYNGAP1</i>-related disorder (SRD) is a developmental and epileptic encephalopathy caused by a disruption of the <i>SYNGAP1</i> gene. At the beginning of 2024, it is one of many rare monogenic brain disorders without disease-modifying treatments, but that is changing. This article chronicles the last 5 years, beginning when treatments for SRD were not publicly in development, to the start of 2024 when many SRD-specific treatments are advancing. We discuss the progress across many realms that have brought SRD to the forefront of drug development and highlight how Patient Advocacy Groups (PAGs) have had direct roles in accelerating the route to meaningful treatments for our children. We start with a summary of why SRD is an attractive pharmaceutical target. Second, we introduce the disease, the clinical features, and the number of patients. Next, we describe our PAG, our international partners and cite examples of the broad range of activities we believe are accelerating our pace toward treatments. We summarize the current <i>SYNGAP1</i> pipeline and the status of each public project. Finally, we discuss two open questions that urgently need to be addressed in advance of clinical trials for SRD.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"6 ","pages":"26330040241308285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}