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{ "count": 24776, "next": "http://api.gregory-ms.com/articles/?format=api&page=2448", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2446", "results": [ { "article_id": 321, "title": "Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care", "summary": "<h2>Summary</h2><p>The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions—multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)—can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30432-4/fulltext", "published_date": "2021-02-01T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 159108, "given_name": "Giulia", "family_name": "Fadda", "ORCID": "http://orcid.org/0000-0001-9658-815X", "country": null }, { "author_id": 241673, "given_name": "Thais", "family_name": "Armangue", "ORCID": null, "country": null }, { "author_id": 210191, "given_name": "Yael", "family_name": "Hacohen", "ORCID": "http://orcid.org/0000-0001-8490-9657", "country": null }, { "author_id": 143340, "given_name": "Tanuja", "family_name": "Chitnis", "ORCID": "http://orcid.org/0000-0002-9897-4422", "country": null }, { "author_id": 241675, "given_name": "Brenda", "family_name": "Banwell", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Paediatric multiple sclerosis", "antibody-associated demyelination", "clinical, imaging, and biological considerations", "diagnosis", "care" ], "doi": "10.1016/S1474-4422(20)30432-4", "access": "open", "takeaways": " The field of acquired CNS neuroimmune demyelination in children is transforming . The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children .", "categories": [] }, { "article_id": 315, "title": "High-dose biotin in multiple sclerosis: the end of the road", "summary": "Since the first pilot study of high-dose biotin in patients with chronic progressive multiple sclerosis 1 and the subsequent phase 2 randomised, double-blind, placebo-controlled trial (MS-SPI), 2 biotin has been discussed as a potentially unique approach to treat progressive multiple sclerosis by targeting remyelination. Biotin, as a cofactor for four essential carboxylases, might support myelin repair by enhancing fatty acid synthesis and protect against hypoxia-driven axonal degeneration by augmenting energy production in neurons. 1 , 3", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30353-7/fulltext", "published_date": "2020-10-22T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 221282, "given_name": "Jeremias", "family_name": "Motte", "ORCID": "http://orcid.org/0000-0002-6624-8565", "country": null }, { "author_id": 147050, "given_name": "Ralf", "family_name": "Gold", "ORCID": "http://orcid.org/0000-0002-7223-3052", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "multiple sclerosis", "the road" ], "doi": "10.1016/S1474-4422(20)30353-7", "access": "restricted", "takeaways": " Biotin has been discussed as a potentially unique approach to treat progressive multiple sclerosis by targeting remyelination . Biotin might support myelin repair by enhancing fatty acid synthesis", "categories": [] }, { "article_id": 320, "title": "Regional and global perspectives on the incidence of multiple sclerosis and neuromyelitis optica and its spectrum disorders from Asia with emphasis on China", "summary": "CNS inflammatory disorders such as multiple sclerosis (MS), neuromyelitis optica/neuromyelitis optica spectrum disorders(NMO/NMOSD) are assuming increasing importance in recent years within Asia [[1]]. In The Lancet Regional Health – Western Pacific, De-Cai Tian and colleagues from China highlight important new data from two nationwide studies on MS/NMO/NMOSD for the first time giving the incidence of MS and NMO/NMOSD in children and adults as well as the burden of disease in terms of hospitalization duration, reimbursement and costs, mortality and common associated comorbidities rarely reported before [[1],[2]]. The study encompasses one of the largest Asian populations sampled to date with better case ascertainments and inclusivity of paediatric and diverse populations. Both studies are large nationwide population-based studies on MS and NMO/NMOSD from a country that houses a fifth of the world's population. Tian et al. accessed information from the national database of the Hospital Quality Monitoring System (HQMS) that covers the entire Chinese population from mainly tertiary hospitals. The authors identified 1665 hospitals covering more than 90% of the tertiary public hospitals, with 11 973 newly diagnosed NMO/NMOSD patients and 9879 pts with MS from 2016–2018[[1],[2]]. Though heterogeneity in methodology prevents head to head comparisons with other studies important points gleaned are as follows: their MS study is large by South-East/East Asian standards although smaller comparatively in absolute numbers than studies from West Asia, United States(US), Continental Europe and Oceania [[3],[4]]. Their NMO/NMOSD study is one of the largest population-based NMO/NMOSD studies to date in terms of absolute numbers [[1],[2],[5],[7],[8]]. It is also noteworthy that this study was done post availability of Anti Aqp4 Ig G antibody testing and the IPND 2015 criteria for NMO/NMOSD resulting in better case ascertainment [[5],[7],[8]]. Further, Tian et al. reported the incidence of MS and NMO/NMOSD in both adults and children. There have been very few studies from within Asia and globally on paediatric MS/NMOSD.6,7 In a recent meta-analysis, global paediatric MS incidence was 0.87 per 100,000 annually which is more than the current study [[6],[7]]. A Japanese study on NMOSD reported rates of 0.06 per 100,000 in paediatrics which is comparable to Tian et al.’s current study [[7]]. Early global MS and NMO/NMOSD studies collected hospital/academic institution-based data within small regions in a country where case ascertainment was abstracted from standard diagnostic criteria. These were good starting points as regional population-based studies but rarely reflected nationwide data. Projecting estimates from one or a few regions to the entire country is of uncertain validity long-term. For instance, a local Malaysian study looking at a small region within the country underestimated the true occurrence of NMO/NMOSD within certain ethnic groups in the country leading to under-representation of cases within the Malay and Indian cohorts [[8]]. Though these efforts at reporting are commendable, it leads to conflicts in health care planning at a national level and unequal disease socio-demographic profiling. A similar nationwide study showed the prevalence of NMO/NMOSD amongst Malays, Chinese and Indians to be 0.9/0.9/0.6 per 100,000 (n=260/256/19) [[9]]. Therefore Tian et al.’s study utilizing the HQMS database, with careful case ascertainment is inclusive and comprehensive as it looks at all regions and increases relevance by covering a large population nationwide rather than extrapolating from a small region [[1],[2]]. The estimated age and sex adjusted incidence for MS for all groups namely adults were comparable to other Asian reports wherein the overall incidence for MS ranged from 0.5 to 0.78 per 100,000 in Malaysia, Taiwan, Japan and Korea respectively [[1],[2],[3],[4],[9],[10]]. However, these rates though increasing are still low compared to high incidence areas in Western Asia like Iran where it is 3.4 per 100,000 and in the US, Europe, Scandinavia, Russia, Australia and New Zealand where it ranges from 1 to >10 per 100,000 [[3],[4],[10]]. This study is further substantiated by the recently published Atlas of MS 3rd Edition, where the prevalence of MS in China is reported to have doubled [[3],[4]]. Thus, though the incidence is increasing in Asia, complex interactions between genetic susceptibility and the environment plausibly accounts for MS partiality to West Asia and Western populations [[3],[4]]. Alternatively, the incidence of NMO/NMOSD in the present study is high and comparable to rates from Japan, Taiwan, Korea and Malaysia ranging from age adjusted 0.287 (adults:0.347 per 100,000) in China to 0.50–0.73 per 100,000 population in other South Asian countries. [[1],[2],[8],[9],[10],[11]] These rates are higher than those reported in Caucasian studies but nearly comparable to Afro–American/Carribean reports [[5],[8]]. Tian et al.’s study interestingly highlights the variability of NMO/NMOSD for certain ethnic groups, gender and regions within Asia with high NMO/NMOSD to MS ratios. The large numbers reported in their Chinese cohort is also seen in other Asian cohorts such as Malaysia where NMOSD is commoner amongst Chinese with NMOSD to MS ratios of 2:1 compared to Indians (MS:NMOSD 8.3:1) and Malays (MS:NMOSD 2:1) [[9]]. A recent Australia-New Zealand study also found Asians to be 3 times more prone for NMO/NMOSD than Caucasians [[11]]. Further, the authors identified a female predominance for both MS and NMOSD which is notably higher amongst their NMOSD patients i.e. 2.0:4.7 (MS: NMOSD). This female preponderance especially in NMOSD is also seen in other Asian MS and NMOSD studies from Japan, Korea, Hong Kong, Taiwan and Malaysia [[5],[9]]. NMO/NMOSD studies from the US, Europe, Australia/New Zealand, West Asia and India also reveal a similar female predominance though less marked than East Asian studies [[5],[8],[11]]. Uniquely, Tian et al.’s study on MS reaffirmed the important effects of latitude seen in Japanese studies, and those from the US, Europe, Russia and Australia/New Zealand [[3],[4]]. However, their study identified not only a negative north–south gradient but also a negative west–east altitude gradient not identified before for MS. This latitude preponderance was not seen in their NMOSD incidence study similar to reports from Australia/New Zealand thus suggesting other genetic factors in pathogenesis [[1],[2],[11]]. In terms of burden of disease, Tian et al.’s study reports mortality rates for MS and NMO/NMOSD of 6 to 7 per 1000 years and the occurrence of associated comorbidities such as hypertension in both conditions. Whilst autoimmune diseases such as SLE/Sjorgen syndromes are seen more with NMOSD than MS. In the past, mortality and morbidity has been scarcely explored in regional studies on MS/NMO/NMOSD [[1],[2]]. The authors also assessed the burden of disease in terms of hospitalization costs, duration and associated comorbidities. This data is vital for budget impact analysis studies for health care planning and medication procurement regionally. Therefore, Tian et al.’s study on hospitalization burden and cost is timely to facilitate MS/NMO/NMOSD resource allocations more so with the advent of newer sophisticated disease modifying therapies, immunosuppressants and biologics for MS and NMO/NMOSD [[1],[2]]. Additionally, their study reports the presence of a universal government based social health insurance which has successfully improved access to care for MS and NMOSD patients in China [[1],[2]]. In summary, the authors provided important updated nationwide information on the epidemiology, burden and cost of disease from China with careful case ascertainment which shows similarities to other regional Asian studies and adds to current worldwide literature on MS and NMO/NMOSD.", "link": "https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(20)30039-0/fulltext", "published_date": "2020-09-29T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Regional Health - Western Pacific", "authors": [ { "author_id": 241677, "given_name": "S.", "family_name": "Viswanathan", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Regional and global perspectives", "the incidence", "multiple sclerosis", "neuromyelitis optica", "its spectrum disorders", "Asia", "emphasis", "China" ], "doi": "10.1016/j.lanwpc.2020.100039", "access": "open", "takeaways": "", "categories": [] }, { "article_id": 314, "title": "Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial", "summary": "<h2>Summary</h2><h3>Background</h3><p>There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort.</p><h3>Methods</h3><p>SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29).</p><h3>Findings</h3><p>From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies.</p><h3>Interpretation</h3><p>This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis.</p><h3>Funding</h3><p>MedDay Pharmaceuticals.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30347-1/fulltext", "published_date": "2020-10-22T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 248491, "given_name": "Bruce A C", "family_name": "Cree", "ORCID": null, "country": null }, { "author_id": 240824, "given_name": "Gary", "family_name": "Cutter", "ORCID": null, "country": null }, { "author_id": 241104, "given_name": "Jerry S", "family_name": "Wolinsky", "ORCID": null, "country": null }, { "author_id": 153178, "given_name": "Mark S", "family_name": "Freedman", "ORCID": "http://orcid.org/0000-0003-1255-9701", "country": "CA" }, { "author_id": 149342, "given_name": "Giancarlo", "family_name": "Comi", "ORCID": "http://orcid.org/0000-0002-6989-1054", "country": null }, { "author_id": 143429, "given_name": "Gavin", "family_name": "Giovannoni", "ORCID": "http://orcid.org/0000-0001-9995-1700", "country": null }, { "author_id": 181330, "given_name": "Hans-Peter", "family_name": "Hartung", "ORCID": "http://orcid.org/0000-0002-0614-6989", "country": null }, { "author_id": 244012, "given_name": "Douglas", "family_name": "Arnold", "ORCID": null, "country": null }, { "author_id": 154809, "given_name": "Jens", "family_name": "Kuhle", "ORCID": "http://orcid.org/0000-0002-6963-8892", "country": "CH" }, { "author_id": 172098, "given_name": "Valerie", "family_name": "Block", "ORCID": "http://orcid.org/0000-0001-6199-5484", "country": "US" }, { "author_id": 247955, "given_name": "Frederick E", "family_name": "Munschauer", "ORCID": null, "country": null }, { "author_id": 248495, "given_name": "Frédéric", "family_name": "Sedel", "ORCID": null, "country": null }, { "author_id": 172546, "given_name": "Fred D", "family_name": "Lublin", "ORCID": "http://orcid.org/0000-0001-5722-0475", "country": null }, { "author_id": 248496, "given_name": "Stephen", "family_name": "Reingold", "ORCID": null, "country": null }, { "author_id": 183403, "given_name": "Pierre", "family_name": "Duquette", "ORCID": "http://orcid.org/0000-0001-7231-1754", "country": null }, { "author_id": 152403, "given_name": "Tobias", "family_name": "Derfuss", "ORCID": "http://orcid.org/0000-0001-8431-8769", "country": null }, { "author_id": 241329, "given_name": "Franz", "family_name": "Fazekas", "ORCID": null, "country": null }, { "author_id": 149329, "given_name": "Maria Pia", "family_name": "Sormani", "ORCID": "http://orcid.org/0000-0001-6892-104X", "country": null }, { "author_id": 248497, "given_name": "Robert P.", "family_name": "Lisak", "ORCID": null, "country": null }, { "author_id": 159536, "given_name": "Jennifer", "family_name": "Graves", "ORCID": "http://orcid.org/0000-0003-1539-1940", "country": null }, { "author_id": 240958, "given_name": "Stephen", "family_name": "Krieger", "ORCID": null, "country": null }, { "author_id": 248498, "given_name": "Rana K.", "family_name": "Zabad", "ORCID": null, "country": null }, { "author_id": 246981, "given_name": "Scott", "family_name": "Newsome", "ORCID": null, "country": null }, { "author_id": 248499, "given_name": "Joshua", "family_name": "Barton", "ORCID": null, "country": null }, { "author_id": 248500, "given_name": "Richard", "family_name": "MacDonell", "ORCID": null, "country": null }, { "author_id": 248501, "given_name": "Mark", "family_name": "Marriott", "ORCID": null, "country": null }, { "author_id": 248502, "given_name": "Nina", "family_name": "De Klippel", "ORCID": null, "country": null }, { "author_id": 231369, "given_name": "Guy", "family_name": "Laureys", "ORCID": "http://orcid.org/0000-0002-1708-4373", "country": null }, { "author_id": 184068, "given_name": "Barbara", "family_name": "Willekens", "ORCID": "http://orcid.org/0000-0002-5212-8837", "country": "BE" }, { "author_id": 245696, "given_name": "Virginia", "family_name": "Devonshire", "ORCID": null, "country": null }, { "author_id": 248503, "given_name": "Mark", "family_name": "Freedman", "ORCID": null, "country": null }, { "author_id": 248504, "given_name": "J Marc", "family_name": "Girard", "ORCID": null, "country": null }, { "author_id": 248506, "given_name": "Paul", "family_name": "Giacomini", "ORCID": null, "country": null }, { "author_id": 248508, "given_name": "Roger", "family_name": "McKelvey", "ORCID": null, "country": null }, { "author_id": 245799, "given_name": "Daniel", "family_name": "Selchen", "ORCID": null, "country": null }, { "author_id": 241547, "given_name": "Galina", "family_name": "Vorobeychik", "ORCID": null, "country": null }, { "author_id": 248511, "given_name": "Ludivine", "family_name": "Witkowski", "ORCID": null, "country": null }, { "author_id": 248513, "given_name": "Radek", "family_name": "Ampapa", "ORCID": null, "country": null }, { "author_id": 150336, "given_name": "Jana Lizrova", "family_name": "Preiningerova", "ORCID": "http://orcid.org/0000-0003-0337-3462", "country": "CZ" }, { "author_id": 248516, "given_name": "Eva", "family_name": "Meluzinova", "ORCID": null, "country": null }, { "author_id": 248517, "given_name": "Radomir", "family_name": "Talab", "ORCID": null, "country": null }, { "author_id": 248518, "given_name": "Marta", "family_name": "Vachova", "ORCID": null, "country": null }, { "author_id": 149649, "given_name": "Orhan", "family_name": "Aktas", "ORCID": "http://orcid.org/0000-0002-2020-9210", "country": null }, { "author_id": 248520, "given_name": "Mathias", "family_name": "Buttmann", "ORCID": null, "country": null }, { "author_id": 248521, "given_name": "Elias-Hamp", "family_name": "Birte", "ORCID": null, "country": null }, { "author_id": 199738, "given_name": "Tania", "family_name": "Kümpfel", "ORCID": "http://orcid.org/0000-0001-7509-5268", "country": null }, { "author_id": 248522, "given_name": "Paul", "family_name": "Friedemann", "ORCID": null, "country": null }, { "author_id": 160585, "given_name": "Daniela", "family_name": "Rau", "ORCID": "http://orcid.org/0000-0002-0288-3762", "country": null }, { "author_id": 248523, "given_name": "Gerd", "family_name": "Reifschneider", "ORCID": null, "country": null }, { "author_id": 248524, "given_name": "Piotr", "family_name": "Sokolowski", "ORCID": null, "country": null }, { "author_id": 157222, "given_name": "Hayrettin", "family_name": "Tumani", "ORCID": "http://orcid.org/0000-0002-1647-6201", "country": null }, { "author_id": 248525, "given_name": "Maria", "family_name": "Satori", "ORCID": null, "country": null }, { "author_id": 150619, "given_name": "Carlo", "family_name": "Pozzilli", "ORCID": "http://orcid.org/0000-0002-6360-4798", "country": null }, { "author_id": 248526, "given_name": "Agata", "family_name": "Klosek", "ORCID": null, "country": null }, { "author_id": 248527, "given_name": "Jozef", "family_name": "Koscielniak", "ORCID": null, "country": null }, { "author_id": 248528, "given_name": "Fryze", "family_name": "Waldemar", "ORCID": null, "country": null }, { "author_id": 248529, "given_name": "Malgorzata", "family_name": "Zajda", "ORCID": null, "country": null }, { "author_id": 248530, "given_name": "Rafael Arroyo", "family_name": "Gonzalez", "ORCID": null, "country": null }, { "author_id": 248532, "given_name": "Victoria Fernandez", "family_name": "Sanchez", "ORCID": null, "country": null }, { "author_id": 248533, "given_name": "Celia Oreja", "family_name": "Guevara", "ORCID": null, "country": null }, { "author_id": 248534, "given_name": "Jose Enrique Martinez", "family_name": "Rodriguez", "ORCID": null, "country": null }, { "author_id": 154801, "given_name": "Xavier", "family_name": "Montalban", "ORCID": "http://orcid.org/0000-0002-0098-9918", "country": "ES" }, { "author_id": 248535, "given_name": "Lluis", "family_name": "Ramio-Torrenta", "ORCID": null, "country": null }, { "author_id": 218790, "given_name": "Lou", "family_name": "Brundin", "ORCID": "http://orcid.org/0000-0003-4408-7817", "country": null }, { "author_id": 173692, "given_name": "Jan", "family_name": "Lycke", "ORCID": "http://orcid.org/0000-0002-7891-8466", "country": null }, { "author_id": 173491, "given_name": "Murat", "family_name": "Terzi", "ORCID": "http://orcid.org/0000-0002-3586-9115", "country": null }, { "author_id": 248539, "given_name": "Joe", "family_name": "Guadagno", "ORCID": null, "country": null }, { "author_id": 242055, "given_name": "Don", "family_name": "Mahad", "ORCID": null, "country": null }, { "author_id": 248542, "given_name": "Adrian", "family_name": "Pace", "ORCID": null, "country": null }, { "author_id": 248543, "given_name": "Klaus", "family_name": "Schmierer", "ORCID": null, "country": null }, { "author_id": 150342, "given_name": "Ahmed", "family_name": "Toosy", "ORCID": "http://orcid.org/0000-0002-4441-3750", "country": null }, { "author_id": 248547, "given_name": "Stewart", "family_name": "Webb", "ORCID": null, "country": null }, { "author_id": 248549, "given_name": "Mark", "family_name": "Agius", "ORCID": null, "country": null }, { "author_id": 247785, "given_name": "Lilyana", "family_name": "Amezcua", "ORCID": null, "country": null }, { "author_id": 248552, "given_name": "Michelle", "family_name": "Apperson", "ORCID": null, "country": null }, { "author_id": 248553, "given_name": "Bridget", "family_name": "Bagert", "ORCID": null, "country": null }, { "author_id": 248554, "given_name": "Daniel", "family_name": "Bandari", "ORCID": null, "country": null }, { "author_id": 191145, "given_name": "Evanthia", "family_name": "Bernitsas", "ORCID": "http://orcid.org/0000-0001-9382-1008", "country": null }, { "author_id": 248555, "given_name": "Jonathan", "family_name": "Calkwood", "ORCID": null, "country": null }, { "author_id": 248556, "given_name": "Jonathan", "family_name": "Carter", "ORCID": null, "country": null }, { "author_id": 248557, "given_name": "Bruce", "family_name": "Cohen", "ORCID": null, "country": null }, { "author_id": 248558, "given_name": "Devon", "family_name": "Conway", "ORCID": null, "country": null }, { "author_id": 248559, "given_name": "Joanna", "family_name": "Cooper", "ORCID": null, "country": null }, { "author_id": 248560, "given_name": "John", "family_name": "Corboy", "ORCID": null, "country": null }, { "author_id": 240686, "given_name": "Patricia", "family_name": "Coyle", "ORCID": null, "country": null }, { "author_id": 248561, "given_name": "Bruce", "family_name": "Cree", "ORCID": null, "country": null }, { "author_id": 248562, "given_name": "Mitchel", "family_name": "Freedman", "ORCID": null, "country": null }, { "author_id": 248563, "given_name": "Corey", "family_name": "Ford", "ORCID": null, "country": null }, { "author_id": 248564, "given_name": "Edward", "family_name": "Fox", "ORCID": null, "country": null }, { "author_id": 248565, "given_name": "Myla", "family_name": "Goldman", "ORCID": null, "country": null }, { "author_id": 244431, "given_name": "Benjamin", "family_name": "Greenberg", "ORCID": null, "country": null }, { "author_id": 248566, "given_name": "Mariko", "family_name": "Kita", "ORCID": null, "country": null }, { "author_id": 248567, "given_name": "Thomas", "family_name": "Leist", "ORCID": null, "country": null }, { "author_id": 236905, "given_name": "Sharon", "family_name": "Lynch", "ORCID": null, "country": null }, { "author_id": 241112, "given_name": "Aaron", "family_name": "Miller", "ORCID": null, "country": null }, { "author_id": 248568, "given_name": "Harold", "family_name": "Moses", "ORCID": null, "country": null }, { "author_id": 185814, "given_name": "Robert", "family_name": "Naismith", "ORCID": "http://orcid.org/0000-0003-0520-4283", "country": null }, { "author_id": 248571, "given_name": "Mary Ann", "family_name": "Picone", "ORCID": null, "country": null }, { "author_id": 248573, "given_name": "Bhatia", "family_name": "Perminder", "ORCID": null, "country": null }, { "author_id": 240594, "given_name": "Alexander", "family_name": "Rae-Grant", "ORCID": null, "country": null }, { "author_id": 208597, "given_name": "Kottil", "family_name": "Rammohan", "ORCID": "http://orcid.org/0000-0003-2467-4280", "country": null }, { "author_id": 248575, "given_name": "Anthony", "family_name": "Reder", "ORCID": null, "country": null }, { "author_id": 248576, "given_name": "Claire", "family_name": "Riley", "ORCID": null, "country": null }, { "author_id": 248577, "given_name": "Derrick", "family_name": "Robertson", "ORCID": null, "country": null }, { "author_id": 248578, "given_name": "Vernon", "family_name": "Rowe", "ORCID": null, "country": null }, { "author_id": 172340, "given_name": "Shiv", "family_name": "Saidha", "ORCID": "http://orcid.org/0000-0001-6387-0714", "country": null }, { "author_id": 248579, "given_name": "Lawrence", "family_name": "Samkoff", "ORCID": null, "country": null }, { "author_id": 248580, "given_name": "Christopher", "family_name": "Severson", "ORCID": null, "country": null }, { "author_id": 248581, "given_name": "Kyle", "family_name": "Smoot", "ORCID": null, "country": null }, { "author_id": 248582, "given_name": "Sharon", "family_name": "Stoll", "ORCID": null, "country": null }, { "author_id": 248583, "given_name": "Randall", "family_name": "Trudell", "ORCID": null, "country": null }, { "author_id": 152480, "given_name": "Bianca", "family_name": "Weinstock-Guttman", "ORCID": "http://orcid.org/0000-0001-6732-151X", "country": null }, { "author_id": 248584, "given_name": "Sanjay", "family_name": "Yathiraj", "ORCID": null, "country": null }, { "author_id": 326667, "given_name": "Guillermo Izquierdo", "family_name": "Ayuso", "ORCID": "http://orcid.org/0000-0002-6340-5609", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Safety", "efficacy", "MD1003", "(high-dose biotin", "patients", "progressive multiple sclerosis", "SPI2", "phase", "3 trial" ], "doi": "10.1016/S1474-4422(20)30347-1", "access": "open", "takeaways": " MS-SPI randomised, double-blind, placebo-controlled study found MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis . The study was designed to assess safety and efficacy of biotin in progressive forms of multiple sclerosis in a larger, more representative patient cohort .", "categories": [] }, { "article_id": 305, "title": "Established and novel therapeutic options for autoimmune hepatitis", "summary": "<h2>Summary</h2><p>Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis. The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine. Although most patients respond satisfactorily to steroid and thiopurine-based treatment regimens, up to 40% relapse and 10% undergo liver transplantation. The cause of autoimmune hepatitis is unknown, but evidence implicates both genetic and environmental factors in its pathogenesis. An imbalance between effector and regulatory mechanisms leads to the breakdown of immune tolerance and the consequent development of an autoimmune attack. Signalling pathways that have been implicated in the pathogenesis of autoimmune hepatitis involve the proinflammatory cytokines interferon-γ, IL-12, tumour necrosis factor-α, IL-6, and IL-23. Numerical and functional defects of regulatory T cells have a permissive role that enables autoimmune liver injury to occur and persist. New therapeutic strategies are needed, with the aim of obtaining long-lasting disease remission without inducing non-specific immunosuppression and a focus on inhibiting the intrahepatic proinflammatory milieu or expanding the pool of regulatory T cells, or both.</p>", "link": "https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30328-9/fulltext", "published_date": "2021-02-08T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Gastroenterology & Hepatology", "authors": [ { "author_id": 241567, "given_name": "Rodrigo", "family_name": "Liberal", "ORCID": null, "country": null }, { "author_id": 241569, "given_name": "Ynto S", "family_name": "de Boer", "ORCID": null, "country": null }, { "author_id": 241571, "given_name": "Michael A", "family_name": "Heneghan", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Established and novel therapeutic options", "autoimmune hepatitis" ], "doi": "10.1016/S2468-1253(20)30328-9", "access": "restricted", "takeaways": " Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis . The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine . Up to 40% relapse and 10% undergo liver transplantation .", "categories": [] }, { "article_id": 308, "title": "Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients", "summary": "<h2>Abstract</h2><h3>Background</h3><p>Optic neuritis (ON) can occur as an isolated episode or will develop to multiple sclerosis (MS) a chronic autoimmune disease. What predicts ON progression to MS remains poorly understood.</p><h3>Methods</h3><p>We characterised the antibody epitope repertoire in three independent clinical cohorts (discovery (<i>n</i> = 62), validation (<i>n</i> = 20) and external cohort (<i>n</i> = 421)) using mimotope variation analysis (MVA), a next generation phage display technology to identify epitopes that associate with prognosis of ON.</p><h3>Findings</h3><p>We observed distinct epitope profiles for ON, MS and the controls, whereas epitope repertoires of sera and CSF were highly similar. Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS. These epitopes A and B were strongly associated with herpesviral antigens (VCA p18 of Epstein-Barr virus (EBV); gB of Cytomegalovirus (CMV)). ROC addressed 75% of MS subjects with ON onset correctly (at 75% sensitivity and 74.22% specificity) based on the two-epitope biomarker analysis.</p><h3>Interpretation</h3><p>This is the first report on epitope diagnostics for MS employing the unbiased strategy of MVA for identification of novel immunological features of disease.</p><h3>Funding</h3><p>The Estonian Ministry of Education, The Estonian Research Council (PRG573, PRG805 and PSG691), H2020-MSCA-RISE-2016 (SZTEST), H2020-NMBP-2017 (PANBIORA), Helsinki University Hospital, Mary and Georg C. Ehrnrooth, Finnish Eye, Sigrid Jusélius and Magnus Ehrnrooth Foundations.</p>", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00004-9/fulltext", "published_date": "2021-01-23T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "EBioMedicine", "authors": [ { "author_id": 241548, "given_name": "Helle", "family_name": "Sadam", "ORCID": null, "country": null }, { "author_id": 241549, "given_name": "Arno", "family_name": "Pihlak", "ORCID": null, "country": null }, { "author_id": 241550, "given_name": "Mariliis", "family_name": "Jaago", "ORCID": null, "country": null }, { "author_id": 241551, "given_name": "Nadežda", "family_name": "Pupina", "ORCID": null, "country": null }, { "author_id": 241552, "given_name": "Annika", "family_name": "Rähni", "ORCID": null, "country": null }, { "author_id": 241553, "given_name": "Maarja", "family_name": "Toots", "ORCID": null, "country": null }, { "author_id": 241554, "given_name": "Antti", "family_name": "Vaheri", "ORCID": null, "country": null }, { "author_id": 241555, "given_name": "Janne K.", "family_name": "Nieminen", "ORCID": null, "country": null }, { "author_id": 241556, "given_name": "Mika", "family_name": "Siuko", "ORCID": null, "country": null }, { "author_id": 176474, "given_name": "Pentti J.", "family_name": "Tienari", "ORCID": "http://orcid.org/0000-0001-5686-2900", "country": null }, { "author_id": 241557, "given_name": "Kaia", "family_name": "Palm", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Identification", "two highly antigenic epitope markers", "multiple sclerosis", "optic neuritis patients" ], "doi": "10.1016/j.ebiom.2021.103211", "access": "open", "takeaways": " What predicts ON progression to MS remains poorly understood . Two unique and highly immunogenic epitopes A and B were detected in subjects with ON progressing to MS . These epitopes were strongly associated with herpesviral antigens .", "categories": [] }, { "article_id": 319, "title": "The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017", "summary": "<h2>Summary</h2><h3>Background</h3><p>Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide.</p><h3>Methods</h3><p>The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were AlzheimerNULLs disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, ParkinsonNULLs disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates.</p><h3>Findings</h3><p>In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5–23·9) in the EU and 41·1 million (36·7–45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09–1·14) in the EU and 1·97 million (1·95–2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3–17·1) of total DALYs and 19·5% (18·0–21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80–84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs.</p><h3>Interpretation</h3><p>Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries.</p><h3>Funding</h3><p>European Academy of Neurology.</p>", "link": "https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(20)30190-0/fulltext", "published_date": "2020-09-30T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Public Health", "authors": [ { "author_id": 241705, "given_name": "Günther", "family_name": "Deuschl", "ORCID": null, "country": null }, { "author_id": 154765, "given_name": "Ettore", "family_name": "Beghi", "ORCID": "http://orcid.org/0000-0003-2542-0469", "country": null }, { "author_id": 241329, "given_name": "Franz", "family_name": "Fazekas", "ORCID": null, "country": null }, { "author_id": 241706, "given_name": "Timea", "family_name": "Varga", "ORCID": null, "country": null }, { "author_id": 241707, "given_name": "Kalliopi A", "family_name": "Christoforidi", "ORCID": null, "country": null }, { "author_id": 241708, "given_name": "Eveline", "family_name": "Sipido", "ORCID": null, "country": null }, { "author_id": 241709, "given_name": "Claudio L", "family_name": "Bassetti", "ORCID": null, "country": null }, { "author_id": 241710, "given_name": "Theo", "family_name": "Vos", "ORCID": null, "country": null }, { "author_id": 241711, "given_name": "Valery L", "family_name": "Feigin", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "The burden", "neurological diseases", "Europe", "an analysis", "the Global Burden", "Disease Study" ], "doi": "10.1016/S2468-2667(20)30190-0", "access": "open", "takeaways": " The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population . The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80–84 years . Stroke, dementias, and headache were the three commonest causes of DALYs in Europe .", "categories": [] }, { "article_id": 310, "title": "Neuroimaging manifestations in children with SARS-CoV-2 infection: a multinational, multicentre collaborative study", "summary": "<h2>Summary</h2><h3>Background</h3><p>The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population.</p><h3>Methods</h3><p>An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The children were categorised on the basis of their time of probable exposure to SARS-CoV-2. In addition, cases were excluded when a direct link to SARS-CoV-2 infection could not be established or an established alternate diagnostic cause could be hypothesised. The accepted referral centre imaging data, from ten countries, were remotely reviewed by a central panel of five paediatric neuroradiologists and a consensus opinion obtained on the imaging findings.</p><h3>Findings</h3><p>38 children with neurological disease related to SARS-CoV-2 infection were identified from France (n=13), the UK (n=8), the USA (n=5), Brazil (n=4), Argentina (n=4), India (n=2), Peru (n=1), and Saudi Arabia (n=1). Recurring patterns of disease were identified, with neuroimaging abnormalities ranging from mild to severe. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms. Splenial lesions (seven patients) and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome. Cerebrovascular complications in children were less common than in adults. Significant pre-existing conditions were absent and most children had favourable outcomes. However, fatal atypical CNS co-infections developed in four previously healthy children infected with SARS-CoV-2.</p><h3>Interpretation</h3><p>Acute-phase and delayed-phase SARS-CoV-2-related CNS abnormalities are seen in children. Recurring patterns of disease and atypical neuroimaging manifestations can be found and should be recognised being as potentially due to SARS-CoV-2 infection as an underlying aetiological factor. Studies of paediatric specific cohorts are needed to better understand the effects of SARS-CoV-2 infection on the CNS at presentation and on long-term follow-up in children.</p><h3>Funding</h3><p>American Society of Pediatric Neuroradiology, University of Manchester (Manchester, UK).</p><h3>Video Abstract</h3><p>Neuroimaging manifestations in children with SARS-CoV-2 infection</p>", "link": "https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30362-X/fulltext", "published_date": "2020-12-15T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Child & Adolescent Health", "authors": [ { "author_id": 277075, "given_name": "Camilla E", "family_name": "Lindan", "ORCID": null, "country": null }, { "author_id": 256312, "given_name": "Kshitij", "family_name": "Mankad", "ORCID": null, "country": null }, { "author_id": 190480, "given_name": "Dipak", "family_name": "Ram", "ORCID": "http://orcid.org/0000-0001-8544-2534", "country": null }, { "author_id": 277078, "given_name": "Larry K", "family_name": "Kociolek", "ORCID": null, "country": null }, { "author_id": 277080, "given_name": "V Michelle", "family_name": "Silvera", "ORCID": null, "country": null }, { "author_id": 277081, "given_name": "Nathalie", "family_name": "Boddaert", "ORCID": null, "country": null }, { "author_id": 277082, "given_name": "Stavros Michael", "family_name": "Stivaros", "ORCID": null, "country": null }, { "author_id": 277083, "given_name": "Susan", "family_name": "Palasis", "ORCID": null, "country": null }, { "author_id": 277084, "given_name": "Sameen", "family_name": "Akhtar", "ORCID": null, "country": null }, { "author_id": 277085, "given_name": "Douglas", "family_name": "Alden", "ORCID": null, "country": null }, { "author_id": 277086, "given_name": "Suraj", "family_name": "Amonkar", "ORCID": null, "country": null }, { "author_id": 277087, "given_name": "Pascale", "family_name": "Aouad", "ORCID": null, "country": null }, { "author_id": 277088, "given_name": "Mélodie", "family_name": "Aubart", "ORCID": null, "country": null }, { "author_id": 277089, "given_name": "Jose Alejandro", "family_name": "Bacalla", "ORCID": null, "country": null }, { "author_id": 277090, "given_name": "Alcino A", "family_name": "Barbosa", "ORCID": null, "country": null }, { "author_id": 277091, "given_name": "Romain", "family_name": "Basmaci", "ORCID": null, "country": null }, { "author_id": 277092, "given_name": "Laureline", "family_name": "Berteloot", "ORCID": null, "country": null }, { "author_id": 277093, "given_name": "Thomas", "family_name": "Blauwblomme", "ORCID": null, "country": null }, { "author_id": 215405, "given_name": "Gilles", "family_name": "Brun", "ORCID": "http://orcid.org/0000-0001-7076-1954", "country": null }, { "author_id": 277094, "given_name": "Olivia", "family_name": "Carney", "ORCID": null, "country": null }, { "author_id": 277095, "given_name": "Judith", "family_name": "Chareyre", "ORCID": null, "country": null }, { "author_id": 277096, "given_name": "Gérard", "family_name": "Chéron", "ORCID": null, "country": null }, { "author_id": 277098, "given_name": "Pablo Picasso De Araujo", "family_name": "Coimbra", "ORCID": null, "country": null }, { "author_id": 277099, "given_name": "Volodia", "family_name": "Dangouloff-Ros", "ORCID": null, "country": null }, { "author_id": 277100, "given_name": "Felice", "family_name": "D'Arco", "ORCID": null, "country": null }, { "author_id": 277101, "given_name": "Rob", "family_name": "Dineen", "ORCID": null, "country": null }, { "author_id": 277102, "given_name": "Loic", "family_name": "De-Pontual", "ORCID": null, "country": null }, { "author_id": 253018, "given_name": "Isabelle", "family_name": "Desguerre", "ORCID": null, "country": null }, { "author_id": 277103, "given_name": "Wissam", "family_name": "Elfallal", "ORCID": null, "country": null }, { "author_id": 277104, "given_name": "D. Gareth", "family_name": "Evans", "ORCID": null, "country": null }, { "author_id": 277105, "given_name": "Suely Fazio", "family_name": "Ferraciolli", "ORCID": null, "country": null }, { "author_id": 263671, "given_name": "Nadine", "family_name": "Girard", "ORCID": null, "country": null }, { "author_id": 277106, "given_name": "Fabrício Guimarães", "family_name": "Gonçalves", "ORCID": null, "country": null }, { "author_id": 277107, "given_name": "Ivan", "family_name": "Gonzalez", "ORCID": null, "country": null }, { "author_id": 277108, "given_name": "P. Ellen", "family_name": "Grant", "ORCID": null, "country": null }, { "author_id": 277109, "given_name": "David", "family_name": "Grévent", "ORCID": null, "country": null }, { "author_id": 277110, "given_name": "Carolina Valduga de Alencastro", "family_name": "Guimaraes", "ORCID": null, "country": null }, { "author_id": 264558, "given_name": "Jane", "family_name": "Hassell", "ORCID": null, "country": null }, { "author_id": 277112, "given_name": "Fabiana C.C.", "family_name": "Hirata", "ORCID": null, "country": null }, { "author_id": 277113, "given_name": "Ian", "family_name": "Kamaly-Asl", "ORCID": null, "country": null }, { "author_id": 277114, "given_name": "Jeffrey", "family_name": "Jacob", "ORCID": null, "country": null }, { "author_id": 277115, "given_name": "Kandise", "family_name": "Jackson", "ORCID": null, "country": null }, { "author_id": 277116, "given_name": "Blaise V.", "family_name": "Jones", "ORCID": null, "country": null }, { "author_id": 277117, "given_name": "Robin", "family_name": "Joseph", "ORCID": null, "country": null }, { "author_id": 277118, "given_name": "Ah Young", "family_name": "Jung", "ORCID": null, "country": null }, { "author_id": 277119, "given_name": "Amna", "family_name": "Kashgari", "ORCID": null, "country": null }, { "author_id": 277120, "given_name": "John-Paul", "family_name": "Kilday", "ORCID": null, "country": null }, { "author_id": 277121, "given_name": "Alyssa", "family_name": "Kirsch", "ORCID": null, "country": null }, { "author_id": 277122, "given_name": "Manoelle", "family_name": "Kossorotoff", "ORCID": null, "country": null }, { "author_id": 277123, "given_name": "Anant", "family_name": "Krishnan", "ORCID": null, "country": null }, { "author_id": 277124, "given_name": "Shilpa", "family_name": "Kulkarni", "ORCID": null, "country": null }, { "author_id": 277125, "given_name": "Marianne", "family_name": "Leruez-Vill", "ORCID": null, "country": null }, { "author_id": 277126, "given_name": "Fabrice", "family_name": "Lesage", "ORCID": null, "country": null }, { "author_id": 277127, "given_name": "Raphaël", "family_name": "Levy", "ORCID": null, "country": null }, { "author_id": 161408, "given_name": "Yi", "family_name": "Li", "ORCID": "http://orcid.org/0000-0003-0520-9068", "country": null }, { "author_id": 277128, "given_name": "Carol Cavalcante de Vasconcelos", "family_name": "Lima", "ORCID": null, "country": null }, { "author_id": 277129, "given_name": "Lokesh", "family_name": "Lingappa", "ORCID": null, "country": null }, { "author_id": 277130, "given_name": "Ulrike", "family_name": "Löbel", "ORCID": null, "country": null }, { "author_id": 277131, "given_name": "Roberto", "family_name": "Lopez-Alberola", "ORCID": null, "country": null }, { "author_id": 212004, "given_name": "Leandro Tavares", "family_name": "Lucato", "ORCID": "http://orcid.org/0000-0001-9181-5245", "country": null }, { "author_id": 277132, "given_name": "Daniela Duarte", "family_name": "Moreira", "ORCID": null, "country": null }, { "author_id": 277133, "given_name": "Jonathan G.", "family_name": "Murnick", "ORCID": null, "country": null }, { "author_id": 277134, "given_name": "Sarah", "family_name": "Nahmani", "ORCID": null, "country": null }, { "author_id": 277135, "given_name": "Shubra", "family_name": "Pagariya", "ORCID": null, "country": null }, { "author_id": 277136, "given_name": "Julija", "family_name": "Pavaine", "ORCID": null, "country": null }, { "author_id": 277137, "given_name": "Bryan", "family_name": "Philbrook", "ORCID": null, "country": null }, { "author_id": 277138, "given_name": "Ana Cláudia", "family_name": "Piovesan", "ORCID": null, "country": null }, { "author_id": 277139, "given_name": "Kelsey E.", "family_name": "Poisson", "ORCID": null, "country": null }, { "author_id": 277140, "given_name": "Nihaal", "family_name": "Reddy", "ORCID": null, "country": null }, { "author_id": 277141, "given_name": "Phil", "family_name": "Riley", "ORCID": null, "country": null }, { "author_id": 277142, "given_name": "Andrea", "family_name": "Romsauerova", "ORCID": null, "country": null }, { "author_id": 277143, "given_name": "Charlies-Joris", "family_name": "Roux", "ORCID": null, "country": null }, { "author_id": 274251, "given_name": "Carlos", "family_name": "Rugilo", "ORCID": null, "country": null }, { "author_id": 277144, "given_name": "Gaurav", "family_name": "Saigal", "ORCID": null, "country": null }, { "author_id": 277145, "given_name": "Gabriel Lucca de Oliveira", "family_name": "Salvador", "ORCID": null, "country": null }, { "author_id": 277146, "given_name": "David", "family_name": "Seidenwurm", "ORCID": null, "country": null }, { "author_id": 277148, "given_name": "Isabelle", "family_name": "Sermet-Gaudelus", "ORCID": null, "country": null }, { "author_id": 277149, "given_name": "Jai", "family_name": "Sidpra", "ORCID": null, "country": null }, { "author_id": 277150, "given_name": "Sniya Valsa", "family_name": "Sudhakar", "ORCID": null, "country": null }, { "author_id": 277152, "given_name": "María Sol", "family_name": "Toronchik", "ORCID": null, "country": null }, { "author_id": 277154, "given_name": "Gilbert", "family_name": "Vézina", "ORCID": null, "country": null } ], "relevant": false, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Neuroimaging manifestations", "children", "SARS-CoV-2 infection", "a multinational, multicentre collaborative study" ], "doi": "10.1016/S2352-4642(20)30362-X", "access": "open", "takeaways": " The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients) Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms . Cerebrovascular complications in children were less common than in adults .", "categories": [] }, { "article_id": 323, "title": "Remyelination in multiple sclerosis: from basic science to clinical translation", "summary": "<h2>Summary</h2><p>The treatment of multiple sclerosis has been transformed by the successful development of immunotherapies that efficiently reduce disease activity and related clinical relapses during the relapsing-remitting phase of the disease. However, the prevention of disability progression, which is due to axonal and neuronal damage and loss, has yet to be achieved and is therapeutically challenging, particularly during the progressive phase of the disease. One strategy to counteract neurodegeneration is to promote neuroprotection by enhancing myelin regeneration, hence restoring nerve conduction and metabolic support to the axon. Animal studies have provided targets for interventions to improve brain and spinal cord remyelination, paving the way for the translation of this research to humans. From these initial and promising forays, further problems have emerged, including questions on how best to design these clinical trials and appropriately measure the outcomes. Solving these problems will need additional work before efficacious pro-remyelination therapies will be ready for people with multiple sclerosis, but there is a real sense of hope that researchers are getting closer to a successful therapy.</p>", "link": "https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30140-X/fulltext", "published_date": "2020-07-31T23:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "The Lancet Neurology", "authors": [ { "author_id": 204624, "given_name": "Catherine", "family_name": "Lubetzki", "ORCID": "http://orcid.org/0000-0001-7164-3175", "country": null }, { "author_id": 150354, "given_name": "Anna", "family_name": "Williams", "ORCID": "http://orcid.org/0000-0002-6329-382X", "country": "GB" }, { "author_id": 146915, "given_name": "Christine", "family_name": "Stadelmann", "ORCID": "http://orcid.org/0000-0003-1766-5458", "country": null }, { "author_id": 149339, "given_name": "Bruno", "family_name": "Stankoff", "ORCID": "http://orcid.org/0000-0002-9631-4674", "country": null }, { "author_id": 329026, "given_name": "Bernard", "family_name": "Zalc", "ORCID": "http://orcid.org/0000-0001-5484-2359", "country": null } ], "relevant": true, "ml_prediction_gnb": true, "ml_prediction_lr": false, "ml_prediction_lsvc": true, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "Remyelination", "multiple sclerosis", "basic science", "clinical translation" ], "doi": "10.1016/S1474-4422(20)30140-X", "access": "open", "takeaways": " The prevention of disability progression, which is due to axonal and neuronal damage and loss, has yet to be achieved . One strategy to counteract neurodegeneration is to promote neuroprotection by enhancing myelin regeneration . Animal studies have provided targets for interventions to improve brain and spinal cord remyelination .", "categories": [] }, { "article_id": 325, "title": "hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts", "summary": "Background With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts. Methods We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts. Findings CP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts. Interpretation This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line. Funding NSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen “Sanming” Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2–10559).", "link": "https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30496-5/fulltext", "published_date": "2020-11-23T00:00:00Z", "sources": [ "The Lancet" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "eBioMedicine", "authors": [ { "author_id": 294922, "given_name": "Dilyana", "family_name": "Todorova", "ORCID": null, "country": null }, { "author_id": 258940, "given_name": "Yue", "family_name": "Zhang", "ORCID": null, "country": null }, { "author_id": 294924, "given_name": "Qu", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 294925, "given_name": "Jingfeng", "family_name": "Liu", "ORCID": null, "country": null }, { "author_id": 294926, "given_name": "Jingjin", "family_name": "He", "ORCID": null, "country": null }, { "author_id": 294928, "given_name": "Xuemei", "family_name": "Fu", "ORCID": null, "country": null }, { "author_id": 294929, "given_name": "Yang", "family_name": "Xu", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-06T11:22:21Z", "noun_phrases": [ "hESC-derived immune suppressive dendritic cells", "immune tolerance", "parental hESC-derived allografts" ], "doi": "10.1016/j.ebiom.2020.103120", "access": "open", "takeaways": " Human embryonic stem cells (hESCs) hold great potential in regenerative medicine . A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of allografts . Using an immune system humanized mouse model, we investigated whether adoptive transfer of CP DCLs can induce long-term immune tolerance . This strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs .", "categories": [] } ] }