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{ "count": 24915, "next": "http://api.gregory-ms.com/articles/?format=api&page=2446", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2444", "results": [ { "article_id": 480, "title": "Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis", "summary": "<div><p>Brain. 2021 Mar 9:awab100. doi: 10.1093/brain/awab100. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970-1994 were identified using the Swedish Total Population Register (n = 2,422,969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11-19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socioeconomic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21-1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06-1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11-3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13-1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30-1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33693538/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33693538</a> | DOI:<a href=\"https://doi.org/10.1093/brain/awab100\">10.1093/brain/awab100</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33693538/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-09-03T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Oxford University Press (OUP)", "container_title": "Brain", "authors": [ { "author_id": 243785, "given_name": "Yin", "family_name": "Xu", "ORCID": null, "country": null }, { "author_id": 170277, "given_name": "Kelsi A", "family_name": "Smith", "ORCID": "http://orcid.org/0000-0002-9811-908X", "country": null }, { "author_id": 315908, "given_name": "Ayako", "family_name": "Hiyoshi", "ORCID": "http://orcid.org/0000-0002-2088-0530", "country": "SE" }, { "author_id": 236966, "given_name": "Fredrik", "family_name": "Piehl", "ORCID": null, "country": null }, { "author_id": 218798, "given_name": "Tomas", "family_name": "Olsson", "ORCID": "http://orcid.org/0000-0002-2938-1877", "country": "SE" }, { "author_id": 234088, "given_name": "Scott", "family_name": "Montgomery", "ORCID": "http://orcid.org/0000-0001-6328-5494", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "Hospital-diagnosed infections", "age", "risk", "a subsequent multiple sclerosis diagnosis" ], "doi": "10.1093/brain/awab100", "access": "open", "takeaways": " The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively . Little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS . The increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, and CNS infections .", "categories": [] }, { "article_id": 479, "title": "Formation and immunomodulatory function of meningeal B-cell aggregates in progressive CNS autoimmunity", "summary": "<div><p>Brain. 2021 Mar 9:awab093. doi: 10.1093/brain/awab093. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic Multiple Sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of Multiple Sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T cell- and B cell-receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of α4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of α4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with α4 integrin-sufficient T cells. B cell-conditional ablation of α4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with α4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20 percent of B cells in organised meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in Multiple Sclerosis.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33693558/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33693558</a> | DOI:<a href=\"https://doi.org/10.1093/brain/awab093\">10.1093/brain/awab093</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33693558/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-07-27T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Oxford University Press (OUP)", "container_title": "Brain", "authors": [ { "author_id": 243773, "given_name": "Meike", "family_name": "Mitsdoerffer", "ORCID": null, "country": null }, { "author_id": 195680, "given_name": "Giovanni", "family_name": "Di Liberto", "ORCID": "http://orcid.org/0000-0001-6788-0215", "country": null }, { "author_id": 243774, "given_name": "Sarah", "family_name": "Dötsch", "ORCID": null, "country": null }, { "author_id": 179237, "given_name": "Christopher", "family_name": "Sie", "ORCID": "http://orcid.org/0000-0002-8066-7539", "country": null }, { "author_id": 157965, "given_name": "Ingrid", "family_name": "Wagner", "ORCID": "http://orcid.org/0000-0003-4437-9799", "country": null }, { "author_id": 243775, "given_name": "Monika", "family_name": "Pfaller", "ORCID": null, "country": null }, { "author_id": 157966, "given_name": "Mario", "family_name": "Kreutzfeldt", "ORCID": "http://orcid.org/0000-0003-0335-2733", "country": null }, { "author_id": 243776, "given_name": "Simon", "family_name": "Fräßle", "ORCID": null, "country": null }, { "author_id": 199739, "given_name": "Lilian", "family_name": "Aly", "ORCID": "http://orcid.org/0000-0002-7051-124X", "country": "DE" }, { "author_id": 150324, "given_name": "Benjamin", "family_name": "Knier", "ORCID": "http://orcid.org/0000-0003-4187-9472", "country": "DE" }, { "author_id": 243777, "given_name": "Dirk H", "family_name": "Busch", "ORCID": null, "country": null }, { "author_id": 195688, "given_name": "Doron", "family_name": "Merkler", "ORCID": "http://orcid.org/0000-0002-0247-2007", "country": null }, { "author_id": 150325, "given_name": "Thomas", "family_name": "Korn", "ORCID": "http://orcid.org/0000-0002-3633-0955", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "Formation and immunomodulatory function", "meningeal B-cell aggregates", "progressive CNS autoimmunity" ], "doi": "10.1093/brain/awab093", "access": "open", "takeaways": " Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic Multiple Sclerosis . We propose that meningeal B cell aggregates might also have an immunoregulatory function as to immunopathology in adjacent spinal cord white matter .", "categories": [] }, { "article_id": 477, "title": "Dimethyl Fumarate Induces Metabolic Crisie to Suppress Pancreatic Carcinoma", "summary": "<div><p>Front Pharmacol. 2021 Feb 22;12:617714. doi: 10.3389/fphar.2021.617714. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Dimethyl fumarate (DMF) is an approved drug used in the treatment of multiple sclerosis (MS) and psoriasis therapy. Multiple studies have demonstrated other pharmacological activities of DMF such as an anti-cancer agent. In particular, studies have shown that DMF can modulate the NRF2/HO1/NQO1 antioxidant signal pathway and inactivate NF-κB to suppress the growth of colon and breast cancer cells, and induce cell death. In this study, we aimed to evaluate the anti-tumor activities of DMF in pancreatic cancer (PC) focusing on cell death as the predominant mechanism of response. We showed that both mitochondrial respiration and aerobic glycolysis were severely depressed following treatment with DMF and the effects could be abrogated by treatment with L-cysteine and N-acetyl-L-cysteine (NAC). Importantly, we verified that DMF induced metabolic crisis and that cell death was not related to alterations in ROS. Our data implied that MTHFD1 could be a potential downstream target of DMF identified by molecular docking analysis. Finally, we confirmed that MTHFD1 is up-regulated in PC and overexpression of MTHFD1 was negatively related to outcomes of PC patients. Our data indicate that DMF induces metabolic crisie to suppress cell growth and could be a potential novel therapy in the treatment of PC.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33692690/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33692690</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7937954/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">PMC7937954</a> | DOI:<a href=\"https://doi.org/10.3389/fphar.2021.617714\">10.3389/fphar.2021.617714</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33692690/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-02-22T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Pharmacology", "authors": [ { "author_id": 243746, "given_name": "Kaiyuan", "family_name": "Chen", "ORCID": null, "country": null }, { "author_id": 243747, "given_name": "Shanshan", "family_name": "Wu", "ORCID": null, "country": null }, { "author_id": 243748, "given_name": "Sisi", "family_name": "Ye", "ORCID": null, "country": null }, { "author_id": 243749, "given_name": "Huimin", "family_name": "Huang", "ORCID": null, "country": null }, { "author_id": 243750, "given_name": "Yi", "family_name": "Zhou", "ORCID": null, "country": null }, { "author_id": 243751, "given_name": "Hongfei", "family_name": "Zhou", "ORCID": null, "country": null }, { "author_id": 243752, "given_name": "Shijia", "family_name": "Wu", "ORCID": null, "country": null }, { "author_id": 243753, "given_name": "Yefan", "family_name": "Mao", "ORCID": null, "country": null }, { "author_id": 243755, "given_name": "Fugen", "family_name": "Shangguan", "ORCID": null, "country": null }, { "author_id": 243757, "given_name": "Linhua", "family_name": "Lan", "ORCID": null, "country": null }, { "author_id": 243758, "given_name": "Bicheng", "family_name": "Chen", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "Dimethyl Fumarate", "Metabolic Crisie", "Suppress Pancreatic Carcinoma" ], "doi": "10.3389/fphar.2021.617714", "access": "open", "takeaways": " Dimethyl fumarate (DMF) is an approved drug used in the treatment of multiple sclerosis (MS) and psoriasis therapy . In this study, we aimed to evaluate the anti-tumor activities of DMF in pancreatic cancer .", "categories": [ { "category_id": 5, "category_description": "Tecfidera is a medicine used to treat multiple sclerosis (MS), a disease in which inflammation damages the protective insulation around nerves (demyelination) as well as the nerves themselves. It is used in adults and children from 13 years of age with a type of MS known as relapsing-remitting MS, where the patient has flare-ups of symptoms (relapses) followed by periods of recovery (remissions).\r\n\r\nTecfidera contains the active substance dimethyl fumarate.\r\n\r\nhttps://www.ema.europa.eu/en/medicines/human/EPAR/tecfidera", "category_name": "Tecfidera", "category_slug": "tecfidera", "category_terms": [ "tecfidera", "dimethyl fumarate" ], "article_count": 164 } ] }, { "article_id": 481, "title": "Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging", "summary": "<div><p>Brain. 2021 Mar 9:awab088. doi: 10.1093/brain/awab088. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study. Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy controls and normal-appearing MS tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P < 0.0001) and peri-plaque white matter (P < 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region (P < 0.0001 and P < 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P < 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P < 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normal-appearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P < 0.01, beta=-10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patients cohort (P < 0.01, beta=-3.60 and P < 0.01, beta=0.13, respectively). These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33693571/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33693571</a> | DOI:<a href=\"https://doi.org/10.1093/brain/awab088\">10.1093/brain/awab088</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33693571/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-07-27T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Oxford University Press (OUP)", "container_title": "Brain", "authors": [ { "author_id": 328934, "given_name": "Sabine", "family_name": "Schaedelin", "ORCID": "http://orcid.org/0000-0002-1150-0962", "country": null }, { "author_id": 231373, "given_name": "Reza", "family_name": "Rahmanzadeh", "ORCID": "http://orcid.org/0000-0002-5091-0585", "country": "CH" }, { "author_id": 243788, "given_name": "Po-Jui", "family_name": "Lu", "ORCID": null, "country": null }, { "author_id": 159621, "given_name": "Muhamed", "family_name": "Barakovic", "ORCID": "http://orcid.org/0000-0001-8557-9223", "country": null }, { "author_id": 170630, "given_name": "M.", "family_name": "Weigel", "ORCID": "http://orcid.org/0000-0002-4910-1414", "country": "CH" }, { "author_id": 191691, "given_name": "Pietro", "family_name": "Maggi", "ORCID": "http://orcid.org/0000-0003-1697-5585", "country": null }, { "author_id": 243789, "given_name": "Thanh D", "family_name": "Nguyen", "ORCID": null, "country": null }, { "author_id": 155660, "given_name": "Simona", "family_name": "Schiavi", "ORCID": "http://orcid.org/0000-0003-1641-186X", "country": null }, { "author_id": 243790, "given_name": "Alessandro", "family_name": "Daducci", "ORCID": null, "country": null }, { "author_id": 169944, "given_name": "Francesco", "family_name": "La Rosa", "ORCID": "http://orcid.org/0000-0002-9224-4664", "country": null }, { "author_id": 147734, "given_name": "Martina", "family_name": "Absinta", "ORCID": "http://orcid.org/0000-0003-0276-383X", "country": null }, { "author_id": 147748, "given_name": "Daniel S.", "family_name": "Reich", "ORCID": "http://orcid.org/0000-0002-2628-4334", "country": null }, { "author_id": 182200, "given_name": "Pascal", "family_name": "Sati", "ORCID": "http://orcid.org/0000-0002-6763-0125", "country": null }, { "author_id": 155850, "given_name": "Yi", "family_name": "Wang", "ORCID": "http://orcid.org/0000-0003-1404-8526", "country": "US" }, { "author_id": 169952, "given_name": "Meritxell", "family_name": "Bach Cuadra", "ORCID": "http://orcid.org/0000-0003-2730-4285", "country": "CH" }, { "author_id": 243792, "given_name": "Ernst-Wilhelm", "family_name": "Radue", "ORCID": null, "country": null }, { "author_id": 181207, "given_name": "Lutz", "family_name": "Achtnichts", "ORCID": "http://orcid.org/0000-0002-3713-9570", "country": null }, { "author_id": 147953, "given_name": "Ludwig", "family_name": "Kappos", "ORCID": "http://orcid.org/0000-0003-4175-5509", "country": null }, { "author_id": 170634, "given_name": "Cristina", "family_name": "Granziera", "ORCID": "http://orcid.org/0000-0002-4917-8761", "country": "CH" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "multiple sclerosis", "myelin water" ], "doi": "10.1093/brain/awab088", "access": "open", "takeaways": " Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis . We applied myelin water and multi-shell diffusion imaging to quantify relative damage to myelin and axons . We also assessed the relation of focal myelin/axon damage with disability .", "categories": [] }, { "article_id": 483, "title": "The 1,000th Transplant for Multiple Sclerosis and Other Autoimmune Disorders at the HSCT-Mexico Program: A Myriad of Experiences and Knowledge", "summary": "<div><p>Front Neurol. 2021 Feb 22;12:647425. doi: 10.3389/fneur.2021.647425. eCollection 2021.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">After gaining experience conducting both auto and allografts in persons with hematological diseases in the HSCT programs in Puebla and Monterrey, México, this study outlines subsequent program autografting patients with autoimmune conditions. The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006. From 2015 we increased activity autografting persons with autoimmune conditions in the two campuses of the HSCT-México program: Puebla and Monterrey. By December 6, 2020, patient number 1,000 in the program was autografted. In our experience, a significant reduction in the expanded disability status scale score was achieved in all of the three phenotypes of the disease (from a median of 5.1 to 4.5 points), whereas the response rate (defined as a decrease of at least 0.5 of EDSS score regardless of baseline EDSS, or unchanged EDSS) was 83, 78, and 73% after 12 months in the relapsing-remitting, primary-progressive and secondary-progressive forms of multiple sclerosis, respectively. In addition to analyzing the viability, safety, and efficacy of our method, this study contributes new knowledge to the field of both stem cell transplantation and multiple sclerosis.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33692748/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33692748</a> | PMC:<a href=\"https://www.ncbi.nlm.nih.gov/pmc/PMC7937693/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">PMC7937693</a> | DOI:<a href=\"https://doi.org/10.3389/fneur.2021.647425\">10.3389/fneur.2021.647425</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33692748/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-02-22T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Frontiers Media SA", "container_title": "Frontiers in Neurology", "authors": [ { "author_id": 302726, "given_name": "Iván", "family_name": "Murrieta-Álvarez", "ORCID": null, "country": null }, { "author_id": 300169, "given_name": "Yahveth", "family_name": "Cantero-Fortiz", "ORCID": null, "country": null }, { "author_id": 302727, "given_name": "Andrés A.", "family_name": "León-Peña", "ORCID": null, "country": null }, { "author_id": 302728, "given_name": "Juan C.", "family_name": "Olivares-Gazca", "ORCID": null, "country": null }, { "author_id": 302729, "given_name": "José Manuel", "family_name": "Priesca-Marín", "ORCID": null, "country": null }, { "author_id": 245099, "given_name": "Guillermo J.", "family_name": "Ruiz-Delgado", "ORCID": null, "country": null }, { "author_id": 302730, "given_name": "Andrés", "family_name": "Gómez-De-León", "ORCID": null, "country": null }, { "author_id": 302731, "given_name": "Elías Eugenio", "family_name": "Gonzalez-Lopez", "ORCID": null, "country": null }, { "author_id": 153483, "given_name": "José Carlos", "family_name": "Jaime-Pérez", "ORCID": "http://orcid.org/0000-0001-6804-9095", "country": null }, { "author_id": 153490, "given_name": "David", "family_name": "Gómez-Almaguer", "ORCID": "http://orcid.org/0000-0002-0460-6427", "country": null }, { "author_id": 149865, "given_name": "Guillermo J.", "family_name": "Ruiz-Argüelles", "ORCID": "http://orcid.org/0000-0002-9335-0653", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "The 1,000th Transplant", "Multiple Sclerosis", "Other Autoimmune Disorders", "the HSCT-Mexico Program", "A Myriad", "Experiences", "Knowledge" ], "doi": "10.3389/fneur.2021.647425", "access": "open", "takeaways": " The first transplant in multiple sclerosis was conducted in Puebla on July 5, 2006 . By December 6, 2020, patient number 1,000 in the program was autografted . A significant reduction in the expanded disability status scale score was achieved in all three phenotypes of the disease .", "categories": [] }, { "article_id": 475, "title": "Common and rare genetic variants that could contribute to severe otitis media in an Australian Aboriginal population", "summary": "<div><p>Clin Infect Dis. 2021 Mar 9:ciab216. doi: 10.1093/cid/ciab216. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">BACKGROUND: Our goal was to identify genetic risk factors for severe otitis media (OM) in Aboriginal Australians.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">METHODS: Illumina ® Omni2.5 BeadChip and imputed data were compared between 21 children with severe OM (multiple episodes chronic suppurative OM and/or perforations or tympanic sclerosis) and 370 individuals without this phenotype, followed by FUnctional Mapping and Annotation (FUMA). Exome data filtered for common (EXaC_all≥0.1) putative deleterious variants influencing protein coding (CADD-scaled scores ≥ 15) were used to compare 15 severe OM cases with 9 mild cases (single episode of acute OM recorded over ≥ 3 consecutive years). Rare (ExAC_all≤0.01) such variants were filtered for those present only in severe OM. Enrichr was used to determine enrichment of genes contributing to pathways/processes relevant to OM.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">RESULTS: FUMA analysis identified two plausible genetic risk loci for severe OM: NR3C1 (Pimputed_1000G=3.62x10 -6) encoding the glucocorticoid receptor, and NREP (Pimputed_1000G=3.67x10 -6) encoding neuronal regeneration related protein. Exome analysis showed: (i) association of severe OM with variants influencing protein coding (CADD-scaled ≥ 15) in a gene-set (GRXCR1, CDH23, LRP2, FAT4, ARSA, EYA4) enriched for Mammalian Phenotype Level 4 abnormal hair cell stereociliary bundle morphology and related phenotypes; (ii) rare variants influencing protein coding only seen in severe OM provided gene-sets enriched for \"abnormal ear\" (LMNA, CDH23, LRP2, MYO7A, FGFR1), integrin interactions, transforming growth factor signalling, and cell projection phenotypes including hair cell stereociliary bundles and cilium assembly.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">CONCLUSIONS: This study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33693626/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311134527&v=2.14.2\">33693626</a> | DOI:<a href=\"https://doi.org/10.1093/cid/ciab216\">10.1093/cid/ciab216</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33693626/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-11-16T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Oxford University Press (OUP)", "container_title": "Clinical Infectious Diseases", "authors": [ { "author_id": 301446, "given_name": "Sarra E", "family_name": "Jamieson", "ORCID": null, "country": null }, { "author_id": 301447, "given_name": "Michaela", "family_name": "Fakiola", "ORCID": null, "country": null }, { "author_id": 301448, "given_name": "Dave", "family_name": "Tang", "ORCID": null, "country": null }, { "author_id": 301449, "given_name": "Elizabeth", "family_name": "Scaman", "ORCID": null, "country": null }, { "author_id": 301450, "given_name": "Genevieve", "family_name": "Syn", "ORCID": null, "country": null }, { "author_id": 301451, "given_name": "Richard W", "family_name": "Francis", "ORCID": null, "country": null }, { "author_id": 301452, "given_name": "Harvey L", "family_name": "Coates", "ORCID": null, "country": null }, { "author_id": 301453, "given_name": "Denise", "family_name": "Anderson", "ORCID": null, "country": null }, { "author_id": 301454, "given_name": "Timo", "family_name": "Lassmann", "ORCID": null, "country": null }, { "author_id": 301455, "given_name": "Heather J", "family_name": "Cordell", "ORCID": null, "country": null }, { "author_id": 212059, "given_name": "Jenefer M", "family_name": "Blackwell", "ORCID": "http://orcid.org/0000-0002-0784-7277", "country": "AU" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T18:45:29Z", "noun_phrases": [ "Common and rare genetic variants", "that", "severe otitis media", "an Australian Aboriginal population" ], "doi": "10.1093/cid/ciab216", "access": "open", "takeaways": " Study highlights interacting genes and pathways related to cilium structure and function that may contribute to extreme susceptibility to OM in Aboriginal Australian children .", "categories": [] }, { "article_id": 473, "title": "Five-Year Trends in Payments for Neurologist-Prescribed Drugs in Medicare Part D", "summary": "<div><p>Neurology. 2021 Mar 10:10.1212/WNL.0000000000011712. doi: 10.1212/WNL.0000000000011712. Online ahead of print.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">OBJECTIVE: To determine whether there was an increase in payments for neurologist-prescribed drugs, we performed a retrospective analysis of prescription claims in the Medicare Part D Prescriber Public Use Files from 2013-2017.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">METHODS: We included claims prescribed by providers with the taxonomy \"Neurology\" and included drugs present in all five years. Drugs were designated in 2013 as generic (GEN), brand name only (BNO), and brand name prescribed even though a generic equivalent is available (BNGE). To observe payment trends, the percentage change in the per claim payment was compared between drug classes.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">RESULTS: We included 520 drugs, of which 322 were GEN, 61 BNO, and 137 BNGE, representing 90,716,536 claims and generating payments of $26,654,750,720. While the number of claims from 2013 to 2017 only increased 7.6%, the total payment increased 50.4%. Adjusted for inflation, claim payments for GEN drug increased 0.6%, compared to significant increases in BNO and BNGE drugs of 42.4% and 45.0% (p<sub>trend</sub><0.001). The percentage of overall GEN claims increased from 81.9% to 88.0%, BNO increased from 4.9% to 6.2%, and BNGE decreased from 13.3% to 5.8%. Neuroimmunology/multiple sclerosis drugs represented over 50% of the total payments despite being only 4.3% of claims.</p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">CONCLUSIONS: Payments for neurologist-prescribed brand name, but not generic, drugs in Medicare Part D increased consistently and well above inflation from 2013-2017. Unless the overall trend stabilizes or is reversed, or high cost-to-claim drugs are addressed, this trend will place an increasing burden on the neurologic Medicare budget.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33692164/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311082527&v=2.14.2\">33692164</a> | DOI:<a href=\"https://doi.org/10.1212/WNL.0000000000011712\">10.1212/WNL.0000000000011712</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33692164/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-04-19T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Ovid Technologies (Wolters Kluwer Health)", "container_title": "Neurology", "authors": [ { "author_id": 264688, "given_name": "Adam", "family_name": "de Havenon", "ORCID": null, "country": null }, { "author_id": 281690, "given_name": "Alen", "family_name": "Delic", "ORCID": null, "country": null }, { "author_id": 281692, "given_name": "Sarah", "family_name": "Dehoney", "ORCID": null, "country": null }, { "author_id": 281694, "given_name": "Presley", "family_name": "Whetman", "ORCID": null, "country": null }, { "author_id": 281696, "given_name": "Nazanin", "family_name": "Sheibani", "ORCID": null, "country": null }, { "author_id": 246582, "given_name": "Brian", "family_name": "Callaghan", "ORCID": null, "country": null }, { "author_id": 245872, "given_name": "John", "family_name": "Ney", "ORCID": null, "country": null }, { "author_id": 245870, "given_name": "Gregory J.", "family_name": "Esper", "ORCID": null, "country": null }, { "author_id": 281697, "given_name": "Brandon", "family_name": "Magliocco", "ORCID": null, "country": null }, { "author_id": 265380, "given_name": "Kavita V.", "family_name": "Nair", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T13:25:28Z", "noun_phrases": [ "Five-Year Trends", "Payments", "Neurologist-Prescribed Drugs", "Medicare Part D" ], "doi": "10.1212/WNL.0000000000011712", "access": "open", "takeaways": " The number of claims from 2013 to 2017 only increased 7.6%, the total payment increased 50.4% . The percentage of overall GEN claims increased from 81.9% to 88.0% . Neuroimmunology/multiple sclerosis drugs represented over 50% of the total payments .", "categories": [] }, { "article_id": 472, "title": "A meta-analysis of the epidemiology of giant cell arteritis across time and space", "summary": "AbstractIntroductionGiant cell arteritis (GCA) is a common large vessel vasculitis in those over age 50 years. This meta-analysis examined the geographical and temporal distribution of the incidence, prevalence, and mortality of GCA.MethodsA systematic review was conducted using EMBASE, Scopus, and PubMed from their inceptions until 2019. Studies were included if they reported at least 50 or more GCA patients and defined the location and time frame. Articles on mortality were included and standardized mortality ratio (SMR) was extracted where possible. Mean pooled prevalence, incidence, and SMR were calculated using a random effects model. Linear regression was used to explore correlations between latitude and incidence, prevalence, and mortality.ResultsOf the 3569 citations identified, 107 were included. The pooled incidence of GCA was 10.00 [9.22, 10.78] cases per 100,000 people over 50 years old. This incidence was highest in Scandinavia 21.57 [18.90, 24.23], followed by North and South America 10.89 [8.78, 13.00], Europe 7.26 [6.05, 8.47], and Oceania 7.85 [− 1.48, 17.19]. Pooled prevalence was 51.74 [42.04, 61.43] cases per 100,000 people over age 50. Annual mortality was 20.44 [17.84, 23.03] deaths/1000. Mortality generally decreased over the years of publication (p = 0.0008). Latitude correlated significantly with incidence (p = 0.0011), but not with prevalence, or mortality.ConclusionsGCA incidence varies nearly 3-fold between regions and is highest in Scandinavia but not significantly. Mortality may be improving over time.", "link": "https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-021-02450-w", "published_date": "2021-03-11T00:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Arthritis Research & Therapy", "authors": [ { "author_id": 243677, "given_name": "Katherine J.", "family_name": "Li", "ORCID": null, "country": null }, { "author_id": 243678, "given_name": "Daniel", "family_name": "Semenov", "ORCID": null, "country": null }, { "author_id": 243679, "given_name": "Matthew", "family_name": "Turk", "ORCID": null, "country": null }, { "author_id": 210785, "given_name": "Janet", "family_name": "Pope", "ORCID": "http://orcid.org/0000-0003-1479-5302", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T12:25:59Z", "noun_phrases": [ "A meta-analysis", "the epidemiology", "giant cell arteritis", "time", "space" ], "doi": "10.1186/s13075-021-02450-w", "access": "open", "takeaways": " A systematic review was conducted using EMBASE, Scopus, and PubMed from their inceptions until 2019 . The pooled incidence of GCA was 10.00 [9.22, 10.78] cases per 100,000 people over 50 years old . This incidence was highest in Scandinavia 21.57 [18.90, 24.23], followed by North and South America 10.89 [8.78, 13.00], Europe 7.26 [6.05", "categories": [] }, { "article_id": 470, "title": "Multiple sclerosis risk gene Mertk is required for microglial activation and subsequent remyelination", "summary": "<div><p>Cell Rep. 2021 Mar 9;34(10):108835. doi: 10.1016/j.celrep.2021.108835.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">In multiple sclerosis (MS) and other neurological diseases, the failure to repair demyelinated lesions contributes to axonal damage and clinical disability. Here, we provide evidence that Mertk, a gene highly expressed by microglia that alters MS risk, is required for efficient remyelination. Compared to wild-type (WT) mice, Mertk-knockout (KO) mice show impaired clearance of myelin debris and remyelination following demyelination. Using single-cell RNA sequencing, we characterize Mertk-influenced responses to cuprizone-mediated demyelination and remyelination across different cell types. Mertk-KO brains show an attenuated microglial response to demyelination but an elevated proportion of interferon (IFN)-responsive microglia. In addition, we identify a transcriptionally distinct subtype of surviving oligodendrocytes specific to demyelinated lesions. The inhibitory effect of myelin debris on remyelination is mediated in part by IFNγ, which further impedes microglial clearance of myelin debris and inhibits oligodendrocyte differentiation. Together, our work establishes a role for Mertk in microglia activation, phagocytosis, and migration during remyelination.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33691116/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311015810&v=2.14.2\">33691116</a> | DOI:<a href=\"https://doi.org/10.1016/j.celrep.2021.108835\">10.1016/j.celrep.2021.108835</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33691116/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-09T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "Cell Reports", "authors": [ { "author_id": 243686, "given_name": "Kimberle", "family_name": "Shen", "ORCID": null, "country": null }, { "author_id": 243687, "given_name": "Mike", "family_name": "Reichelt", "ORCID": null, "country": null }, { "author_id": 243688, "given_name": "Roxanne V.", "family_name": "Kyauk", "ORCID": null, "country": null }, { "author_id": 243689, "given_name": "Hai", "family_name": "Ngu", "ORCID": null, "country": null }, { "author_id": 243690, "given_name": "Yun-An A.", "family_name": "Shen", "ORCID": null, "country": null }, { "author_id": 243691, "given_name": "Oded", "family_name": "Foreman", "ORCID": null, "country": null }, { "author_id": 243693, "given_name": "Zora", "family_name": "Modrusan", "ORCID": null, "country": null }, { "author_id": 192043, "given_name": "Brad A.", "family_name": "Friedman", "ORCID": "http://orcid.org/0000-0002-5864-5253", "country": "US" }, { "author_id": 243696, "given_name": "Morgan", "family_name": "Sheng", "ORCID": null, "country": null }, { "author_id": 330416, "given_name": "Tracy J.", "family_name": "Yuen", "ORCID": "http://orcid.org/0000-0002-3451-9279", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T06:58:12Z", "noun_phrases": [ "Multiple sclerosis risk gene Mertk", "microglial activation", "subsequent remyelination" ], "doi": "10.1016/j.celrep.2021.108835", "access": "open", "takeaways": " Mertk gene highly expressed by microglia that alters MS risk is required for efficient remyelination . Failure to repair demyelinated lesions contributes to axonal damage and clinical disability .", "categories": [] }, { "article_id": 466, "title": "Itaconate confers tolerance to late NLRP3 inflammasome activation", "summary": "<div><p>Cell Rep. 2021 Mar 9;34(10):108756. doi: 10.1016/j.celrep.2021.108756.</p><p><b>ABSTRACT</b></p><p xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" xmlns:p1=\"http://pubmed.gov/pub-one\" xmlns:xlink=\"http://www.w3.org/1999/xlink\">Itaconate is a unique regulatory metabolite that is induced upon Toll-like receptor (TLR) stimulation in myeloid cells. Here, we demonstrate major inflammatory tolerance and cell death phenotypes associated with itaconate production in activated macrophages. We show that endogenous itaconate is a key regulator of the signal 2 of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation after long lipopolysaccharide (LPS) priming, which establishes tolerance to late NLRP3 inflammasome activation. We show that itaconate acts synergistically with inducible nitric oxide synthase (iNOS) and that the ability of various TLR ligands to establish NLRP3 inflammasome tolerance depends on the pattern of co-expression of IRG1 and iNOS. Mechanistically, itaconate accumulation upon prolonged inflammatory stimulation prevents full caspase-1 activation and processing of gasdermin D, which we demonstrate to be post-translationally modified by endogenous itaconate. Altogether, our data demonstrate that metabolic rewiring in inflammatory macrophages establishes tolerance to NLRP3 inflammasome activation that, if uncontrolled, can result in pyroptotic cell death and tissue damage.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33691097/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311015810&v=2.14.2\">33691097</a> | DOI:<a href=\"https://doi.org/10.1016/j.celrep.2021.108756\">10.1016/j.celrep.2021.108756</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33691097/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-03-09T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "Cell Reports", "authors": [ { "author_id": 300695, "given_name": "Amanda", "family_name": "Swain", "ORCID": null, "country": null }, { "author_id": 307889, "given_name": "Sebastian", "family_name": "Hayes", "ORCID": null, "country": null }, { "author_id": 307890, "given_name": "Ryan D.", "family_name": "Sheldon", "ORCID": null, "country": null }, { "author_id": 307891, "given_name": "Hyeryun", "family_name": "Kim", "ORCID": null, "country": null }, { "author_id": 307892, "given_name": "Unnati", "family_name": "Kapadnis", "ORCID": null, "country": null }, { "author_id": 307893, "given_name": "Abigail E.", "family_name": "Ellis", "ORCID": null, "country": null }, { "author_id": 307894, "given_name": "Christine", "family_name": "Isaguirre", "ORCID": null, "country": null }, { "author_id": 307895, "given_name": "Samantha", "family_name": "Burdess", "ORCID": null, "country": null }, { "author_id": 307896, "given_name": "Anwesha", "family_name": "Laha", "ORCID": null, "country": null }, { "author_id": 307897, "given_name": "Gaya K.", "family_name": "Amarasinghe", "ORCID": null, "country": null }, { "author_id": 307898, "given_name": "Victor", "family_name": "Chubukov", "ORCID": null, "country": null }, { "author_id": 307899, "given_name": "Thomas P.", "family_name": "Roddy", "ORCID": null, "country": null }, { "author_id": 307900, "given_name": "Michael S.", "family_name": "Diamond", "ORCID": null, "country": null }, { "author_id": 307901, "given_name": "Russell G.", "family_name": "Jones", "ORCID": null, "country": null }, { "author_id": 307902, "given_name": "Donald M.", "family_name": "Simons", "ORCID": null, "country": null }, { "author_id": 300706, "given_name": "Maxim N.", "family_name": "Artyomov", "ORCID": null, "country": null }, { "author_id": 307884, "given_name": "Monika", "family_name": "Bambouskova", "ORCID": null, "country": null }, { "author_id": 307885, "given_name": "Lucie", "family_name": "Potuckova", "ORCID": null, "country": null }, { "author_id": 307886, "given_name": "Tomas", "family_name": "Paulenda", "ORCID": null, "country": null }, { "author_id": 268031, "given_name": "Martina", "family_name": "Kerndl", "ORCID": null, "country": null }, { "author_id": 307887, "given_name": "Denis A.", "family_name": "Mogilenko", "ORCID": null, "country": null }, { "author_id": 307888, "given_name": "Kate", "family_name": "Lizotte", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-11T06:58:12Z", "noun_phrases": [ "tolerance", "late NLRP3 inflammasome activation" ], "doi": "10.1016/j.celrep.2021.108756", "access": "open", "takeaways": " Itaconate is a unique regulatory metabolite that is induced upon Toll-like receptor (TLR) stimulation in myeloid cells . If uncontrolled, if uncontrolled, it can result in pyroptotic cell death and tissue damage .", "categories": [] } ] }