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{ "count": 24916, "next": "http://api.gregory-ms.com/articles/?format=api&page=2444", "previous": "http://api.gregory-ms.com/articles/?format=api&page=2442", "results": [ { "article_id": 501, "title": "Genetic and molecular biology of autism spectrum disorder among Middle East population: a review", "summary": "Background: Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing. It is more frequent among males. All of these clinical manifestations are associated with atypical neural development. Various genetic and environmental risk factors are involved in the etiology of autism. Genetic assessment is essential for the early detection and intervention which can improve social communications and reduce abnormal behaviors. Although, there is a noticeable ASD incidence in Middle East countries, there is still a lack of knowledge about the genetic and molecular biology of ASD among this population to introduce efficient diagnostic and prognostic methods.Main bodyIn the present review, we have summarized all of the genes which have been associated with ASD progression among Middle East population. We have also categorized the reported genes based on their cell and molecular functions.ConclusionsThis review clarifies the genetic and molecular biology of ASD among Middle East population and paves the way of introducing an efficient population based panel of genetic markers for the early detection and management of ASD in Middle East countries.", "link": "https://humgenomics.biomedcentral.com/articles/10.1186/s40246-021-00319-2", "published_date": "2021-03-12T00:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Human Genomics", "authors": [ { "author_id": 243990, "given_name": "Zahra", "family_name": "Rahmani", "ORCID": null, "country": null }, { "author_id": 243991, "given_name": "Mohammad Reza", "family_name": "Fayyazi Bordbar", "ORCID": null, "country": null }, { "author_id": 243992, "given_name": "Mohsen", "family_name": "Dibaj", "ORCID": null, "country": null }, { "author_id": 243993, "given_name": "Maliheh", "family_name": "Alimardani", "ORCID": null, "country": null }, { "author_id": 153753, "given_name": "Meysam", "family_name": "Moghbeli", "ORCID": "http://orcid.org/0000-0001-9680-0309", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T13:59:52Z", "noun_phrases": [ "Genetic and molecular biology", "autism", "disorder", "Middle East population" ], "doi": "10.1186/s40246-021-00319-2", "access": "open", "takeaways": " Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing . Various genetic and environmental risk factors are involved in the etiology of autism . There is still a lack of knowledge about the genetic and molecular biology of ASD among this population .", "categories": [] }, { "article_id": 498, "title": "Mitochondrial associated ER membrane (MAM) compartment and its dysregulation in Amyotrophic lateral sclerosis (ALS)", "summary": "<div><p>Semin Cell Dev Biol. 2021 Mar 8:S1084-9521(21)00026-4. doi: 10.1016/j.semcdb.2021.02.002. 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 endoplasmic reticulum (ER) and mitochondria connect at multiple contact sites to form a unique cellular compartment, termed the 'mitochondria-associated ER membranes' (MAMs). MAMs are hubs for signalling pathways that regulate cellular homeostasis and survival, metabolism, and sensitivity to apoptosis. MAMs are therefore involved in vital cellular functions, but they are dysregulated in several human diseases. Whilst MAM dysfunction is increasingly implicated in the pathogenesis of neurodegenerative diseases, its role in amyotrophic lateral sclerosis (ALS) is poorly understood. However, in ALS both ER and mitochondrial dysfunction are well documented pathophysiological events. Moreover, alterations to lipid metabolism in neurons regulate processes linked to neurodegenerative diseases, and a link between lipid metabolism dysfunction and ALS has also been proposed. In this review we discuss the structural and functional relevance of MAMs in ALS and how targeting MAM could be therapeutically beneficial in this disorder this disoefdisorder.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33707063/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210312080752&v=2.14.3\">33707063</a> | DOI:<a href=\"https://doi.org/10.1016/j.semcdb.2021.02.002\">10.1016/j.semcdb.2021.02.002</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33707063/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-04T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "Seminars in Cell & Developmental Biology", "authors": [ { "author_id": 314013, "given_name": "Sonam", "family_name": "Parakh", "ORCID": "http://orcid.org/0000-0002-7048-9695", "country": null }, { "author_id": 314015, "given_name": "Julie D.", "family_name": "Atkin", "ORCID": "http://orcid.org/0000-0003-2427-499X", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T13:07:55Z", "noun_phrases": [ "Mitochondrial", "ER membrane (MAM) compartment", "its dysregulation", "Amyotrophic lateral sclerosis", "ALS" ], "doi": "10.1016/j.semcdb.2021.02.002", "access": "restricted", "takeaways": " MAM dysfunction is increasingly implicated in the pathogenesis of neurodegenerative diseases, but its role in amyotrophic lateral sclerosis (ALS) is poorly understood . In ALS both ER and mitochondrial dysfunction are well documented pathophysiological events .", "categories": [] }, { "article_id": 499, "title": "In Vivo Profiling of a Natural Alkaloid, Anatabine, in Rodents: Pharmacokinetics and Anti-Inflammatory Efficacy", "summary": "<div><p>J Nat Prod. 2021 Mar 11. doi: 10.1021/acs.jnatprod.0c01044. 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\">Natural alkaloids, a large class of plant-derived substances, have attracted considerable interest because of their pharmacological activities. In this study, the <i>in vivo</i> pharmacokinetics and anti-inflammatory profile of anatabine, a naturally occurring alkaloid, were characterized in rodents. Anatabine was found to be bioavailable and brain-penetrant following systemic administration. Following intraperitoneal (i.p.) administration (1, 2, and 5 mg/kg), anatabine caused a dose-dependent reduction in carrageenan-induced paw edema in rats; in mice, it inhibited the production of pro-inflammatory cytokines and simultaneously elevated the levels of an anti-inflammatory cytokine in a dose-dependent manner 2 h after lipopolysaccharide challenge. Furthermore, anatabine (∼10 and ∼20 mg/kg/day for 4 weeks; inhalation exposure) had effects in a murine model of multiple sclerosis, reducing neurological deficits and bodyweight loss. Comparative studies of the pharmacokinetics and anti-inflammatory activity of anatabine demonstrated its bioequivalence in rats following i.p. administration and inhalation exposure. This study not only provides the first detailed profile of anatabine pharmacokinetics in rodents but also comprehensively characterizes the anti-inflammatory activities of anatabine in acute and chronic inflammatory models. These findings provide a basis for further characterizing and optimizing the anti-inflammatory properties of anatabine.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33706515/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210312080752&v=2.14.3\">33706515</a> | DOI:<a href=\"https://doi.org/10.1021/acs.jnatprod.0c01044\">10.1021/acs.jnatprod.0c01044</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33706515/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-04-22T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "American Chemical Society (ACS)", "container_title": "Journal of Natural Products", "authors": [ { "author_id": 185577, "given_name": "Wenhao", "family_name": "Xia", "ORCID": "http://orcid.org/0000-0003-3087-5441", "country": null }, { "author_id": 243934, "given_name": "Aditya Reddy", "family_name": "Kolli", "ORCID": null, "country": null }, { "author_id": 243935, "given_name": "Kyoko", "family_name": "Koshibu", "ORCID": null, "country": null }, { "author_id": 243936, "given_name": "Florian", "family_name": "Martin", "ORCID": null, "country": null }, { "author_id": 243937, "given_name": "Athanasios", "family_name": "Kondylis", "ORCID": null, "country": null }, { "author_id": 243938, "given_name": "Arkadiusz", "family_name": "Kuczaj", "ORCID": null, "country": null }, { "author_id": 243939, "given_name": "Wei Teck", "family_name": "Tan", "ORCID": null, "country": null }, { "author_id": 243940, "given_name": "Ying Shan", "family_name": "Yeo", "ORCID": null, "country": null }, { "author_id": 243941, "given_name": "Glenda", "family_name": "Tan", "ORCID": null, "country": null }, { "author_id": 243942, "given_name": "Charles", "family_name": "Teng", "ORCID": null, "country": null }, { "author_id": 243944, "given_name": "Kaing", "family_name": "Woon", "ORCID": null, "country": null }, { "author_id": 243946, "given_name": "Thomas", "family_name": "Schneider", "ORCID": null, "country": null }, { "author_id": 243948, "given_name": "Marja", "family_name": "Talikka", "ORCID": null, "country": null }, { "author_id": 243950, "given_name": "Blaine W.", "family_name": "Phillips", "ORCID": null, "country": null }, { "author_id": 185589, "given_name": "Patrick", "family_name": "Vanscheeuwijck", "ORCID": "http://orcid.org/0000-0002-8232-1734", "country": null }, { "author_id": 243953, "given_name": "Manuel C.", "family_name": "Peitsch", "ORCID": null, "country": null }, { "author_id": 243955, "given_name": "Julia", "family_name": "Hoeng", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T13:07:55Z", "noun_phrases": [ "Vivo Profiling", "a Natural Alkaloid", "Anatabine", "Rodents", "Pharmacokinetics", "Anti-Inflammatory Efficacy" ], "doi": "10.1021/acs.jnatprod.0c01044", "access": "open", "takeaways": " Anatabine was found to be bioavailable and brain-penetrant following systemic administration . It had effects in a murine model of multiple sclerosis, reducing neurological deficits and bodyweight loss . These findings provide a basis for further characterizing and optimizing the anti-inflammatory properties of anatabine .", "categories": [] }, { "article_id": 497, "title": "SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation", "summary": "Background: Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC). However, HPV infection related radioresistance caused poor prognosis of ESCC. The function of SOCS6, which has been shown to be a tumor suppressor in several cancers, has not been fully investigated up till now. In this manuscript, we aim to further investigate the role of SOCS6 in regulating ESCC radioresistance.MethodsFifty-seven ESCC patients were enrolled for survival analysis. SOCS6 was stably overexpressed in HPV+ ESCC and ESCC cells, and cells were treated with radiation and then subjected to colony formation assays. Expression of DNA damage repair regulating proteins were examined by Western blotting. Cell growth, cell migration and cisplatin sensitivity were then analyzed. Sphere formation assays and flow cytometry were used to investigate changes in cancer stem cell (CSC) properties. Immunofluorescent staining and confocal microscopy were used to locate SOCS6 and c-Kit. Ubiquitylation level of c-Kit were analyzed after immunoprecipitation. Then, coimmunoprecipitation (CoIP) of SOCS6 and c-Kit were performed. In vivo, xenograft animal models were treated with radiation to examine the radiosensitivity.ResultsSOCS6 is correlated with better prognosis in ESCC patients. Radioresistance is impaired by SOCS6 upregulation, which inhibited cell growth, migration and increased sensitivity to cisplatin. SOCS6 significantly decreased the population of CSCs expressing the surface biomarker CD271 or CD24low/CD44high and their ability of sphere formation. SOCS6 and c-Kit were collocated in the cytoplasm. Blotting of ubiquitin and CoIP experiments indicated that the mechanism was related to ubiquitylation and degradation of the receptor c-Kit. Xenograft tumor mouse model showed that SOCS6 inhibited tumor growth and promoted radiosensitivity in vivo.ConclusionsOur findings suggest that SOCS6 can promote the radiosensitivity of HPV+ ESCC and ESCC cells and reduce their stemness via ubiquitylation and degradation of c-Kit. Thus, SOCS6 is a potential target for overcoming radioresistance of ESCC.", "link": "https://cancerci.biomedcentral.com/articles/10.1186/s12935-021-01859-2", "published_date": "2021-03-12T00:00:00Z", "sources": [ "BioMedCentral" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Springer Science and Business Media LLC", "container_title": "Cancer Cell International", "authors": [ { "author_id": 243958, "given_name": "Xuanzi", "family_name": "Sun", "ORCID": null, "country": null }, { "author_id": 243959, "given_name": "Yuchen", "family_name": "Sun", "ORCID": null, "country": null }, { "author_id": 173945, "given_name": "Jing", "family_name": "Li", "ORCID": "http://orcid.org/0000-0002-5102-4315", "country": null }, { "author_id": 243960, "given_name": "Xu", "family_name": "Zhao", "ORCID": null, "country": null }, { "author_id": 243962, "given_name": "Xiaobo", "family_name": "Shi", "ORCID": null, "country": null }, { "author_id": 243963, "given_name": "Tuotuo", "family_name": "Gong", "ORCID": null, "country": null }, { "author_id": 243965, "given_name": "Shupei", "family_name": "Pan", "ORCID": null, "country": null }, { "author_id": 243967, "given_name": "Zhongqiang", "family_name": "Zheng", "ORCID": null, "country": null }, { "author_id": 190241, "given_name": "Xiaozhi", "family_name": "Zhang", "ORCID": "http://orcid.org/0000-0002-3988-2181", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T12:47:08Z", "noun_phrases": [ "SOCS6", "radiosensitivity", "cancer cell", "esophageal squamous cell carcinoma", "c-Kit ubiquitylation" ], "doi": "10.1186/s12935-021-01859-2", "access": "open", "takeaways": " Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC) However, HPV infection related radioresistance caused poor prognosis of ESCC . The function of SOCS6, which has been shown to be a tumor suppressor in several cancers, has not been fully investigated .", "categories": [] }, { "article_id": 496, "title": "Circulating cell-free DNA as potential diagnostic tools for amyotrophic lateral sclerosis", "summary": "<div><p>Neurosci Lett. 2021 Mar 8:135813. doi: 10.1016/j.neulet.2021.135813. 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\">DNA methylation has garnered much attention in recent years for its diagnostic potential in multiple conditions including cancer and neurodegenerative diseases. Conversely, advances regarding the potential diagnostic relevance of DNA methylation status have been sparse in the field of amyotrophic lateral sclerosis (ALS) even though patients diagnosed with this condition would significantly benefit from improved molecular assays aimed at furthering the current diagnostic and therapeutic options available. This review will provide an overview of the current diagnostic approaches available for ALS diagnosis and discuss the potential clinical usefulness of DNA methylation. We will also present examples of DNA methylation as a diagnostic tool in various types of cancer and neurodegenerative conditions and expand on how circulating cfDNA methylation may be leveraged for the early detection of ALS. In general, this article will reinforce the importance of cfDNA methylation as diagnostic tools and will further highlight its clinical relevance for persons diagnosed with ALS.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33705931/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210312070529&v=2.14.3\">33705931</a> | DOI:<a href=\"https://doi.org/10.1016/j.neulet.2021.135813\">10.1016/j.neulet.2021.135813</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33705931/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-04-16T23:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Elsevier BV", "container_title": "Neuroscience Letters", "authors": [ { "author_id": 218845, "given_name": "Philippe-Pierre", "family_name": "Robichaud", "ORCID": "http://orcid.org/0000-0002-8707-0655", "country": null }, { "author_id": 218846, "given_name": "Michael", "family_name": "Arseneault", "ORCID": "http://orcid.org/0000-0003-4524-5661", "country": null }, { "author_id": 218847, "given_name": "Colleen", "family_name": "O’Connell", "ORCID": "http://orcid.org/0000-0002-4760-4093", "country": null }, { "author_id": 243920, "given_name": "Rodney J.", "family_name": "Ouellette", "ORCID": null, "country": null }, { "author_id": 243921, "given_name": "Pier Jr", "family_name": "Morin", "ORCID": null, "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T12:05:32Z", "noun_phrases": [ "cell-free DNA", "potential diagnostic tools", "amyotrophic lateral sclerosis" ], "doi": "10.1016/j.neulet.2021.135813", "access": "restricted", "takeaways": " DNA methylation has garnered much attention in recent years for its diagnostic potential in multiple conditions including cancer and neurodegenerative diseases . ALS patients would benefit from improved molecular assays aimed at furthering the current diagnostic and therapeutic options available .", "categories": [] }, { "article_id": 495, "title": "The latitude gradient for multiple sclerosis prevalence is established in the early lifecourse", "summary": "<div><p>Brain. 2021 Mar 11:awab104. doi: 10.1093/brain/awab104. 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 strongest epidemiological clue that the environment at the population level has a significant impact on the risk of developing multiple sclerosis (MS) is the well-established, and in many instances, increasing latitudinal gradient of prevalence, incidence and mortality globally, with prevalence increasing by up to 10-fold between the equator and 60 degrees North and South. The drivers of this gradient are thought to be environmental with latitude seen as a proxy for ultraviolet radiation and thus vitamin D production, however other factors may also play a role. However several important questions remain unanswered, particularly when in the life course is the gradient established, does lifetime migration mitigate or exacerbate previously reported latitude gradients at location of diagnosis, and do factors such as sex or MS disease phenotype influence the timing or significance of the gradient? Utilising life time residence calendars collected as part of the New Zealand national MS prevalence study, we constructed lifetime latitudinal gradients for MS from birth to prevalence day 2006 taking into account migration internally and externally and then analysed by sex and MS clinical course phenotype. 2127 of 2917 people living in NZ on prevalence day 7 March 2006 with MS completed the life course questionnaire and of these 1587 were born in NZ. All cohorts and sub cohorts were representative of the overall MS population in NZ on prevalence day. We found that the prevalence gradient was present at birth and was in fact stronger than at census day, and the slope of the gradient persisted until the age of 12 before gradually declining. We found that internal and external migration into NZ had little if any effect on the gradient except to decrease the significance of the gradient somewhat. Finally, we found as we had reported previously that the lifetime prevalence gradients were largely driven by females with relapse onset MS. These findings confirm for the first time the importance of early life environmental exposures in the risk of MS indicating strongly that exposures as early as in utero and at birth drive the latitudinal gradient. Consequently, prevention studies should be focussed on high risk individuals and populations from the earliest possible time points especially, when appropriate, on females.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33704407/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311230527&v=2.14.3\">33704407</a> | DOI:<a href=\"https://doi.org/10.1093/brain/awab104\">10.1093/brain/awab104</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33704407/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-08-16T23:00:00Z", "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": 158352, "given_name": "Clive E", "family_name": "Sabel", "ORCID": "http://orcid.org/0000-0001-9180-4861", "country": null }, { "author_id": 243931, "given_name": "John F", "family_name": "Pearson", "ORCID": null, "country": null }, { "author_id": 243932, "given_name": "Deborah F", "family_name": "Mason", "ORCID": null, "country": null }, { "author_id": 243359, "given_name": "Ernest", "family_name": "Willoughby", "ORCID": null, "country": null }, { "author_id": 243933, "given_name": "David A", "family_name": "Abernethy", "ORCID": null, "country": null }, { "author_id": 177179, "given_name": "Bruce V.", "family_name": "Taylor", "ORCID": "http://orcid.org/0000-0003-2807-0070", "country": "AU" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T04:05:29Z", "noun_phrases": [ "The latitude gradient", "multiple sclerosis prevalence", "the early lifecourse" ], "doi": "10.1093/brain/awab104", "access": "open", "takeaways": " MS prevalence increases by up to 10-fold between the equator and 60 degrees North and South . Drivers of this gradient are thought to be environmental with latitude seen as a proxy for ultraviolet radiation and thus vitamin D production .", "categories": [] }, { "article_id": 493, "title": "Re-examining the effects of high-dose intravenous methylprednisolone for secondary progressive multiple sclerosis", "summary": "<div><p>Neurodegener Dis Manag. 2021 Mar 11. doi: 10.2217/nmt-2020-0051. 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\"><b>Background/objective:</b> Intravenous methylprednisolone (IVMP) is previously given to secondary progressive multiple sclerosis (SPMS) patients. This study aimed to re-examine the effects of IVMP in SPMS. <b>Materials & methods:</b> Major electronic databases were searched for randomized controlled trials. <b>Results:</b> Four randomized controlled trials were included. IVMP may be inferior to mitoxantrone (MTX) in terms of expanded disability status scale (EDSS) improvement. There was no significant difference in terms of EDSS reduction and magnetic resonance imaging (MRI) plaque reduction when IVMP + MTX were compared with MTX. There is no significant difference between IVMP and cyclophosphamide based on EDSS progression and relapse reduction. <b>Conclusion:</b> IVMP should not be routinely used as treatment for SPMS and is not recommended as an alternative treatment for SPMS.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33703936/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311230527&v=2.14.3\">33703936</a> | DOI:<a href=\"https://doi.org/10.2217/nmt-2020-0051\">10.2217/nmt-2020-0051</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33703936/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-04T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Future Medicine Ltd", "container_title": "Neurodegenerative Disease Management", "authors": [ { "author_id": 185684, "given_name": "Francis Gerwin", "family_name": "U Jalipa", "ORCID": "http://orcid.org/0000-0002-0844-4381", "country": "PH" }, { "author_id": 185685, "given_name": "Adrian", "family_name": "I Espiritu", "ORCID": "http://orcid.org/0000-0001-5621-1833", "country": "PH" }, { "author_id": 185686, "given_name": "Paul Matthew", "family_name": "D Pasco", "ORCID": "http://orcid.org/0000-0002-1533-2214", "country": "PH" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T04:05:29Z", "noun_phrases": [ "the effects", "high-dose intravenous methylprednisolone", "secondary progressive multiple sclerosis" ], "doi": "10.2217/nmt-2020-0051", "access": "restricted", "takeaways": " Intravenous methylprednisolone (IVMP) may be inferior to mitoxantrone (MTX) in terms of expanded disability status scale (EDSS) improvement . IVMP should not be routinely used as treatment for SPMS and is not recommended as an alternative treatment .", "categories": [] }, { "article_id": 486, "title": "Genetic variation in WNT9B increases relapse hazard in multiple sclerosis", "summary": "<div><p>Ann Neurol. 2021 Mar 11. doi: 10.1002/ana.26061. 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: Many multiple sclerosis (MS) genetic susceptibility variants have been identified, but understanding disease heterogeneity remains a key challenge. Relapses are a core feature of MS and a common primary outcome of clinical trials, with prevention of relapses benefiting patients immediately and potentially limiting long-term disability accrual. We aim to identify genetic variation associated with relapse hazard in MS by analyzing the largest study population to date.</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 performed a genome-wide association study (GWAS) in a discovery cohort and investigated the genome-wide significant variants in a replication cohort. Combining both cohorts, we captured a total of 2231 relapses occurring before the start of any immunomodulatory treatment in 991 patients. For assessing time to relapse, we applied a survival analysis utilizing Cox proportional hazards models. We also investigated the association between MS genetic risk scores and relapse hazard and performed a gene ontology pathway analysis.</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: The low-frequency genetic variant rs11871306 within WNT9B reached genomewide significance in predicting relapse hazard and replicated (meta-analysis hazard ratio (HR) = 2.15, 95% confidence interval (CI) = 1.70-2.78, p = 2.07 × 10<sup>-10</sup> ). A pathway analysis identified an association of the pathway \"response to vitamin D\" with relapse hazard (p = 4.33 × 10<sup>-6</sup> ). The MS genetic risk scores, however, were not associated with relapse hazard.</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\">INTERPRETATION: Genetic factors underlying disease heterogeneity differ from variants associated with MS susceptibility. Our findings imply that genetic variation within the Wnt signaling and vitamin D pathways contributes to differences in relapse occurrence. The present study highlights these cross-talking pathways as potential modulators of MS disease activity. This article is protected by copyright. All rights reserved.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33704824/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311230527&v=2.14.3\">33704824</a> | DOI:<a href=\"https://doi.org/10.1002/ana.26061\">10.1002/ana.26061</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33704824/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-05T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Wiley", "container_title": "Annals of Neurology", "authors": [ { "author_id": 194598, "given_name": "Marijne", "family_name": "Vandebergh", "ORCID": "http://orcid.org/0000-0001-9645-2615", "country": null }, { "author_id": 152384, "given_name": "Till FM", "family_name": "Andlauer", "ORCID": "http://orcid.org/0000-0002-2917-5889", "country": null }, { "author_id": 225887, "given_name": "Yuan", "family_name": "Zhou", "ORCID": "http://orcid.org/0000-0003-1962-2574", "country": "AU" }, { "author_id": 243876, "given_name": "Klara", "family_name": "Mallants", "ORCID": null, "country": null }, { "author_id": 243877, "given_name": "Friederike", "family_name": "Held", "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": 243306, "given_name": "Bruce V.", "family_name": "Taylor", "ORCID": null, "country": null }, { "author_id": 147080, "given_name": "Bernhard", "family_name": "Hemmer", "ORCID": "http://orcid.org/0000-0001-5985-6784", "country": null }, { "author_id": 192872, "given_name": "Bénédicte", "family_name": "Dubois", "ORCID": "http://orcid.org/0000-0003-0604-8702", "country": null }, { "author_id": 187012, "given_name": "An", "family_name": "Goris", "ORCID": "http://orcid.org/0000-0002-1276-6682", "country": "BE" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T04:05:29Z", "noun_phrases": [ "Genetic variation", "WNT9B", "relapse hazard", "multiple sclerosis" ], "doi": "10.1002/ana.26061", "access": "open", "takeaways": " Relapses are a core feature of MS and a common primary outcome of clinical trials, with prevention of relapses benefiting patients immediately and potentially limiting long-term disability accrual . We aim to identify genetic variation associated with relapse hazard in MS by analyzing the largest study population to date .", "categories": [] }, { "article_id": 488, "title": "QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions", "summary": "<div><p>Ann Clin Transl Neurol. 2021 Mar 11. doi: 10.1002/acn3.51338. 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: Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron.</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 characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions.</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: MS brain slabs were imaged with MRI and QSM, and processed for histology. Immunolabeled cells were quantified in the lesion rim, center, and adjacent normal-appearing white matter (NAWM). Iron<sup>+</sup> myeloid cell densities at the rims were correlated with susceptibilities. Human-induced pluripotent stem cell (iPSC)-derived microglia were used to determine the effect of iron on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines.</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: QSM hyperintensity at the lesion perimeter correlated with activated iron<sup>+</sup> myeloid cells in the rim and NAWM. Lesions with high punctate or homogenous QSM signal contained no or minimally activated iron<sup>-</sup> myeloid cells. In vitro, iron accumulation was highest in M1-polarized human iPSC-derived microglia, but it did not enhance ROS or cytokine production.</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\">CONCLUSION: A high QSM signal outlining the lesion rim but not punctate signal in the center is a biomarker for chronic inflammation in white matter lesions.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33704933/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311230527&v=2.14.3\">33704933</a> | DOI:<a href=\"https://doi.org/10.1002/acn3.51338\">10.1002/acn3.51338</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33704933/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2021-01-04T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "Wiley", "container_title": "Annals of Clinical and Translational Neurology", "authors": [ { "author_id": 183277, "given_name": "Kelly M.", "family_name": "Gillen", "ORCID": "http://orcid.org/0000-0003-1319-4900", "country": "US" }, { "author_id": 243861, "given_name": "Mayyan", "family_name": "Mubarak", "ORCID": null, "country": null }, { "author_id": 243862, "given_name": "Calvin", "family_name": "Park", "ORCID": null, "country": null }, { "author_id": 243863, "given_name": "Gerald", "family_name": "Ponath", "ORCID": null, "country": null }, { "author_id": 184171, "given_name": "Shun", "family_name": "Zhang", "ORCID": "http://orcid.org/0000-0002-0001-1880", "country": null }, { "author_id": 243864, "given_name": "Alexey", "family_name": "Dimov", "ORCID": null, "country": null }, { "author_id": 243865, "given_name": "Maya", "family_name": "Levine‐Ritterman", "ORCID": null, "country": null }, { "author_id": 243866, "given_name": "Steven", "family_name": "Toro", "ORCID": null, "country": null }, { "author_id": 243867, "given_name": "Weiyuan", "family_name": "Huang", "ORCID": null, "country": null }, { "author_id": 243868, "given_name": "Stephanie", "family_name": "Amici", "ORCID": null, "country": null }, { "author_id": 322788, "given_name": "Ulrike W.", "family_name": "Kaunzner", "ORCID": "http://orcid.org/0000-0001-9449-7369", "country": null }, { "author_id": 150183, "given_name": "Susan A.", "family_name": "Gauthier", "ORCID": "http://orcid.org/0000-0002-4015-1781", "country": null }, { "author_id": 243870, "given_name": "Mireia", "family_name": "Guerau‐de‐Arellano", "ORCID": null, "country": null }, { "author_id": 155850, "given_name": "Yi", "family_name": "Wang", "ORCID": "http://orcid.org/0000-0003-1404-8526", "country": "US" }, { "author_id": 243872, "given_name": "Thanh D.", "family_name": "Nguyen", "ORCID": null, "country": null }, { "author_id": 183278, "given_name": "David", "family_name": "Pitt", "ORCID": "http://orcid.org/0000-0002-6407-9542", "country": null } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T04:05:29Z", "noun_phrases": [ "QSM", "an imaging biomarker", "chronic glial activation", "multiple sclerosis lesions" ], "doi": "10.1002/acn3.51338", "access": "open", "takeaways": " Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI . Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping . Iron+ myeloid cell densities at the rims were correlated with susceptibilities .", "categories": [] }, { "article_id": 492, "title": "Successful Management of Natalizumab-Associated Primary Central Nervous System Lymphoma through Autologous Stem Cell Transplant", "summary": "<div><p>Curr Oncol. 2020 Dec 30;28(1):203-208. doi: 10.3390/curroncol28010022.</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\">Natalizumab is used as a second-line treatment for multiple sclerosis (MS). Some reports have linked natalizumab to primary central nervous system lymphoma (PCNSL), although few have described its management. A 45-year-old woman with Balo's Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab. Magnetic resonance imaging (MRI) and a brain biopsy confirmed the diagnosis of PCNSL. The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant (ASCT) as a consolidation therapy. Thirty months later, she is still in complete remission of her PCNSL and MS. In this case, whole brain radiotherapy was excluded because it may be associated with an increased risk of neurotoxicity in MS. ASCT was preferred because it has been shown to prevent disability progression in less advanced MS stages. Our patient is the second to receive an ASCT in this context and this option of treatment should be the preferred if the patient is eligible.</p><p>PMID:<a href=\"https://pubmed.ncbi.nlm.nih.gov/33704187/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc=20210216052009&ff=20210311230527&v=2.14.3\">33704187</a> | DOI:<a href=\"https://doi.org/10.3390/curroncol28010022\">10.3390/curroncol28010022</a></p></div>", "link": "https://pubmed.ncbi.nlm.nih.gov/33704187/#x3D;Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=10guX6I3SqrbUeeLKSTD6FCRM44ewnrN2MKKTQLLPMHB4xNsZU&fc&#x", "published_date": "2020-12-30T00:00:00Z", "sources": [ "PubMed" ], "teams": [ { "id": 1, "name": "Team Gregory" } ], "subjects": [ { "subject_name": "Multiple Sclerosis", "description": null } ], "publisher": "MDPI AG", "container_title": "Current Oncology", "authors": [ { "author_id": 202212, "given_name": "Karine", "family_name": "Moineau-Vallée", "ORCID": "http://orcid.org/0000-0003-0929-1601", "country": null }, { "author_id": 296642, "given_name": "Justine", "family_name": "Rinfret", "ORCID": null, "country": null }, { "author_id": 296643, "given_name": "My Hanh", "family_name": "Luu Hoai", "ORCID": null, "country": null }, { "author_id": 296644, "given_name": "Valérie", "family_name": "St-Louis", "ORCID": null, "country": null }, { "author_id": 296645, "given_name": "France", "family_name": "Berthelet", "ORCID": null, "country": null }, { "author_id": 202217, "given_name": "Laurent", "family_name": "Létourneau-Guillon", "ORCID": "http://orcid.org/0000-0002-6325-7538", "country": "CA" }, { "author_id": 296646, "given_name": "Émilie", "family_name": "Lemieux-Blanchard", "ORCID": null, "country": null }, { "author_id": 156897, "given_name": "Alexandre", "family_name": "Prat", "ORCID": "http://orcid.org/0000-0001-6188-0580", "country": "CA" }, { "author_id": 202219, "given_name": "Jean-Philippe", "family_name": "Adam", "ORCID": "http://orcid.org/0000-0002-7938-0944", "country": "CA" } ], "relevant": null, "ml_prediction_gnb": false, "ml_prediction_lr": false, "ml_prediction_lsvc": false, "discovery_date": "2021-03-12T04:05:29Z", "noun_phrases": [ "Successful Management", "Natalizumab", "-Associated Primary Central Nervous System Lymphoma", "Autologous Stem Cell Transplant" ], "doi": "10.3390/curroncol28010022", "access": "open", "takeaways": " A 45-year-old woman with Balo's Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab . The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant", "categories": [ { "category_id": 7, "category_description": "", "category_name": "Natalizumab", "category_slug": "natalizumab", "category_terms": [ "natalizumab", "tysabri" ], "article_count": 305 } ] } ] }