This study introduces RheumaLinguisticpack (RheumaLpack), the first specialised linguistic web corpus designed for the field of musculoskeletal disorders. By combining web mining (i.e., web scraping) and natural language processing (NLP) techniques, as well as clinical expertise, RheumaL-pack systematically captures and curates data across a spectrum of web sources including clinical trials registers (i.e., ClinicalTrials.gov), bibliographic databases (i.e., PubMed), medical agencies (i.e. EMA), social media (i.e., Reddit), and accredited health websites (i.e., MedlinePlus, Hardvard Health Publishing, and Cleveland Clinic). Given the complexity of rheumatic and musculoskeletal diseases (RMDs) and their significant impact on quality of life, this resource can be proposed as a useful tool to train algorithms that could mitigate the diseases’ effects. Therefore, the corpus aims to improve the training of artificial intelligence (AI) algorithms and facilitate knowledge discovery in RMDs. The development of RheumaLpack involved a systematic six-step methodology covering data identification, characterisation, selection, collection, processing, and corpus description. The result is a non-annotated, monolingual, and dynamic corpus, featuring almost 3 million records spanning from 2000 to 2023. RheumaLpack represents a pioneering contribution to rheumatology research, providing a useful resource for the development of advanced AI and NLP applications. This corpus highlights the value of web data to address the challenges posed by musculoskeletal diseases, illustrating the corpus’s potential to improve research and treatment paradigms in rheumatology. Finally, the methodology shown can be replicated to obtain data from other medical specialities. The code and details on how to build RheumaL(inguistic)pack are also provided to facilitate the dissemination of such resource.
{"title":"From Web to RheumaLpack: Creating a Linguistic Corpus for Exploitation and Knowledge Discovery in Rheumatology","authors":"Alfredo Madrid-García, Beatriz Merino-Barbancho, Dalifer Freites-Núñez, Luis Rodríguez-Rodríguez, Ernestina Menasalvas-Ruíz, Alejandro Rodríguez-González, Anselmo Peñas","doi":"10.1101/2024.04.26.24306269","DOIUrl":"https://doi.org/10.1101/2024.04.26.24306269","url":null,"abstract":"This study introduces <em>RheumaLinguisticpack</em> (<em>RheumaLpack</em>), the first specialised linguistic web corpus designed for the field of musculoskeletal disorders. By combining web mining (i.e., web scraping) and natural language processing (NLP) techniques, as well as clinical expertise, <em>RheumaL-pack</em> systematically captures and curates data across a spectrum of web sources including clinical trials registers (i.e., ClinicalTrials.gov), bibliographic databases (i.e., PubMed), medical agencies (i.e. EMA), social media (i.e., Reddit), and accredited health websites (i.e., MedlinePlus, Hardvard Health Publishing, and Cleveland Clinic). Given the complexity of rheumatic and musculoskeletal diseases (RMDs) and their significant impact on quality of life, this resource can be proposed as a useful tool to train algorithms that could mitigate the diseases’ effects. Therefore, the corpus aims to improve the training of artificial intelligence (AI) algorithms and facilitate knowledge discovery in RMDs. The development of <em>RheumaLpack</em> involved a systematic six-step methodology covering data identification, characterisation, selection, collection, processing, and corpus description. The result is a non-annotated, monolingual, and dynamic corpus, featuring almost 3 million records spanning from 2000 to 2023. <em>RheumaLpack</em> represents a pioneering contribution to rheumatology research, providing a useful resource for the development of advanced AI and NLP applications. This corpus highlights the value of web data to address the challenges posed by musculoskeletal diseases, illustrating the corpus’s potential to improve research and treatment paradigms in rheumatology. Finally, the methodology shown can be replicated to obtain data from other medical specialities. The code and details on how to build <em>RheumaL(inguistic)pack</em> are also provided to facilitate the dissemination of such resource.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.1101/2024.04.12.24305730
Begonya Alcacer-Pitarch, Marco Di Battista, Anthony C. Redmond, Anne-Maree Keenan, Stefano Di Donato, Maya H. Buch, Francesco Del Galdo
Introduction Peripheral Sensory Neuropathy (PSN) is an under-recognized feature in systemic sclerosis (SSc). Moreover, SSc foot involvement is frequent but poorly investigated. We aimed to provide a detailed characterization of foot peripheral neuropathy in a large cohort of SSc patients, describing its associations with disease-specific features, physical disability and Quality of Life (QoL).
{"title":"Prevalence and impact of foot peripheral neuropathy in Sytemic Sclerosis (SSc): results from a single centre cross-sectional study","authors":"Begonya Alcacer-Pitarch, Marco Di Battista, Anthony C. Redmond, Anne-Maree Keenan, Stefano Di Donato, Maya H. Buch, Francesco Del Galdo","doi":"10.1101/2024.04.12.24305730","DOIUrl":"https://doi.org/10.1101/2024.04.12.24305730","url":null,"abstract":"<strong>Introduction</strong> Peripheral Sensory Neuropathy (PSN) is an under-recognized feature in systemic sclerosis (SSc). Moreover, SSc foot involvement is frequent but poorly investigated. We aimed to provide a detailed characterization of foot peripheral neuropathy in a large cohort of SSc patients, describing its associations with disease-specific features, physical disability and Quality of Life (QoL).","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-14DOI: 10.1101/2024.04.12.24305747
Hannah F. Bradford, Christophe J. Lalaurie, Jayesh Gor, Xin Gao, Charis Pericleous, Stephen J. Perkins, Hannah Britt, Konstantinos Thalassinos, Ian Giles, Anisur Rahman, Mihaela Delcea, Paul A. Dalby, Thomas C.R. McDonnell
Beta-2-Glycoprotein I (β2GPI) is the main autoantigenic target of antiphospholipid syndrome (APS) with antibodies leading to clinical manifestations. There are two known structural isomers of β2GPI, a J shape and a circular shaped one. The transition between these structures is incompletely understood, with the functional implications unknown. β2GPI is a substrate of the protease plasmin, which cleaves within the fifth domain of β2GPI leading to altered cellular binding. Very little is currently known regarding the structure and function of this protein variant. We present the first comprehensive structural characterisation plasmin-clipped β2GPI and the associated implications for pathogenic antibody binding to this protein.
{"title":"Plasmin Cleavage of Beta-2-Glycoprotein I Alters its Structure and Ability to Bind to Pathogenic Antibodies","authors":"Hannah F. Bradford, Christophe J. Lalaurie, Jayesh Gor, Xin Gao, Charis Pericleous, Stephen J. Perkins, Hannah Britt, Konstantinos Thalassinos, Ian Giles, Anisur Rahman, Mihaela Delcea, Paul A. Dalby, Thomas C.R. McDonnell","doi":"10.1101/2024.04.12.24305747","DOIUrl":"https://doi.org/10.1101/2024.04.12.24305747","url":null,"abstract":"Beta-2-Glycoprotein I (β2GPI) is the main autoantigenic target of antiphospholipid syndrome (APS) with antibodies leading to clinical manifestations. There are two known structural isomers of β2GPI, a J shape and a circular shaped one. The transition between these structures is incompletely understood, with the functional implications unknown. β2GPI is a substrate of the protease plasmin, which cleaves within the fifth domain of β2GPI leading to altered cellular binding. Very little is currently known regarding the structure and function of this protein variant. We present the first comprehensive structural characterisation plasmin-clipped β2GPI and the associated implications for pathogenic antibody binding to this protein.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1101/2024.04.09.24305328
Ben Hammond, Aliaksandra Baranskaya, Nicola Adderley, Dawit Zemedikun, Alexander d’Elia, Marie Falahee, Christian Mallen, Elspeth Insch, Joht Singh Chandan, Krishnarajah Nirantharakumar, Kym Snell, Karim Raza
Background Rheumatoid Arthritis (RA) is a chronic rheumatological condition which causes inflammation of both the joint lining and extra-articular sites. It affects around 1% of the UK population and, if not properly treated, can lead joint damage, disability, and significant socioeconomic burden. The risk of long-term damage is reduced if treatment is started in an early disease stage with treatment in the first 3 months being associated with significantly improved clinical outcomes. However, treatment is often delayed due to long referral waits and challenges in identifying early RA in primary care. We plan to use large primary care datasets to develop and validate an RA risk prediction model for use in primary care, with the aim to provide an additional mechanism for early diagnosis and referral for treatment.
背景类风湿性关节炎（RA）是一种慢性风湿病，会引起关节内膜和关节外部位的炎症。英国约有 1% 的人患有此病，如果治疗不当，会导致关节损伤、残疾和严重的社会经济负担。如果在疾病早期就开始治疗，长期损害的风险就会降低。然而，由于转诊等待时间过长以及在初级保健中识别早期 RA 的挑战，治疗往往被延误。我们计划利用大型初级保健数据集来开发和验证用于初级保健的 RA 风险预测模型，目的是为早期诊断和转诊治疗提供额外的机制。
{"title":"Protocol for the development and validation of a Rheumatoid Arthritis PredIction moDel using primary care health records (RAPID)","authors":"Ben Hammond, Aliaksandra Baranskaya, Nicola Adderley, Dawit Zemedikun, Alexander d’Elia, Marie Falahee, Christian Mallen, Elspeth Insch, Joht Singh Chandan, Krishnarajah Nirantharakumar, Kym Snell, Karim Raza","doi":"10.1101/2024.04.09.24305328","DOIUrl":"https://doi.org/10.1101/2024.04.09.24305328","url":null,"abstract":"<strong>Background</strong> Rheumatoid Arthritis (RA) is a chronic rheumatological condition which causes inflammation of both the joint lining and extra-articular sites. It affects around 1% of the UK population and, if not properly treated, can lead joint damage, disability, and significant socioeconomic burden. The risk of long-term damage is reduced if treatment is started in an early disease stage with treatment in the first 3 months being associated with significantly improved clinical outcomes. However, treatment is often delayed due to long referral waits and challenges in identifying early RA in primary care. We plan to use large primary care datasets to develop and validate an RA risk prediction model for use in primary care, with the aim to provide an additional mechanism for early diagnosis and referral for treatment.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-27DOI: 10.1101/2024.03.26.24304925
Mickael Essouma, Daniel Brito de Araujo, Jessica Day, Latika Gupta, Adina Kay Knight, Ann Reed, Elie Naddaf, Adriana Maluf Elias Sallum, Edoardo Marrani, Edoardo Conticini, Simone Appenzeller, Adina Kay Knight, Mazen Dimachkie, Tamima Mohamad Abou, Daren Gibson, Eva Kirkhus, Anneke J van der Koi, James B Lilleker, Matteo Lucchini, Pedro Machado, Mary Anne Riopel, Helga Sanner, Adam Schiffenbauer, Julio Brandao Guimaraes, Claudia Saad-Magalhaes, Susan O'Hanlon, Clarissa Harumi Omori, Susan Phaneuf, Helga Sanner, Siamak Moghadam-Kia, Mirkamal Tolend, Iazsmin Bauer Ventura, Lisa G Rider, Lisa Christopher-Stine, Julie J Paik, Brian Feldman, Samuel Katsuyuki Shinjo, Andrea Schwarz Doria
Background. Currently, there is lack of standardization of magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults among treatment centres across the globe. Therefore, we will perform scoping reviews of the literature to inform available semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs with the final goal of providing evidence-based information for the future development of a universal standardized MRI scoring system in specific research and clinical settings in this population. Methods. Electronic databases (PubMed, EMBASE, and Cochrane) will be searched to select relevant articles published from January 2000 to October 2023. Data will be synthesized narratively. Discussion. This scoping review will extensively map evidence on the indications, utility for diagnosis and assessment of disease activity and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for MRI assessment of skeletal muscle changes in patients with IIMs.
{"title":"A protocol for a scoping review on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies","authors":"Mickael Essouma, Daniel Brito de Araujo, Jessica Day, Latika Gupta, Adina Kay Knight, Ann Reed, Elie Naddaf, Adriana Maluf Elias Sallum, Edoardo Marrani, Edoardo Conticini, Simone Appenzeller, Adina Kay Knight, Mazen Dimachkie, Tamima Mohamad Abou, Daren Gibson, Eva Kirkhus, Anneke J van der Koi, James B Lilleker, Matteo Lucchini, Pedro Machado, Mary Anne Riopel, Helga Sanner, Adam Schiffenbauer, Julio Brandao Guimaraes, Claudia Saad-Magalhaes, Susan O'Hanlon, Clarissa Harumi Omori, Susan Phaneuf, Helga Sanner, Siamak Moghadam-Kia, Mirkamal Tolend, Iazsmin Bauer Ventura, Lisa G Rider, Lisa Christopher-Stine, Julie J Paik, Brian Feldman, Samuel Katsuyuki Shinjo, Andrea Schwarz Doria","doi":"10.1101/2024.03.26.24304925","DOIUrl":"https://doi.org/10.1101/2024.03.26.24304925","url":null,"abstract":"Background. Currently, there is lack of standardization of magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults among treatment centres across the globe. Therefore, we will perform scoping reviews of the literature to inform available semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs with the final goal of providing evidence-based information for the future development of a universal standardized MRI scoring system in specific research and clinical settings in this population.\u0000Methods. Electronic databases (PubMed, EMBASE, and Cochrane) will be searched to select relevant articles published from January 2000 to October 2023. Data will be synthesized narratively.\u0000Discussion. This scoping review will extensively map evidence on the indications, utility for diagnosis and assessment of disease activity and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for MRI assessment of skeletal muscle changes in patients with IIMs.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26DOI: 10.1101/2024.03.25.24304836
Josephine Yen Fang, Saravanan Ayyadurai, Alyssa F. Pybus, Hiroshi Sugimoto, Mark G. Qian
Fabry disease, an X-linked lysosomal storage disorder caused by galactosidase alpha (GLA) gene mutations, exhibits diverse clinical manifestations, and poses significant diagnostic challenges. Early diagnosis and treatment are crucial for improved patient outcomes, pressing the need for reliable biomarkers. In this study, we aimed to identify miRNA candidates as potential biomarkers for Fabry disease using the KingFisher™ automated isolation method and NanoString nCounter® miRNA detection assay. Clinical serum samples were collected from both healthy subjects and Fabry disease patients. RNA extraction from the samples was performed using the KingFisher™ automated isolation method with the MagMAX mirVanaTM kit or manually using the Qiagen miRNeasy kit. The subsequent NanoString nCounter® miRNA detection assay showed consistent performance and no correlation between RNA input concentration and raw count, ensuring reliable and reproducible results. Interestingly, the detection range and highly differential miRNA between the control and disease groups were found to be distinct depending on the isolation method employed. Nevertheless, enrichment analysis of miRNA-targeting genes consistently revealed significant associations with angiogenesis pathways in both isolation methods. Additionally, our investigation into the impact of enzyme replacement therapy on miRNA expression indicated that some differential miRNAs may be sensitive to treatment. Our study provides valuable insights to identify miRNA biomarkers for Fabry disease. While different isolation methods yielded various detection ranges and highly differential miRNAs, the consistent association with angiogenesis pathways suggests their significance in disease progression. These findings lay the groundwork for further investigations and validation studies, ultimately leading to the development of non-invasive and reliable biomarkers to aid in early diagnosis and treatment monitoring for Fabry disease.
{"title":"Exploring the Diagnostic Potential of miRNA Signatures in the Fabry Disease Serum: A Comparative Study of Automated and Manual Sample Isolations","authors":"Josephine Yen Fang, Saravanan Ayyadurai, Alyssa F. Pybus, Hiroshi Sugimoto, Mark G. Qian","doi":"10.1101/2024.03.25.24304836","DOIUrl":"https://doi.org/10.1101/2024.03.25.24304836","url":null,"abstract":"Fabry disease, an X-linked lysosomal storage disorder caused by galactosidase alpha (GLA) gene mutations, exhibits diverse clinical manifestations, and poses significant diagnostic challenges. Early diagnosis and treatment are crucial for improved patient outcomes, pressing the need for reliable biomarkers. In this study, we aimed to identify miRNA candidates as potential biomarkers for Fabry disease using the KingFisher™ automated isolation method and NanoString nCounter® miRNA detection assay. Clinical serum samples were collected from both healthy subjects and Fabry disease patients. RNA extraction from the samples was performed using the KingFisher™ automated isolation method with the MagMAX mirVanaTM kit or manually using the Qiagen miRNeasy kit. The subsequent NanoString nCounter® miRNA detection assay showed consistent performance and no correlation between RNA input concentration and raw count, ensuring reliable and reproducible results. Interestingly, the detection range and highly differential miRNA between the control and disease groups were found to be distinct depending on the isolation method employed. Nevertheless, enrichment analysis of miRNA-targeting genes consistently revealed significant associations with angiogenesis pathways in both isolation methods. Additionally, our investigation into the impact of enzyme replacement therapy on miRNA expression indicated that some differential miRNAs may be sensitive to treatment. Our study provides valuable insights to identify miRNA biomarkers for Fabry disease. While different isolation methods yielded various detection ranges and highly differential miRNAs, the consistent association with angiogenesis pathways suggests their significance in disease progression. These findings lay the groundwork for further investigations and validation studies, ultimately leading to the development of non-invasive and reliable biomarkers to aid in early diagnosis and treatment monitoring for Fabry disease.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140302643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26DOI: 10.1101/2024.03.25.24304643
Luis Miguel Pedraza-Meza, Ana Laura Hernandez-Ledesma, Alejandra E. Ruiz-Contreras, Alejandra Medina-Rivera, Domingo Martinez
Neurological and psychiatric manifestations affect most lupus individuals and include depression, anxiety, mood disorders, and cognitive dysfunction. Although there is evidence supporting suboptimal decision-making in lupus and its association with glucocorticoids consumption, it is not clear what variables impact such decisions. The aim of this study is to explore how social, clinical, psychological, and demographic factors impact social and temporal decision-making in people with lupus. Through a within-subjects experimental-design, our participants responded to social, clinical, psychological, and demographic electronic questionnaires. Then, they participated in two behavioral economics experiments: the third-party dictator game, and the delay discounting task. Our results show that hostility, and age are essential predictors of social decisions, whereas obsessive-compulsiveness and anxiety better predict temporal decisions. These variables behave as expected, but anxiety shows unexpected results: most anxious people act patiently and prefer delayed but bigger rewards. Finally, clinical factors are critical decision predictors for social and temporal decisions. When people are in remission, they tend to impose higher punishment on those who violate the social norm, and they also tend to prefer immediate rewards. When taking glucocorticoids, they also prefer immediate rewards, and as the dosage of glucocorticoids intake increases, they tend to impose higher punishment on norm violators. Clinicians, researchers, and practitioners must consider the side effects of glucocorticoids on decision-making.
{"title":"Clinical, psychosocial and demographic factors affect decisions in SLE people","authors":"Luis Miguel Pedraza-Meza, Ana Laura Hernandez-Ledesma, Alejandra E. Ruiz-Contreras, Alejandra Medina-Rivera, Domingo Martinez","doi":"10.1101/2024.03.25.24304643","DOIUrl":"https://doi.org/10.1101/2024.03.25.24304643","url":null,"abstract":"Neurological and psychiatric manifestations affect most lupus individuals and include depression, anxiety, mood disorders, and cognitive dysfunction. Although there is evidence supporting suboptimal decision-making in lupus and its association with glucocorticoids consumption, it is not clear what variables impact such decisions. The aim of this study is to explore how social, clinical, psychological, and demographic factors impact social and temporal decision-making in people with lupus. Through a within-subjects experimental-design, our participants responded to social, clinical, psychological, and demographic electronic questionnaires. Then, they participated in two behavioral economics experiments: the third-party dictator game, and the delay discounting task. Our results show that hostility, and age are essential predictors of social decisions, whereas obsessive-compulsiveness and anxiety better predict temporal decisions. These variables behave as expected, but anxiety shows unexpected results: most anxious people act patiently and prefer delayed but bigger rewards. Finally, clinical factors are critical decision predictors for social and temporal decisions. When people are in remission, they tend to impose higher punishment on those who violate the social norm, and they also tend to prefer immediate rewards. When taking glucocorticoids, they also prefer immediate rewards, and as the dosage of glucocorticoids intake increases, they tend to impose higher punishment on norm violators. Clinicians, researchers, and practitioners must consider the side effects of glucocorticoids on decision-making.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140302917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.1101/2024.03.19.24304536
Jie Zhang, Xinyu Fang, Jingwei Wu, Zixing Zhang, Min Mu, Dongqing Ye
Genomics-driven drug discovery holds significant promise in identifying and developing novel therapeutic targets. Here, we utilized large-scale genomic data including genome-wide association studies (GWAS), rare variant burden tests in exome sequencing studies (Exome), and protein quantitative trait loci (pQTL), to prioritize therapeutic targets or repurpose drugs in rheumatoid arthritis (RA). We found that prioritized genes covering two approved RA treatment targets (IL6R and CD86), along with several targets currently undergoing active clinical trials for RA. Fifteen proteins were identified as having causalities with RA risk, and three out of them showed strong support for colocalization. BRD2 was nominated as one of the most promising candidates for clinical translation as its wide expression in joint synovial tissues and validation in observational analyses associating with RA incidence. Collectively, our systematic prioritization of drug targets from different genetically informed approaches, and provided a comprehensive insight into therapeutic strategies for RA.
基因组学驱动的药物发现在确定和开发新型治疗靶点方面大有可为。在这里，我们利用大规模基因组数据，包括全基因组关联研究（GWAS）、外显子组测序研究（Exome）中的罕见变异负荷测试和蛋白质定量性状位点（pQTL），来确定类风湿关节炎（RA）治疗靶点的优先顺序或药物的再利用。我们发现，被优先考虑的基因涵盖了两个已获批准的类风湿关节炎治疗靶点（IL6R 和 CD86），以及几个目前正在积极进行类风湿关节炎临床试验的靶点。有 15 个蛋白质被确定为与 RA 风险有因果关系，其中有 3 个蛋白质显示出强烈的共定位支持。BRD2在关节滑膜组织中广泛表达，并在与RA发病率相关的观察分析中得到验证，因此被提名为最有希望进行临床转化的候选蛋白之一。总之，我们从不同的基因信息方法中对药物靶点进行了系统的优先排序，并对 RA 的治疗策略提供了全面的见解。
{"title":"Identifying therapeutic targets for rheumatoid arthritis by genomics-driven integrative approaches","authors":"Jie Zhang, Xinyu Fang, Jingwei Wu, Zixing Zhang, Min Mu, Dongqing Ye","doi":"10.1101/2024.03.19.24304536","DOIUrl":"https://doi.org/10.1101/2024.03.19.24304536","url":null,"abstract":"Genomics-driven drug discovery holds significant promise in identifying and developing novel therapeutic targets. Here, we utilized large-scale genomic data including genome-wide association studies (GWAS), rare variant burden tests in exome sequencing studies (Exome), and protein quantitative trait loci (pQTL), to prioritize therapeutic targets or repurpose drugs in rheumatoid arthritis (RA). We found that prioritized genes covering two approved RA treatment targets (IL6R and CD86), along with several targets currently undergoing active clinical trials for RA. Fifteen proteins were identified as having causalities with RA risk, and three out of them showed strong support for colocalization. BRD2 was nominated as one of the most promising candidates for clinical translation as its wide expression in joint synovial tissues and validation in observational analyses associating with RA incidence. Collectively, our systematic prioritization of drug targets from different genetically informed approaches, and provided a comprehensive insight into therapeutic strategies for RA.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"276 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140205606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-19DOI: 10.1101/2024.03.18.24304149
Lennart Seizer, Johanna Gostner, Christoph Garbers, Melina Licht, Sebastian Sager, Christian Schubert
Rheumatoid arthritis (RA) is a chronic autoimmune disease of widely unknown etiology and pathophysiology. In this integrative single-case study on a patient with RA, we had the unique opportunity to closely monitor the individual dynamics of endocrine, immune and disease variables during a naturally occurring flare-up and subsequent medication change. The female RA patient collected her entire urine over 30 days in 12-h intervals (60 consecutive measurements in total). Subsequently, interleukin-6 (IL-6), orosomucoid-2, cortisol (ELISA), neopterin and creatinine (HPLC) levels were determined in the urine samples. Further, each morning and evening, the patient completed the DIARI, a set of questionnaires on variables such as subjective pain, subjective RA disease activity and emotional states. Once a week, besides an online video interview, the patient had an appointment at her rheumatologist, in which several indices of RA disease activity were determined: SDAI, CDAI and DAS28. From these data various time series were constructed for statistical analysis. RA disease state increased from low to high activity during the first 12 study days. Thereupon, the medication was changed, which proved effective in reducing RA disease activity. However, the levels of urinary neopterin, urinary orosomucoid-2 and urinary IL-6 did not show any response, neither to the increasing disease activity nor the medication change. The patient's daily reports on pain, RA disease activity and emotional states, however, mirrored the course of the rheumatologic indices. For the patient studied, urinary neopterin, urinary orosomucoid-2 and urinary IL-6 levels did not represent adequate biomarkers of short-term variations in RA disease activity. Patient-reported outcomes on the other hand might be a useful tool in the ambulatory and longitudinal monitoring of RA.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，其病因和病理生理学广为人知。在这项针对一名类风湿关节炎患者的单病例综合研究中，我们获得了一个独特的机会，可以在自然发作和随后换药期间密切监测内分泌、免疫和疾病变量的个体动态变化。这名女性 RA 患者在 30 天内以 12 小时为间隔收集了全部尿液（共连续测量 60 次）。随后，测定了尿样中的白细胞介素-6（IL-6）、类橙皮甙-2、皮质醇（ELISA）、新蝶呤和肌酐（HPLC）水平。此外，患者每天早晚都要填写 DIARI 问卷，这是一套关于主观疼痛、主观 RA 疾病活动和情绪状态等变量的问卷。除了在线视频访谈外，患者每周还去看一次风湿免疫科医生，医生会在访谈中确定几种 RA 疾病活动指数：SDAI、CDAI 和 DAS28。根据这些数据构建了各种时间序列，用于统计分析。在最初的 12 天研究中，RA 的疾病状态从低活动度上升到高活动度。随后，医生更换了药物，事实证明这有效降低了 RA 的疾病活动度。然而，尿液中的蝶呤、尿液中的类橙皮苷-2 和尿液中的 IL-6 水平并未显示出任何反应，无论是对疾病活动度的增加还是药物的改变都是如此。然而，患者每天关于疼痛、RA 疾病活动和情绪状态的报告反映了风湿病学指标的变化过程。对于所研究的患者来说，尿蝶呤、尿卵清蛋白-2 和尿 IL-6 水平并不能充分反映 RA 疾病活动的短期变化。另一方面，患者报告的结果可能是对 RA 进行动态和纵向监测的有用工具。
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Pub Date : 2024-03-19DOI: 10.1101/2024.03.18.24304464
CLAUDIA DINIZ LOPES MARQUES, Marcelo Pinheiro, Jeniffer Lopes, Sandra Lucia Euzebio Ribeiro, Mary Vania Marinho Castro, Lilian David de Azevedo Valadares, Aline Ranzolin, Nicole Pamplona Bueno de Andrada, Rafaela Cavalheiro do Espirito Santo, Nafice Costa Araujo, Cintya Martins Vieira, Valeria Valim, Flavia Santos, Laurindo Ferreira da Rocha Junior, Adriana Maria Kakehasi, Ana Paula Monteiro Gomides Reis, Edgard Torres Neto, Gecilmara Pilegii, Gilda Aparecida Ferreira, Licia Mota, Odirlei Monticielo, Ricardo Machado Xavier
Objectives: To compare the impact of COVID-19 on clinical status and psychological condition in patients with immune-mediated rheumatic diseases (IMRD) infected by SARS-CoV-2 with IMRD controls not infected, during a 6-month follow-up. Methods: The ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. The FACIT-F (Functional Assessment of Chronic Illness Therapy) and DASS 21 (Depression, Anxiety and Stress Scale - 21 Items) questionnaires were also applied at 6 months after COVID-19 in both groups before large-scale vaccination. The significance level was set as p<0.05, with a 95% confidence interval. Results: A total of 601 patients were evaluated, being 321 cases (IMRD COVID-19+) and 280 controls (IMRD COVID-19 -), predominantly female with similar median age. No significant differences were noted in demographic data between the groups, including comorbidities, disease duration, and IMRD. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. While mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR=7.15), while TNF inhibitors showed a protective effect (OR=0.51). Comparing SLEDAI pre- and post-COVID-19, a minority showed increased scores, with few requiring treatment changes. Fatigue, depression, anxiety, and stress were significantly higher in cases compared to controls. Worsening disease activity post-COVID correlated with worsened FACIT-F and DASS-21 stress scale in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity or psychological assessments. Conclusions: Post-COVID-19 IMRD patients show significant psychological well-being deterioration despite similar disease activity scores. The variability in reports on IMRD flares and the potential trigger of SARS-CoV-2 for autoimmune manifestations underline the need for detailed clinical assessment and a comprehensive approach to managing them.
{"title":"COVID-19 Impact on Patients with Immune-Mediated Rheumatic Disease: A Comparative Study of Disease Activity and Psychological Well-Being Over Six Months","authors":"CLAUDIA DINIZ LOPES MARQUES, Marcelo Pinheiro, Jeniffer Lopes, Sandra Lucia Euzebio Ribeiro, Mary Vania Marinho Castro, Lilian David de Azevedo Valadares, Aline Ranzolin, Nicole Pamplona Bueno de Andrada, Rafaela Cavalheiro do Espirito Santo, Nafice Costa Araujo, Cintya Martins Vieira, Valeria Valim, Flavia Santos, Laurindo Ferreira da Rocha Junior, Adriana Maria Kakehasi, Ana Paula Monteiro Gomides Reis, Edgard Torres Neto, Gecilmara Pilegii, Gilda Aparecida Ferreira, Licia Mota, Odirlei Monticielo, Ricardo Machado Xavier","doi":"10.1101/2024.03.18.24304464","DOIUrl":"https://doi.org/10.1101/2024.03.18.24304464","url":null,"abstract":"Objectives: To compare the impact of COVID-19 on clinical status and psychological condition in patients with immune-mediated rheumatic diseases (IMRD) infected by SARS-CoV-2 with IMRD controls not infected, during a 6-month follow-up.\u0000Methods: The ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. The FACIT-F (Functional Assessment of Chronic Illness Therapy) and DASS 21 (Depression, Anxiety and Stress Scale - 21 Items) questionnaires were also applied at 6 months after COVID-19 in both groups before large-scale vaccination. The significance level was set as p<0.05, with a 95% confidence interval.\u0000Results: A total of 601 patients were evaluated, being 321 cases (IMRD COVID-19+) and 280 controls (IMRD COVID-19 -), predominantly female with similar median age. No significant differences were noted in demographic data between the groups, including comorbidities, disease duration, and IMRD. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. While mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR=7.15), while TNF inhibitors showed a protective effect (OR=0.51). Comparing SLEDAI pre- and post-COVID-19, a minority showed increased scores, with few requiring treatment changes. Fatigue, depression, anxiety, and stress were significantly higher in cases compared to controls. Worsening disease activity post-COVID correlated with worsened FACIT-F and DASS-21 stress scale in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity or psychological assessments. Conclusions: Post-COVID-19 IMRD patients show significant psychological well-being deterioration despite similar disease activity scores. The variability in reports on IMRD flares and the potential trigger of SARS-CoV-2 for autoimmune manifestations underline the need for detailed clinical assessment and a comprehensive approach to managing them.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140168066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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