tbuckley/cabot-search huggingface dataset:
Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis
Authors: Shi-Cong Tao, Ji-Yan Huang, Yuan Gao, Zi-Xiang Li, Zhan-Ying Wei, Helen Dawes, Shang-Chun Guo
Journal: Bioactive Materials (2021)

Osteoarthritis (OA), characterized by chondrocyte apoptosis and disturbance of the balance between catabolism and anabolism of the extracellular matrix (ECM), is the most common age-related degenerative joint disease worldwide. As sleep has been found to be beneficial for cartilage repair, and circular RNAs (circRNAs) have been demonstrated to be involved in the pathogenesis of OA, we performed RNA sequencing (RNA-seq), and found circRNA3503 was significantly increased after melatonin (MT)-induced cell sleep. Upregulation of circRNA3503 expression completely rescued the effects of interleukin-1β (IL-1β), which was used to simulate OA, on apoptosis, ECM degradation- and synthesis-related genes. Mechanistically, circRNA3503 acted as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p. Moreover, as we previously showed that small extracellular vesicles (sEVs) derived from synovium mesenchymal stem cells (SMSCs) can not only successfully deliver nucleic acids to chondrocytes, but also effectively promote chondrocyte proliferation and migration, we assessed the feasibility of sEVs in combination with sleep-related circRNA3503 as an OA therapy. We successfully produced and isolated circRNA3503-loaded sEVs (circRNA3503-OE-sEVs) from SMSCs. Then, poly(D,l-lactide)-b-poly(ethylene glycol)-b-poly(D,l-lactide) (PDLLA-PEG-PDLLA, PLEL) triblock copolymer gels were used as carriers of sEVs. Through in vivo and in vitro experiments, PLEL@circRNA3503-OE-sEVs were shown to be a highly-effective therapeutic strategy to prevent OA progression. Through multiple pathways, circRNA3503-OE-sEVs alleviated inflammation-induced apoptosis and the imbalance between ECM synthesis and ECM degradation by acting as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p. In addition, circRNA3503-OE-sEVs promoted chondrocyte renewal to alleviate the progressive loss of chondrocytes. Our results highlight the potential of PLEL@circRNA3503-OE-sEVs for preventing OA progression.
AB0063 DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: A BIOMARKER SCREENING PILOT STUDY
Authors: J. Baloun, A. Pekacova, H. Mann, J. Vencovský, K. Pavelka, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2021)

Background: Despite modern therapeutic approaches, many patients with rheumatoid arthritis (RA) remain symptomatic after several cycles of treatment and may become so called Difficult-To-Treat (D2T)1. D2T RA is a multifactorial condition in which different factors may be major determinants of the persistence of signs and symptoms, which is seldom caused by drug resistance only2. Discovering new biomarkers is necessary to develop tailored therapies that will be effective in an individual patient at each stage of the disease. Objectives: The primary aim of this pilot study was to validate a target proteomic technique for the proteome profiling of the two cohorts of RA patients and controls. Moreover, we searched for potential plasma biomarker(s) predicting D2T RA. Methods: Seven RA patients with persistent remission on biological therapy in two consecutive examinations 12 wks apart (mean age 59.6±14 yrs), seven D2T RA patients fulfilling proposed EULAR definition of D2T RA1 (mean age 59.3±13 yrs), and six healthy controls (mean age 58.8±15 yrs) were included in this study. All subjects were females and their samples were collected before starting biological therapy. We employed Thermo Orbitrap Fusion paired with nano-flow UHPLC Dionex Ultimate 3000. Prior to quantification, 125 plasma proteins were modified by Peptiquant Plus Human kit to increase the sensitivity. Data were analysed by ANOVA and Tukey`s posthoc test with false-discovery-rate adjustment. Results: The target proteome profiling reliably quantified 92 from 125 labelled proteins. Our follow-up statistical analysis revealed ten plasma proteins, which significantly differed among groups. Notably, we found significantly different plasma levels of paraoxonase/arylesterase 1 (PON1), an esterase with an antioxidant characteristic preventing lipid peroxidation 3 , between RA patients and controls and between RA patients with persistent remission and D2T RA patients. Conclusion: Using target proteome profiling technique, we demonstrated PON1 as a potential biomarker of D2T RA. However, these results have to be validated on a larger cohort. References: [1]Nagy G, Roodenrijs NMT, Welsing PMJ, et al. EULAR definition of difficult-To-Treat rheumatoid arthritis. Annals of the Rheumatic Diseases 2021;80:31-5. [2]de Hair MJH, Jacobs JWG, Schoneveld JLM, van Laar JM. Difficult-to-treat rheumatoid arthritis: an area of unmet clinical need. Rheumatology (Oxford, England) 2018 Jul 1;57(7):1135-1144. [3]Isik A, Koca SS, Ustundag B, Celik H, Yildirim A. Paraoxonase and arylesterase levels in rheumatoid arthritis. Clinical Rheumatology 2007;26:342-8. Acknowledgements: This research was supported by MHCR No. 023728 and authors thank Proteomics Service Laboratory, Faculty of Science, Charles University for performing the LC–MS/MS analysis. Disclosure of Interests: None declared
Abstract 12098: Pharmaco-omics of Clopidogrel Response in African Americans- An African-American Cardiovascular Pharmacogenetic CONsorTium Study
Authors: Tanima De, Cristina Alarcon, Layan Nahlawi, Juan Avitia, Bianca Lec, Mohammed Shaazuddin, Mohammed Nooruddin, Diana Moreno, Myurani Sathyanarayanan, Edith Nutescu, April Barbour, Jeff Banagan, Olivia Gordon, Tharani Jeyaram, Mary Harris, Sarah Bradbury, Ramesh Subrahmanyam, Matthew Tuck, Arthur Harralson, Paula Friedman, David Meltzer, Travis O’Brien, Minoli A Perera
Journal: Circulation (2019)

Introduction: Clopidogrel therapy is associated with substantial inter-patient differences in response. African Americans (AAs) are disproportionately affected by death and disability from cardiova...
3D‐Printed Hydrogel‐Filled Microneedle Arrays
Authors: Lindsay Barnum, Jacob Quint, Hossein Derakhshandeh, Mohamadmahdi Samandari, Fariba Aghabaglou, Ali Farzin, Laleh Abbasi, Sidi Bencherif, Adnan Memic, Pooria Mostafalu, Ali Tamayol
Journal: Advanced Healthcare Materials (2021)

Microneedle arrays (MNAs) have been used for decades to deliver drugs transdermally and avoid the obstacles of other delivery routes. Hydrogels are another popular method for delivering therapeutics because they provide tunable, controlled release of their encapsulated payload. However, hydrogels are not strong or stiff, and cannot be formed into constructs that penetrate the skin. Accordingly, it has so far been impossible to combine the transdermal delivery route provided by MNAs with the therapeutic encapsulation potential of hydrogels. To address this challenge, a low cost and simple, but robust, strategy employing MNAs is developed. These MNAs are formed from a rigid outer layer, 3D printed onto a conformal backing, and filled with drug-eluting hydrogels. Microneedles of different lengths are fabricated on a single patch, facilitating the delivery of various agents to different tissue depths. In addition to spatial distribution, temporal release kinetics can be controlled by changing the hydrogel composition or the needles' geometry. As a proof-of-concept, MNAs are used for the delivery of vascular endothelial growth factor (VEGF). Application of the rigid, resin-based outer layer allows the use of hydrogels regardless of their mechanical properties and makes these multicomponent MNAs suitable for a range of drug delivery applications.
Meningococcal Serogroup ACWYX Conjugate Vaccine in Malian Toddlers
Authors: Milagritos D. Tapia, Samba O. Sow, Abdi Naficy, Fatoumata Diallo, Fadima C. Haidara, Amol Chaudhari, Lionel Martellet, Awa Traore, Kelly Townsend-Payne, Ray Borrow, Nancy Hosken, Igor Smolenov, Sambhaji S. Pisal, F. Marc LaForce, Rajeev M. Dhere, Dhananjay Kapse, Yuxiao Tang, Mark R. Alderson, Prasad S. Kulkarni
Journal: New England Journal of Medicine (2021)

Neisseria meningitidis serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development.
Predictors of death and new disability after critical illness: a multicentre prospective cohort study
Authors: A. M. Higgins, A. Serpa Neto, M. Bailey, J. Barrett, R. Bellomo, D. J. Cooper, B. J. Gabbe, N. Linke, P. S. Myles, M. Paton, S. Philpot, M. Shulman, M. Young, C. L. Hodgson
Journal: Intensive Care Medicine (2021)
AB0121 DOES CIGARETTE SMOKING INFLUENCE DISEASE ACTIVITY IN SEROPOSITIVE (ACPA POSITIVE) PATIENTS WITH EARLY RHEUMATOID ARTHRITIS?
Authors: N. Papadopoulos, N. Koletsos, D. Pantelidis, L. Mentesidou, V. Galanopoulou
Journal: Annals of the Rheumatic Diseases (2021)

Background: Many studies revealed that cigarette smoking is correlated with more active and severe Rheumatoid Arthritis (RA), mainly through the presence of positive RF or ACPA [1]. Objectives: To investigate the influence of cigarette smoking, in disease activity, in a cohort of Greek patients with ACPA positive early RA. Methods: From January 2000 until December 2019, 137 patients with seropositive early RA (disease duration ≤ 3 months), and under the age of 75 years old, were diagnosed and subsequently were followed-up as outpatients in Rheumatology Unit of our hospital. All of them were treated by the same therapeutic protocol, were followed-up every 3 months and had at least one visit during 2019. Demographic, therapeutic, clinical and laboratory parameters were evaluated at the time of diagnosis and in every follow-up. At the end of the study we re-evaluated the above parameters, dividing patients in smokers and non smokers. Analysis were performed using Student’s t-test and non-parametric Mann-Whitney was used to estimate differences between mean values. Pearson’s and Spearman’s correlations were used, based on the variable’s normality of distribution with the “Enter” method was used to identify the statistically significant predicting factors of DAS28/associations with DAS28. Results: Mean age of our cohort were 57±10.2 years and 76.6% were females. From 137 patients 55 were current smokers. Univariable analysis at the time of diagnosis revealed, that current smokers presented with more tender (p&lt;0.001), more swollen joints (p&lt;0.001) and higher levels of CRP (p&lt;0.001). Also current smokers presented with higher disease activity measuring by DAS-28 4v, than non smokers (6.2±1.0 vs 5.6±0.9 respective, p&lt;0.001). At the end of the study there were not found differences between the two groups. Multivariable analysis revealed that high DAS-28 was correlated with the intensity of smoking (p=0.049). Concerning the presence of extra-articular manifestations, smokers were presented more often with rheumatoid nodes (p=0.026). Conclusion: Current smokers presented with more active disease at the time of diagnosis and have more often rheumatoid nodes. After the establishment of treatment there were no differences in disease activity between smokers and non smokers. References: [1]Papadopoulos NG et al, Clin Exp Rheum 2005;23:861-66. Disclosure of Interests: None declared
Is There a Place for Chimeric Antigen Receptor–T Cells in the Treatment of Chronic Autoimmune Rheumatic Diseases?
Authors: Cindy Orvain, Morgane Boulch, Philippe Bousso, Yannick Allanore, Jérôme Avouac
Journal: Arthritis & Rheumatology (2021)

Chimeric antigen receptor-T (CAR-T) cell therapy is based on specific targeting of tumor antigens, leading to lysis and destruction of tumor cells. The high potency of CAR-T cells in the management of B cell malignancies has been demonstrated. Following the success of this therapeutic strategy, new CAR-T cell-derived constructs that have the ability to eradicate pathogenic B cells or restore tolerance have been developed. The present review discusses how the knowledge and technology generated by the use of CAR-T cells may be translated and integrated into ongoing therapeutic strategies for autoimmune rheumatic diseases. To this end, we describe the details of CAR-T cell technology, as well as the meaningful achievements attained with the use of CAR-T cells in onco-hematology. In addition, we review the preliminary data obtained with CAR-T cells and their derivative constructs in experimental models of autoimmune diseases. Finally, we focus on how CAR-T cell engineering interferes with the pathogenesis of 3 chronic autoimmune rheumatic diseases-rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis-and discuss whether these constructs might yield greater efficacy and be associated with fewer adverse events compared to current treatment strategies.
Axillary Glomus Tumor Revealed by FDG PET/CT
Authors: Guohua Shen, Rang Wang, Lili Pan, Anren Kuang
Journal: Clinical Nuclear Medicine (2021)

Glomus tumors are vascular neoplasms arising from glomus bodies. They are typically found in tissues where glomus bodies are concentrated, including the subungual layer of the fingers or the deep dermis of the palm, wrist, forearm, and foot but rarely occur in the axillary region. Herein, we reported the MRI and FDG PET/CT findings of a glomus tumor presenting as an axillary mass in a 25-year-old woman.
Trends in the Use of Conventional and New Pharmaceuticals for Hemophilia Treatments Among Medicaid Enrollees, 2005-2020
Authors: Inmaculada Hernandez, Deanna Rowe, Walid F Gellad, Chester B. Good
Journal: JAMA Network Open (2021)

the use of each pharmaceutical.The unavailability of discount data prevented us from estimating net spending on hemophilia pharmaceuticals.Our findings are relevant to state Medicaid budgets, particularly because state agencies face coverage decisions after the expected approval of multiple gene therapies for hemophilia in the next decade.These gene therapies, which will cost between $2 to $3 million per patient, 2 have the potential to decrease requirements for factor replacement dramatically. 5
Association of New Perioperative Benzodiazepine Use With Persistent Benzodiazepine Use
Authors: Jason D. Wright, Jacob C. Cogan, Yongmei Huang, Ana I. Tergas, Caryn M. St. Clair, June Y. Hou, Fady Khoury-Collado, Allison Gockley, Melissa Accordino, Alexander Melamed, Dawn L. Hershman
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Increased use of benzodiazepines has resulted in increasing rates of misuse and adverse effects associated with these drugs. Little is known about the initial exposure and source of benzodiazepines among those who use them persistently. <h3>Objective</h3> To examine the frequency of use and persistent use of benzodiazepines among patients undergoing major and minor surgical procedures. <h3>Design, Setting, and Participants</h3> This cohort study included 2 509 599 adult patients who underwent 1 of 11 common surgical procedures in the United States from 2009 to 2017 and were recorded in the MarketScan database. The rates of perioperative and persistent benzodiazepine use were examined in benzodiazepine-naive patients. Data analysis was conducted from July to November 2020. <h3>Main Outcomes and Measures</h3> Receipt of a perioperative benzodiazepine prescription and persistent use (ie, fill of a second prescription 90-180 days after surgery) among those who received a benzodiazepine perioperatively. <h3>Results</h3> Among 2 509 599 included patients, the mean (SD) age was 54.4 (15.3) years, and 1 596 137 (63.6%) were women. Perioperative benzodiazepine use was noted in 63 931 patients (2.6%). The median (interquartile range) benzodiazepine supply was 10 (5-23) days. Among benzodiazepine-naive patients prescribed a perioperative benzodiazepine, the rate of persistent benzodiazepine use was 19.5% (95% CI, 19.2%-19.8%). During the 90 to 180–day period after surgery, 7013 of 12 468 patients (56.2%) received 1 prescription for benzodiazepines while 5455 (43.8%) received 2 or more prescriptions. Among patients prescribed a benzodiazepine, persistent use was more common in Medicaid recipients (vs patients with commercial insurance: adjusted rate ratio [aRR], 1.29; 95% CI, 1.03-1.62), patients 70 years or older (vs those aged 40-49 years: aRR, 1.14; 95% CI, 1.05-1.23), in women (vs men: aRR, 1.10; 95% CI, 1.06-1.15), in patients with more medical comorbidities (eg, Elixhauser comorbidity score ≥3 vs 0: aRR, 1.11; 95% CI, 1.04-1.19), and in those with diagnoses of anxiety, depression, insomnia or substance use disorder (eg, with vs without anxiety: aRR, 1.43; 95% CI, 1.37-1.50). <h3>Conclusions and Relevance</h3> In this study, a relatively small percentage of surgical patients were prescribed benzodiazepines in the perioperative period; however, 1 in 5 of these patients went on to persistent benzodiazepine use.
POS0567 HEPCIDIN IS POTENTIAL BIOMARKER TO DISTINGUISH BETWEEN IRON DEFICIENCY ANEMIA AND ANEMIA OF INFLAMMATION IN RHEUMATOID ARTHRITIS
Authors: E. Galushko, A. Semashko, A. Gordeev, A. Lila
Journal: Annals of the Rheumatic Diseases (2021)

Background: Anemia of inflammation (AI) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia in patients with rheumatoid arthritis (RA). Diagnosis becomes challenging if AI is associated with true ID (AI/ID), as there is still a lack of a gold standard for differentiation between AI and AI/ID. However, as therapies to overcome anemia differ, proper diagnosis and understanding of underlying pathophysiological regulations are necessary. Objectives: The aim of the study was to evaluate the clinical efficiency of hepcidin, a key regulator of iron metabolism, in the diagnosis of IDA, as well as the differential diagnosis of AI/ID and AI in patients with RA. Methods: The study was undertaken 96 patients with RA, 67 of them were diagnosed anemia according to WHO criteria (104,3±21,4 g/l). Anemic patients and anemia-free patients with RA (n=29) were comparable (p&gt;0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9). All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. Patients with RA and anemia were divided two groups: 25 patients with IDA and 42 - with AI. The AI cases were subdivided into pure AI and AI with coexistent ID (n=15). Results: The mean serum hepcidin concentration was significantly increased in pure AI patients (123.85±25.8 ng/mL) as compared to those in IDA patients (63.9±22.8 ng/mL, P &lt; 0.05) and anemia-free patients with RA (88.1±39.09 ng/mL). Also, compared to pure AI patients [normal sTfR levels (&lt;3 µg/mL)], the serum hepcidin concentration was reduced significantly in AI patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 79.0±23.97 ng/mL. Conclusion: Hepcidin measurement can provide a useful tool for differentiating AI from IDA and also help to identify an iron deficiency in AI patients. This might aid in the appropriate selection of therapy for these patients. Disclosure of Interests: None declared
Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype
Authors: Yaomin Li, Xiran Wang, Songtao Qi, Lei Gao, Guanglong Huang, Zhonglu Ren, Kaishu Li, Yuping Peng, Guozhong Yi, Jinglin Guo, Runwei Yang, Hai Wang, Xian Zhang, Yawei Liu
Journal: Neuro-Oncology (2021)

The glioblastoma (GBM) mesenchymal (MES) phenotype, induced by NF-κB activation, is characterized by aggressive tumor progression and poor clinical outcomes. Our previous analysis indicated that MES GBM has a unique alternative splicing (AS) pattern; however, the underlying mechanism remains obscure. We aimed to reveal how splicing regulation contributes to MES phenotype promotion in GBM.We screened novel candidate splicing factors that participate in NF-κB activation and MES phenotype promotion in GBM. In vitro and in vivo assays were used to explore the function of RSRP1 in MES GBM.Here, we identified that arginine/serine-rich protein 1 (RSRP1) promotes the MES phenotype by facilitating GBM cell invasion and apoptosis resistance. Proteomic, transcriptomic, and functional analyses confirmed that RSRP1 regulates AS in MES GBM through mediating spliceosome assembly. One RSRP1-regulated AS event resulted in skipping PARP6 exon 18 to form truncated, oncogenic PARP6-s. This isoform was unable to effectively suppress NF-κB. Cotreatment of cultured GBM cells and GBM tumor-bearing mice with spliceosome and NF-κB inhibitors exerted a synergistic effect on MES GBM growth.We identified a novel mechanism through which RSRP1-dependent splicing promotes the GBM MES phenotype. Targeting AS via RSRP1-related spliceosomal factors might constitute a promising treatment for GBM.
AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS
Authors: S. Ahmed, E. Nikiphorou, J. Bayliss
Journal: Annals of the Rheumatic Diseases (2021)

Background: The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt. Objectives: To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA. Methods: A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer. Results: Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further. Conclusion: This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA. Disclosure of Interests: None declared