tbuckley/cabot-search huggingface dataset:
AB0148 ANALYSIS OF DIFFERENTIALLY EXPRESSED GENES AND MICRORNAS OF B CELLS IN PRIMARY SJOGREN’S SYNDROME BY RNA SEQUENCING
Authors: H. Zhang, H. Zhang, D. Gao, F. Zhang, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Primary Sjogren’s syndrome (pSS) is a chronic autimmune disease mainly characterized by the inflammation of exocrine glands. There two key insights into pSS pathogenesis, which included “IFN signature” and hyperactivity of B cells. mRNA and microRNA (miRNA) are very important to control the gene expression. Objectives: In this research, we analyzed the differentially expressed genes (DEG) and miRNA of B cells in pSS patients by RNA-sequencing. And we aim to preliminarily screen out some special miRNAs and target gene loci that may be involved in transcription regulation of B cells of pSS. Methods: Peripheral blood samples from 3 pSS patients and 3 age-matched healthy controls (HC) were collected. CD19 + B cells were sorted by Magnetic cell sorting method. Total RNA was extracted and cDNA of transcriptome or miRNA analysis were prepared and RNA-sequencing was performed to screen the DEG and miRNA. The GO Terms was used to uncover the biological function of DEGs, and the KEGG pathway enrichment was used to find out the related signal pathway. The mRNA-miRNA conjoint analysis was also performed. Results: There were a total of 73 significantly DEGs in B cells of pSS patients compared to HC, including 51 upregulated DEGs (such as IFI44L , IFI44 , IFIT1 , IFITM1 , IFIT3 , IFIT2 , IRF7 , IFI6 and ISG15 )and 22 downregulated DEGs (such as ESR2 and EGR1 ). GO Terms and KEGG pathway analyses showed that most of the upregulated DEGs were enriched in IFN signaling and IFN regulatory pathway, and also showed the relationship with microbial infection, such as influenza A virus, hepatitis C virus, measles and herpes simplex virus. There were five significantly differentially expressed miRNAs, including hsa-miR-4485-3p, hsa-miR-144-5p, hsa-miR-144-3p, hsa-miR-451a, hsa-miR-4732-3p. GO Terms and KEGG pathway analyses showed that most of the target genes which regulated by those miRNAs were enrichment on herpes simplex virus and TGF-β signaling pathway. DEG and differentially expressed miRNAs conjoint analysis showed that the target DEGs which regulated by those miRNAs participated in cytoskeleton formation and modification of DNA or RNA, such as RASD2 , CKAP4 , SPARS2L METTL . Conclusion: There were 51 upregulated DEGs and 22 downregulated DEGs in B cells of pSS patients. GO Terms and KEGG pathway analyses showed that most of the upregulated DEGs were enriched in IFN related signaling pathway, and also showed the significant relationship with microbial infection. Conjoint analysis showed that the target DEGs which regulated by differentially expressed miRNAs participated in cytoskeleton formation and modification of DNA or RNA. There maybe more than one regulatory methods lead to DEGs in B cells of pSS patients. Disclosure of Interests: None declared
Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins
Authors: Quan D. Zhou, Xun Chi, Min Sub Lee, Wei Yuan Hsieh, Jonathan J. Mkrtchyan, An-Chieh Feng, Cuiwen He, Autumn G. York, Viet L. Bui, Eliza B. Kronenberger, Alessandra Ferrari, Xu Xiao, Allison E. Daly, Elizabeth J. Tarling, Robert Damoiseaux, Philip O. Scumpia, Stephen T. Smale, Kevin J. Williams, Peter Tontonoz, Steven J. Bensinger
Journal: Nature Immunology (2020)
Erik Waaler (1903–1997): one of the founders of rheumatological immunology who discovered rheumatoid factor
Authors: Roland Jonsson
Journal: Annals of the Rheumatic Diseases (2020)

Erik Waaler was born at Hamar, Norway on 22 February 1903 and died in Bergen on 3 March 1997 (figure 1). He graduated from the Medical Faculty, University of Oslo, in 1927. Thereafter, he spent some time as intern at Hamar Hospital, as well as general practitioner. Waaler started his scientific career in 1930 at the Army Laboratory for Bacteriology in Oslo. There he got training in bacteriology and carried out the studies which led to his doctoral dissertation, ‘On the Dissociation of the Dysentry Bacillus’, with creation as Doctor Medicinae in 1935. In the mean time, he worked as resident in internal medicine for 2 years at Aker’s Hospital and the University Hospital in Oslo, Rikshopitalet. In 1936, he obtained a university scholarship in clinical bacteriology, and he spent part of that time at Columbia University in New York.



Figure 1 
Portrait of Erik Waaler.



Probably the most exciting moment in Waaler’s academic life took place in 1937 when he was working at Ulleval Hospital, Department of Pathology in …
Idelalisib Interferes with the Crosstalk of Follicular Lymphoma and Its Immune Microenvironment and Potentiates the Activity of ABT-199
Authors: Martina Guerrero-Hernandez, Alba Matas-Cespedes, Neus Serrat, Anella Yahiaoui, Juan G Valero, Laura Magnano, Alfredo Rivas-Delgado, Dolors Colomer, Elias Campo, Armando Lopez-Guillermo, Gael Roue, Stacey Tannheimer, Patricia Pérez-Galán
Journal: Blood (2017)
THU0017 Chloroquine resistance in human cem (t) cells is mediated by multidrug resistance protein 1
Authors: G Jansen, RJ Scheper, B Dijkmans
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Drug resistance may play a role in the lack of efficacy of Disease Modifying Anti Rheumatic Drugs (DMARDs). <h3>Objectives</h3> (1) Delineate mechanism of drug resistance to chloroquine (CHQ) and (2) does CHQ resistance confer resistance to other DMARDs. <h3>Methods</h3> Human CEM (T) cells were made resistant to CHQ following a 4 months <i>in vitro</i> exposure to stepwise increasing extracellular CHQ concentrations. <h3>Results</h3> CHQ resistant CEM cells (CEM/CHQ) displayed 3.3-fold resistance to CHQ compared to CEM cells (IC<sub>50</sub>: 129 μM vs 39 μM, respectively, following 72 h drug exposure). The resistant phenotype was stable for at least one month when CEM/CHQ cells were grown in the absence of CHQ. CEM/CHQ cells exhibited full sensitivity to methotrexate (MTX) and were even collaterally sensitive (1.7-fold) to sulfasalazine. Interestingly, CEM/CHQ cells displayed cross-resistance to doxorubicin and daunorubicin, suggesting that multidrug resistance proteins play a role in the resistant phenotype. In fact, immunological detection (Western blots) revealed a markedly increased expression of multidrug resistance protein 1 (MRP1) in CEM/CHQ cells compared to CEM cells. Involvement of MRP1 in CHQ resistance was further illustrated by observations that inhibitors of MRP1, probenecid and MK571, were able to reverse CHQ resistance in CEM/CHQ cells. Beyond MRP1, we noted that also cells transfected with MRP2 and MRP3 displayed resistance to CHQ (2.1- and 1.8-fold, respectively). <h3>Conclusion</h3> Overexpression of multidrug resistance proteins (MRP1, MRP2 and MRP3) can confer <i>in vitro</i> resistance to CHQ and should be considered as a mechanism of lack of drug efficacy in a clinical setting.
Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study
Authors: Giovanni Caocci, Olga Mulas, Isabella Capodanno, Elisabetta Abruzzese, Alessandra Iurlo, Luigiana Luciano, Francesco Albano, Mario Annunziata, Mario Tiribelli, Massimiliano Bonifacio, Sara Galimberti, Fausto Castagnetti, Nicola Sgherza, Fabio Stagno, Antonella Gozzini, Ester Maria Orlandi, Debora Luzi, Gianni Binotto, Patrizia Pregno, Claudio Fozza, Fabio Efficace, Maria Pina Simula, Malgorzata Monika Trawinska, Daniele Cattaneo, Fiorenza De Gregorio, Immacolata Attolico, Rossella Stella, Luigi Scaffidi, Claudia Baratè, Gabriele Gugliotta, Emilia Scalzulli, Chiara Elena, Francesca Pirillo, Robin Foà, Massimo Breccia, Giorgio La Nasa
Journal: Blood Cancer Journal (2020)
FRI0048 NUMBER NEEDED TO TREAT TO ACHIEVE MINIMUM CLINICALLY SIGNIFICANT DIFFERENCES IN PATIENT-REPORTED OUTCOMES IN PATIENTS TREATED WITH BARICITINIB
Authors: V. Strand, L. Sun, J. Ross Terres, C.L. Kannowski
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Background:</h3> Baricitinib (BARI) provided rapid and sustained improvements in patient-reported outcomes (PROs) in randomized, controlled trials (RCTs) in patients (pts) with active rheumatoid arthritis (RA) and inadequate responses (IR) to methotrexate (MTX) (RA-BEAM; NCT01710358)<sup>1,2</sup> and biologic DMARDs (bDMARD-IR; RA-BEACON; NCT01721044)<sup>3,4</sup>. <h3>Objectives:</h3> To determine the number needed to treat (NNT) to report improvements ≥minimum clinically important differences (MCIDs) in multiple PROs at Week (Wk) 12 after treatment with BARI 4-mg in RA-BEAM and BARI 2-mg or BARI 4-mg in RA-BEACON. NNTs ≤10 vs placebo (PBO) are considered clinically meaningful. <h3>Methods:</h3> Evaluated PROs with respective MCID definitions included Patient Global Assessment of Disease Activity (PtGA, 0-100 mm visual analog scale [VAS], MCID ≥10 mm), pain (0-100 mm VAS, MCID ≥10 mm), physical function (Health Assessment Questionnaire-Disability Index, MCID ≥0.22 points), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], MCID≥4.0), and health-related quality of life (SF-36 physical component summary [PCS: MCID ≥2.5] and domain scores: physical function [PF], role physical [RP], bodily pain [BP], general health [GH], vitality [VT], social functioning [SF], role emotional [RE], mental health [MH], MCID ≥5.0).<sup>5</sup> The percentages of pts reporting improvements ≥MCID were determined at Wk 12. NNTs were calculated as 1/difference in response rates between BARI 2-mg or 4-mg and PBO. <h3>Results:</h3> At Wk 12, percentages of pts reporting clinically meaningful improvements were greater and statistically different from PBO (p&lt;0.01) with BARI 2-mg and 4-mg across most PROs in both RCTs. Most NNTs were ≤10. (Figure) <h3>Conclusion:</h3> Across different populations, MTX-IR and bDMARD-IR pts with active RA reported clinically meaningful improvements in PROs after BARI treatment. The NNTs in these analyses indicate that &lt;10 pts need to be treated with BARI 2- or 4-mg to report a clinically meaningful benefit. <h3>References:</h3> [1]Taylor et al. NEJM, 2017;376: 652-62 [2]Keystone et al. Ann Rheum Dis, 2017;76:1853-61 [3]Genovese et al. NEJM, 2016; 374: 1243-52 [4]Smolen et al. Ann Rheum Dis, 2017; 76: 694-700 [5]Strand et al. J Rheumatol, 2011; 38: 1720-27 <h3>Disclosure of Interests:</h3> Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Luna Sun Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jorge Ross Terres Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Carol L. Kannowski Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company
High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays
Authors: Nathalie Brandenberg, Sylke Hoehnel, Fabien Kuttler, Krisztian Homicsko, Camilla Ceroni, Till Ringel, Nikolce Gjorevski, Gerald Schwank, George Coukos, Gerardo Turcatti, Matthias P. Lutolf
Journal: Nature Biomedical Engineering (2020)
SAT0469 PROSPECTIVE STUDY ASSESSING BONE MINERAL DENSITY AND RISK FACTORS FOR OSTEOPOROSIS IN PATIENTS WITH ANDROGEN DEPRIVATION THERAPY. PRELIMINARY CROSS-SECTIONAL RESULTS
Authors: L. Gifre, F. Elias, P. Servian, R. Freixa, O. Buisan Rueda
Journal: Annals of the Rheumatic Diseases (2020)

Background: Few studies have analysed the incidence and risk factors for osteoporosis (OP) development in patients with prostate cancer (PC) and androgen deprivation therapy (ADT). Objectives: To assess risk factors for OP, bone turnover markers (BTM) and bone mineral density (BMD) in a cohort of patients with ADT, as well as the duration of ADT and previous treatments received for PC. Methods: Ongoing prospective study including patients with ADT for PC. Risk factors for OP, BTM (total ALP, bone ALP, CTx), spinal X-Ray and BMD (Lunar, DPX) were assessed yearly since inclusion in the study (April 2018). Patients with known OP or previous antiosteoporotic treatment were excluded. The study was approved by the ethics committee, and all patients gave their signed consent. Herein we present the preliminary cross-sectional study at inclusion. Results: Of the 83 patients attended at the Rheumatology Department during the study period, 75 were included with a mean age 75±5years and median ADT duration of 1 year. 18 were receiving concomitant radiotherapy and 7 docetaxel. When assessing risk factors for OP: 28% had previous fragility fractures and 24% had current alcohol intake. After X-Ray assessment, 14% had morphometric vertebral fractures. Mean 25OHD at inclusion was 19±9ng/ml (73% had 25OHD &lt;30ng/ml) and mean testosterone was 82±162ng/dL (75% had levels &lt;50ng/dl). All patients had increased values of CTx and 9% had increased bone ALP levels. BMD showed up to 28% with densitometric OP and osteopenia in 56%. Patients with OP were older (83±7 vs 74±8 years, p=0.021), had lower testosterone levels (16 vs 89 ng/dl, p=0.004), as expected lower BMD (at spine, proximal femur and even distal radius) and had more previous fragility fracture (75 vs 19%, p=0.022). But it should be noted that 16% had high bone mass (HBM) mostly affecting spine BMD (in 6 patients combined with femoral osteopenia). All patients with HBM had high bone metastatic disease, and no differences were observed between patients with/without HBM when comparing BTM or calcium-phosphate metabolism. Conclusion: Low bone mass (including osteoporosis and osteopenia) is frequent in patients with ADT as well as previous fragility fractures. Up to 16% had high bone mass, being mostly in patients with high volume metastatic disease. Thus, all patients with ADT should undergo a bone health assessment and start antiosteoporotic treatment if required. Disclosure of Interests: None declared
THU0019 INTRON REGIONS OF PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES ARE DIFFERENTIALLY METHYLATED IN PATIENTS WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME
Authors: E. Lovšin, J. Kovac, T. Tesovnik, N. Toplak, D. Perko, T. Rozmarič, M. Debeljak, T. Avcin
Journal: Annals of the Rheumatic Diseases (2020)

Background: Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. Objectives: We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus a group of healthy young individuals. Methods: A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions. Of identified candidate genes, two with most significantly different methylation leves were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR). Results: The analysis showed that PIK3AP1 and SPON2 intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved as a quick, reliable and cost-effective method to confirm results from MeDIP and MBD. Conclusion: Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation. References: [1]Wekell P. Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome – PFAPA syndrome. Press Medicale [Internet]. 2019;48(1):e77–87. Available from: https://doi.org/10.1016/j.lpm.2018.08.016 [2]K. Theodoropoulou, F. Vanoni, and M. Hofer, “Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis,” Curr. Rheumatol. Rep. , vol. 18:18, 2016. [3]Carpentier SJ, Ni M, Duggan JM, James RG, Cookson BT, Hamerman JA. The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1. Sci Signal. 2019;12(581). [4]He YW, Li H, Zhang J, Hsu CL, Lin E, Zhang N, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5(1):88–97. Disclosure of Interests: None declared
Why can’t I exercise during pregnancy? Time to revisit medical ‘absolute’ and ‘relative’ contraindications: systematic review of evidence of harm and a call to action
Authors: Victoria L Meah, Gregory A Davies, Margie H Davenport
Journal: British Journal of Sports Medicine (2020)

Background Clinical guidelines recommend pregnant women without contraindication engage in regular physical activity. This is based on extensive evidence demonstrating the safety and benefits of prenatal exercise. However, certain medical conditions or contraindications warrant a reduction, modification or cessation of activity due to potential health risks. Aim To review and evaluate the evidence related to medical disorders which may warrant contraindication to prenatal exercise. Methods Online databases were searched up to 5 April 2019. Forty-four unique studies that reported data on our Population (pregnant women with contraindication to exercise), Intervention (subjective/objective measures of acute or chronic exercise), Comparator (not essential) and Outcomes (adverse maternal or fetal outcomes) were included in the review. Key findings We found that the majority of medical conditions listed as contraindications were based on expert opinion; there is minimal empirical evidence to demonstrate harm of exercise and benefit of activity restriction. We identified 11 complications (eg, gestational hypertension, twin pregnancy) previously classified as contraindications where women may in fact benefit from regular prenatal physical activity with or without modifications. However, the evidence suggests that severe cardiorespiratory disease, placental abruption, vasa previa, uncontrolled type 1 diabetes, intrauterine growth restriction, active preterm labour, severe pre-eclampsia and cervical insufficiency are associated with strong potential for maternal/fetal harm and warrant classification as absolute contraindications. Conclusion Based on empirical evidence, we provide a call to re-evaluate clinical guidelines related to medical disorders that have previously been considered contraindications to prenatal exercise. Removing barriers to physical activity during pregnancy for women with certain medical conditions may in fact be beneficial for maternal–fetal health outcomes.
Sparse Activity of Hippocampal Adult-Born Neurons during REM Sleep Is Necessary for Memory Consolidation
Authors: Deependra Kumar, Iyo Koyanagi, Alvaro Carrier-Ruiz, Pablo Vergara, Sakthivel Srinivasan, Yuki Sugaya, Masatoshi Kasuya, Tzong-Shiue Yu, Kaspar E. Vogt, Masafumi Muratani, Takaaki Ohnishi, Sima Singh, Catia M. Teixeira, Yoan Chérasse, Toshie Naoi, Szu-Han Wang, Pimpimon Nondhalee, Boran A.H. Osman, Naoko Kaneko, Kazunobu Sawamoto, Steven G. Kernie, Takeshi Sakurai, Thomas J. McHugh, Masanobu Kano, Masashi Yanagisawa, Masanori Sakaguchi
Journal: Neuron (2020)
Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia
Authors: Benjamin J. Andreone, Laralynne Przybyla, Ceyda Llapashtica, Anil Rana, Sonnet S. Davis, Bettina van Lengerich, Karin Lin, Ju Shi, Yuan Mei, Giuseppe Astarita, Gilbert Di Paolo, Thomas Sandmann, Kathryn M. Monroe, Joseph W. Lewcock
Journal: Nature Neuroscience (2020)
Using socioeconomics to counter health disparities arising from the covid-19 pandemic
Authors: Geoffrey Anderson, John William Frank, C David Naylor, Walter Wodchis, Patrick Feng
Journal: BMJ (2020)

Principles and methods drawn from decades of work showing that lower socioeconomic status is associated with poorer health should guide efforts to monitor and mitigate the impact of the covid-19 pandemic argue <b>Geoffrey Anderson and colleagues</b>
AB0959 FREQUENCY OF SEXUAL DYSFUNCTION IN WOMEN WITH FIBROMYALGIA
Authors: O. Teplyakova, A. Popov
Journal: Annals of the Rheumatic Diseases (2020)

Background: The impact of rheumatic diseases on patients’sexual life has been gathering the attention of the scientific community over the last decade. The existing studies, especially related to fibromyalgia, are scarce. Objectives: To assess the prevalence of sexual dysfunction in women with fibromyalgia followed up at the Outpatient Clinic of the Medical Hospital in Russia. Methods: The main group consisted of 54 women aged from 18 to 55 who sequentially applied for rheumatologist consultation. All subjects fulfilled ACR 2016 Fibromyalgia criteria. The comparison group included 100 healthy women adjusted by age who came for a scheduled health check up and signed the informed consent form. The Female Sexual Function Index (FSFI), obtained by applying a 19-item questionnaire that assesses six domains (sexual desire, arousal, vaginal lubrication, orgasm, sexual satisfaction and pain) and Hospital Anxiety and Depression questionnaire (HADS) were used. The data are presented as means and standard deviations. Results: 26 (48,1%) of the patients interviewed reported no sexual activity over the past 4 weeks. fibromyalgia patients reported no sexual activity during the previous 4 weeks. Fibromyalgia group had significantly lower values of all FSFI domains than those of the comparison group: desire 1.98±1.28 and 3.19±1.45; arousal 1.98±1.46 and 3.74±1.45; lubrification 2.35±2.25 and 4.37±1.32; orgasm 1.75±1.68 and 4.06±1.66; satisfaction 2.28±1.19 and 3.95±1.61; no pain 2.49±1.77 and 4.30±1.42. In General, total FSFI score was 12.86±10.97 on fibromyalgia group versus 23.55±8.24 in the healthy group (maximum possible being 36 points, p&lt; 0.0001). We tried to see if sexual function was affected by psychological status or stile of life. We found that only arousal, lubrification, orgasm and satisfaction had minimal values for clinically expressed anxiety while all parameters of sexual dysfunction were reduced in women on fibromyalgia group with borderline and clinically significant depression. There was the best index of sexual function married patients compared to divorced women. Unexpectedly, the minimal scores for all FSFI domains were in the fibromyalgia subgroup of 8 women with body mass deficiency and 20 women with Overweight, while normal body mass index and obesity were protective factors in sexual function. Conclusion: Thus, a significant sexual function decrease was detected in female with fibromyalgia. The most severe dysfunction being associated with the abnormal anxiety, borderline and abnormal depression, divorced status, body mass deficiency and overweight. Disclosure of Interests: None declared