tbuckley/cabot-search huggingface dataset:
Design, synthesis and immunological evaluation of self-assembled antigenic peptides from dual-antigen targets: a broad-spectrum candidate for an effective antibreast cancer therapy
Authors: Wei Shi, Qianqian Qiu, Ziying Feng, Zhenzhen Tong, Weiwei Guo, Feng Zou, Na Yue, Wenlong Huang, Hai Qian
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Considering the narrow immune response spectrum of a single epitope, and the nanoparticles (NPs) as a novel adjuvant can achieve efficient delivery of antigenic peptides safely, a nano-system (denoted as DSPE-PEG-Man@EM-NPs) based on cathepsin B-responsive antigenic peptides was designed and synthesized. Methods Highly affinitive antigenic peptides were delivered by self-assembled NPs, and targeted erythrocyte membranes acted as a peptide carrier to improve antigenic peptides presentation and to strengthen cytotoxic T-cells reaction. Cathepsin B coupling could release antigenic peptides rapidly in dendritic cells. Results Evaluations showed that DSPE-PEG-Man@EM-NPs had obvious inhibitory effects towards both MCF-7 and MDA-MB-231 human breast cancer cell lines. Conclusion Overall, this strategy provides a novel strategy for boosting cytotoxic T lymphocytes response, thereby expanding the adaptation range of tumor antigenic peptides and improving the therapeutic effect of tumor immunotherapy with nanomedicine.
Metabolic Effects of Empagliflozin in Heart Failure: A Randomized, Double-Blind, and Placebo-Controlled Trial (Empire HF Metabolic)
Authors: Jesper Jensen, Massar Omar, Caroline Kistorp, Christian Tuxen, Ida Gustafsson, Lars Køber, Finn Gustafsson, Jens Faber, Julie L. Forman, Jacob E. Møller, Morten Schou
Journal: Circulation (2021)
Clinical outcomes in COVID-19 patients infected with different SARS-CoV-2 variants in Marseille, France
Authors: Thi Loi Dao, Van Thuan Hoang, Nhu Ngoc Nguyen, Jérémy Delerce, Hervé Chaudet, Anthony Levasseur, Jean Christophe Lagier, Didier Raoult, Philippe Colson, Philippe Gautret
Journal: Clinical Microbiology and Infection (2021)
POS0566 CATASTROPHIZING IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: C. Traverson, B. Coste, E. Filhol, C. Daien, S. Laurent-Chabalier, S. Benamar, B. Combe, C. Lukas, J. Morel, C. Hua, C. Gaujoux-Viala
Journal: Annals of the Rheumatic Diseases (2021)

Background: Catastrophizing is conceptualized as a negative cognitive–affective response to an anxiety-provoking stimulus, especially anticipated or actual pain. Catastrophizing can be assessed quickly using a validated questionnaire: the Pain Catastrophizing Scale (PCS) 1 . Catastrophizing plays a role in maintaining chronic pain and is associated with several pain-related outcomes in osteoarthritis and low back pain. Objectives: To assess the prevalence of catastrophizing and associated factors in rheumatoid arthritis (RA). Methods: We performed an observational, prospective, bi-centric study. All patients aged 18 or over with RA and fulfilling the ACR-EULAR 2010 criteria were consecutively included. Sociodemographic data, information on the disease and its treatments were collected as well as questionnaires for disease activity (DAS28), function (HAQ), quality of life (SF12, EQ5D), anxiety and depression (HADS, GAD7), fibromyalgia (FiRST), insomnia (ISI) and catastrophizing scores (PCS). Statistical analysis included the samples t-test, one-way variance analysis, the Spearman’s correlation test, the Chi 2 test, Fisher’s exact test, the Wilcoxon test, multivariate linear regression (considering catastrophizing as a continuous variable) and multivariate logistics regression (considering catastrophizing as a categorical variable: PCS ≥ 20 = high level catastrophizing). Results: From September 2019 to March 2020, 201 patients with RA were included: 78.1% were women and the median age was 63.0 years. In all, 64.1% of patients were RF+, 65.7% ACPA+, and 46% had erosive disease. Median DAS28 CRP was 2.9 [2.1-4.0]. with 45% of patients in remission, 14.8% with low, 31.2% moderate and 9 % high activity. The majority of patients (92 %) had a disease lasting for more than 2 years. The prevalence of a PCS score ≥20 was 48.0% [41.0;54.9]. The median PCS score was 18 [7-28]. In multivariate logistics regression, high-level catastrophizing was significantly associated with DAS28-CRP (OR= 1.61 [1.18-2.20]), HADS anxiety score (OR=1.25 [1.11-1.40]) and the HADS depression score (OR=1.19 [1.07-1.33]). In multivariate linear regression, catastrophizing was significantly associated with the HADS anxiety score (p&lt; 0.0001), HADS depression score (p=0.0055), HAQ (p=0.0015) and the ISI insomnia score (p=0.005). Conclusion: Almost half the patients with RA were high catastrophizers. Catastrophizing is linked to anxiety, depression, disease activity, function impairment and insomnia. It may be interesting to detect catastrophizing in order to improve the management of our patients. References: [1]Sullivan MJL. et al. Psychological Assessment. 1995;7(4):524–32 Disclosure of Interests: None declared
AB0314 SEMAPHORIN 3A LEVELS IN LUPUS WITH AND WITHOUT SECONDARY ANTIPHOSPHOLIPID ANTIBODY SYNDROME AND RENAL INVOLVEMENT
Authors: G. S. Kart-Bayram, D. Bayram, A. Erden, S. C. Güven, B. Özdemir, H. Apaydin, A. Omma, Ö. Karakaş, B. Armagan, K. Gok, Y. Maraş, O. Ateş, C. Topçuoğlu, O. Küçükşahin, S. Erten
Journal: Annals of the Rheumatic Diseases (2021)

Background: In this study, we aimed to evaluate sema3A levels in SLE patients with and without renal involvementor secondary antiphospholipid antibody syndrome (APS), to further elucidate the contribution ofsema3A in etiopathogenesis these conditions Objectives: Aim of this study is to evaluate sema3A levels in systemic lupus erythematosus patients (SLE) with and without renal involvement and secondary antiphospholipid antibody syndrome (APS). Methods: SLE patients were grouped according to presence of secondary APS or renal involvement. The control group consisted of age-matched, non-smoker, healthy volunteers. Sema3A levels were compared among groups. All SLE patients were regrouped according to presence of thrombotic events, miscarriages and proteinuria and sema3A levels were investigated. Finally, sema3A levels of all SLE patients as a single group were compared to controls. Results: The mean sema3A values were 16.16±2.84 ng/dL in the control group, 11.28±5.23 ng/dL in SLE patients without nephritis and APS, 9.05±5.65 ng/dL in SLE with APS group, and 8.53±5.11 ng/dL in lupus nephritis group. When all three patient groups were examined as a single group, mean sema3A value was significantly lower than that of the control group. Sema3A was reduced in SLE patients with thromboembolism and/or miscarriage. Conclusion: Sema3A levels were lower in all patient groups compared to the control group. Moreover, the reduced sema3A levels in patients with a history of thromboembolism and/or miscarriage suggests that sema3A may play an important role in the pathogenesis of vasculopathy Table 1. Comparison of sema3A levels between SLE patient groups and control subjects Patient groups Group A (N=20) Group B (N=20) Group C (N=19) Control (N=19) p Sema3A, ng/dL, mean ± SD 9.05 ± 5.65 11.28 ± 5.23 8.53 ± 5.11 16.16 ± 2.84 Group A vscontrol&lt;0.001 Group B vscontrol&lt;0.001 Group C vscontrol&lt;0.001 Group A vs B = 0.203 Group A vs C = 0.766 Group B vs C = 0.106 All patients (N=59 ) Control (N=19 ) &lt;0.001 9.64 ± 5.38 16.16 ± 2.84 Patients with thrombotic events and/or miscarriages (N=31 ) Patients without thrombotic events and/or miscarriages (N=48 ) 0.032 9.96 ± 5.11 12.33 ± 5.84 Patients with proteinuria and/or thrombotic events and/or miscarriages (N=45 ) Patients without proteinuria and/or thrombotic events and/or miscarriages (N=34 ) &lt;0.001 9.05 ± 5.09 14.91± 4.50 Disclosure of Interests: None declared
AB0512 CLINICAL AND RADIOLOGICAL FEATURES OF SHOULDER INVOLVEMENT IN SPONDYLARTHRITIS
Authors: C. Ines, H. Ferjani, K. Maatallah, S. Miri, H. Hajji, M. Yasmine, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Peripheral joint involvement is frequent among patients with peripheral spondylarthritis (SA). However, the root joint involvement, such as hip involvement, has been described as being associated with axial spondylarthritis, while data for shoulder involvement are scarce. Cuff tendonitis and enthesitis are common features in the shoulder in patients with SA. Objectives: This study aimed to identify the prevalence of shoulder involvement in SA patients and describe its clinical and radiological features. Methods: We conducted a retrospective study including SA patients, all fulfilling the assessment of Spondyloarthritis International Society (ASAS) criteria. For all patients, we collected the following data: Age, the clinical presentation of SA, the inflammatory biomarkers C-reactive protein (CRP), and the disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Regarding shoulder involvement, we assessed the following items: tenderness, mobility, rotator cuff tests, as well as the results of X-ray and Ultrasound examination (US). Results: We included one hundred and thirty-one SA patients (mean age 39,77 years). Among them, sixty-two percent were male. Ten percent of patients were smokers, 46,6% had the peripheral beginning of the disease. Fourteen patients complained of shoulder pain. The majority of them were male. X-rays showed no abnormalities (n=2), while a destructive form was noted in (n=7). Rotator cuff rupture or enthesopathy was also revealed by the reduction of subacromial space (n=5), condensation of the greater tuberosity (n=3), crooked aspect of the acromion (n=2), and Moloney’s line disruption(n=1). US showed no abnormalities (n=1), supraspinatus tendinopathy (n=5), supraspinatus transfixing tear (n=1), infraspinatus tendinopathy (n=2), supraspinatus enthesopathy (n=2), infraspinatus enthesopathy (n=1), moderate synovitis (n=1), subacromiodeltoid bursitis (n=1). Shoulder involvement was correlated significantly with the peripheral beginning of SA (P &lt; 0.05). There were no significant differences in gender, tobacco use, CRP value, and the disease activity between the two groups (P &gt; 0.05). Conclusion: The shoulder involvement was rare in our study. It is characterized by cuff tendonitis and enthesitis, especially in supraspinatus insertion. However, the glenohumeral synovitis was uncommon in our series, even in the peripheral form of the disease. References: [1]Hip and Shoulder Involvement and Their Management in Axial Spondyloarthritis: a Current Review Clementina López-Medina1,2,3,4 &amp; M. Carmen Castro-Villegas1,2,3 &amp; Eduardo Collantes-Estévez1,2,3, 23 July 2020. Acknowledgements: I would like to thank all the authors listed above, for they helped me make writing my first abstract less harder. Disclosure of Interests: None declared.
CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors: Qingya Cui, Chongsheng Qian, Nan Xu, Liqing Kang, Haiping Dai, Wei Cui, Baoquan Song, Jia Yin, Zheng Li, Xiaming Zhu, Changju Qu, Tianhui Liu, Wenhong Shen, Mingqing Zhu, Lei Yu, Depei Wu, Xiaowen Tang
Journal: Journal of Hematology & Oncology (2021)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92-99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117-261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.
AB0707 RHEUMATOLOGY PATIENT CARE IN THE COVID-19 PANDEMIC: TELEMEDICINE, DELEGATION, PATIENT SATISFACTION AND VACCINATION BEHAVIOUR
Authors: T. Thiele, S. Beider, H. Kühl, G. Miehlke, A. Cossmann, A. Holz, C. Happle, K. Hoeper, T. Witte, A. Jabonka, D. Ernst
Journal: Annals of the Rheumatic Diseases (2021)

Background: Use of telemedicine in Germany has increased due to the COVID-19 lockdown. Between March and May 2020, government restrictions led to cancellation of routine outpatient appointments to limit viral spread and optimize resources. Objectives: This study assesses patient satisfaction of follow-up telemedicine appointments among patients known to be in disease remission, attending either secondary or tertiary care Rheumatology clinics. Appointments were conducted either by a rheumatologist or a qualified medical assistant for rheumatology (RFA). Additional data regarding perceived concerns arising from the COVID-19 pandemic as well as attitudes to vaccination were collected. Methods: Methods: Patients not requiring adjustment of their DMARDs at the two previous attendances were considered stable. At cancellation of the planned attendance, patients were offered participation in the study and provided verbal informed consent. Participants were randomized to a telemedicine appointment by either a physician or RFA. Telemedicine appointments consisted of a standardized patient interview, including assessment of disease activity (modified CDAI score), attitudes to vaccination as well as current vaccine status and concerns about COVID-19. Following participation, all patients received a pseudonymized postal questionnaire to evaluate appointment satisfaction (FAPI-Score). Results: In total 112/116 (96%) patients that were offered appointments, participated in the study (RA 50%, axSpA 30%, PsA 20%). Of these 88/112 (79%) returned their postal questionnaires. Overall patient satisfaction was excellent (mean 4.3/5 modified FAPI score) and did not differ between care setting or clinical status of the interviewer. RFAs conducted 19/112 (17%) of appointments, 6 (32%) of which required additional physician intervention. Change of DMARDs occurred in 19/112 (17%) appointments. Patients reporting a pain score ≥7 (VAS 1-10) were most dissatisfied with the telemedicine appointment (p=0.036). Concerns about COVID-19 correlated with disease activity: high disease activity (p = 0.031), presence of tender joints (p=0.001), high pain levels (p=0.009) correlated with concern of contracting COVID-19 or experiencing severe disease course. Only 38% of the patients had been vaccinated against pneumococci in the past 5 years and 54% had been vaccinated against influenza in 2019/2020. Conclusion: Telemedicine can contribute to patient care in stable patients. RFAs can also contribute to patient care especially for follow-up appointment when patients are in remission. Vaccination rates and motivation needs to be improved as influenza and pneumococcal vaccination is recommended to all patients with rheumatic diseases without contraindications. Disclosure of Interests: None declared
OP0007 MUC5B PROMOTER VARIANT AND LONG-TERM INCIDENCE OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS: A POPULATION BIOBANK STUDY OF 250,000 INDIVIDUALS
Authors: A. Palomäki, T. Laitinen, J. Koskela, A. Palotie, N. Mars
Journal: Annals of the Rheumatic Diseases (2021)

Background: The promoter variant rs35705950 in MUC5B is the strongest known genetic risk factor for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) [1]. There is, however, no large-scale data on the impact of MUC5B on the long-term incidence of RA-ILD. Objectives: To describe long term risk of RA-ILD in RA patients carrying MUC5B variant compared to non-carriers with RA. Methods: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, linking genotypes with up to 46 years of follow-up within nationwide registries. Diagnoses of RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80. MUC5B is a common variant and has an allele frequency of 0.1 in the Finnish population. Results: Out of the 248,400 individuals, 5534 patients have been diagnosed with RA, out of whom 178 (3.2%) developed ILD. MUC5B was a strong predictor of ILD in RA patients (HR 2.14, 95%CI 1.56-2.92). In patients with RA, MUC5B conferred a lifetime risk of 14.5% (95%CI 10.7-18.1%), compared to 5.2% (4.1-6.2%) in MUC5B non-carriers with RA (Figure). In the population, MUC5B carriers and MUC5B non-carriers had lifetime risks of 3.9% and 1.3%, respectively. The risk difference started to emerge at age 65. The risk was highest in men with RA who are MUC5B carriers: 18.5% (11.1-25.2%) developed ILD, compared to 8.5% (6.1-10.9%) of MUC5B non-carriers with RA. Conclusion: We report findings from a large longitudinal study, showing that MUC5B confers a considerable lifetime risk of RA-ILD, and contributes to increased morbidity. These findings have clinical implications for improving identification of RA patients at high risk of developing ILD. References: [1]Juge P-A, Lee JS, Ebstein E, et al. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. N Engl J Med 2018;379:2209–19 Disclosure of Interests: Antti Palomäki Speakers bureau: MSD, Pfizer, Sanofi, Consultant of: Pfizer, Abbvie, Tarja Laitinen: None declared, Jukka Koskela Speakers bureau: Pfizer, Aarno Palotie: None declared, Nina Mars: None declared
POS0045 LEAST SIGNIFICANT CHANGE IN BONE DENSITOMETRY IN PATIENTS WITH OBESITY
Authors: D. Claire, M. Geoffroy, L. Kanagaratnam, C. Isabelle, A. Hittinger, B. Loïs, C. Clément, J. H. Salmon
Journal: Annals of the Rheumatic Diseases (2021)

Background: Dual energy X-ray absoprtiometry is the reference method to mesure bone mineral density (1). Loss of bone mineral density is significant if it exceeds the least significant change. The threshold value used in general population is 0,03 g/cm 2 (2). Patients with obesity are known for having a higher bone mineral density due to metabolism and physiopathology characteristics (3,4). Objectives: The aim of our study was to determine the least significant change in bone densitometry in patients with obesity. Methods: We conducted an interventionnal study in 120 patients with obesity who performed a bone densitometry. We measured twice the bone mineral density at the lumbar spine, the femoral neck and the total hip in the same time (5,6). We determined the least significant change in bone densitometry from each pair of measurements, using the Bland and Altman method. We also determined the least significant change in bone densitometry according to each stage of obesity. Results: The least significant change in bone densitometry in patients with obesity is 0,046g/cm 2 at the lumbar spine, 0.069 g/cm 2 at the femoral neck and 0.06 g/cm 2 at the total hip. Conclusion: The least significant change in bone densitometry in patients with obesity is higher than in general population. These results may improve DXA interpretation in this specific population, and may personnalize their medical care. References: [1]Lees B, Stevenson JC. An evaluation of dual-energy X-ray absorptiometry and comparison with dual-photon absorptiometry. Osteoporos Int. mai 1992;2(3):146-52. [2]Briot K, Roux C, Thomas T, Blain H, Buchon D, Chapurlat R, et al. Actualisation 2018 des recommandations françaises du traitement de l’ostéoporose post-ménopausique. Rev Rhum. oct 2018;85(5):428-40. [3]Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res N Y N. mars 2017;39:1-13. [4]Savvidis C, Tournis S, Dede AD. Obesity and bone metabolism. Hormones. juin 2018;17(2):205-17. [5]Roux C, Garnero P, Thomas T, Sabatier J-P, Orcel P, Audran M, et al. Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis. Jt Bone Spine Rev Rhum. janv 2005;72(1):26-31. [6]Ravaud P, Reny JL, Giraudeau B, Porcher R, Dougados M, Roux C. Individual smallest detectable difference in bone mineral density measurements. J Bone Miner Res. août 1999;14(8):1449-56. Disclosure of Interests: None declared.
Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study
Authors: Ify R. Mordi, R. Thomas Lumbers, Colin N.A. Palmer, Ewan R. Pearson, Naveed Sattar, Michael V. Holmes, Chim C. Lang
Journal: Diabetes Care (2021)

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).