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Flow-induced rotation of an S-shaped rotor is investigated using an adaptive numerical scheme based on a vortex particle method. The boundary integral equation with respect to Bernoulli’s function is solved using a panel method for obtaining the pressure distribution on the rotor surface which applies the torque to the rotor. The present work first addresses the validation of the scheme against the previous studies of a rotating circular cylinder. Then, we compute the automatic rotation start of an S-shaped rotor from a quiescent state for various values of the moment of inertia. The computed flow patterns where the rotor supplies (or is supplied with) the torque to (or from) the fluid are shown during one cycle of rotation. The vortex shedding from the tip of the advancing bucket is found to play a key role in generating positive torque on the rotor. A remarkable finding is the fact that, after the rotor reaches a stable rotation, the trajectory of the limit cycle in the present autonomous system accounts for the stable rotating movement of the rotor. Furthermore, the hydrodynamic scenario of the rotor automatically starting up from a quiescent state and entering the limit cycle is elucidated for various values of the moment of inertia and the initial angle of the rotor.

The initial flow past an impulsively started rotating and translating circular cylinder is asymptotically analysed using a Brinkman penalization method on the Navier–Stokes equation. In our previous study (J. Fluid Mech., vol. 929, 2021, A31), the asymptotic solution was obtained within the second approximation with respect to the small parameter, $\\epsilon$, that is of the order of $1 / \\lambda$. Here, $\\lambda$ is the penalization parameter. In addition, the Reynolds number based on the cylinder radius and the translating velocity is assumed to be of the order of $\\epsilon$. The previous study asymptotically analysed the initial flow past an impulsively started translating circular cylinder and investigated the influence of the penalization parameter $\\lambda$ on the drag coefficient. It was concluded that the drag coefficient calculated from the integration of the penalization term exhibits a half-value of the results of Bar-Lev & Yang (J. Fluid Mech., vol. 72, 1975, pp. 625–647) as $\\lambda \\to \\infty$. Furthermore, the derivative of vorticity in the normal direction was found to be discontinuous on the cylinder surface, which is caused by the tangential gradient of the pressure on the cylinder surface. The present study hence aims to investigate the variance on the drag coefficient against the result of Bar-Lev & Yang (1975). First, we investigate the problem of an impulsively started rotating circular cylinder. In this situation, the moment coefficient is independent of the pressure on the cylinder surface so that we can elucidate the role of the pressure to the hydrodynamic coefficients. Then, the problem of an impulsively started rotating and translating circular cylinder is investigated. In this situation, the pressure force induced by the unsteady flow far from the cylinder is found to play a key role on the drag force for the agreement with the result of Bar-Lev & Yang (1975), whereas the variance still exists on the lift force. To resolve the variance, an alternative formula to calculate the hydrodynamic force is derived, assuming that there is the pressure jump between the outside and inside of the cylinder surface. The pressure jump is obtained in this analysis asymptotically. Of particular interest is the fact that this pressure jump can cause the variance on the lift force calculated by the integration of the penalization term.

The initial flow past an impulsively started translating circular cylinder is asymptotically analysed using a Brinkman penalization method on the Navier–Stokes equations. The asymptotic solution obtained shows that the tangential and normal slip velocities on the cylinder surface are of the order of $1/\\sqrt {\\lambda }$ and $1/\\lambda$, respectively, within the second approximation of the present asymptotic analysis, where $\\lambda$ is the penalization parameter. This result agrees with the estimation of Carbou & Fabrie (Adv. Diff. Equ., vol. 8, 2003, pp. 1453–1480). Based on the asymptotic solution, the influence of the penalization parameter $\\lambda$ is discussed on the drag coefficient that is calculated using the adopted three formulae. It can then be found that the drag coefficient calculated from the integration of the penalization term exhibits a half-value of the results of Bar-Lev & Yang (J. Fluid Mech., vol. 72, 1975, pp. 625–647) as $\\lambda \\to \\infty$.

High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled. Patients who achieved complete remission (CR) were randomly assigned to receive therapy containing Hd-MTX (3 g/m2 ) or Id-MTX (0.5 g/m2 ). A total of 360 patients were enrolled. The CR rate was 86%. A total of 115 and 114 patients were assigned to the Hd-MTX and Id-MTX groups, respectively. The estimated 5-year disease-free survival rate of the Hd-MTX group was 58%, which was significantly better than that of the Id-MTX group at 32% (P=0.0218). The frequencies of severe adverse events were not significantly different. We herein demonstrated the effectiveness and safety of Hd-MTX therapy for adult Ph-negative ALL. Our results provide a strong rationale for protocols containing Hd-MTX therapy being applied to the treatment of adult ALL.

In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09, P <0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48, P <0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively ( P <0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%, P =0.044; ganciclovir, 84% vs 58%, P =0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.

Algae are often cultivated in closed system of photobioreactors. In the cultivation, algae cells grow to adhere on the wall surface of a reactor, which results in inhibiting photosynthesis of culture solution. This short paper visualizes the microalgae adhesion on the oil coated wall of a cultivation reactor. A remarkable finding is the fact that the coating of silicone oil could protect the wall surface from the microalgae adhesion. In particular, the coating of silicone oil with the kinematic viscosity larger than 20 [cSt] can be found to reduce the adhesion area on the reactor wall to less than half that on an uncoated reactor. Graphical abstract

Background:Patient-reported outcomes (PROs) are associated with prognosis and commonly used as a component of disease activity measurements and core sets of outcomes in several connective tissue diseases. However, there is no single PRO tool that is universally accepted as the gold standard in patients with systemic lupus erythematosus (SLE) [1], and the predictive validity of PRO tools for SLE-specific quality of life (QOL) has not been examined.Objectives:To examine the predictive validity of LupusPRO [2,3], one of PRO tools to assess the SLE-specific QOL, for damage accrual in patients with SLE using a longitudinal multicenter cohort study.Methods:Patients with SLE enrolled in the nationwide multicenter registry in Japan (LUNA) with ≥2 LupusPRO measurements were included. The SLE-specific QOL was assessed using the Japanese version of the LupusPRO questionnaire which contains both health-related (HR)-QOL and non-HR-QOL measures. The damage accrual was evaluated as an outcome using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We examined the association between the LupusPRO score at baseline and longitudinal SDI scores using mixed-effects models adjusted for prognostic factors, such as age, sex, disease duration, disease activity, and medications.Results:Among 1295 patients (88.6% women, mean age 47.4 years), both the SDI scores and HR-QOL of LupusPRO were increased with the median follow-up of 2.0 years while the SLE disease activity index 2000 scores were decreased according to the treat-to-target strategy (Figure 1). Patients with higher HR-QOL of LupusPRO at baseline demonstrated a significantly lower increase in SDI (-0.005/year, 95% confidence interval: -0.007 to -0.004, p<0.001, Table 1). According to categorization of HR-QOL based on tertile, a similar dose-dependent effect of HR-QOL on longitudinal SDI was identified (2nd vs. 1st tertile category: -0.101/year, 95% confidence interval: -0.172 to -0.030, p=0.005; 3rd vs. 1st tertile category: -0.211/year, 95% confidence interval: -0.281 to -0.142, p<0.001, Table 1). Among HR-QOL domains, cognition, procreation, and physical health were significantly associated with total SDI score over time. HR-QOL was associated with both corticosteroid-dependent and -independent SDI scores. The association between HR-QOL and SDI was prominent in patients with the physician’s global assessment score <1 and with lupus low disease activity state. Non-HR-QOL was not significantly associated with SDI scores.Conclusion:Higher HR-QOL of LupusPRO was associated with lower increase in SDI scores. Because HR-QOL of LupusPRO measures seemed to provide unique information about the impact of disease that is not captured by physician-assessed measures, incorporating disease-specific QOL into a core set of outcomes in SLE may be warranted.REFERENCES:[1] van Tuyl LH et al. Patient-reported outcomes in core domain sets for rheumatic diseases. Nat Rev Rheumatol. 2015;11(12):705-12.[2] Jolly M et al. Disease-specific patient reported outcome tools for systemic lupus erythematosus. Semin Arthritis Rheum. 2012;42(1):56-65.[3] Inoue M et al. The Japanese LupusPRO: A cross-cultural validation of an outcome measure for lupus. Lupus. 2017;26(8):849-56.Figure 1.Score changes from enrollment. (A) SLICC/ACR damage index, (B) SLE disease activity index 2000, (C) Lupus patient-reported outcome: health-related quality of life.Table 1. The association between lupus patient-reported outcome and SLICC/ACR damage index scores.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundBeta-2-glycoprotein I complexed with HLA-DR molecules (β2GPI/HLA-DR) was found to be a major autoantibody target in APS.ObjectivesWe aim to reveal the association between anti-β2GPI/HLA-DR antibodies and vascular thrombosis or obstetric morbidities in females with various systemic rheumatic diseases.MethodsThis was a single-center, retrospective longitudinal study of female patients in our center from 2020 to 2021. Clinical and laboratory data were retrieved from medical records and questionnaires. Anti-β2GPI/HLA-DR antibody was compared with the risk score reported as an adjusted global APS score (aGAPSS). The optimal cutoff value was calculated using receiver operating characteristic (ROC) analysis to detect arterial thrombosis. Finally, we assessed the impact of anti-β2GPI/HLA-DR antibodies on arterial thrombosis in addition to the conventional risk model with multivariable logistic regression analysis.ResultsWe evaluated 704 patients, including 66 (obstetric or thrombotic) APS, 13 primary APS, and 78 asymptomatic aPL carriers, that comorbid 260 Systemic Lupus Erythematosus (SLE) or Mixed Connective tissue diseases (MCTD). Seventy-seven patients had one or more histories of arterial thrombosis, and 14 patients of them had a history of both arterial and venous thrombosis. The titers were significantly higher in patients with arterial and venous thrombosis than in those without thrombosis. In cases with aGAPSS>10 or triple positive aPL, the titers tended to be higher. The ROC showed that the sensitivity, specificity, and area under the curve (AUC) for arterial thrombosis were 33.8%, 91.4%, and 0.60 with a cutoff value of 172.359 U/ml. By the multivariable logistic regression analysis with multiple imputation, the odds ratio of anti-β2GPI/HLA-DR antibody ≧172.359 was 5.11(95% confidence interval: 2.84-9.19; P<0.001) (Table 1). When adding the cutoff value to conventional cardiovascular risk factors improved the AUC from 0.677 to 0.730 (p = 0.088). Determined net reclassification improvement and integrated discrimination improvement were statistically significant (Figure 1).ConclusionAnti-β2GPI/HLA-DR antibody is associated with arterial thrombosis in females with various systemic rheumatic diseases.References[1] Blood. 2015;125(18):2835-2844.[2] Arthritis Rheumatol. 2020;72(11):1882-1891.Table 1.Univariable and Multivariable logistic regression analysisUnivariateMultivariateComplete-cases(n = 409)Multiple imputation(n = 704)Conventionalcardiovascular risk factorsalone(model 1)the addition ofanti-β2GPI/HLA-DRantibody status(model 2)VariablesOR(95%CI)p-valueOR(95%CI)p-valueOR(95%CI)p-valueOR(95%CI)p-valueAge1.02 (1.00-1.03)0.0501.02 (1.00-1.04)0.0431.03 (1.00-1.05)0.0271.01 (0.99-1.03)0.059Disease duration1.01 (0.99-1.03)0.3411.00 (0.98-1.03)0.7901.00 (0.98-1.03)0.8501.00 (0.98-1.02)0.610Body mass index1.04 (0.97-1.10)0.2701.02 (0.95-1.09)0.6511.01 (0.94-1.09)0.7301.01 (0.94-1.08)0.750Pack-year smoking1.04 (1.02-1.07)0.0021.03 (1.00-1.07)0.0631.03 (1.00-1.07)0.0731.04 (1.01-1.07)0.007Current doses of prednisolone1.07 (1.01-1.13)0.0141.11 (1.02-1.20)0.0121.11 (1.03-1.20)0.0091.07 (1.01-1.13)0.018Dyslipidemia1.13 (0.68-1.89)0.6320.73 (0.35-1.49)0.3870.78 (0.37-1.61)0.5000.77 (0.42-1.40)0.401Arterial hypertension2.54 (1.56-4.16)<0.0011.82 (0.93-3.58)0.0811.81 (0.91-3.61)0.0922.37 (1.33-4.23)0.003Diabetes1.62 (0.83-3.17)0.1551.04 (0.42-2.56)0.9321.26 (0.51-3.12)0.6201.15 (0.52-2.52)0.723Anti-β2GPI/HLA-DRantibody status(cutoff = 172.359 U/ml)5.10 (2.94-8.87)<0.001——4.39 (2.14-9.03)<0.0015.13 (2.85-9.24)<0.001Figure 1.Comparison of ROC curves between multivariate models and reclassification analysisAcknowledgements:NIL.Disclosure of InterestsKatsuhiko Yoneda: None declared, Yo Ueda: None declared, Hirotaka Yamada: None declared, Keisuke Nishimura: None declared, Sho Sendo Speakers bureau: Abbvie, Chugai, Kenji Tanimura: None declared, Hisashi Arase: None declared, Hideto Yamada: None declared, Jun Saegusa: None declared.

2022 EULAR recommendation announced that both biological disease-modifying antirheumatic drugs (bDMARDs) and janus kinase inhibitors (JAKi) are considered in the phase Ⅱ treatment of rheumatoid arthritis (RA). However, we still lack reliable evidence of direct comparison between these agents' retention, which may reflect effectiveness and safety. The aim of this multi-center (7 university-related hospitals)[1]-[3], retrospective study is to clarify the factors affecting treatment retention of bDMARDs and JAKi in a real-world setting. This study assessed 6,666 treatment courses of bDMARDs and JAKi introduced from 2001 to 2022 (TNF inhibitors [TNFi]=3,577, anti-IL-6 receptor antibody [aIL-6R]=1,497, cytotoxic T lymphocyte-associated antigen-4-Ig [CTLA4-Ig]=1,139, JAKi=453; Bio/JAK naive cases 55.4%, baseline age 58.8 years, female 82.6%, disease duration 9.7 years, DAS28-ESR 4.3, concomitant methotrexate [MTX] [52.8%], other csDMARDs [26.0%], and oral glucocorticoid [GC] [36.4%]). Reasons for discontinuation were classified into four categories by each attending physician: 1) lack of effectiveness (primary and secondary), 2) toxic adverse events (infection, malignancies, and cardiovascular events, et al.), 3) non-toxic reasons (patient preference, change in hospital, and pregnancy, et al.), and 4) remission. Retention rates of each discontinuation reason were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, concomitant GC, MTX, and other csDMARDs, switched number of bDMARDs or JAKi, and prior use of TNFi, aIL-6R, CTLA4-Ig, or JAKi) using Cox proportional hazards modeling. Adjusted retention rates for each discontinuation reason were as follows: due to lack of effectiveness was aIL-6R=80.9%, JAKi=75.2%, CTLA4-Ig=73.6%, and TNFi=66.1% (Cox P<0.001 between 4 groups) (figure 1a), due to toxic adverse events was CTLA4-Ig=88.0%, JAKi=86.4%, aIL-6R=84.1%, and TNFi=83.6% (Cox P=0.052) (figure 1b), due to non-toxic reasons was aIL-6R=86.9%, TNFi=85.9%, JAKi=85.9%, and CTLA4-Ig=82.6% (Cox P=0.064), and due to remission was JAKi=97.1%, CTLA4-Ig=96.7%, aIL-6R=96.0%, and TNFi=94.9% (Cox P=0.18). Compared to TNFi, aIL-6R (hazard ratio [HR]=0.54, 95%CI=0.47–0.61, P<0.001), JAKi (HR=0.69, 95%CI=0.56–0.85, P<0.001), and CTLA4-Ig (HR=0.75, 95%CI=0.66–0.86, P<0.001) showed lower discontinuation rate due to lack of effectiveness. Compared to TNFi, CTLA4-Ig showed lower discontinuation rate due to toxic adverse events (HR=0.77, 95%CI=0.63–0.93, P=0.008) and remission (HR=0.67, 95%CI=0.46–0.98, P=0.041). Other factors increasing drug discontinuation due to lack of effectiveness was switched number of bDMARDs or JAKi (HR=1.42, 95%CI=1.24–1.63, P<0.001), concomitant GC (HR=1.17, 95%CI=1.06–1.29, P=0.0018), and prior aIL-6R use (HR=1.24, 95%CI=1.05–1.45, P=0.011). On the other hand, higher age (HR=1.01, 95%CI=1.00–1.02, P<0.001) and concomitant GC (HR=1.29, 95%CI=0.47–0.61, P<0.001) increased drug discontinuation due to toxic adverse events. Adjusted by potential confounders, aIL-6R showed lowest discontinuation due to lack of effectiveness, and CTLA4-Ig showed lowest discontinuation due to toxic adverse events. Besides the difference of bDMARDs and JAKi, concomitant GC increased drug discontinuation due to lack of effectiveness and toxic adverse events. [1]Ebina K, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis-the ANSWER cohort study. Arthritis Res Ther. Apr 11 2019;21(1):91. [2]Ebina K, et al. Drug retention of 7 biologics and tofacitinib in biologics-naive and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther. Jun 15 2020;22(1):142. [3]Ebina K, et al. Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. Sci Rep. Jan 7 2022;12(1):134. NIL. Kosuke Ebina Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho, and UCB Japan., Consultant of: Asahi-Kasei and Taisho., Grant/research support from: AbbVie, Asahi-Kasei, Eisai, Mitsubishi-Tanabe, and Teijin Pharma. Affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho., Yuki Etani Grant/research support from: Eli Lilly, Yuichi Maeda Speakers bureau: Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation, Grant/research support from: Eli Lilly, Yasutaka Okita Speakers bureau: Chugai Pharmaceutical, Pfizer, and Ono, Makoto Hirao Speakers bureau: Astellas, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Pfizer, Ayumi, and Takeda, Wataru Yamamoto: None declared, Motomu Hashimoto Speakers bureau: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Grant/research support from: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Koichi Murata Speakers bureau: AbbVie GK, Eisai Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd., and Asahi Kasei Pharma Corp., Grant/research support from: Daiichi Sankyo, Ryota Hara Speakers bureau: AbbVie and Eisai, Koji Nagai: None declared, Yuri Hiramatsu: None declared, Yonsu Son: None declared, Hideki Amuro: None declared, Takayuki Fujii Speakers bureau: Asahi Kasei Pharma, Abbvie, Jansen, Tanabe Mitsubishi Pharma, and Eisai, Takaichi Okano: None declared, Yo Ueda: None declared, Masaki Katayama: None declared, Tadashi Okano Speakers bureau: Abbvie, Chugai, Eli Lilly, Janssen and Novartis Pharma., Grant/research support from: Abbvie, Asahi Kasei, Chugai, Eisai, Eli Lilly and Tanabe Mitsubishi., Atsushi Kumanogoh Speakers bureau: Chugai, Eisai, Tanabe-Mitsubishi, Abbvie, and Ono, Grant/research support from: Chugai, Seiji Okada: None declared, Ken Nakata Grant/research support from: Astellas. [Display omitted]

Background:Although rheumatoid arthritis (RA) patients with large joint involvement (LJI) have higher disease activity and lower physical function compared to patients without LJI,[1] the association between LJI and drug retention has not been examined. In addition, the pathophysiologies of patients with and without LJI may differ,[2] and therefore the characteristics and treatments of patients to modify the association between LJI and disease activity may exist.Objectives:The objectives of the multicenter longitudinal cohort study are twofold: (1) to examine the association of LJI with disease activity and drug retention, and (2) to explore the potential effect modifiers of changes in disease activity in patients with RA who started receiving biological disease-modifying antirheumatic drugs or Janus kinase inhibitors.Methods:Patients with RA from a Japanese multicenter observational registry were enrolled. According to the American College of Rheumatology/European League Against Rheumatism 2010 criteria,[3] we defined large joints as the shoulder, elbow, hip, knee, and ankle joints. Linear mixed-effects models were used to examine changes in the clinical disease activity index (CDAI) score at week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We also examined the potential effect modifications of changes in CDAI by baseline characteristics.Results:A total of 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in the CDAI score from baseline at week 24 (difference in change in CDAI: -5.84 [-6.65 to -5.03], P < 0.001), CDAI scores were significantly higher in patients with LJI over time (Figure 1A). Retention rates were similar in both groups (hazard ratio: 0.99 [0.85–1.14], P = 0.87) (Figure 1B). The association of LJI compared with that of no LJI with change in the CDAI score was more prominent in patients with short disease duration than in patients with long duration (Δ = -2.94, 95% CI: -6.86 to 0.98, P for interaction = 0.14), in patients with negative ACPA than in patients with positive ACPA (Δ = 0.94, 95% CI: -0.39 to -2.28, P for interaction = 0.17), and in patients using a IL-6 receptor inhibitor than in patients using a tumor necrosis factor inhibitor (Δ = -1.19, 95% CI: -2.29 to -0.08, P for interaction = 0.035) (Table 1).Conclusion:Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat-to-target strategy using an IL-6 receptor inhibitor may be beneficial for patients with LJI.REFERENCES:[1] Rubbert-Roth A, et al. Ann Rheum Dis. Jul 2018;77(7):1085-1086.[2] Chen DY, et al. Gerontology. 2009;55(3):250-258.[3] Aletaha D, et al. Ann Rheum Dis. 2010;69(9):1580-1588.Acknowledgements:NIL.Disclosure of Interests:Iku Shirasugi: None declared, Akira Onishi Pfizer Inc., Bristol-Myers Squibb., Advantest, Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Ono Pharmaceutical Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., Abbvie Inc., Takeda Pharmaceutical Co. Ltd., and Daiichi Sankyo Co. Ltd., Pfizer Inc., Bristol-Myers Squibb., Advantest, Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Ono Pharmaceutical Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., Abbvie Inc., Takeda Pharmaceutical Co. Ltd., and Daiichi Sankyo Co. Ltd., Keisuke Nishimura Pfizer Inc., Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Ono Pharmaceutical Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., Abbvie Inc., Janssen Pharmaceutical K.K., Taisho Pharmaceutical Co., Ltd, and Viatris Inc., Wataru Yamamoto: None declared, Kosaku Murakami Eisai Co. Ltd., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, UCB Japan Co. Ltd., Daiichi Sankyo Co. Ltd., and Astellas Pharma Inc., Eisai Co. Ltd., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, UCB Japan Co. Ltd., Daiichi Sankyo Co. Ltd., and Astellas Pharma Inc., Hideo Onizawa AbbVie, Asahi Kasei, Astellas Pharma Inc., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and Daiichi Sankyo Co. Ltd., AbbVie, Asahi Kasei, Astellas Pharma Inc., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and Daiichi Sankyo Co. Ltd., Yuichi Maeda Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation., Kosuke Ebina AbbVie, Amgen, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho Teijin Pharma, and UCB Japan., AbbVie, Amgen, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho Teijin Pharma, and UCB Japan., Yonsu Son Bristol-Myers Squibb, Chugai, Janssen, Eisai, and Abbvie., Hideki Amuro: None declared, Masaki Katayama: None declared, Ryota Hara AbbVie, Eli Lilly, Eisai, and Asahi-Kasei., Koji Nagai Pfizer Inc., Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., Ono Pharmaceutical Co., UCB Japan Co., Mitsubishi Tanabe Pharma Co., Eisai Co. Ltd., Abbvie Inc., Janssen Pharmaceutical K.K., Taisho Pharmaceutical Co., Ltd, and Viatris Inc., Yuri Hiramatsu Bristol-Myers Squibb, Astellas Pharma Inc, Asahi-Kasei, and UCB Japan Co. Ltd., Motomu Hashimoto Abbvie, Asahi Kasei, Astellas, Brystol Meyers, Chugai, EA Pharma, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taisho Toyama, Tanabe Mitsubishi., Tadashi Okano Asahi-Kasei, Eisai, Mitsubishi-Tanabe, AbbVie, Chugai, Eli Lilly, Janssen and Novartis Pharma., Toshihisa Maeda: None declared, Shinya Hayashi: None declared, Sadao Jinno AbbVie, Asahi Kasei Pharma., Bristol-Myers Squibb., Chugai, Ltd., Eisai, Eli Lilly, Janssen, and Mitsubishi Tanabe, and Ono., Yuzuru Yamamoto: None declared, Hirotaka Yamada AbbVie, Asahi Kasei Pharma, Astellas, Chugai, Eisai, Gilead Sciences, and Taiho Pharmaceutical., Sho Sendo: None declared, Yo Ueda AbbVie, Asahi Kasei Pharma, Astellas, Bristol Meyers Squibb, Chugai, Eisai, Eli Lilly, Gilead Sciences, and Taiho Pharmaceutical., Jun Saegusa Asahi Kasei Pharma, Abbie Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K, Pfizer Inc., Eisai, Janssen Pharmaceutical K.K., and Mitsubishi Tanabe Pharma.