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Background:Anemia is a condition that can cause symptoms such as fatigue, headaches, palpitations, shortness of breath during exertion, and depression. If left untreated, it can lead to a decrease in quality of life and shortened life expectancy.1) Anemia is frequently observed in patients with rheumatoid arthritis (RA), and various factors are cited as the cause, including not only inflammation due to RA but also gastrointestinal bleeding, chronic kidney disease, and side effects of anti-rheumatic drugs. One of the side effects of JAK inhibitors is anemia, which can be problematic for RA patients. Reports on anemia caused by JAK inhibitors in actual clinical practice are still scarce worldwide. Filgotinib (FIL) is a JAK inhibitor with high JAK1 selectivity, and it is known not to inhibit JAK2, which mediates the signal of erythropoietin. 2) In this study, we examined whether there were differences in the incidence of anemia in RA patients treated with each JAK inhibitor.Objectives:To compare and examine the incidence of anemia in RA patients receiving JAK inhibitors at our hospital between patients being treated with FIL and patients with JAK inhibitors other than FIL (Non-FIL).Methods:We divided 73 RA patients who had used four JAK inhibitors (Filgotinib, Tofacitinib, Baricitinib, Upadacitinib) since 2013 into FIL group (34 cases) and Non-FIL group (103 cases). Cases of hemorrhagic anemia were excluded. We conducted a retrospective investigation of the transition of Hemoglobin values (Hb) at 12 and 24 weeks after the start of treatment. In addition, we performed propensity score matching for age, sex, baseline Hb value, CRP value, serum creatinine value, presence or absence of anemia treatment, presence or absence of steroids or anti-rheumatic drugs, and history of treatment with bDMARDs/JAK inhibitors. Furthermore, we examined the discontinuation rate of JAK inhibitors in both groups due to anemia during the observation period using the Kaplan-Meier method.Results:The mean age was 69.0 years in the Non-FIL group and 74.5 years in the FIL group, indicating that the latter was older. The Hb value at the start of use was significantly lower in the FIL group (10.6 g/dl) than in the Non-FIL group (11.8 g/dl). In addition, the FIL group had a significantly higher number of cases of prior treatment with bDMARDs or JAK inhibitors and use of anemia treatment drugs. The reasons for starting FIL were insufficient effectiveness of the previous treatment and anemia, in that order. There was no difference in CRP value or RA disease activity during the observation period in either group. In the FIL group, there was a statistically significant increase in Hb value at 12 and 24 weeks after the start of JAK inhibitor treatment (0-12 weeks +0.72 g/dl, 0-24 weeks +0.99 g/dl). Furthermore, the same result was obtained by analyzing using propensity score matching (P<0.05), indicating that anemia improved in the FIL group. On the other hand, the Hb value at 12 weeks after the start of treatment was significantly lower than that at the start of treatment in the Non-FIL group, but it had stopped decreasing by 24 weeks (Graph 1). Next, the discontinuation rate of JAK inhibitors in both groups due to anemia (0-48 weeks) was zero in the FIL group. In the Non-FIL group, seven cases were discontinued by 24 weeks, but the number of discontinuations thereafter was relatively small (Graph 2).Conclusion:Filgotinib, which has high JAK1 selectivity, was confirmed to cause less anemia than other JAK inhibitors in actual clinical practice for RA treatment. Furthermore, anemia caused by JAK inhibitors is likely to occur within 24 weeks after the start of treatment, and it is considered necessary to observe this period carefully.REFERENCES:[1] Iron deficiency anaemia: assessment, prevention, and control. A guide for programme managers. Geneva: World Health Organization; 2001.[2] The safety of JAK-1 inhibitors: Rheumatology.60;ii24-ii30; 2021.Graph 1.Graph 2.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundRecently, the safety of JAK inhibitors in the treatment of rheumatoid arthritis(RA) about malignancy and major adverse cardiac events has been highlighted [1], but there are still few reports on their effects on anemia. Filgotinib (FIL) is known to be a highly JAK1-selective agent with little effect on EPO-mediated JAK2 signaling [2].ObjectivesWe investigated the effect of FIL on anemia in RA patients treated with JAK inhibitors at our hospital, comparing with other JAK inhibitors (non-FIL).Methods73 patients who used 4 JAK inhibitors (filgotinib, tofacitinib, baricitinib, upadacitinib) after 2013 were divided into FIL group (16 patients) and non-FIL group (57 patients) respectively. Hemoglobin (Hb) trends at 3 and 6 months after the start of JAK inhibitors were investigated retrospectively. Subsequently, the investigation was performed with propensity score matching by age, gender, baseline Hb, CRP, s-Cre, presence of anemia treatments, presence of corticosterids/DMARDs, and history of previous bDMARDs/JAK inhibitor use. And, among the FIL group, we also examined whether there was a difference in Hb change depending on the history of JAK inhibitor use.ResultsHb levels at the baseline were 10.5 g/dl in the FIL group and 11.6 g/dl in the non-FIL group, but there was no significant difference. The patients in the FIL group were significantly more likely to have used bDMARDs, other JAK inhibitors, and anemia treatments on starting FIL. Both at 3 and 6 months, although Hb levels were significantly increased in the FIL group (P<0.05), the anemia progressed over time in the non-FIL group despite exclusion of hemorrhagic anemia (Figures 1,2). The results after propensity score matching were also similar (P<0.05). There were no differences in CRP or RA disease activity at 0, 3, and 6 months. And then, compared to the FIL group with no history of JAK inhibitor use, the group that switched to FIL as a 2nd JAK inhibitor showed a significant Hb increase (P<0.05).ConclusionCompared to other JAK inhibitors, FIL did not reduce Hb levels and that could be maintained for a long time. In patients with anemia concerned with JAK inhibitors, switching to FIL is possible to make RA treatment safer and more successful.References[1]FDA Drug Safety Communication issued on February 4, 2021.[2]Traves PG, Murray B, Campigotto F, et al. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signaling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021; 80: 865-875.Figure 1.Figure 2.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. NCT00543543; NCT00943722.

Controlled access to the border of the Mott insulating state by variation of control parameters offers exotic electronic states such as anomalous and possibly high-transition-temperature ( T c ) superconductivity. The alkali-doped fullerides show a transition from a Mott insulator to a superconductor for the first time in three-dimensional materials, but the impact of dimensionality and electron correlation on superconducting properties has remained unclear. Here we show that, near the Mott insulating phase, the upper critical field H c2 of the fulleride superconductors reaches values as high as ∼90 T—the highest among cubic crystals. This is accompanied by a crossover from weak- to strong-coupling superconductivity and appears upon entering the metallic state with the dynamical Jahn–Teller effect as the Mott transition is approached. These results suggest that the cooperative interplay between molecular electronic structure and strong electron correlations plays a key role in realizing robust superconductivity with high- T c and high- H c2 . Alkali-doped fullerides are superconductors but the impact of dimensionality and electron correlation remains unclear. Here, Kasahara et al . report an upper critical field about 90 T, suggesting cooperative interplay between molecular electronic structure and strong electron correlations.

A muon linear accelerator is under development at J-PARC for precise measurement of the muon anomalous magnetic moment ( g –2) and electric dipole moment (EDM). A disk-and-washer (DAW) structure is employed to accelerate muons from 30% of the speed of light (kinetic energy = 4MeV) to 70% (40MeV) at 1296 MHz. The muon DAW consists of tanks accelerating the muons and bridge couplers that couple the tanks and focus the beam using an internal quadrupole doublet. A bridge-coupler prototype is currently being fabricated and will be tested. This paper presents the design and performance evaluation of the bridge coupler prototype.

We developed a gas electron multiplier (GEM) that is highly reliable against discharge using a Low Temperature Co-fired Ceramic (LTCC) as an insulating layer (LTCC-GEM). Because LTCC is an inorganic anti-carbonized material, LTCC-GEM is expected to be strong against breakdown. The gain properties of a single layer of 100 µm-thick LTCC-GEM with an effective area of 100 × 100 mm2 was evaluated in the gas mixture of 70% Ar and 30% CO2 at 1 atm. The maximum gain was approximately 3,500 at an applied voltage of 730 V and the gain variation was less than 3% over 14 hours of operation. In addition, the LTCC-GEM remained unbroken during the experiment despite more than 20,000 discharges at a high applied voltage of 730 V. We confirm that the LTCC-GEM is discharge-tolerant and has the same performance as traditional GEMs.

Low-temperature germination is one of the major determinants for stable stand establishment in the direct seeding method in temperate regions, and at high altitudes of tropical regions. Quantitative trait loci (QTLs) controlling low-temperature germinability in rice were identified using 122 backcross inbred lines (BILs) derived from a cross between temperate japonica varieties, Italica Livorno and Hayamasari. The germination rate at 15°C was measured to represent low-temperature germination and used for QTL analysis. The germination rate at 15°C for 7 days of Italica Livorno and Hayamasari was 98.7 and 26.8%, respectively, and that of BILs ranged from 0 to 83.3%. Using restriction fragment length polymorphism (RFLP) and simple sequence repeat (SSR) markers, we constructed a linkage map which corresponded to about 90% of the rice genome. Three putative QTLs associated with low-temperature germination were detected. The most effective QTL, qLTG-3-1 on chromosome 3, accounted for 35.0% of the total phenotypic variation for low-temperature germinability. Two additional QTLs, qLTG-3-2 on chromosome 3 and qLTG-4 on chromosome 4, were detected and accounted for 17.4 and 5.5% of the total phenotypic variation, respectively. The Italica Livorno alleles in all detected QTLs increased the low-temperature germination rate.

Abstract This paper investigates the removal of radon from purified and ambient airs by Ag-zeolite. Ag-zeolite is known to have very high performance in terms of airborne radon removal. The dependence on zeolite type and silver content of the performance of radon removal was evaluated. The performance of radon removal by a single pass and radon emanation were also evaluated. In addition, the adsorption performance due to zeolite solidification and the change in adsorption performance due to moisture in the gas were evaluated in order to investigate properties that should be considered for future practical use. These properties will be applicable to the development of air purification systems for large-volume ultra-low-radioactivity experiments.

The disk-loaded structures (DLS) in the muon LINAC are under development for the J-PARC muon g–2/EDM experiment. Four DLSs with an accelerating gradient of 20 MV/m take charge of muon acceleration from 40 MeV to 212 MeV, which corresponds to 70% to 94% of the speed of light. The quasi-constant gradient type TM01-2π/3 mode DLSs with gradually varying disk spacing was designed and it was confirmed that the cumulative phase slip due to the mismatch between muon and phase velocity can be suppressed to less than 2 degrees at the frequency of 2592 MHz. In addition, the optimum synchronous phase and the lattice were investigated to satisfy the requirements of the total emittance less than 1.5π mm mrad and the momentum spread less than 0.1% in RMS.

We conducted a high-power test of a prototype cavity of a 324-MHz interdigital H-mode drift tube linac (IH-DTL) for the precise measurement of the muon anomalous magnetic moment (g−2) and electric dipole moment (EDM). This prototype cavity (short IH) was developed to verify the fabrication methodology for the IH-DTL cavity with a monolithic drift tube structure. The electromagnetic field distribution was measured and compared with the finite element method simulation results, and the fabrication accuracy of the monolithic drift tube was confirmed to satisfy the requirements. After 40 h of conditioning, the short IH was stably operated with an rf power of 88 kW, which corresponds to a 10% higher accelerating field than the design field (E0) of3.0MV/m. In addition, the thermal characteristics and frequency response were measured, verifying that the experimental data were consistent with the three-dimensional model. In this paper, the design, fabrication, and low-power and high-power tests of this IH-DTL for muon acceleration are described.