Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study

Objectives: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent. Methods: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18. Results: 53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): –1.03 (–1.66 to –0.40) vs –0.58 (–1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement. Conclusions: Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA. Trial registration number: NCT04991753

A Second Order Characteristic Method for Approximating Incompressible Miscible Displacement in Porous Media

An approximation scheme is defined for incompressible miscible displacement in porous media. This scheme is constructed by two methods. Under the regularity assumption for the pressure, cubic Hermite finite element method is used for the pressure equation, which ensures the approximation of the velocity smooth enough. A second order characteristic finite element method is presented to handle the material derivative term of the concentration equation. It is of second order accuracy in time increment, symmetric, and unconditionally stable. The optimal L2-norm error estimates are derived for the scalar concentration

Corrigendum to “Modeling Inhibitory Effect on the Growth of Uninfected T Cells Caused by Infected T Cells: Stability and Hopf Bifurcation”

We consider a class of viral infection dynamic models with inhibitory effect on the growth of uninfected T cells caused by infected T cells and logistic target cell growth. The basic reproduction number R0 is derived. It is shown that the infection-free equilibrium is globally asymptotically stable if R0<1. Sufficient conditions for the existence of Hopf bifurcation at the infected equilibrium are investigated by analyzing the distribution of eigenvalues. Furthermore, the properties of Hopf bifurcation are determined by the normal form theory and the center manifold. Numerical simulations are carried out to support the theoretical analysis

Modeling Inhibitory Effect on the Growth of Uninfected T Cells Caused by Infected T Cells: Stability and Hopf Bifurcation

We consider a class of viral infection dynamic models with inhibitory effect on the growth of uninfected T cells caused by infected T cells and logistic target cell growth. The basic reproduction number R0 is derived. It is shown that the infection-free equilibrium is globally asymptotically stable if R0<1. Sufficient conditions for the existence of Hopf bifurcation at the infected equilibrium are investigated by analyzing the distribution of eigenvalues. Furthermore, the properties of Hopf bifurcation are determined by the normal form theory and the center manifold. Numerical simulations are carried out to support the theoretical analysis

Research on hydrogen fuel cell backup power for metal hydride hydrogen storage system

Hydrogen fuel cells are characterized by non-pollution, high efficiency and long power supply time, and they are increasingly used as backup power systems in substations, communication base stations and other fields. In this paper, based on the thermodynamic model of the hydride hydrogen storage system, the relationship between pressure, composition, and temperature in metal hydride hydrogen storage is quantitatively analyzed using a PCT curve. The hydrogen fuel power supply is used as the overall backup power supply of the DC system, and the hydrogen-fuel integrated backup power supply is established to realize the uninterrupted switching between the utility power and the backup power supply. Finally, the working process of the backup power supply and the reaction process of hydrogen are analyzed to test the feasibility of a hydrogen fuel cell backup power supply. The results show that the operating current climbs to the end of 80 A under the 5 kW workload demand of the communication equipment. In addition, the hydrogen absorption reaction rate was 0.29 Mpa, and the hydrogen release reaction rate was 0.21 Mpa at a temperature of 291 K. This study has developed a fuel cell backup power system that can provide uninterruptible backup power and has a wide market capacity and application prospects

Effect of Gluten and Wheat Starch on the Frozen Storage Quality of Reconstituted Dough

The frozen preservation quality of dough cannot meet the requirements of industrial production of fresh and wet noodles. To investigate the effect of the main dough components (gluten protein and starch) on the quality of the frozen dough, dough restructuring with high gluten wheat flour (50%) and different proportions of gluten and wheat starch, and the water distribution, rheological properties, pasting characteristics, gel strength, microstructure and hydrogen bond strength were analyzed after freezing storage at 18 ℃ for 20 days, with 100% raw wheat flour as the control group. The results showed that the water in the frozen reconstituted dough gradually migrated from bound water to free water, and the elastic modulus decreased from 125900 Pa to 73020 Pa as the ratio of gluten to wheat starch decreased from 4:1 to 1:4, the pasting parameters increased, andgel hardness from 114.30 g to 181.39 g. Scanning electron microscope showed that the lower the ratio of gluten to wheat starch, the more unfavorable the uniformity of the gluten protein network structure. The hydrogen bond strength in the reconstituted dough was greater than that in the control group after adding gluten and wheat starch, and it continued to increase as the ratio of gluten to wheat starch decreased. When the ratio of gluten to wheat starch was 4:1, the elastic modulus of the reconstituted dough frozen for 20 days was 49.95% higher than that of the control group, which delayed the quality deterioration of the dough during the frozen storage. Reconstituting the dough with a certain ratio of starch to gluten can improve the viscoelasticity of the dough, which was beneficial to its cryopreservation quality

Association between CBS gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region and coronary artery disease: a meta-analysis

ABSTRACTBackground Several studies indicate that the cystathionine β-synthase (CBS) gene T833C, G919A and 844ins68 polymorphisms in the 8th exon region may be correlated with coronary artery disease (CAD) susceptibility, but the results have been inconsistent and inconclusive. Thus, a meta-analysis was conducted to provide a comprehensive estimate of these associations.Methods On the basis of searches in the PubMed, EMBASE, Cochrane Library, Wanfang, VIP, and CNKI databases, we selected 14 case – control studies including 2123 cases and 2368 controls for this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated accordingly using a fixed-effect or random-effect model.Results The results indicated an increased risk between the CBS T833C gene polymorphisms and susceptibility to CAD under the dominant model (CC+CT vs. TT: OR = 1.92, 95% CI: 1.11 ~ 3.32), recessive model (CC vs. CT+TT: OR = 1.88, 95% CI: 1.17 ~ 3.03), and homozygous model (CC vs. TT: OR = 2.46, 95% CI: 1.04 ~ 5.83). In these three genetic models, no significant association was identified for CBS G919A (AA+AG vs. GG: OR = 1.48, 95% CI: 0.45 ~ 4.82),(AA vs. AG+GG: OR = 1.58, 95% CI: 0.93 ~ 2.70),(AA vs. GG: OR = 1.66, 95% CI: 0.40 ~ 6.92) or CBS 844ins68 (II+ID vs. DD: OR = 1.04, 95% CI: 0.80 ~ 1.35),(II vs. ID+DD: OR = 1.09, 95% CI: 0.51 ~ 2.36),(II vs. DD: OR = 1.10, 95% CI: 0.51 ~ 2.39).Conclusions This meta-analysis suggests that the CBS T833C gene polymorphism is significantly associated with the risk of CAD and it shows a stronger association in Asian populations. Individuals with the C allele of the CBS gene T833C polymorphism might be particularly susceptible to CAD