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Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that exhibited favorable response to upadacitinib. A 69-year-old man, former smoker, was diagnosed with RA-ILD based on persistent symmetric polyarthritis, elevated C-reactive protein levels and erythrocyte sedimentation rate, reduced diffusing capacity for carbon monoxide/alveolar volume (DLCO 69.9%), and bilateral ground-glass attenuation with traction bronchiectasis, predominantly in the lower lung lobe. Initial treatment with oral prednisolone and methotrexate was started; however, the patient showed worsening dyspnea, chest high-resolution computed tomography abnormalities, and decreased pulmonary function. The dose of prednisolone was increased, and methotrexate was shifted to tacrolimus; however, tacrolimus was eventually discontinued because of renal dysfunction. Subsequent treatment changes included abatacept followed by intravenous cyclophosphamide, but ILD activity continued to worsen and met the criteria of progressive pulmonary fibrosis. Approximately 4.5 years after the RA diagnosis, dyspnea, radiological abnormalities, and DLCO improved following treatment switch to upadacitinib, one of JAKis. JAKi therapy may have potential as a treatment option for refractory RA-ILD.

Summary: Despite recent therapeutic advances for multiple myeloma (MM), relapse is very common. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of MM cells from a patient with relapsed MM, treated with multiple anti-myeloma drugs. We observed five subclusters of MM cells, which appeared and/or disappeared in response to the therapeutic pressure, and identified cluster 3 which emerged during lenalidomide treatment and disappeared after proteasome inhibitor (PI) treatment. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin-protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death in in vitro assay. Kaplan-Meier survival analysis of database revealed that higher expression of PELI2 is associated with a better prognosis. Our integrated strategy combining longitudinal scRNA-seq analysis, in vitro functional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug-response genes.

Abstract In a linear dilaton background, it has been argued that an unstable D-brane can decay to the tachyon vacuum without leaving behind a remnant of tachyon matter. Here we address the question of how the D-brane can decay to the tachyon vacuum when the tachyon vacuum does not support physical fluctuations. Using the formalism of open string field theory, we find that the tachyon vacuum can support fluctuations provided they are “hidden” as nonperturbative effects behind a pure gauge asymptotic series.

Abstract We study profiles and gauge invariant observables of classical solutions corresponding to a constant magnetic field on a torus in open string field theory. We numerically find that the profile is not discontinuous on the torus, although the solution describes topologically nontrivial configurations in the context of low energy effective theory. From the gauge invariant observables, we show that the solution provide correct couplings of closed strings to a D-brane with constant magnetic field.

Abstract We show how conformal field theory topological defects can relate solutions of open string field theory for different boundary conditions. To this end we generalize the results of Graham and Watts to include the action of defects on boundary condition changing fields. Special care is devoted to the general case when nontrivial multiplicities arise upon defect action. Surprisingly the fusion algebra of defects is realized on open string fields only up to a (star algebra) isomorphism.

This paper presents the analysis of a simplified model for the design of a module structure that avoids the risk of self-excited oscillation(SE-Osc). A necessary and sufficient simplified model that can extract the critical oscillation mode is proposed based on a comparison of several simplifying steps. The differential equation of the simplified model is solved, and the solution is plotted in the frequency domain to analyze the oscillatory conditions. The simplified model is verified via a time-domain full-model simulation modeled by 3-D electromagnetic simulation and solved by finite-element simulation. Measurements of test modules show consistent oscillatory conditions and frequency. SE-Osc modes are eliminated by reducing the inductance connected to the emitter and increasing the inductance connected to the collector. Increasing the ratio of CCE to CGC increases the risk of self-exciting oscillation. Suppressions of SE-Osc from a common package design with state-of-the-art Si-insulated gate bipolar transistors (IGBTs) presenting small feedback capacitance, SiC-MOS, and hybrids of state-of-art Si-IGBTs and SiC-Schottky barrier diodes are verified. [ABSTRACT FROM AUTHOR]