Real-world impact of dupilumab on asthma disease burden in Japan: The CROSSROAD study.

Background: Dupilumab, a human monoclonal anti-interleukin (IL)-4Ra antibody blocks the shared receptor component of IL-4 and IL-13, drivers of type 2 inflammation. Dupilumab is approved for severe/refractory asthma inadequately controlled by existing therapies, but knowledge of its effect on real-world disease burden is lacking. This study investigates real-world effects of dupilumab on asthma exacerbation risk and oral corticosteroid (OCS) use in Japanese individuals with asthma.

Investigation of time profile of FEV across the onset of potential COPD: a retrospective cohort study using medical checkup data in Japan.

This study compared the time profile of FEV after COPD diagnosis among rapid decliners, slow decliners, and sustainers in the year of COPD diagnosis. COPD subjects were identified from the annual medical checkup records of Hitachi, Ltd., employees in Japan (April 1998-March 2019).

Efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma recruited from Japanese centers in the phase 3 LIBERTY ASTHMA TRAVERSE study.

Background: Safety and efficacy data for dupilumab beyond 1 year are lacking for patients from Japan with moderate-to-severe asthma.

Methods: The TRAVERSE open-label extension (OLE) study (NCT02134028) assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in 2282 patients who completed a previous dupilumab asthma study. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs).

Machine Learning Methods for the Diagnosis of Chronic Obstructive Pulmonary Disease in Healthy Subjects: Retrospective Observational Cohort Study.

Background: Airflow limitation is a critical physiological feature in chronic obstructive pulmonary disease (COPD), for which long-term exposure to noxious substances, including tobacco smoke, is an established risk. However, not all long-term smokers develop COPD, meaning that other risk factors exist.

Objective: This study aimed to predict the risk factors for COPD diagnosis using machine learning in an annual medical check-up database.

Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials.

Objective: To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms.

Methods: Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores).

Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review.

Objectives: To identify, describe and summarize evidence on residual symptoms and disease burdens in rheumatoid arthritis (RA) patients qualified as being in remission or low disease activity (LDA).

Methods: A systematic literature review (SLR) was conducted according to Cochrane collaboration guidelines. The population of interest was adult patients with RA in remission or LDA.

Syk-dependent signaling pathways in neutrophils and macrophages are indispensable in the pathogenesis of anti-collagen antibody-induced arthritis.

Spleen tyrosine kinase (Syk) is associated with Fcγ receptors (FcγRs) and transmits activation signals through FcγRs in myeloid cells. Thus, application of drugs to inhibit Syk activity can affect the development of immune diseases mediated by autoantibodies, while unexpected systemic effects by the inhibition may be concerned because Syk has multiple physiological functions. We used tamoxifen-inducible systemic conditional Syk knockout (KO) mice to evaluate the role of Syk in the pathogenesis of autoimmune arthritis and to investigate the systemic effects of Syk deletion.

Effects of overtraining on extinction in newts (Cynops pyrrhogaster).

The overtraining extinction effect (OEE), a phenomenon in which extended training facilitates extinction, has been found in mammals and reptiles. However, fish have never shown OEE. No study has yet investigated OEE in newts, a representative amphibian species.

Alteration of the PKC theta-Vav1 complex and phosphorylation of Vav1 in TCDD-induced apoptosis in the lymphoblastic T cell line, L-MAT.

We have previously reported that protein kinase C (PKC) theta (theta) and protein tyrosine kinase are involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced apoptosis of L-MAT, a human lymphoblastic T cell line. In the current report, we show that Vav1, a GDP/GTP exchange factor for Rho-like small GTPases, could be detected by Western blotting in the membrane fraction of L-MAT cells after TCDD treatment and was precipitated by incubating with an antibody against PKC theta. Furthermore, the degree of phosphorylation of Vav1, which can be detected using the phosphotyrosine-specific antibody PY-20 or 4G10, is significantly increased after treatment with TCDD.

Calcium/calmodulin signaling elicits release of cytochrome c during 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced apoptosis in the human lymphoblastic T-cell line, L-MAT.

We have reported previously that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces apoptosis in the human lymphoblastic T-cell line L-MAT, although these cells do not express the aromatic hydrocarbon receptor (AhR). The AhR-dependent pathway for the induction of immunotoxicity by TCDD has been studied extensively, but the AhR-independent pathway is not understood. Several studies have reported that TCDD elevates the concentration of free intracellular calcium ([Ca(2+)](i)) in various types of cells.

Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation.

Daxx has been shown to play an essential role in type I IFN-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify the molecular mechanisms of how Daxx acts on growth suppression of B lymphocytes, we examined functions of a sumoylation-defective Daxx KA mutant (Daxx K630/631A), which substituted Lys 630 and Lys 631 to Ala.

Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines.

Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. Here, we identified threonine-265 (Thr265) in ZIPK as a major autophosphorylation site. Mutational analyses revealed that autophosphorylation of Thr265 were essential for its full catalytic activity toward an exogenous substrate as well as for cell death induction.

Physical and functional interactions between STAT3 and ZIP kinase.

Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor that can be activated by cytokines and growth factors. It plays important roles in cell growth, apoptosis and cell transformation, and is constitutively active in a variety of tumor cells. In this study, we provide evidence that zipper-interacting protein kinase (ZIPK) interacts physically with STAT3.

Controlled release of vitamin E from thermo-responsive polymeric physico-gel.

Thermo-sensitive copolymer consists of poly(2-ethoxyethyl vinyl ether) and poly(hydroxyethyl vinyl ether) (EOVE200-HOVE400), whose sol-gel transition temperature was 20.5 degrees C, was synthesized and its applicability to a drug delivery system was examined. Vitamin E (VE) was enclosed in EOVE200-HOVE400 and the release of VE was measured by varying the temperature 10<-->30 degrees C.

Pattern Memory and Resistance to Extinction in Double Alternating Reinforcement.

Interval between acquisition and extinction (A-E interval) was varied in order to investigate effects of regularly alternated partial reinforcement on resistance to extinction and to assess the notion of pattern memory which was suggested on the basis of single alternation study. Random alternation (RA) and double alternation (DA) groups were trained with extensive trials and then extinguished under one-day's (RA1, DA1) or 23-days' (RA23, DA23) A-E interval. RA1 was more resistant to extinction than DA1, but DA23 did not differ from RA23.