International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?

Study Design And Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit.

Dexamethasone potentiates chimeric antigen receptor T cell persistence and function by enhancing IL-7Rα expression.

Dexamethasone (dex) is a glucocorticoid that is a mainstay for the treatment of inflammatory pathologies, including immunotherapy-associated toxicities, yet the specific impact of dex on the activity of CAR T cells is not fully understood. We assessed whether dex treatment given ex vivo or as an adjuvant in vivo with CAR T cells impacted the phenotype or function of CAR T cells. We demonstrated that CAR T cell expansion and function were not inhibited by dex.

The increasing burden of asthma acute care in Singapore: an update on 15-year population-level evidence.

Background: In Singapore, there is currently scarce population-based research informing the recent trends of asthma-related healthcare burdens. In this study, we investigated the past 25-year trends of asthma-related hospitalisations, emergency department (ED) visits and deaths in Singapore and projected the future burdens from 2023 to 2040.

Methods: We acquired annually-measured data from the Singapore Ministry of Health Clinical and National Disease Registry, containing 25-year asthma-related hospitalisation and death rates as well as 15-year ED visit rates.

Impact of Guideline-Based Asthma Treatment on Health Services Use in Singapore Before and During COVID-19 Outbreak.

Introduction: To date, the role of standard asthma care in reducing asthma-related health services use (HSU) during the COVID-19 pandemic remains unclear. This study examined the impact of guideline-based asthma treatment on the use of asthma-related emergency department (ED) visits, polyclinic visits (total visits and urgent visits characterized by nebuliser use) before and during the pandemic.

Methods: Data from April 2017 to October 2020 was obtained from the National University Health System, one of the three healthcare clusters in Singapore.

Mediation analysis with multiple mediators under unmeasured mediator-outcome confounding.

It is often of interest in the health and social sciences to investigate the joint mediation effects of multiple post-exposure mediating variables. Identification of such joint mediation effects generally require no unmeasured confounding of the outcome with respect to the whole set of mediators. As the number of mediators under consideration grows, this key assumption is likely to be violated as it is often infeasible to intervene on any of the mediators.

Pre-clinical data supporting immunotherapy for HIV using CMV-HIV-specific CAR T cells with CMV vaccine.

T cells engineered to express HIV-specific chimeric antigen receptors (CARs) represent a promising strategy to clear HIV-infected cells, but to date have not achieved clinical benefits. A likely hurdle is the limited T cell activation and persistence when HIV antigenemia is low, particularly during antiretroviral therapy (ART). To overcome this issue, we propose to use a cytomegalovirus (CMV) vaccine to stimulate CMV-specific T cells that express CARs directed against the HIV-1 envelope protein gp120.

CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma.

CD19-directed chimeric antigen receptor (CD19CAR) T-cell therapy has been successful in treating several B-cell lineage malignancies, including B-cell non-Hodgkin lymphoma (NHL). This modality has not yet been extended to NHL manifesting in the central nervous system (CNS), primarily as a result of concerns for potential toxicity. CD19CAR T cells administered IV are detectable in cerebrospinal fluid (CSF), suggesting that chimeric antigen receptor (CAR) T cells can migrate from the periphery into the CNS, where they can potentially mediate antilymphoma activity.

Conditionally Replicating Vectors Mobilize Chimeric Antigen Receptors against HIV.

Human immunodeficiency virus (HIV) is an attractive target for chimeric antigen receptor (CAR) therapy. CAR T cells have proved remarkably potent in targeted killing of cancer cells, and we surmised that CAR T cells could prove useful in eradicating HIV-infected cells. Toward this goal, we interrogate several neutralizing single-chain variable fragments (scFvs) that target different regions of the HIV envelope glycoprotein, gp120.

The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma.

Lymphomas with central nervous system (CNS) involvement confer a worse prognosis than those without CNS involvement, and patients currently have limited treatment options. T cells genetically engineered with CD19-targeted chimeric antigen receptors (CAR) are effective against B-cell malignancies and show tremendous potential in the treatment of systemic lymphoma. We aimed to leverage this strategy toward a more effective therapy for patients with lymphoma with CNS disease.

, a new species of Cyclophoridae (Gastropoda: Caenogastropoda), discovered and described on a field course to Kuala Belalong rainforest, Brunei.

Background: Terrestrial Caenogastropoda form an important but threatened component of the Borneo tropical rainforest malacofauna, where the group is nearly as rich in species as the Stylommatophora. They are, however, more sensitive to drought, temperature extremes and forest degradation.

New Information: On a field course at Kuala Belalong Field Studies Centre in Brunei Darussalam (Borneo), a new caenogastropod species, belonging to the genus , was discovered by the course participants.

Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma.

Multiple myeloma remains an incurable malignancy of plasma cells despite considerable advances in treatment. The purpose of the study was to develop novel chimeric antigen receptors (CAR) for the treatment of multiple myeloma and explore combinatorial therapy using CAR T cells and immunomodulatory drugs such as lenalidomide for increasing treatment efficacy. We redirected central memory T cells to express second-generation CAR-specific for CS1 and adoptively transferred them into multiple myeloma tumor-bearing mice to test their anti-multiple myeloma activity.

Preclinical data support leveraging CS1 chimeric antigen receptor T-cell therapy for systemic light chain amyloidosis.

Background Aims: Light chain amyloidosis (AL) is a protein deposition disorder that is a result of a plasma cell dyscrasia, similar to multiple myeloma (MM). Immunotherapy is an attractive approach because of the low burden of disease, but the optimal target for AL is unclear. CS1 and B-cell maturation antigen (BCMA) are two potential targets because they are expressed on normal plasma cells and MM cells.

Ex vivo Akt inhibition promotes the generation of potent CD19CAR T cells for adoptive immunotherapy.

Background: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation.

The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle mass in mice.

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size.

The effect of caffeine ingestion on human neutrophil oxidative burst responses following time-trial cycling.

Following fixed-duration exercise of submaximal intensity, caffeine ingestion is associated with an attenuation of the exercise-induced decline in N-formyl-methionyl-phenyl-alanine (f-MLP) stimulated neutrophil oxidative burst. However, the response following high-intensity exhaustive exercise is unknown. Nine endurance-trained male cyclists ingested 6 mg caffeine or placebo per kilogram of body mass 60 min before cycling for 90 min at 70% of maximal oxygen consumption (VO2max) and then performing a time-trial requiring an energy expenditure equivalent to 30 min cycling at 70% maximum power output.