Publications by authors named "M J Keir"
Background: Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides.
View Article and Find Full Text PDFBackground And Aims: Efmarodocokin alfa is an interleukin (IL)-22 agonist, with favorable pharmacokinetic (PK) properties and an acceptable safety profile. This study further explored the therapeutic potential of efmarodocokin alfa compared to vedolizumab in patients with ulcerative colitis (UC).
Methods: This randomized phase 2 trial evaluated the efficacy, safety, PK, and pharmacodynamics of 3 doses of efmarodocokin alfa administered intravenously every 4 weeks (30 μg/kg [n=43], 60 μg/kg [n=44], and 90 μg/kg [n=43]) compared with placebo (n=22) and with vedolizumab (n=43) in the treatment of moderate to severe UC.
Article Synopsis
- The conservation community is focusing on recovering species at risk of extinction, particularly in Maui, by implementing climate-resilient recovery plans for 36 native plant species.
- A tailored spatial conservation prioritization (SCP) approach was developed, emphasizing transparency, flexibility, and expert engagement, consisting of generating multiple prioritization solutions and selecting the best based on expert-agreed criteria.
- This method reduced the necessary conservation area by 36% while still ensuring high-quality habitats for species, proving more effective than existing tools like prioritizr by enhancing local recovery planning efforts.
Macrophages exhibit remarkable functional plasticity, a requirement for their central role in tissue homeostasis. During chronic inflammation, macrophages acquire sustained inflammatory 'states' that contribute to disease, but there is limited understanding of the regulatory mechanisms that drive their generation. Here we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary murine macrophages with transcriptional and cytokine profiling of genetic perturbations in primary human macrophages to uncover regulatory circuits of inflammatory states.
View Article and Find Full Text PDFArticle Synopsis
- This study examined the impact of high-dose influenza vaccination on patients with adult congenital heart disease (ACHD) compared to those without ACHD, focusing on all-cause mortality and cardiopulmonary hospitalizations.
- 272 ACHD patients were included, revealing that they were generally younger and had specific health conditions compared to the non-ACHD group of 4,988 individuals.
- Results showed no significant difference in the primary outcomes between ACHD and non-ACHD groups, indicating that both high- and standard-dose vaccines had similar effects on health outcomes.