Triclabendazole (TCB) is a well-established anthelmintic effective in treating fascioliasis, a neglected tropical disease. This study employs quality by design (QbD) to investigate the impact of TCB polymorphism and pharmacotechnical variables, from the development of immediate-release tablets to process optimization and green analysis. Critical process parameters (CPPs) and critical material attributes (CMAs), characterized by type of polymorph, composition of excipients (talc, lactose, cornstarch, and magnesium stearate), and compression force, were screened using a Plackett-Burman design (n = 24), identifying polymorphic purity and cornstarch as a CPP.
View Article and Find Full Text PDFObjective: The study aimed to explore the utility of contrast-enhanced ultrasound (CEUS) as a tool for detecting minimal inflammation in rheumatoid arthritis (RA) patients in sustained remission (SR) and to correlate the findings with Disease Activity Score 28 (DAS28) status scores and various ultrasound (US) scores.
Patients And Methods: Thirty RA patients in SR (minimum 6 months), 12 with active disease, and 10 healthy controls were included. Clinical evaluations and US assessments were performed, including grayscale US (GSUS), power Doppler US (PDUS), and Global OMERACT-EULAR Synovitis Score (GLOESS).
Most genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells.
View Article and Find Full Text PDFAlthough chimeric antigen receptor (CAR) T cells are effective against B-lineage malignancies, post-CAR relapse is common, and efficacy in other tumors is limited. These challenges may be addressed through rational manipulations to control CAR T cell function. Here we examine the impact of cognate T cell antigen experience on subsequent CD8 CAR T cell activity.
View Article and Find Full Text PDFThe everyday harms of structural racism and discrimination, perpetuated through institutions, laws, policies, and practices, constitute social determinants of health, but measures that account for their debilitating effects are largely missing in genetic studies of complex diseases. Drawing on insights from the social sciences and public health, we propose critical methodologies for incorporating tools that measure structural racism and discrimination within genetic analyses. We illustrate how including these measures may strengthen the accuracy and utility of findings for diverse communities, clarify elusive relationships between genetics and environment in a racialized society, and support greater equity within genomics and precision health research.
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