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| http://dx.doi.org/10.5935/0103-507X.20210052 | DOI Listing |
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TCR transgenic clone selection guided by immune receptor analysis and single-cell RNA expression of polyclonal responders.
Elife
December 2024
Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
Since the precursor frequency of naive T cells is extremely low, investigating the early steps of antigen-specific T cell activation is challenging. To overcome this detection problem, adoptive transfer of a cohort of T cells purified from T cell receptor (TCR) transgenic donors has been extensively used but is not readily available for emerging pathogens. Constructing TCR transgenic mice from T cell hybridomas is a labor-intensive and sometimes erratic process, since the best clones are selected based on antigen-induced CD69 upregulation or IL-2 production in vitro, and TCR chains are polymerase chain reaction (PCR)-cloned into expression vectors.
View Article and Find Full Text PDFStructure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.
Proc Natl Acad Sci U S A
January 2025
Cellular and Structural Physiology Laboratory, Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo-ku, Tokyo 113-8510, Japan.
Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).
View Article and Find Full Text PDFEvaluating Meta-Learners to Analyze Treatment Heterogeneity in Survival Data: Application to Electronic Health Records of Pediatric Asthma Care in COVID-19 Pandemic.
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Department of Biostatistics and Health Data Science, University of Pittsburgh, Pittsburgh, Pennsylvania.
An important aspect of precision medicine focuses on characterizing diverse responses to treatment due to unique patient characteristics, also known as heterogeneous treatment effects (HTE) or individualized treatment effects (ITE), and identifying beneficial subgroups with enhanced treatment effects. Estimating HTE with right-censored data in observational studies remains challenging. In this paper, we propose a pseudo-ITE-based framework for analyzing HTE in survival data, which includes a group of meta-learners for estimating HTE, a variable importance metric for identifying predictive variables to HTE, and a data-adaptive procedure to select subgroups with enhanced treatment effects.
View Article and Find Full Text PDFGenome-Wide Genomic Analysis and Evolutionary Insights into Bovine Coronavirus Strains in Southwest China.
Vet Sci
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Guangxi Key Laboratory of Veterinary Biotechnology, Guangxi Veterinary Research Institute, Nanning 530001, China.
The global epidemic of bovine coronavirus (BCoV) has caused enormous economic losses. The characterisation and genetic composition of endemic strains in Southwest China remain elusive. This study aimed to fill this gap by isolating three BCoV strains from this region and sequencing their whole genomes.
View Article and Find Full Text PDFExploring Future Pandemic Preparedness Through the Development of Preventive Vaccine Platforms and the Key Roles of International Organizations in a Global Health Crisis.
Vaccines (Basel)
January 2025
Pharmaceutical Regulatory Affairs, Department of Pharmaceutical Industry, Graduate School, Chung-Ang University, Seoul 06974, Republic of Korea.
The emergence of more than 40 new infectious diseases since the 1980s has emerged as a serious global health concern, many of which are zoonotic. In response, many international organizations, including the US Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), and the European Center for Disease Prevention and Control (ECDC), have developed strategies to combat these health threats. The need for rapid vaccine development has been highlighted by Coronavirus disease 2019 (COVID-19), and mRNA technology has shown promise as a platform.
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