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TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation.
Nat Cancer
December 2024
Genentech, South San Francisco, CA, USA.
Blockade of immune checkpoints PD-1 and TIGIT has demonstrated activity in mouse tumor models and human patients with cancer. Although these coinhibitory receptors can restrict signaling in CD8 T cells by regulating their associated co-stimulatory receptors CD28 and CD226, the functional consequences of combining PD-1 and TIGIT blockade remain poorly characterized. In mouse tumor models, we show that combination blockade elicited CD226-driven clonal expansion of tumor antigen-specific CD8 T cells.
View Article and Find Full Text PDFCLEMENT: genomic decomposition and reconstruction of non-tumor subclones.
Nucleic Acids Res
August 2024
Department of Biomedical Systems Informatics, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Genome-level clonal decomposition of a single specimen has been widely studied; however, it is mostly limited to cancer research. In this study, we developed a new algorithm CLEMENT, which conducts accurate decomposition and reconstruction of multiple subclones in genome sequencing of non-tumor (normal) samples. CLEMENT employs the Expectation-Maximization (EM) algorithm with optimization strategies specific to non-tumor subclones, including false variant call identification, non-disparate clone fuzzy clustering, and clonal allele fraction confinement.
View Article and Find Full Text PDFPersistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children.
Nat Commun
May 2024
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Standard diagnostics used in longitudinal antimalarial studies are unable to characterize the complexity of submicroscopic parasite dynamics, particularly in high transmission settings. We use molecular markers and amplicon sequencing to characterize post-treatment stage-specific malaria parasite dynamics during a 42 day randomized trial of 3- versus 5 day artemether-lumefantrine in 303 children with and without HIV (ClinicalTrials.gov number NCT03453840).
View Article and Find Full Text PDFMolecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression.
Cancers (Basel)
March 2024
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected.
View Article and Find Full Text PDFPHARE: a bioinformatics pipeline for compositional profiling of multiclonal Plasmodium falciparum infections from long-read Nanopore sequencing data.
J Antimicrob Chemother
May 2024
University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
Background: The emergence of drug-resistant clones of Plasmodium falciparum is a major public health concern, and the ability to detect and track the spread of these clones is crucial for effective malaria control and treatment. However, in endemic settings, malaria infected people often carry multiple P. falciparum clones simultaneously making it likely to miss drug-resistant clones using traditional molecular typing methods.
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