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Exploring Canine Picornavirus Diversity in the USA Using Wastewater Surveillance: From High-Throughput Genomic Sequencing to Immuno-Informatics and Capsid Structure Modeling.
Viruses
July 2024
Biodesign Center for Environmental Health Engineering, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
The SARS-CoV-2 pandemic resulted in a scale-up of viral genomic surveillance globally. However, the wet lab constraints (economic, infrastructural, and personnel) of translating novel virus variant sequence information to meaningful immunological and structural insights that are valuable for the development of broadly acting countermeasures (especially for emerging and re-emerging viruses) remain a challenge in many resource-limited settings. Here, we describe a workflow that couples wastewater surveillance, high-throughput sequencing, phylogenetics, immuno-informatics, and virus capsid structure modeling for the genotype-to-serotype characterization of uncultivated picornavirus sequences identified in wastewater.
View Article and Find Full Text PDFPharmacogenomic discovery of genetically targeted cancer therapies optimized against clinical outcomes.
NPJ Precis Oncol
August 2024
Leapfrog Bio, San Mateo, USA.
Despite the clinical success of dozens of genetically targeted cancer therapies, the vast majority of patients with tumors caused by loss-of-function (LoF) mutations do not have access to these treatments. This is primarily due to the challenge of developing a drug that treats a disease caused by the absence of a protein target. The success of PARP inhibitors has solidified synthetic lethality (SL) as a means to overcome this obstacle.
View Article and Find Full Text PDFPhase II study of talazoparib in advanced cancers with BRCA1/2, DNA repair, and PTEN alterations.
NPJ Precis Oncol
July 2024
Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer cells with BRCA1/2 deficiencies are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We evaluated the efficacy of talazoparib in DNA-Damage Repair (DDR)-altered patients. In this phase II trial, patients were enrolled onto one of four cohorts based on molecular alterations: (1) somatic BRCA1/2, (2) other homologous recombination repair pathway, (3) PTEN and (4) germline BRCA1/2.
View Article and Find Full Text PDFMarket Factors, Not Quality, Influence Reimbursement for Pancreaticoduodenectomy in an Era of Price Transparency.
Ann Surg Oncol
November 2024
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Background: The Centers for Medicare and Medicaid Services (CMS) price transparency rule tries to facilitate cost-conscious decision-making. For surgical services, such as pancreaticoduodenectomy (PD), factors mediating transparency and real-world reimbursement are not well described.
Methods: The Leapfrog Survey was used to identify United States hospitals performing PD.
Characterization of a lipid-based jumbo phage compartment as a hub for early phage infection.
Cell Host Microbe
July 2024
Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:
Article Synopsis
- Viral genomes are most susceptible to host defenses at the beginning of infection, making early protection crucial.
- Jumbo phages like ΦKZ create a phage nucleus to safeguard their DNA, but the process before this nucleus forms involves an early phage infection (EPI) vesicle that interacts with host proteins.
- The EPI vesicle helps protect the viral genome, facilitates early transcription with vRNAP, and keeps out harmful enzymes, ensuring effective gene expression and safe genome transfer to the developing nucleus.
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