Proteomic evidence of dietary sources in ancient dental calculus.

Archaeological dental calculus has emerged as a rich source of ancient biomolecules, including proteins. Previous analyses of proteins extracted from ancient dental calculus revealed the presence of the dietary milk protein β-lactoglobulin, providing direct evidence of dairy consumption in the archaeological record. However, the potential for calculus to preserve other food-related proteins has not yet been systematically explored. Here we analyse shotgun metaproteomic data from 100 archaeological dental calculus samples ranging from the Iron Age to the post-medieval period (eighth century BC to nineteenth century AD) in England, as well as 14 dental calculus samples from contemporary dental patients and recently deceased individuals, to characterize the range and extent of dietary proteins preserved in dental calculus. In addition to milk proteins, we detect proteomic evidence of foodstuffs such as cereals and plant products, as well as the digestive enzyme salivary amylase. We discuss the importance of optimized protein extraction methods, data analysis approaches and authentication strategies in the identification of dietary proteins from archaeological dental calculus. This study demonstrates that proteomic approaches can robustly identify foodstuffs in the archaeological record that are typically under-represented due to their poor macroscopic preservation

Case Report of AdAPT-001-Mediated Sensitization to a Previously Failed Checkpoint Inhibitor in a Metastatic Chordoma Patient

Chordoma is a rare, but aggressive bone tumor with a high recurrence rate that primarily arises at the cranial and caudal ends of the axial skeleton. Systemic chemotherapies are not effective against the tumor, and outside of surgical resection and radiation, no approved options are available. Prognosis depends on the extent of surgical resection, with the more the better, and adjuvant radiotherapy. Herein is presented the first-ever case of a recurrent chordoma patient that responded to the combination of one dose of an experimental TGF-beta trap carrying oncolytic adenovirus, known as AdAPT-001, followed by immune checkpoint inhibitor therapy, despite prior progression on an anti-PD-1. This case report highlights the potential of AdAPT-001 as a treatment modality in combination with checkpoint inhibition for recurrent chordoma

Case Report of AdAPT-001-Mediated Sensitization to a Previously Failed Checkpoint Inhibitor in a Metastatic Chordoma Patient.

Chordoma is a rare, but aggressive bone tumor with a high recurrence rate that primarily arises at the cranial and caudal ends of the axial skeleton. Systemic chemotherapies are not effective against the tumor, and outside of surgical resection and radiation, no approved options are available. Prognosis depends on the extent of surgical resection, with the more the better, and adjuvant radiotherapy. Herein is presented the first-ever case of a recurrent chordoma patient that responded to the combination of one dose of an experimental TGF-beta trap carrying oncolytic adenovirus, known as AdAPT-001, followed by immune checkpoint inhibitor therapy, despite prior progression on an anti-PD-1. This case report highlights the potential of AdAPT-001 as a treatment modality in combination with checkpoint inhibition for recurrent chordoma

In Situ Coral Nurseries Serve as Genetic Repositories for Coral Reef Restoration After an Extreme Cold-Water Event

During an unusual cold-water event in January 2010, reefs along the Florida Reef Tract suffered extensive coral mortality, especially in shallow reef habitats in close proximity to shore and with connections to coastal bays. The threatened staghorn coral, Acropora cervicornis, is the focus of propagation and restoration activities in Florida and one of the species that exhibited high susceptibility to low temperatures. Complete mortality of wild staghorn colonies was documented at 42.9% of donor sites surveyed after the cold event. Remarkably, 72.7% of sites with complete A. cervicornis mortality had fragments surviving within in situ coral nurseries. Thus, coral nurseries served as repositories for genetic material that would have otherwise been completely lost from donor sites. The location of the coral nurseries at deeper habitats and distanced from shallow nearshore habitats that experienced extreme temperature conditions buffered the impacts of the cold-water event and preserved essential local genotypes for future Acropora restoration activities

Racial Differences in the Evaluation and Treatment of Hepatitis C Among Veterans: A Retrospective Cohort Study

Objectives. We examined the association between race and hepatitis C virus (HCV) evaluation and treatment of veterans in the Northwest Network of the Department of Veterans Affairs (VA)

BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors.

AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-β receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-β. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated \u27cold\u27 tumors as well as distant untreated tumors, and, from its induction of systemic CD8+ T cell-mediated antitumor immunity, protected the mice from rechallenge with tumor cells. AdAPT-001 also sensitized resistant tumors to checkpoint blockade. This manuscript describes the rationale and design of the first-in-human phase I, dose-escalation and dose-expansion study of AdAPT-001 alone and in combination with a checkpoint inhibitor in adults with treatment-refractory superficially accessible solid tumors. Trial registration: ClinicalTrials.gov NCT04673942. Keywords: AdAPT-001; BETA PRIME; TGF-β trap; abscopal effect; oncolytic adenovirus; solid tumors; study protocol