Structure-Based Design of Novel TLR7/8 Agonist Payloads Enabling an Immunomodulatory Conjugate Approach.

Dual activation of the TLR7 and TLR8 pathways leads to the production of type I interferon and proinflammatory cytokines, resulting in efficient antigen presentation by dendritic cells to promote T-cell priming and antitumor immunity. We developed a novel series of TLR7/8 dual agonists with varying ratios of TLR7 and TLR8 activity for use as payloads for an antibody-drug conjugate approach. The agonist-induced production of several cytokines in human whole blood confirmed their functional activity.

Contrast-enhanced computed tomography for ex vivo assessment of human kidneys: A proof-of-concept study.

Background: Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information.

Effector-specific improvements in action prediction in left-handed individuals after short-term physical practice.

Research has established the influence of short-term physical practice for enhancing action prediction in right-handed (RH) individuals. In addition to benefits of physical practice for these later assessed perceptual-cognitive skills, effector-specific interference has been shown through action-incongruent secondary tasks (motor interference tasks). Here we investigated this experience-driven facilitation of action predictions and effector-specific interference in left-handed (LH) novices, before and after practicing a dart throwing task.

Liver Transplant Costs and Activity After United Network for Organ Sharing Allocation Policy Changes.

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level.

Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation.