The Significant Role of PA28αβ in CD8 T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands.

The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent.

Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML.

Although the landscape for treating acute myeloid leukemia (AML) patients has changed substantially in recent years, the majority of patients will eventually relapse and succumb to their disease. Allogeneic stem cell transplantation provides the best anti-AML treatment strategy, but is only suitable in a minority of patients. In contrast to B-cell neoplasias, chimeric antigen receptor (CAR) T-cell therapy in AML has encountered challenges in target antigen heterogeneity, safety, and T-cell dysfunction.

[Reduction of greenhouse gas emissions by inhaler choice in the therapy of asthma and COPD patients].

Background: The global warming potential of inhaled medication depends on the applied inhaler. Pressurised metered dose inhalers (pMDI) contain green-house gases (GHG) and are associated with a 10 to 40 times higher CO-footprint than GHG-free dry-powder inhalers (DPI).

Aim: Feasibility and relevance of prescription conversion from pMDI to DPI were investigated in a pulmonology outpatient clinic regarding the CO-footprint and the economic costs under real-world conditions.

Standard and line-to-line cementation of a polished short hip stem: Long-term in vitro implant stability.

The current trend is toward shorter hip stems. While there is a general agreement on the need for a cement mantle thicker than 2 mm, some surgeons prefer line-to-line cementation, where the mantle has only the thickness provided by the cement-bone interdigitation. The aim of this study was to assess if a relatively short, polished hip stem designed for a standard cementation can also be cemented line-to-line without increasing the risk of long-term loosening.

The need for human breast cancer resistance protein substrate and inhibition evaluation in drug discovery and development: why, when, and how?

Although the multiplicity in transport proteins assessed during drug development is continuously increasing, the clinical relevance of the breast cancer resistance protein (BCRP) is still under debate. Here, our aim is to rationalize the need to consider BCRP substrate and inhibitor interactions and to define optimum selection and acceptance criteria between cell-based and vesicle-based assays in vitro. Information on the preclinical and clinical pharmacokinetics (PK), drug-drug interactions, and pharmacogenomics data was collated for 13 marketed drugs whose PK is reportedly associated with BCRP interaction.