De novo identification of CD4+ T cell epitopes.

CD4+ T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4+ T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4+ T cell antigen discovery. SABR-IIs can present epitopes to CD4+ T cells and induce signaling upon their recognition, allowing a readable output. Furthermore, the SABR-II design is modular in signaling and deployment to T cells and B cells. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery in the context of type 1 diabetes. SABR-II libraries provide a rapid, flexible, scalable and versatile approach for de novo identification of CD4+ T cell ligands from single-cell RNA sequencing data using experimental and computational approaches.

Implementation of a digital early warning score (NEWS2) in a cardiac specialist and general hospital settings in the COVID-19 pandemic: a qualitative study.

OBJECTIVES: To evaluate implementation of digital National Early Warning Score 2 (NEWS2) in a cardiac care setting and a general hospital setting in the COVID-19 pandemic. DESIGN: Thematic analysis of qualitative semistructured interviews using the non-adoption, abandonment, scale-up, spread, sustainability framework with purposefully sampled nurses and managers, as well as online surveys from March to December 2021. SETTINGS: Specialist cardiac hospital (St Bartholomew's Hospital) and general teaching hospital (University College London Hospital, UCLH). PARTICIPANTS: Eleven nurses and managers from cardiology, cardiac surgery, oncology and intensive care wards (St Bartholomew's) and medical, haematology and intensive care wards (UCLH) were interviewed and 67 were surveyed online. RESULTS: Three main themes emerged: (1) implementing NEWS2 challenges and supports; (2) value of NEWS2 to alarm, escalate and during the pandemic; and (3) digitalisation: electronic health record (EHR) integration and automation. The value of NEWS2 was partly positive in escalation, yet there were concerns by nurses who undervalued NEWS2 particularly in cardiac care. Challenges, like clinicians' behaviours, lack of resources and training and the perception of NEWS2 value, limit the success of this implementation. Changes in guidelines in the pandemic have led to overlooking NEWS2. EHR integration and automated monitoring are improvement solutions that are not fully employed yet. CONCLUSION: Whether in specialist or general medical settings, the health professionals implementing early warning score in healthcare face cultural and system-related challenges to adopting NEWS2 and digital solutions. The validity of NEWS2 in specialised settings and complex conditions is not yet apparent and requires comprehensive validation. EHR integration and automation are powerful tools to facilitate NEWS2 if its principles are reviewed and rectified, and resources and training are accessible. Further examination of implementation from the cultural and automation domains is needed.