Ulcerative Colitis Severity Classification and Localised Extent (UC-SCALE): An Artificial Intelligence scoring system for a spatial assessment of disease severity in Ulcerative Colitis.

Background & Aims: Validated scoring methods such as the Mayo Clinic Endoscopic Subscore (MCES) evaluate ulcerative colitis (UC) severity at the worst colon segment, without considering disease extent. We present the Ulcerative Colitis Severity Classification and Localised Extent (UC-SCALE) algorithm, which provides a comprehensive and automated evaluation of endoscopic severity and disease extent in UC.

Methods: UC-SCALE consists of 3 main elements: 1) a quality filter selecting readable images (frames) from colonoscopy videos, 2) a scoring system assigning a MCES to each readable frame, and 3) a camera localisation algorithm assigning each frame to a location within the colon.

Discovery and Mechanistic Elucidation of NQO1-Bioactivatable Small Molecules That Overcome Resistance to Degraders.

Degraders hold the promise to efficiently inactivate previously intractable disease-relevant targets. Unlike traditional inhibitors, degraders act substoichiometrically and rely on the hijacked proteolysis machinery, which can also act as an entry point for resistance. To fully harness the potential of targeted protein degradation, it is crucial to comprehend resistance mechanisms and formulate effective strategies to overcome them.

Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α.

Many functional aspects of the protein kinase p38α have been illustrated by more than three hundred structures determined in the presence of reducing agents. These structures correspond to free forms and complexes with activators, substrates, and inhibitors. Here we report the conformation of an oxidized state with an intramolecular disulfide bond between Cys119 and Cys162 that is conserved in vertebrates.

Characterization of p38α autophosphorylation inhibitors that target the non-canonical activation pathway.

p38α is a versatile protein kinase that can control numerous processes and plays important roles in the cellular responses to stress. Dysregulation of p38α signaling has been linked to several diseases including inflammation, immune disorders and cancer, suggesting that targeting p38α could be therapeutically beneficial. Over the last two decades, numerous p38α inhibitors have been developed, which showed promising effects in pre-clinical studies but results from clinical trials have been disappointing, fueling the interest in the generation of alternative mechanisms of p38α modulation.

Evaluation of the impact of the COVID-19 lockdown on the quality of life of patients monitored for cancer who practice an adapted physical activity: rugby for health.

Purpose: The benefits of regular physical exercise on the tolerability of cancer treatments, quality of life and survival rates post-diagnosis have been demonstrated but all supervised physical activities have been interrupted due to the global health crisis and the need for lockdown to halt the spread of SARS-CoV-2. To reintroduce activities post-lockdown, we wanted to assess the impact of the COVID-19 lockdown on the quality of life and the psychological status of patients who practice an adapted physical activity such as rugby for health.

Methods: The evaluation was conducted in two phases: an initial self-questionnaire comprised of 42 questions sent to all participants to assess the impact of lockdown and a second assessment phase in the presence of the participants.