Investigation of a Novel Noninvasive Risk Analytics Algorithm With Laboratory Central Venous Oxygen Saturation Measurements in Critically Ill Pediatric Patients.

Background: Accurate assessment of oxygen delivery relative to oxygen demand is crucial in the care of a critically ill patient. The central venous oxygen saturation (Svo) enables an estimate of cardiac output yet obtaining these clinical data requires invasive procedures and repeated blood sampling. Interpretation remains subjective and vulnerable to error.

Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Intracellular Pocket Conformations Determine Signaling Efficacy through the μ Opioid Receptor.

It has been challenging to determine how a ligand that binds to a receptor activates downstream signaling pathways and to predict the strength of signaling. The challenge is compounded by functional selectivity, in which a single ligand binding to a single receptor can activate multiple signaling pathways at different levels. Spectroscopic studies show that in the largest class of cell surface receptors, 7 transmembrane receptors (7TMRs), activation is associated with ligand-induced shifts in the equilibria of intracellular pocket conformations in the absence of transducer proteins.

The power of personas: Exploring an innovative model for understanding stakeholder perspectives in an oncology learning health network.

Introduction: Learning health networks (LHNs) improve clinical outcomes by applying core tenets of continuous quality improvements (QI) to reach community-defined outcomes, data-sharing, and empowered interdisciplinary teams including patients and caregivers. LHNs provide an ideal environment for the rapid adoption of evidence-based guidelines and translation of research and best practices at scale. When an LHN is established, it is critical to understand the needs of all stakeholders.

Ligand Reorganization for End-Point Binding Free Energy Calculations: Identifying Preferred Poses of Fentanyls in the μ Opioid Receptor.

We have developed a method that uses energy landscapes of unbound and bound ligands to compute reorganization free energies for end-point binding free-energy calculations. The method is applied to our previous simulations of fentanyl derivatives bound to the μ opioid receptor in different orientations. Whereas the mean interaction energy provides an ambiguous ranking of binding poses, interaction entropy and ligand reorganization strongly penalize geometric decoys such that native poses observed in CryoEM structures are best ranked.