Interplay of halogen bonding and solvation in protein-ligand binding.

Halogen bonding is increasingly utilized in efforts to achieve high affinity and selectivity of molecules designed to bind proteins, making it paramount to understand the relationship between structure, dynamics, and thermodynamic driving forces. We present a detailed analysis addressing this problem using a series of protein-ligand complexes involving single halogen substitutions - F, Cl, Br, and I - and nearly identical structures. Isothermal titration calorimetry reveals an increasingly favorable binding enthalpy from F to I that correlates with the halogen size and σ-hole electropositive character, but is partially counteracted by unfavorable entropy, which is constant from F to Cl and Br, but worse for I.

The Prognostic and Predictive Value of Human Gastrointestinal Microbiome and Exosomal mRNA Expression of PD-L1 and IFNγ for Immune Checkpoint Inhibitors Response in Metastatic Melanoma Patients: PROTOCOL TRIAL.

Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response.

Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study.

Interpretation threshold values for patient-reported outcomes in patients participating in a digitally delivered first-line treatment program for hip or knee osteoarthritis.

Objective: Establish proportions of patients reporting important improvement, acceptable symptoms and treatment failure and define interpretation threshold values for pain, patient-reported function and quality-of-life after participating in digital first-line treatment including education and exercise for hip and knee osteoarthritis (OA).

Methods: Observational study. Responses to the pain Numeric Rating Scale (NRS, 0-10 best to worst), Knee injury and Osteoarthritis Outcome Score 12 (KOOS-12) and Hip disability and Osteoarthritis Outcome Score 12 (HOOS-12, both 0-100 worst to best) were obtained for 4383 (2987) and 2041 (1264) participants with knee (hip) OA at 3 and 12 months post intervention.

Within-person change in patient-reported outcomes and their association with the wish to undergo joint surgery during a digital first-line intervention for osteoarthritis.

Aim: To study the association between within-person changes in patient-reported outcomes (PROMs) and wish for joint surgery during participation in a digital first-line intervention comprising exercise and education for knee/hip osteoarthritis (OA).

Methods: Retrospective observational registry study. Participants enrolled between June 1, 2018 and October 30, 2021, with follow-up data at three months (n = 13,961).

Digital self-management of hip and knee osteoarthritis and trajectories of work and activity impairments.

Objective: To investigate the trajectories of work and activity impairments among people participating in a digital self-management program for osteoarthritis (OA).

Methods: We conducted an observational longitudinal study using data for baseline, 3, 6, 9 and 12 months follow ups from people participating in a digital OA treatment between June 2018 and September 2021. The Work Productivity and Activity Impairment-Osteoarthritis (WPAI-OA) questionnaire was used to measure work and activity impairments.