Participation in Advance Care Planning Among Medically At-Risk Rural Veterans: Protocol for a Personalized Engagement Model.

Background: Many of the challenges in advanced care planning (ACP) conversations are linked to the waxing and waning progress of serious illnesses. Conversations with patients about future medical care decisions by a surrogate decision maker have historically been left until late in the patient's disease trajectory. These conversations often happen at a time when the patient is already very ill.

Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies.

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is an essential effector of B-cell receptor (BCR) signaling. Chronic activation of BTK-mediated BCR signaling is a hallmark of many hematological malignancies, which makes it an attractive therapeutic target. Pharmacological inhibition of BTK enzymatic function is now a well-proven strategy for the treatment of patients with these malignancies.

Discovery of Reversible Covalent Bruton's Tyrosine Kinase Inhibitors PRN473 and PRN1008 (Rilzabrutinib).

Bruton's tyrosine kinase (BTK), a Tec family tyrosine kinase, is critical in immune pathways as an essential intracellular signaling element, participating in both adaptive and immune responses. Currently approved BTK inhibitors are irreversible covalent inhibitors and limited to oncology indications. Herein, we describe the design of covalent reversible BTK inhibitors and the discoveries of PRN473 () and rilzabrutinib (PRN1008, ).

Phase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168).

Bruton's tyrosine kinase (BTK), expressed in B cells and cells of innate immunity, including microglia, is an essential signaling element downstream of the B-cell receptor and Fc-receptors. Tolebrutinib (PRN2246, SAR442168) is a potent BTK inhibitor that covalently binds the kinase, resulting in durable inhibition with the potential to target inflammation in the periphery and central nervous system (CNS). Tolebrutinib crosses the blood-brain barrier and potently inhibits BTK in microglial cells isolated from the CNS.

Demystifying and unravelling the molecular structure of the biopolymer sporopollenin.

Rationale: We report the unsolved molecular structure of the complex biopolymer sporopollenin exine extracted from Lycopodium clavatum pollen grains.

Methods: TOF-SIMS and CID-MS/MS, MALDI-TOF-MS and CID-TOF/TOF-MS/MS were used for the analysis of this complex biopolymer sporopollenin exine extracted from Lycopodium clavatum pollen grains. Solid-state H- and C-NMR, 2D H- H NOESY, Rotor-synchronized C{ H} HSQC, and C{ H} multi CP-MAS NMR experiments were used to confirm the structural assigments revealed by MS and MS/MS studies.