Discovery of CHD1 Antagonists for PTEN-Deficient Prostate Cancer.

CHD1 is a chromodomain-helicase DNA-binding protein that preferentially recognizes di- and trimethylated lysine 4 on histone H3 (H3K4me2/3). Genetic studies have established CHD1 as a synthetic lethal target in phosphatase and tensin homologue (PTEN)-deficient cancers. Despite this attractive therapeutic link, no inhibitors or antagonists of CHD1 have been reported to date.

Uncertainty Estimation for Dual View X-ray Mammographic Image Registration Using Deep Ensembles.

Techniques are developed for generating uncertainty estimates for convolutional neural network (CNN)-based methods for registering the locations of lesions between the craniocaudal (CC) and mediolateral oblique (MLO) mammographic X-ray image views. Multi-view lesion correspondence is an important task that clinicians perform for characterizing lesions during routine mammographic exams. Automated registration tools can aid in this task, yet if the tools also provide confidence estimates, they can be of greater value to clinicians, especially in cases involving dense tissue where lesions may be difficult to see.

Non-constant mean relative potency for antibody-dependent cellular cytotoxicity assays.

Bioassays are regulated, analytical methods used to ensure proper activity (potency) of biological products at release and during long-term storage. Potency is commonly reported on a relative basis by comparing and calibrating a concentration-response curve from the test material to that of a reference standard material. The relative potency approach depends on an assumption that the two concentration-response curves exhibit similar (equivalent) shapes, except for a potency shift.

Implementation and Interim Analysis of a Standardized Renal Trauma Imaging and Urinary Extravasation Management Protocol.

Introduction: The AUA recommends delayed-phase imaging (DPI) in renal injuries to evaluate the collecting system. A renal trauma imaging protocol for early conservative management of urinary extravasation (UE) was implemented to improve guideline adherence. We aimed to determine if increased adherence led to changes in outcomes.

Gut microbial β-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.

Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial β-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation.