SUNi mutagenesis: Scalable and uniform nicking for efficient generation of variant libraries.

Multiplexed assays of variant effects (MAVEs) have made possible the functional assessment of all possible mutations to genes and regulatory sequences. A core pillar of the approach is generation of variant libraries, but current methods are either difficult to scale or not uniform enough to enable MAVEs at the scale of gene families or beyond. We present an improved method called Scalable and Uniform Nicking (SUNi) mutagenesis that combines massive scalability with high uniformity to enable cost-effective MAVEs of gene families and eventually genomes.

Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer.

Background: Alpelisib (α-selective phosphatidylinositol 3-kinase inhibitor) plus fulvestrant is approved in multiple countries for men and postmenopausal women with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib's safety profile should inform adverse event (AE) management and enhance patient care.

Patients And Methods: AEs in the phase III SOLAR-1 trial were assessed in patients with and without PIK3CA mutations.

Intraprostatic Fiducials Compared with Bony Anatomy and Skin Marks for Image-Guided Radiation Therapy of Prostate Cancer.

Purpose Prostate motion occurs during radiotherapy for localized prostate cancer. We evaluated the input of intraprostatic fiducials for image-guided radiation therapy and compared it with bony anatomy and skin marks. Methods Eleven patients were implanted with three fiducial markers in the prostate.