Discovery of AZD8421: A Potent CDK2 Inhibitor with Selectivity Against Other CDK Family Members and the Human Kinome.

Targeting CDK2 with first generation CDK2 inhibitors suffered from a reduced therapeutic index likely due to toxicity stemming from lack of selectivity against the CDK family and other kinases. Recently, CDK2 has been identified as a mediator of resistance to CDK4/6 inhibitors in the context of high levels of cyclin E expression. Discovery of highly selective CDK2 inhibitors may minimize off-target effects, reduce toxicity observed with first generation CDK2 inhibitors, and allow precise targeting of aberrant cell cycle progression and resistance mechanisms mediated by high cyclin E/CDK2 activity.

Micrometastasis and Isolated Tumor Cells in Oral Squamous Cell Carcinoma: Refining Nodal Staging with Emerging Technologies.

Purpose: Cervical lymph node metastasis significantly influence prognosis in oral squamous cell carcinoma (OSCC), guiding staging, treatment decisions, and overall survival. Sentinel lymph node biopsy (SLNB) offers a minimally invasive approach for early detection of subclinical nodal metastasis, including micrometastases (0.2-2 mm) and isolated tumor cells (ITCs, < 0.

Black clients' perceptions of therapists' cultural comfort, alliance, and outcome and the discussion of anti-Black racism in psychotherapy.

Prior scholarship has helped demonstrate therapists' perceptions of the value of discussing anti-Black racism with Black clients in a manner that espouses cultural comfort or the ability to be at ease when discussing lived experiences related to clients' culture during treatment. Better understanding cultural comfort, an aspect of multicultural orientation, when discussing anti-Black racism with Black clients could help clarify paths by which psychotherapy does not perpetuate harm reflected in the dehumanization of such racism. However, Black clients' perspectives are missing in the literature.

Outcomes for Gastrointestinal Oncologic Surgery Episodes in the Bundled Payments for Care Improvement Advanced Program.

Objective: The goal of this study was to understand the association of participation in a bundled payment program with financial and clinical outcomes for patients who underwent gastrointestinal operations for malignancy.

Summary Background Data: Multidisciplinary cancer care is complex and expensive. Medicare alternative payment models aiming to reduce costs and improve outcomes have been designed for chemotherapy and radiation therapy, but oncologic surgery has yet to be directly targeted by such attempts at payment reform.

Hierarchical Event Descriptor library schema for EEG data annotation.

Standardizing terminology to annotate electrophysiological events can improve both computational research and clinical care. Enriching data with standard terms facilitates data exploration, from case studies to mega-analyses. The machine readability of such electrophysiological event annotations is essential for performing automated analyses.