Long-Term Natural Hydroxyapatite and Synthetic Collagen Hydroxyapatite Enhance Bone Regeneration and Implant Fixation Similar to Allograft in a Sheep Model of Implant Integration.

There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep.

Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models.

The combination of CDK4/6 and MEK inhibition as a therapeutic strategy has shown promise in various cancer models, particularly in those harboring RAS mutations. An initial high-throughput drug screen identified high synergy between the CDK4/6 inhibitor palbociclib and the MEK inhibitor trametinib when used in combination in soft tissue sarcomas. In RAS mutant models, combination treatment with palbociclib and trametinib induced significant G1 cell cycle arrest, resulting in a marked reduction in cell proliferation and growth.

Real-World Experience among Elderly Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitor-Based Therapy.

The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study.

Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression.

The tumor microenvironment (TME) profoundly influences tumorigenesis, with gene expression in the breast TME capable of predicting clinical outcomes. The TME is complex and includes distinct cancer-associated fibroblast (CAF) subtypes whose contribution to tumorigenesis remains unclear. Here, we identify a subset of myofibroblast CAFs (myCAF) that are senescent (senCAF) in mouse and human breast tumors.

Neutron instrument concepts for a high intensity moderator at the European spallation source.

In the course of the Horizon 2020 project HighNESS, a second moderator concept has been developed for the European Spallation Source, which complements the currently built moderator and is optimized for high intensity with a large viewable surface area. In this work we introduce conceptual designs for neutron instruments for condensed matter research designed to make optimal use of the capabilities of this moderator. The focus is on two concepts for small-angle neutron scattering and one neutron imaging instrument, which are intended to complement corresponding instruments that are already under construction at the European Spallation Source.