Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors.

To better understand drug resistance mechanisms to CDK4/6 inhibitors and inform precision medicine, we analyze real-world multi-omics data from 400 HR+/HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors plus endocrine therapies, including 200 pre-treatment and 227 post-progression samples. The prevalences of ESR1 and RB1 alterations significantly increase in post-progression samples. Integrative clustering analysis identifies three subgroups harboring different resistance mechanisms: ER driven, ER co-driven and ER independent.

Therapist-Guided Internet-Delivered Acceptance-Enhanced Behavior Therapy for Skin-Picking Disorder: A Randomized Controlled Trial.

Despite its high prevalence, individuals suffering from skin-picking disorder (SPD) face limited access to treatment due to several factors, including geographical and economic barriers, as well as a shortage of properly trained therapists. Offering Internet-delivered therapy could be a solution to these barriers. This study aimed to evaluate the efficacy of therapist-guided Internet-delivered acceptance-enhanced behavior therapy (iBT) for SPD compared to a wait-list control condition.

Microorganism Strains, Environmentally Friendly and Biological Preparations Against Chitwood, 1949 and Their Impact on Fruit Quality and Tomato Crop Structure.

The primary aim of this research was to study the effectiveness of various strains of antagonist microorganisms and biological preparations against , in addition to their impact on the quality of tomato fruits and crop structure. Four microorganism strains and three registered environmentally safe nematicides were used in the experiment presented herein. The results showed that the strains F-22BK/6 and F-22BK/4 had the greatest biological efficacy, reducing the number of galls on tomato plants by 91.

A Novel Pot-Economy Approach to the Synthesis of Triantennary GalNAc-Oligonucleotide.

N-Acetylgalactosamine (GalNAc) is an efficient and multifunctional delivery tool in the development and synthesis of chemically modified oligonucleotide therapeutics (conjugates). Such therapeutics demonstrate improved potency in vivo due to the selective and efficient delivery to hepatocytes in the liver via receptor-mediated endocytosis, which is what drives the high interest in this molecule. The ways to synthesize such structures are relatively new and have not been optimized in terms of the yields and stages both in lab and large-scale synthesis.