The main sources of molecular organization in the cell. Atlas of self-organized and self-regulated dynamic biostructures.

One of the most important goals of contemporary biology is to understand the principles of the molecular order underlying the complex dynamic architecture of cells. Here, we present an overview of the main driving forces involved in the cellular molecular complexity and in the emergent functional dynamic structures, spanning from the most basic molecular organization levels to the complex emergent integrative systemic behaviors. First, we address the molecular information processing which is essential in many complex fundamental mechanisms such as the epigenetic memory, alternative splicing, regulation of transcriptional system, and the adequate self-regulatory adaptation to the extracellular environment.

Quality-adjusted time without symptoms or toxicity analysis of trastuzumab deruxtecan versus trastuzumab emtansine in HER2- positive metastatic breast cancer patients based on secondary use of the DESTINY-Breast03 trial.

Objective: DESTINY-Breast03, a randomised, phase 3 trial, evaluated trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor (HER2)-positive unresectable and/or metastatic breast cancer who progressed on or after treatment with trastuzumab and a taxane. At the current data cut off overall survival analysis, T-DXd demonstrated a substantial improvement in overall survival over T-DM1. This secondary analysis use of DESTINY-Breast03 aimed to further evaluate the treatment differences using quality-adjusted survival time without symptoms or toxicity (Q-TWiST) methods.

Caught in the Crossfire: Unmasking the Silent Renal Threats of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.

Background: Renal adverse drug reactions (ADRs) associated with tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) are relatively rare, and there is currently no standardized protocol for their management. Therefore, this study aimed to summarize renal ADRs related to TKIs use in CML and propose an evidence-based approach to monitor and manage these ADRs.

Methods: A systematic literature review was performed to identify renal ADRs associated with TKIs in CML.

Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis.

Background: Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small.

Dysregulation of mTOR signalling is a converging mechanism in lissencephaly.

Cerebral cortex development in humans is a highly complex and orchestrated process that is under tight genetic regulation. Rare mutations that alter gene expression or function can disrupt the structure of the cerebral cortex, resulting in a range of neurological conditions. Lissencephaly ('smooth brain') spectrum disorders comprise a group of rare, genetically heterogeneous congenital brain malformations commonly associated with epilepsy and intellectual disability.