Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis.

Background: The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.

Methods: We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset.

Datopotamab Deruxtecan Versus Chemotherapy in Previously Treated Inoperable/Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Primary Results From TROPION-Breast01.

Purpose: The global, phase 3, open-label, randomized TROPION-Breast01 study assessed the trophoblast cell surface antigen 2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) versus investigator's choice of chemotherapy (ICC) in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.

Methods: Adult patients with inoperable/metastatic HR+/HER2‒ breast cancer, who had disease progression on endocrine therapy, for whom endocrine therapy was unsuitable, and had received one to two previous lines of chemotherapy in the inoperable/metastatic setting, were randomly assigned 1:1 to Dato-DXd (6 mg/kg once every 3 weeks) or ICC (eribulin/vinorelbine/capecitabine/gemcitabine). Dual primary end points were progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS).

Adventures with the β-adrenoceptor Receptor: A Career Long Interest in Agonising One of the Most Widely Studied GPCRs.

Drug discovery is a multi-disciplinary effort in which groups with expertise in a range of areas combine in a unified way to achieve a common goal: to deliver a clinical candidate to evaluate a hypothesis for improving human health. As a medicinal chemist this environment has provided multiple opportunities to be involved in cross-discipline interactions that have been both rewarding and led to outcomes that would not have been possible without an intimate interdisciplinary curiosity. Within this article I aim to share some of my experiences with the β2-adrenoceptor that have fostered such synergistic relationships with several disciplines, but in particular with in vitro pharmacologists looking at different ways to stimulate this G protein-coupled receptor (GPCR).

Pf7: an open dataset of genome variation in 20,000 worldwide samples.

We describe the MalariaGEN Pf7 data resource, the seventh release of genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.