Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

RNA Modifications and Their Role in Regulating KSHV Replication and Pathogenic Mechanisms.

Kaposi's sarcoma-associated herpesvirus is an oncogenic gammaherpesvirus that plays a major role in several human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The complexity of KSHV biology is reflected in the sophisticated regulation of its biphasic life cycle, consisting of a quiescent latent phase and virion-producing lytic replication. KSHV expresses coding and noncoding RNAs, including microRNAs and long noncoding RNAs, which play crucial roles in modulating viral gene expression, immune evasion, and intercellular communication.

"Placing community in the driver's seat": Key strategies and critical enablers of an equitable place-based COVID-19 vaccination response.

Addressing health inequities requires both national and local-level action. In the case of COVID-19, locally-led place-based programs were instrumental in addressing vaccination inequities that resulted from implementation gaps in national and state-level universal COVID-19 vaccination programs. To prepare for future pandemics, understanding which local strategies are effective and the conditions that enable their effectiveness is crucial.

The pathogenicity of PSEN2 variants is tied to Aβ production and homology to PSEN1.

Introduction: Though recognized as a potential cause of autosomal dominant Alzheimer's disease, the pathogenicity of many PSEN2 variants remains uncertain. We compared amyloid beta (Aβ) production across all missense PSEN2 variants in the AlzForum database and, when possible, to corresponding PSEN1 variants.

Methods: We expressed 74 PSEN2 variants, 21 of which had known, homologous PSEN1 pathogenic variants with the same amino acid substitution, in HEK293 cells lacking presenilin 1/2.