The Beginning of a "Regulatory Renaissance": Positioning Regulatory Coverage at the Interface of Human Expertise and Digital Support.

Following the largest reorganization in its history, the U.S. Food and Drug Administration (FDA) is now working to modernize how it defines and engages in regulatory oversight of the quality of products that the agency regulates.

Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients.

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8 T cell activation without exhaustion.

Brief Report: Potential Gains in PrEP Coverage and Effect on Racial Disparities After Introduction of On-Demand and Long-Acting Injectable PrEP: Preferences of Men Who Have Sex With Men in the United States, 2021-2022.

Introduction: There are persistent race- and ethnicity-based disparities in HIV incidence among gay and bisexual men who have sex with men (GBMSM) in the United States, partially driven by inequities in distribution of pre-exposure prophylaxis (PrEP). We assessed how additional modalities of PrEP beyond daily oral might affect the uptake of PrEP and ongoing disparities in HIV incidence in the United States.

Methods: In an online survey of GBMSM in the United States, we presented participants with descriptions of each PrEP modality.

The Hippo effector TEAD1 regulates postnatal murine cerebellar development.

The Hippo signalling cascade is an evolutionarily conserved pathway critical for the development of numerous organ systems and is required for the development of many parts of the mammalian nervous system, including the cerebellum. The Hippo pathway converges, via the nuclear YAP/TAZ co-transcription factors, on transcription factors of the TEA Domain (TEAD) family (TEAD1-4) and promotes the expression of pro-proliferative genes. Despite the importance of TEAD function, our understanding of spatial and temporal expression of this family is limited, as is our understanding of which TEAD family members regulate Hippo-dependent organ development.

Corticotropin-Releasing Factor in the Nucleus Accumbens Does Not Drive High Levels of Cocaine Consumption.

Uncovering the neurobiological processes underlying substance use disorder informs future therapeutic interventions. Prior research implicates the corticotropin releasing factor (CRF) system as a major player in a wide variety of substance use disorder -like phenotypes. However, the complexity of the CRF system in regard to brain region specific effects and experience-dependent changes in activity is poorly understood.