A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

Retrospective observational cohort study of premature neonates screened for ROP with 7 years of follow-up assessing the visual outcomes and adequacy of preschool visual screening.

Background: Very premature infants screened for retinopathy of prematurity (ROP) that do not develop ROP still experience serious visual developmental challenges, and while it is recommended that all children in the UK are offered preschool visual screening, we aimed to explore whether this vulnerable group requires dedicated follow-up.

Methods: We performed a real-world retrospective observational cohort study of children previously screened for ROP in NHS Greater Glasgow and Clyde (Scotland) between 2013 and 2015. We excluded those with any severity of ROP identified during screening.