New approach methodologies to confirm developmental toxicity of pharmaceuticals based on weight of evidence.

The aim of embryo-fetal developmental toxicity assessments for pharmaceuticals is to inform potential risk of adverse pregnancy outcome, which has traditionally relied on studies in pregnant animals. Recent updates to international safety guidelines (ICH S5R3) have incorporated information on how to use weight of evidence and alternative assays to reduce animal use while still informing risk of fetal harm. Uptake of these alternative approaches has been slow due to limitations in understanding how alternative assays translate to in vivo effects and then relevance to human exposure.

Automation preserves product consistency and quality for the formulation, fill, and finish of T cell-based therapies.

Scaling up the manufacture of cell therapies can be complex and challenging. Maintaining critical quality attributes of the cell product during its final formulation and fill-finish into multiple containers can be especially difficult and laborious. Here, we tested the automated Finia™ Fill and Finish System to efficiently scale up the formulation and fill-finish of a T cell product, and then assessed cell quality and product consistency across different sub-lots filled during this expanded process.

Fibroblast growth factor receptor 1 gene mutation as a potential risk factor for spontaneous intracranial hemorrhage in pediatric low-grade glioma patients.

Background: Fibroblast growth factor receptor 1 () mutations have been associated with poorer prognoses in pediatric central nervous system tumor patients. A recent study highlighted a link between mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all patients with an alteration experienced hemorrhage at some point during their course of treatment.

Methods: The current study examined 50 out of 67 pediatric patients with low-grade gliomas (LGGs) who had genomic testing between 2011 and 2022 at our institution to determine whether a correlation exists between mutations and spontaneous ICH.

Reversible effects on female rat fertility with abrocitinib, a Janus kinase 1 inhibitor.

Background: Abrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets.