Impact of Day 11 Methotrexate Dose Adjustments due to Mucositis on the Outcomes Following Allogeneic Stem Cell Transplant in the Setting of Anti Thymocyte Globulin (ATG) Based GVHD Prophylaxis.

Background: Dose adjustments of Day 11 Methotrexate (MTx) for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation (HCT) are common due to mucositis, renal injury, or other reasons. The impact of omitting or adjusting doses of MTx in the era of ATG-based GVHD prophylaxis remains unexplored.

Methods: We retrospectively analyzed the outcomes of all adult patients undergoing allogeneic HCT who received ATG-based GVHD prophylaxis at The Ottawa Hospital from January 2019 to December 2022.

The ribosome-associated quality control pathway supports survival in the absence of non-stop ribosome rescue factors.

Unlabelled: In bacteria, if a ribosome translates an mRNA lacking a stop codon it becomes stalled at the 3' end of the message. These ribosomes must be rescued by -translation or the alternative rescue factors (ArfA or ArfB). However, mounting evidence suggests that the ribosome quality control (RQC) pathway may also rescue non-stop ribosomes.

YebC2 resolves ribosome stalling at polyprolines independent of EF-P and the ABCF ATPase YfmR.

Polyproline motifs are essential structural features of many proteins, and recent evidence suggests that EF-P is one of several factors that facilitate their translation. For example, YfmR was recently identified as a protein that prevents ribosome stalling at proline-containing sequences in the absence of EF-P. Here, we show that the YebC-family protein YebC2 (formerly YeeI) functions as a translation factor in that resolves ribosome stalling at polyprolines.

Systemic T-cell activation and IFN-γ activity in indeterminate severe hepatitis are reminiscent of hemophagocytic lymphohistiocytosis: Implications for T-cell- and IFN-γ-directed therapies.

Background: Severe hepatitis cases in children are increasingly recognized, but the exact etiology remains unknown in a significant proportion of patients. Cases of indeterminate severe hepatitis (iSH) may progress to indeterminate pediatric acute liver failure (iPALF), so understanding its immunobiology is critical to preventing disease progression. Hemophagocytic lymphohistiocytosis (HLH) is a systemic hyperinflammatory disorder associated with T-cell and macrophage activation with liver injury.