Using Implementation Science to Assess Barriers to Agreement on Sedation Goal Setting and Assessment.

Objectives: Sedation assessment and goal setting using a validated assessment tool are key components of the ICU Liberation bundle. Appropriate integration of these bundle elements into daily practice remains challenging. Understanding barriers is an important step toward implementation of these best practice bundle elements.

Comparing the Quality of Domain-Specific Versus General Language Models for Artificial Intelligence-Generated Differential Diagnoses in PICU Patients.

Objectives: Generative language models (LMs) are being evaluated in a variety of tasks in healthcare, but pediatric critical care studies are scant. Our objective was to evaluate the utility of generative LMs in the pediatric critical care setting and to determine whether domain-adapted LMs can outperform much larger general-domain LMs in generating a differential diagnosis from the admission notes of PICU patients.

Design: Single-center retrospective cohort study.

Curcumin inhibits Aspergillus flavus infection and aflatoxin production possibly by inducing ROS burst.

Aspergillus flavus contamination is common in various food and feed ingredients, and it poses to serious threats to human and animal health. Curcumin is a plant-derived polyphenol that exhibits antifungal activity. In this study, the antifungal effect of curcumin on A.

Implementation Science in Pediatric Critical Care - Sedation and Analgesia Practices as a Case Study.

Sedation and analgesia (SA) management is essential practice in the pediatric intensive care unit (PICU). Over the past decade, there has been significant interest in optimal SA management strategy, due to reports of the adverse effects of SA medications and their relationship to ICU delirium. We reviewed 13 studies examining SA practices in the PICU over the past decade for the purposes of reporting the study design, outcomes of interest, SA protocols used, strategies for implementation, and the patient-centered outcomes.

Implementation of an Analgesia-Sedation Protocol Is Associated With Reduction in Midazolam Usage in the PICU.

Objectives: Examine the association of a revised analgesia-sedation protocol with midazolam usage in the PICU.

Design: A single-center nonrandomized before-after study.

Setting: PICU at a quaternary pediatric hospital (Boston Children's Hospital, Boston, MA).

A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis.

The embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent AML progression is unknown.

Akt phosphorylates the transcriptional repressor bmi1 to block its effects on the tumor-suppressing ink4a-arf locus.

The Polycomb group protein Bmi1 is a transcriptional silencer of the Ink4a-Arf locus, which encodes the cell cycle regulator p16(Ink4a) and the tumor suppressor p19(Arf). Bmi1 plays a key role in oncogenesis and stem cell self-renewal. We report that phosphorylation of human Bmi1 at Ser³¹⁶ by Akt impaired its function by triggering its dissociation from the Ink4a-Arf locus, which resulted in decreased ubiquitylation of histone H2A and the inability of Bmi1 to promote cellular proliferation and tumor growth.

SALL4 is a key transcription regulator in normal human hematopoiesis.

Background: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored.

The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations.

The mixed-lineage leukemia (MLL) H3K4 methyltransferase protein, and the heterodimeric RUNX1/CBFβ transcription factor complex, are critical for definitive and adult hematopoiesis, and both are frequently targeted in human acute leukemia. We identified a physical and functional interaction between RUNX1 (AML1) and MLL and show that both are required to maintain the histone lysine 4 trimethyl mark (H3K4me3) at 2 critical regulatory regions of the AML1 target gene PU.1.

SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes.

Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells.

Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex.

Background: The embryonic stem cell (ESC) factor, SALL4, plays an essential role in both development and leukemogenesis. It is a unique gene that is involved in self-renewal in ESC and leukemic stem cell (LSC).

Methodology/principal Findings: To understand the mechanism(s) of SALL4 function(s), we sought to identify SALL4-associated proteins by tandem mass spectrometry.