Expression-Driven Genetic Dependency Reveals Targets for Precision Medicine.

Cancer cells are heterogeneous, each harboring distinct molecular aberrations and are dependent on different genes for their survival and proliferation. While successful targeted therapies have been developed based on driver DNA mutations, many patient tumors lack druggable mutations and have limited treatment options. Here, we hypothesize that new precision oncology targets may be identified through "expression-driven dependency", whereby cancer cells with high expression of a targeted gene are more vulnerable to the knockout of that gene.

Pediatric to adult transition care in neurogastroenterology and motility: A position paper from the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility.

Transition services-programs that support adolescents and young adults (AYAs) as they move from a child-centered to a more autonomous, adult-orientated healthcare system-have been associated with improved short- and long-term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders.

Mutant FOXO1 controls an oncogenic network via enhancer accessibility.

Transcriptional dysregulation is a hallmark of diffuse large B cell lymphoma (DLBCL), as transcriptional regulators are frequently mutated. However, our mechanistic understanding of how normal transcriptional programs are co-opted in DLBCL has been hindered by a lack of methodologies that provide the temporal resolution required to separate direct and indirect effects on transcriptional control. We applied a chemical-genetic approach to engineer the inducible degradation of the transcription factor FOXO1, which is recurrently mutated (mFOXO1) in DLBCL.

PAX3-FOXO1 coordinates enhancer architecture, eRNA transcription, and RNA polymerase pause release at select gene targets.

Transcriptional control is a highly dynamic process that changes rapidly in response to various cellular and extracellular cues, making it difficult to define the mechanism of transcription factor function using slow genetic methods. We used a chemical-genetic approach to rapidly degrade a canonical transcriptional activator, PAX3-FOXO1, to define the mechanism by which it regulates gene expression programs. By coupling rapid protein degradation with the analysis of nascent transcription over short time courses and integrating CUT&RUN, ATAC-seq, and eRNA analysis with deep proteomic analysis, we defined PAX3-FOXO1 function at a small network of direct transcriptional targets.

Working together better for mental health in children and young people during a pandemic: experiences from North Central London during the first wave of COVID-19.

Direct risk from infection from COVID-19 for children and young people (CYP) is low, but impact on services, education and mental health (so-called collateral damage) appears to have been more significant. In North Central London (NCL) during the first wave of the pandemic, in response to the needs and demands for adults with COVID-19, general paediatric wards in acute hospitals and some paediatric emergency departments were closed. Paediatric mental health services in NCL mental health services were reconfigured.

Pearlescent Mica-Doped Alginate as a Stable, Vibrant Medium for Two-Dimensional and Three-Dimensional Art.

Emergent technologies are driving forces in the development of innovative art media that progress the field of modern art. Recently, artists have capitalized on the versatility of a new technology to create, restore, and modify art: additive manufacturing or three-dimensional (3D) printing. Additively manufactured art relies heavily on plastic-based materials, which typically require high heat to induce melting for workability.

The utility of universal screening for somatization in a pediatric emergency department: A prospective evaluation.

Objective: To evaluate clinical utility and feasibility of universal somatization screening in the pediatric emergency department (ED) using a standardized approach of (1) identifying potential somatizing symptoms within the ED, (2) introducing these patients and their caregivers to the concept of the 'mind-body connection', (3) corroborating the likelihood of a somatization diagnosis via brief psychiatric assessment, and (4) inviting families to a psychoeducational follow-up session.

Methods: We conducted a cross-sectional study to carry out this approach with families visiting a pediatric ED. Our primary outcome of screening utility was measured as the proportion of youth who screened positive for somatization by the ED clinician.

Definition of a small core transcriptional circuit regulated by AML1-ETO.

Transcription factors regulate gene networks controlling normal hematopoiesis and are frequently deregulated in acute myeloid leukemia (AML). Critical to our understanding of the mechanism of cellular transformation by oncogenic transcription factors is the ability to define their direct gene targets. However, gene network cascades can change within minutes to hours, making it difficult to distinguish direct from secondary or compensatory transcriptional changes by traditional methodologies.

Pediatric somatization in the emergency department: assessing missed opportunities for early management.

Objective: Somatization is a common phenomenon that can severely complicate youths' functioning and health. The burden of somatization on pediatric acute care settings is currently unclear; better understanding it may address challenges clinicians experience in effectively caring for somatizing patients. In this study, we estimate the prevalence of somatization in a pediatric emergency department (ED).

Histone deacetylase 3 controls a transcriptional network required for B cell maturation.

Histone deacetylase 3 (Hdac3) is a target of the FDA approved HDAC inhibitors, which are used for the treatment of lymphoid malignancies. Here, we used Cd19-Cre to conditionally delete Hdac3 to define its role in germinal center B cells, which represent the cell of origin for many B cell malignancies. Cd19-Cre-Hdac3-/- mice showed impaired germinal center formation along with a defect in plasmablast production.

Electrolyte Effect on the Electrochemical Performance of Mild Aqueous Zinc-Electrolytic Manganese Dioxide Batteries.

Recently, mild aqueous rechargeable Zn-MnO batteries have attracted increasing interest for energy storage due to the low cost of Zn and Mn resources, high safety, and environmental benignity. Extensive types of MnO have been proposed as the cathodes in the literature, but the different reported performance and lack of a thorough understanding of reactions in MnO cathodes greatly hinder the practical applications of mild aqueous Zn-MnO batteries. Here, we revealed the correlation between the reaction mechanisms and the used electrolytes for the mild aqueous zinc-electrolytic manganese dioxide (EMD) batteries.