BET bromodomain inhibition potentiates radiosensitivity in models of H3K27-altered diffuse midline glioma.

Diffuse midline glioma (DMG) H3K27-altered is one of the most malignant childhood cancers. Radiation therapy remains the only effective treatment yet provides a 5-year survival rate of only 1%. Several clinical trials have attempted to enhance radiation antitumor activity using radiosensitizing agents, although none have been successful.

Integrative Genomic Analyses Identify LncRNA Regulatory Networks across Pediatric Leukemias and Solid Tumors.

Unlabelled: Long noncoding RNAs (lncRNA) play an important role in gene regulation and contribute to tumorigenesis. While pan-cancer studies of lncRNA expression have been performed for adult malignancies, the lncRNA landscape across pediatric cancers remains largely uncharted. Here, we curated RNA sequencing data for 1,044 pediatric leukemia and extracranial solid tumors and integrated paired tumor whole genome sequencing and epigenetic data in relevant cell line models to explore lncRNA expression, regulation, and association with cancer.

Assessing the impact of a leadership and advocacy elective course in a college of pharmacy curriculum.

Introduction And Leadership Framework: While the scope of a pharmacist's work has grown, continued advocacy is needed to ensure that their skillset is used to the best advantage of the patient. To accomplish this aim, the University of Utah College of Pharmacy created an elective advocacy and leadership class to train students in leadership and advocacy methods, with a focus on enabling students to practice advocacy within the state of Utah throughout the class.

Educational Context And Methods: In addition to traditional lectures, this class asked students to apply the knowledge learned in class to projects within their sphere of influence.

Assessing the impact of a payor-funded embedded clinical pharmacist on patient and provider satisfaction in a private primary care practice.

Purpose: With expanding roles of clinic-embedded pharmacists comes the need to identify routes for optimization, soliciting and addressing feedback, and justifying the position(s) to the employing institution. Studies have demonstrated the benefit of integrating pharmacists into healthcare teams, but these opportunities remain largely limited to major health systems due to a lack of billing avenues for and familiarity with the services pharmacists can provide.

Methods: With funding from and partnership with a third-party payor, a pharmacist was incorporated into a private physician-owned clinic to be a resource to the providers and provide comprehensive medication management to patients.

Novel genetically engineered H3.3G34R model reveals cooperation with ATRX loss in upregulation of cluster genes and promotion of neuronal lineage.

Background: Pediatric high-grade gliomas (pHGGs) are aggressive pediatric CNS tumors and an important subset are characterized by mutations in , the gene that encodes Histone H3.3 (H3.3).

Use of Ripple Effects Mapping to assess student-perceived benefits of undergraduate research and learning objective attainment with Irish nutrition students.

Ripple Effects Mapping (REM) is a qualitative data analysis approach that combines mind mapping with inductive analysis to condense data obtained from group interviews. One benefit of REM is the ability to identify unintended outcomes, or "ripples," of the intervention of interest. Ripples are visually represented by a mind map created during the REM session.

Implementation of Test-to-Stay programming to minimize learning loss in a pre-K-8 school district.

Objectives: Determine if a school-based Test-to-Stay (TTS) program designed to minimize learning loss reduced the incidence of COVID-19 in a US primary school district.

Study Design: Observational, simple summary analysis of attendance and effectiveness of a TTS program implemented in a California school district.

Methods: Retrospective analysis of nested medical and demographic data.

Genetic changes associated with relapse in favorable histology Wilms tumor: A Children's Oncology Group AREN03B2 study.

Over the last decade, sequencing of primary tumors has clarified the genetic underpinnings of Wilms tumor but has not affected therapy, outcome, or toxicity. We now sharpen our focus on relapse samples from the umbrella AREN03B2 study. We show that over 40% of relapse samples contain mutations in SIX1 or genes of the MYCN network, drivers of progenitor proliferation.

A novel mouse model of diffuse midline glioma initiated in neonatal oligodendrocyte progenitor cells highlights cell-of-origin dependent effects of H3K27M.

Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells-of-origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs.

Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?: An English Retrospective Cohort Study.

Background: Cancer survivors have a higher risk for developing cardiovascular diseases than the general population.

Objectives: The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death.

Methods: This cohort study used linked English electronic health records, including death registration data.

A tumor suppressor role for EZH2 in diffuse midline glioma pathogenesis.

Pediatric high-grade gliomas, specifically diffuse midline gliomas, account for only 20% of clinical cases but are 100% fatal. A majority of the DMG cases are characterized by the signature K27M mutation in histone H3. The H3K27M mutation opposes the function of enhancer of zeste homolog 2 (EZH2), the methyltransferase enzyme of the polycomb repressor complex 2.

The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care.

Background: For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries.

Identifying key roles of the pharmacy technician in primary care settings.

Purpose: As the pharmacist's role expands, particularly in primary care practice settings, there is an opportunity for expansion of pharmacy technician duties to aid in administrative and clinical tasks that do not require the pharmacist's professional judgment. Identifying, defining, and expanding the roles of pharmacy technicians has been deemed a key part of the pharmacy practice model. These roles have been shown to enhance pharmacist efficiency and patient outreach; however, examples of the various innovative activities performed by technicians in the primary care setting are lacking in the literature.

Prenatal overexpression of platelet-derived growth factor receptor A results in central nervous system hypomyelination.

Background: Platelet-derived growth factor (PDGF) signaling, through the ligand PDGF-A and its receptor PDGFRA, is important for the growth and maintenance of oligodendrocyte progenitor cells (OPCs) in the central nervous system (CNS). PDGFRA signaling is downregulated prior to OPC differentiation into mature myelinating oligodendrocytes. By contrast, PDGFRA is often genetically amplified or mutated in many types of gliomas, including diffuse midline glioma (DMG) where OPCs are considered the most likely cell-of-origin.

Health behavior changes associated with weight gain among first-year international students studying at an American university.

To characterize the health behaviors and outcomes of first-year international students (FYIS) studying in the U.S. Three different cohorts of FYIS from a large midwestern university in the U.

Health Behaviors of Higher Education Students from 7 Countries: Poorer Sleep Quality during the COVID-19 Pandemic Predicts Higher Dietary Risk.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study.

Use of directed acyclic graphs (DAGs) to identify confounders in applied health research: review and recommendations.

Background: Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require conditioning when estimating causal effects. This review examined the use of DAGs in applied health research to inform recommendations for improving their transparency and utility in future research.

Methods: Original health research articles published during 1999-2017 mentioning 'directed acyclic graphs' (or similar) or citing DAGitty were identified from Scopus, Web of Science, Medline and Embase.

Abuse-Deterrent Opioid Formulations and the Opioid Crisis: A Pharmacist's Perspective.

Background: For over 20 years, the United States has suffered the detrimental effects of an opioid epidemic. Extended-release opioid products are particularly prone to abuse due to the high amount of opioid present. By bypassing the controlled-release mechanisms and nonoral administration, individuals experience intense and dangerous "highs.

Analysing trajectories of a longitudinal exposure: A causal perspective on common methods in lifecourse research.

Longitudinal data is commonly analysed to inform prevention policies for diseases that may develop throughout life. Commonly methods interpret the longitudinal data as a series of discrete measurements or as continuous patterns. Some of the latter methods condition on the outcome, aiming to capture 'average' patterns within outcome groups, while others capture individual-level pattern features before relating these to the outcome.

Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases.

Background: The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.

Prohibitin is a prognostic marker and therapeutic target to block chemotherapy resistance in Wilms' tumor.

Wilms' tumor is the most common type of childhood kidney cancer. To improve risk stratification and identify novel therapeutic targets for patients with Wilms' tumor, we used high-resolution mass spectrometry proteomics to identify urine tumor markers associated with Wilms' tumor relapse. We determined the urine proteomes at diagnosis of 49 patients with Wilms' tumor, non-Wilms' tumor renal tumors, and age-matched controls, leading to the quantitation of 6520 urine proteins.

Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study.

Background: Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.

Methods: We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality.

ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis.

Diffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor, with approximately 25% of DIPGs harboring activating ACVR1 mutations that commonly co-associate with H3.1K27M mutations. Here we show that in vitro expression of ACVR1 R206H with and without H3.