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.

Varying Utilization Rates but Superior Outcomes in Liver Transplantation From Hepatitis C-positive Donors in the United States: An Analysis of the OPTN/UNOS Database.

Background: Liver transplantation (LT) from hepatitis C virus (HCV)-positive donors [antibody positive (Ab+) or nucleic acid test-positive (NAT+) donors] has been reported to achieve successful outcomes. However, donor and recipient selection has not been well-characterized.

Methods: Data between 2015 and 2019 were obtained from the United Network for Organ Sharing database.

Racial and Ethnic Variation in Genetic Susceptibility: Are Disparities in Infertility Prevalence and Outcomes more than Black and White?

Race, as a social construct without a clear genetic underpinning, is frequently referenced in medicine as predictor of multiple diseases including that of infertility. The authors will discuss how systematic racism can have downstream consequences ranging from overt physician bias to use of medical algorithms that may potentiate the same disparities they attempt to narrow. Then, the authors explore the utility and pragmatic use of genetic ancestry to estimate disease prevalence, instead of racial categories.

Semi-automated Segmentation and Quantification of Perivascular Spaces at 7 Tesla in COVID-19.

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes.

Monoclonal antibody pairs against SARS-CoV-2 for rapid antigen test development.

Background: The focus on laboratory-based diagnosis of coronavirus disease 2019 (COVID-19) warrants alternative public health tools such as rapid antigen tests. While there are a number of commercially available antigen tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), all cross-react with the genetically similar SARS-CoV-1 or require an instrument for results interpretation.

Methodology/principal Findings: We developed and validated rapid antigen tests that use pairs of murine-derived monoclonal antibodies (mAbs), along with gold nanoparticles, to detect SARS-CoV-2 with or without cross-reaction to SARS-CoV-1 and other coronaviruses.

American Society of Echocardiography Algorithm for Degenerative Mitral Regurgitation: Comparison With CMR.

Objectives: The purpose of this study was to compare the American Society of Echocardiography (ASE) algorithm for assessing mitral regurgitation (MR) to cardiac magnetic resonance (CMR) and left ventricular (LV) remodeling following mitral intervention.

Background: The ASE recommends integrating multiple echocardiographic parameters for assessing MR. The ASE guidelines include an algorithm that weighs the parameters and highlights those considered indicative of definitely mild or definitely severe MR.

Derivation of extra-embryonic and intra-embryonic macrophage lineages from human pluripotent stem cells.

Tissue-resident macrophages are increasingly recognized as important determinants of organ homeostasis, tissue repair, remodeling and regeneration. Although the ontogeny and function of tissue-resident macrophages has been identified as distinct from postnatal hematopoiesis, the inability to specify, in vitro, similar populations that recapitulate these developmental waves has limited our ability to study their function and potential for regenerative applications. We took advantage of the concept that tissue-resident macrophages and monocyte-derived macrophages originate from distinct extra-embryonic and definitive hematopoietic lineages to devise a system to generate pure cultures of macrophages that resemble tissue-resident or monocyte-derived subsets.

One Side of the Story; Clues to Etiology in Patients with Asymmetric Chorea.

Background: Chorea can be due to a large number of etiologies. Unilateral chorea is classically related to a contralateral structural lesion, e.g.

Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in borderline resectable/locally advanced pancreatic cancer patients.

Background: The 2020 National Comprehensive Cancer Network guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC).

Aim: The purpose of our study was to compare treatment outcomes, toxicity profiles, costs, and quality-of-life measures between these two treatments to further inform clinical decision-making.

Methods And Results: We developed a decision-analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G-nP over 12 years.

Improving Resuscitation Timing: Random Assignment of Interprofessional Team Leaders in Simulated Resuscitation.

Objectives: The aims of the study were to assess whether preassigning a team leader influences resuscitation timing using simulation and to examine relationship between response timeliness and designated leader's profession, whether physician or nurse.

Methods: This is a prospective study of intervention (leader assigned) and control (no assigned leader) teams of residents and nurses participating in a simulated scenario. The primary outcome was time to bag-valve-mask (BVM) ventilation.

Albumin-Methotrexate Prodrug Analogues That Undergo Intracellular Reactivation Following Entrance into Cancerous Glioma Cells.

A family of monomodified bovine serum albumin (BSA) linked to methotrexate (MTX) through a variety of spacers was prepared. All analogues were found to be prodrugs having low MTX-inhibitory potencies toward dihydrofolate reductase in a cell-free system. The optimal conjugates regenerated their antiproliferative efficacies following entrance into cancerous glioma cell lines and were significantly superior to MTX in an insensitive glioma cell line.

Digital Survey Assessment of Factors Associated with Musculoskeletal Complaints Among US Ophthalmologists.

Purpose: To quantify features of musculoskeletal (MSK) complaints among US ophthalmologists and analyze factors related to symptom severity.

Methods: Cornea, glaucoma, retina, and comprehensive practitioners were invited to complete a web-based survey via email. Data on demographics, practice and procedural volumes, wellness activities, job stress, MSK health, the Total Disability Index (TDI), and ergonomics were collected.

Point-of-Care Ultrasonography for Ankle Injuries in Children.

Objectives: The aim of the study was to determine whether point-of-care ultrasound (US) can decrease x-rays in children with ankle injuries. Secondary objectives were to determine the test performance characteristics for ankle US, analyze diagnostic errors, and compare US with the Ottawa Ankle Rules (OAR).

Methods: This was a prospective study of children younger than 21 years presenting to an emergency department with an ankle injury requiring x-rays.

DCRM Multispecialty Practice Recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions. This evolution in CVOT evidence calls for practice recommendations that are not constrained by a single discipline to help clinicians manage patients with complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases.

Adrenal MT melatonin receptor expression is linked with seasonal variation in social behavior in male Siberian hamsters.

Many animals exhibit pronounced changes in physiology and behavior on a seasonal basis, and these adaptations have evolved to promote survival and reproductive success. While the neuroendocrine pathways mediating seasonal reproduction are well-studied, far less is known about the mechanisms underlying seasonal changes in social behavior, particularly outside of the context of the breeding season. Our previous work suggests that seasonal changes in melatonin secretion are important in regulating aggression in Siberian hamsters (Phodopus sungorus); it is unclear, however, how melatonin acts via its receptors to modulate seasonal variation in social behavior.

Dissolution Study on Grape Polyphenol Hard Gelatin Capsule Dietary Supplements.

Methods for a dissolution study by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC-QqQ/MS) analysis of grape polyphenol dietary supplements, namely, grape seed extract (GSE) and resveratrol (RSV) capsules, were developed following the guidance of United States Pharmacopeia (USP) <2040>. Two dissolution media, 0.1 N hydrochloric acid (pH 1.

Dynamic regulation of N,2'-O-dimethyladenosine (mAm) in obesity.

The prevalent mAm mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established mA mRNA modification. However, the deposition and dynamics of mAm in regulating obesity are unknown. Here, we investigate the liver mA/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice.

Surfing the Big Data Wave: Omics Data Challenges in Transplantation.

In both research and care, patients, caregivers, and researchers are facing a leap forward in the quantity of data that are available for analysis and interpretation, marking the daunting "big data era." In the biomedical field, this quantitative shift refers mostly to the -omics that permit measuring and analyzing biological features of the same type as a whole. Omics studies have greatly impacted transplantation research and highlighted their potential to better understand transplant outcomes.

Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages.

During definitive erythropoiesis, maturation of erythroid progenitors into enucleated reticulocytes requires the erythroblastic island (EBI) niche comprising a central macrophage attached to differentiating erythroid progenitors. Normally, the macrophage provides a nurturing environment for maturation of erythroid cells. Its critical physiologic importance entails aiding in recovery from anemic insults, such as systemic stress or acquired disease.

Flavivirus infections induce a Golgi stress response in vertebrate and mosquito cells.

The stress of the Golgi apparatus is an autoregulatory mechanism that is induced to compensate for greater demand in the Golgi functions. No examples of Golgi stress responses due to physiological stimuli are known. Furthermore, the impact on this organelle of viral infections that occupy the vesicular transport during replication is unknown.

Intubation outcomes and practice trends during the initial New York SARS-COV-19 surge at an academic, level 1 trauma, urban emergency department.

Objectives: The goal of this study was to describe outcomes and associated characteristics of patients who were intubated during the initial (3/2020-4/2020) New York City surge of the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic, during which time we were confronted by an unknown and unprecedented respiratory distress syndrome with extremely high degrees of morbidity and mortality. Our secondary aim was to analyze our physician's rapidly evolving approaches to COVID-19 airway management.

Methods: A retrospective cohort analysis of all patients intubated at two emergency departments (EDs) for COVID-19 suspected respiratory failure.

Loneliness, sadness, and feelings of social disconnection in older adults during the COVID-19 pandemic.

Background: Public health measures to control the COVID-19 pandemic have led to feelings of loneliness among older adults, which, prior to COVID, has been associated with subsequent morbidity and mortality. We sought to identify differences in feelings of loneliness, sadness, and social disconnection early in the pandemic across racial groups, and possible mitigating factors.

Methods: We performed a cross-sectional analysis using the weighted nationally-representative Medicare Current Beneficiaries Survey COVID-19 supplement, collected summer 2020.