De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma.

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH).

Centriole signaling restricts hepatocyte ploidy to maintain liver integrity.

Hepatocyte polyploidization is a tightly controlled process that is initiated at weaning and increases with age. The proliferation of polyploid hepatocytes in vivo is restricted by the PIDDosome-P53 axis, but how this pathway is triggered remains unclear. Given that increased hepatocyte ploidy protects against malignant transformation, the evolutionary driver that sets the upper limit for hepatocyte ploidy remains unknown.

Medicaid Expansion and Change in Federally Qualified Health Center Accessibility From 2008 to 2016.

Background: The Affordable Care Act expanded health coverage for low-income residents through Medicaid expansion and increased funding for Health Center Program New Access Points from 2009 to 2015, improving federally qualified health center (FQHC) accessibility. The extent to which these provisions progressed synergistically as intended when states could opt out of Medicaid expansion is unknown.

Objective: To compare change in FQHC accessibility among census tracts in Medicaid expansion and nonexpansion states.

Battle of the buttress: 5-year propensity-matched analysis of staple-line reinforcement techniques from the MBSAQIP database.

Background: Vertical sleeve gastrectomy (VSG) has demonstrated to be safe; however, controversy remains on how to decrease major complications, particularly bleeding and leaks. There are variations in staple-line reinforcement techniques, including no reinforcement, oversewing, and buttressing. We sought to evaluate the effect of those methods on post-operative complications using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program (MBSAQIP) database.

Aromatase inhibition increases blood pressure and markers of renal injury in female rats.

Aromatase is a monooxygenase that catalyzes the rate-limiting step of estrogen biosynthesis from androgens. Aromatase inhibitors are widely used for the treatment of patients with hormone receptor-positive breast cancer. However, the effects of aromatase inhibitors on cardiovascular and renal health in females are understudied.

Mycoprotein as novel functional ingredient: Mapping of functionality, composition and structure throughout the Quorn fermentation process.

This study provides the first mapping of mycoprotein functionality, composition and structure throughout the Quorn fermentation process. The fermentation broth, RNA-reduced broth (RNA-broth), centrate and their centrifugation deposits and supernatants were characterised. The broth, RNA-broth and their deposits displayed high concentrations of fungal filaments, which contributed to their high gelling properties (with a 5,320 Pa elastic modulus reported for RNA-broth deposits gels).

Structural clues to articular calcified cartilage function: A descriptive review of this crucial interface tissue.

Articular calcified cartilage (ACC) has been dismissed, by some, as a remnant of endochondral ossification without functional relevance to joint articulation or weight-bearing. Recent research indicates that morphologic and metabolic ACC features may be important, reflecting knee joint osteoarthritis (OA) predisposition. ACC is less investigated than neighbouring joint tissues, with its component chondrocytes and mineralised matrix often being either ignored or integrated into analyses of hyaline articular cartilage and subchondral bone tissue respectively.

Exploring the Readability of Ingredients Lists of Food Labels with Existing Metrics.

Healthy diet and dietary behaviors are key components in prevention of chronic disease and management of chronic illness. Nutritional literacy has been associated with dietary behaviors and consumer choice of healthy foods. Nutritional literacy can be measured, for example, by examining consumer food label use, but current research focuses largely on the Nutrition Facts panel of a food product.

The impact of employment programs on common mental disorders: A systematic review.

Background: While employment programs were not created with the intent to improve common mental disorders (CMDs), they may have a positive impact on the prevalence, incidence, and severity of CMD by reducing poverty and increasing access to economic mobility.

Aim: To examine and synthesize the available quantitative evidence of the impact of employment programs on outcomes of CMD.

Methods: Embase, Econlit, Global Health, MEDLINE, APA PsychINFO, and Social Policy and Practice were searched for experimental and quasi-experimental studies which investigated the impact of employment programs on primary and secondary outcomes of a CMD.

Early introduction of the multi-disciplinary team through student Schwartz Rounds: a mixed methodology study.

Background: Medical education has changed continually throughout the covid-19 pandemic, creating additional stress for medical students. Personal reflection can empower an individual to adapt to new challenges, and reflection has gradually become incorporated into medical student training. Schwartz Rounds (SR) offer a compassionate group reflective forum for healthcare staff.

The novel application of an emerging device for salvage of primary repair in high-risk complex esophageal atresia.

Introduction: Preservation of native esophagus is a tenet of esophageal atresia (EA) repair. However, techniques for delayed primary anastomosis are severely limited for surgically and medically complex patients at high-risk for operative repair. We report our initial experience with the novel application of the Connect-EA, an esophageal magnetic compression anastomosis device, for salvage of primary repair in 2 high-risk complex EA patients.

Health professionals' initial experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic paediatric early warning system (the DETECT study): a qualitative interview study.

Background: Paediatric early warning systems (PEWS) alert health professionals to signs of a child's deterioration with the intention of triggering an urgent review and escalating care. They can reduce unplanned critical care transfer, cardiac arrest, and death. Electronic systems may be superior to paper-based systems.

Pollinator identity and behavior affect pollination in kiwifruit ( Planch.).

Many crop plants rely on insect pollination, particularly insect-pollinated crops which are functionally dioecious. These crops require insects to move pollen between separate plants which are functionally male or female. While honey bees are typically considered the most important crop pollinator species, many other insects are known to visit crops but the pollination contribution of the full diversity of these flower visitors is poorly understood.

Critical Care Response During the COVID-19 Pandemic.

Hospitals and health care systems with active critical care organizations (CCOs) that unified ICU units before the onset of the COVID-19 Pandemic were better positioned to adapt to the demands of the pandemic, due to their established standardization of care and integration of critical care within the larger structure of the hospital or health care system. CCOs should continue to make changes, based on the real experience of COVID-19 that would lead to improved care during the ongoing pandemic, and beyond.

Standardized testing and written communication improve patient understanding of beta-lactam allergy testing outcomes: A multicenter, prospective study.

Background: Historical penicillin allergy is commonly reported, but the lack of standardized allergy clinic practices may diminish the ability to delabel beta-lactam allergy appropriately.

Objective: We sought to improve beta-lactam allergy testing and patient understanding of their antibiotic allergy status by standardizing testing and communication practices between 7 adult and pediatric hospital centers.

Methods: Phase 1 prospectively described the beta-lactam allergy testing practices at each center.

Tuberous sclerosis complex-associated nonfunctional pancreatic neuroendocrine tumors: Management and surgical outcomes.

We aimed to further characterize pancreatic involvement in tuberous sclerosis complex (TSC), with a focus on management of TSC-associated nonfunctional pancreatic neuroendocrine tumors (PNETs). This was a retrospective chart review of a large cohort of TSC patients. A total of 637 patients with a confirmed diagnosis of TSC were seen at the Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital.

Chemokines, soluble PD-L1, and immune cell hyporesponsiveness are distinct features of SARS-CoV-2 critical illness.

Critically ill patients manifest many of the same immune features seen in coronavirus disease 2019 (COVID-19), including both "cytokine storm" and "immune suppression." However, direct comparisons of molecular and cellular profiles between contemporaneously enrolled critically ill patients with and without severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited. We sought to identify immune signatures specifically enriched in critically ill patients with COVID-19 compared with patients without COVID-19.

Factors associated with poor self-management documented in home health care narrative notes for patients with heart failure.

Background: Patients with heart failure (HF) who actively engage in their own self-management have better outcomes. Extracting data through natural language processing (NLP) holds great promise for identifying patients with or at risk of poor self-management.

Objective: To identify home health care (HHC) patients with HF who have poor self-management using NLP of narrative notes, and to examine patient factors associated with poor self-management.

Improving patient and clinician safety during COVID-19 through rapidly adaptive simulation and a randomised controlled trial: a study protocol.

Introduction: COVID-19 required healthcare systems to iteratively adapt for safe and up-to-date care as knowledge of the disease rapidly evolved. Rates of COVID-19 infections continue to fluctuate and patients without COVID-19 increasingly return to the emergency department (ED) for care. This leads to new challenges and threats to patient and clinician safety as suspected patients with COVID-19 need to be quickly detected and isolated among other patients with non-COVID-19-related illnesses.

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline.

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU).

Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives.

The Evolution of the National Special Pathogen System of Care.

Infectious disease outbreaks and pandemics have repeatedly threatened public health and have severely strained healthcare delivery systems throughout the past century. Pathogens causing respiratory illness, such as influenza viruses and coronaviruses, as well as the highly communicable viral hemorrhagic fevers, pose a large threat to the healthcare delivery system in the United States and worldwide. Through the Hospital Preparedness Program, within the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, a nationwide Regional Ebola Treatment Network (RETN) was developed, building upon a state- and jurisdiction-based tiered hospital approach.