Introduction: The seeds of many plants are dormant and unable to germinate at maturity, but gain the ability to germinate through after-ripening during dry storage. The hormone abscisic acid (ABA) stimulates seed dormancy, whereas gibberellin A (GA) stimulates dormancy loss and germination.
Methods: To determine whether dry after-ripening alters the potential to accumulate ABA and GA, hormone levels were measured during an after-ripening time course in dry and imbibing ungerminated seeds of wildtype Landsberg (L) and of the highly dormant GA-insensitive mutant ().
Background: Per Centers for Disease Control and Prevention guidance, students with COVID-19 may end isolation after 5 days if symptoms are improving; some individuals may still be contagious. Rapid antigen testing identifies possibly infectious virus. We report on a test-to-return (TTR) program in a Massachusetts school district to inform policy decisions about return to school after COVID-19.
View Article and Find Full Text PDFBackground: Racial disparities have been shown to influence rates of surgery for patients with rotator cuff disease. Some individuals have attributed adverse social determinants of health (SDOHs) as potential confounders of this relationship between race and surgery rate. However, there is a paucity of literature observing whether adverse SDOHs and race independently influence rotator cuff surgery rates.
View Article and Find Full Text PDFThe storage, sharing, and analysis of genomic data poses technical and logistical challenges that have precipitated the development of cloud-based computing platforms designed to facilitate collaboration and maximize the scientific utility of data. To understand cloud platforms' policies and procedures and the implications for different stakeholder groups, in summer 2021, we reviewed publicly available documents (N = 94) sourced from platform websites, scientific literature, and lay media for five NIH-funded cloud platforms (the All of Us Research Hub, NHGRI AnVIL, NHLBI BioData Catalyst, NCI Genomic Data Commons, and the Kids First Data Resource Center) and a pre-existing data sharing mechanism, dbGaP. Platform policies were compared across seven categories of data governance: data submission, data ingestion, user authentication and authorization, data security, data access, auditing, and sanctions.
View Article and Find Full Text PDFUnlabelled: Short chain fatty acids (SCFAs) are products of bacterial fermentation that help maintain important gut functions such as the intestinal barrier, signaling, and immune homeostasis. The main SCFAs acetate, propionate, and butyrate have demonstrated beneficial effects for the host, including importance in combatting infections caused by pathogens such as . Despite the potential role of SCFAs in mitigating infection, their direct effect on remains unclear.
View Article and Find Full Text PDFLatent Epstein-Barr virus (EBV) infection promotes undifferentiated nasopharyngeal carcinomas (NPCs) in humans, but the mechanism(s) for this effect has been difficult to study because EBV cannot transform normal epithelial cells in vitro and the EBV genome is often lost when NPC cells are grown in culture. Here we show that the latent EBV protein, LMP1 (Latent membrane protein 1), induces cellular proliferation and inhibits spontaneous differentiation of telomerase-immortalized normal oral keratinocytes (NOKs) in growth factor-deficient conditions by increasing the activity of the Hippo pathway effectors, YAP (Yes-associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif). We demonstrate that LMP1 enhances YAP and TAZ activity in NOKs both by decreasing Hippo pathway-mediated serine phosphorylation of YAP and TAZ and increasing Src kinase-mediated Y357 phosphorylation of YAP.
View Article and Find Full Text PDFGrowth Differentiation Factor-15 (GDF15) is a circulating polypeptide linked to cellular stress and metabolic adaptation. GDF15's half-life is ~3 h and activates the glial cell line-derived neurotrophic factor family receptor alpha-like (GFRAL) receptor expressed in the area postrema. To characterize sustained GFRAL agonism on food intake (FI) and body weight (BW), we tested a half-life extended analog of GDF15 (Compound H [CpdH]) suitable for reduced dosing frequency in obese cynomolgus monkeys.
View Article and Find Full Text PDFA 43-year-old man with a growing mass in the right groin, concerned for liposarcoma, underwent MRI and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT before surgery. Fibroblast activation protein inhibitor PET/CT demonstrated increased uptake (SUV max , 3.2) predominantly in the solid portion, where MRI showed gadolinium enhancement.
View Article and Find Full Text PDFTechnology is transforming service delivery in many health professions, particularly with the rapid shift to virtual care during the COVID-19 pandemic. Health profession regulators must navigate legal and ethical complexities to facilitate virtual care while upholding their mandate to protect the public interest. The objectives of this scoping review were to examine how the public interest is protected when regulating health professionals who provide virtual care, discuss policy and practice implications of virtual care, and make recommendations for future research.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
September 2023
Context: The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM).
Objective: Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals.
Methods: We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .
Nuclear factor erythroid-related 2-factor 2 (Nrf2) is a transcription factor traditionally thought of as a cellular protector. However, in many cancers, Nrf2 is constitutively activated and correlated with therapeutic resistance. Nrf2 heterodimerizes with small musculoaponeurotic fibrosarcoma Maf (sMAF) transcription factors, allowing binding to the antioxidant responsive element (ARE) and induction of transcription of Nrf2 target genes.
View Article and Find Full Text PDFObjective: To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.
Methods: We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.
Somatic and germline gain-of-function point mutations in RAF, one of the first oncogenes to be discovered in humans, delineate a group of tumor-prone syndromes known as the RASopathies. In this study, we document the first human phenotype resulting from the germline loss-of-function of the proto-oncogene RAF1 (a.k.
View Article and Find Full Text PDFEmerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) possess mutations that prevent antibody therapeutics from maintaining antiviral binding and neutralizing efficacy. Monoclonal antibodies (mAbs) shown to neutralize Wuhan-Hu-1 SARS-CoV-2 (ancestral) strain have reduced potency against newer variants. Plasma-derived polyclonal hyperimmune drugs have improved neutralization breadth compared with mAbs, but lower titers against SARS-CoV-2 require higher dosages for treatment.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic placed intense pressure on nursing regulatory bodies to ensure an adequate healthcare workforce while maintaining public safety.
Purpose: Our objectives were to analyze regulatory bodies' responses during the pandemic, examine how nursing regulators conceptualize the public interest during a public health crisis, and explore the influence of a public health crisis on the balancing of regulatory principles. We aimed to develop a clearer understanding of regulating during a crisis by identifying themes within regulatory responses.
Understanding how habitat fragmentation affects individual species is complicated by challenges associated with quantifying species-specific habitat and spatial variability in fragmentation effects within a species' range. We aggregated a 29-year breeding survey data set for the endangered marbled murrelet (Brachyramphus marmoratus) from >42,000 forest sites throughout the Pacific Northwest (Oregon, Washington, and northern California) of the United States. We built a species distribution model (SDM) in which occupied sites were linked with Landsat imagery to quantify murrelet-specific habitat and then used occupancy models to test the hypotheses that fragmentation negatively affects murrelet breeding distribution and that these effects are amplified with distance from the marine foraging habitat toward the edge of the species' nesting range.
View Article and Find Full Text PDFUnlabelled: The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease.
View Article and Find Full Text PDFPurpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.
Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene.
Monoubiquitination of proteins governs diverse physiological processes, and its dysregulation is implicated in multiple pathologies. The difficulty of preparing sufficient material often complicates the biophysical studies of monoubiquitinated recombinant proteins. Here we describe a robust avidity-based method that overcomes this problem.
View Article and Find Full Text PDFTransformer is the latest deep neural network (DNN) architecture for sequence data learning that has revolutionized the field of natural language processing. This success has motivated researchers to explore its application in the healthcare domain. Despite the similarities between longitudinal clinical data and natural language data, clinical data presents unique complexities that make adapting Transformer to this domain challenging.
View Article and Find Full Text PDFDiamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations, and an increased risk of developing cancer. The chromatin-binding special AT-rich sequence-binding protein-1 (SATB1) is downregulated in megakaryocyte/erythroid progenitors (MEPs) in patients and cell models of DBA, leading to a reduction in MEP expansion. Here we demonstrate that SATB1 expression is required for the upregulation of the critical erythroid factors heat shock protein 70 (HSP70) and GATA1 which accompanies MEP differentiation.
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