Publications by authors named "David Dai"

Lipid nanoparticles (LNPs) are widely used for delivering therapeutic nucleic acids, yet the relationship between their internal structure and intracellular behavior, particularly before RNA release, remains unclear. Here, we elucidate how lipid-siRNA organization within LNPs can modulate their intracellular delivery dynamics. We use cryo-electron microscopy and photochemical assays to reveal that increased siRNA loading can reduce helper lipids' distribution to the LNP surface, while siRNA consistently localizes near the surface.

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There is increasing interest in health professions education (HPE) in applying argument-based validity approaches, such as Kane's, to assessment design. The critical first step in employing Kane's approach is to specify the interpretation-use argument (IUA). However, in the HPE literature, this step is often poorly articulated.

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Antisense oligonucleotide (ASO) represents a class of practical tools for targeting undruggable oncogenes with several candidates currently undergoing clinical investigation. The advancement of antisense therapeutics necessitates comprehensive approaches for evaluating their efficacy and improving their accuracy. Molecular imaging techniques offer a qualitative and quantitative means to assess therapeutics at the molecular, cellular, and levels, as well as to elucidate biodistribution and pharmacokinetics.

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Article Synopsis
  • Resilience helps people handle challenges better, and this study looked at how two groups of pharmacy students—older graduate students and younger undergraduates—build their resilience during their studies.!* -
  • The researchers used surveys and interviews to find out how students deal with stress, and while the younger and older students didn't experience different levels of burnout, older students had a more positive outlook on resilience.!* -
  • It was found that having support from friends and family helped the younger students perform better academically, and common ways both groups coped with stress included exercising and distracting themselves from their worries.!*
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Article Synopsis
  • The article discusses the need for reliable assessment tools in health professions education (HPE) and critiques Kane's four-inference model for its limitations in validation practices.
  • It proposes an expanded seven-inference argument-based validation framework, commonly used in language testing and assessment (LTA), to enhance the understanding of validity in HPE assessments.
  • The authors encourage HPE researchers to adopt this new framework and foster collaboration between HPE and LTA fields to address shared concerns about assessment validity.
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We introduce density imbalanced electron-hole bilayers at a commensurate 2:1 density ratio as a platform for realizing novel phases of electrons, excitons, and trions. Through the independently tunable carrier densities and interlayer spacing, competition between kinetic energy, intralayer repulsion, and interlayer attraction yields a rich phase diagram. By a combination of theoretical analysis and numerical calculation, we find a variety of strong-coupling phases in different parameter regions, including quantum crystals of electrons, excitons, and trions.

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Microbial electrosynthesis (MES) is an electrically driven technology that can be used for converting CO/CO into chemicals. The unique electronic and substrate properties of CO make it an important research target for MES. However, CO can poison the cathode and increase the overpotential of hydrogen evolution reaction (HER), thus reducing the electron transfer rate via H.

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The regulation of drug-metabolizing enzymes and transporters by cytokines has been extensively studied in vitro and in clinic. Cytokine-mediated suppression of cytochrome P450 (CYP) or drug transporters may increase or decrease the systemic clearance of drug substrates that are primarily cleared via these pathways; neutralization of cytokines by therapeutic proteins may thereby alter systemic exposures of such drug substrates. The Food and Drug Administration recommends evaluating such clinical drug interactions during clinical development and has provided labeling recommendations for therapeutic proteins.

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Acyl carrier protein (ACP) is the work horse of polyketide (PKS) and fatty acid synthases (FAS) and acts as a substrate shuttling domain in these mega enzymes. In fungi, FAS forms a 2.6 MDa symmetric assembly with six identical copies of FAS1 and FAS2 polypeptides.

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Astrocytes are one of the brain's major cell types and are responsible for maintaining neuronal homeostasis via regulating the extracellular environment, providing metabolic support, and modulating synaptic activity. In neurodegenerative diseases, such as Alzheimer's disease, astrocytes can take on a hypertrophic appearance. These reactive astrocytes are canonically associated with increases in cytoskeletal proteins, such as glial fibrillary acidic protein and vimentin.

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Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a supervised deep learning algorithm that leverages gene expression and spatial location relationships learned from spatial transcriptomics to recover the spatial origins of cells in scRNA-seq.

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Fatty acid synthase (FASN) catalyzes the de novo synthesis of palmitate, a 16-carbon chain fatty acid that is the primary precursor of lipid metabolism and an important intracellular signaling molecule. FASN is an attractive drug target in diabetes, cancer, fatty liver diseases, and viral infections. Here, we develop an engineered full-length human FASN (hFASN) that enables isolation of the condensing and modifying regions of the protein post-translation.

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Metastasis is the leading cause of breast cancer-related deaths and is often driven by invasion and cancer-stem like cells (CSCs). Both the CSC phenotype and invasion are associated with increased hyaluronic acid (HA) production. How these independent observations are connected, and which role metabolism plays in this process, remains unclear due to the lack of convergent approaches integrating engineered model systems, computational tools, and cancer biology.

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The transition towards digital pathology and an extensive selection of video conferencing platforms have helped provide continuity to education even during the COVID-19 pandemic. Innovative approaches for pathology education, will likely persist beyond the pandemic, as they have powerful didactic potential. While there is a wide selection of software for use as educational tools, an environment to access all resources with ease is clearly lacking.

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Objective: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS).

Methods: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .

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Unlabelled: Mutant isocitrate dehydrogenase 1 (IDH1) and IDH2 block the differentiation of acute myeloid leukemia (AML) cells through production of R-2-hydroxyglutarate (R-2-HG). IDH inhibitors can induce differentiation of AML cells by lowering R-2-HG but have limited clinical efficacy as single agents. Here, we performed a genome-wide CRISPR knockout screen in an Idh1-mutated hematopoietic progenitor cell line to identify genes that increased the differentiation response to ivosidenib, an IDH1 inhibitor.

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Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein.

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Article Synopsis
  • Pleural effusions are a common issue after liver transplantation, and chronic cases can lead to worse health outcomes for patients.
  • A study at UCLA analyzed 1,722 liver transplant patients and found that 7% experienced persistent pleural effusions, with 21.4% of them developing a condition called "trapped lung."
  • Patients with trapped lung required more surgeries, had longer hospital stays, and faced a higher risk of mortality compared to those without this complication, indicating significant impacts on health and healthcare resources.
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Contact-mediated interactions between the astrocytic endfeet and infiltrating immune cells within the perivascular space are underexplored, yet represent potential regulatory check-points against CNS autoimmune disease and disability. Reactive astrocytes upregulate junctional adhesion molecule-A, an immunoglobulin-like cell surface receptor that binds to T cells via its ligand, the integrin, lymphocyte function-associated antigen-1. Here, we tested the role of astrocytic junctional adhesion molecule-A in regulating CNS autoinflammatory disease.

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Background: The Expanded Disability Status Scale (EDSS) score is a widely used measure to monitor disability progression in people with multiple sclerosis (MS). However, extracting and deriving the EDSS score from unstructured electronic health records can be time-consuming.

Objective: We aimed to compare rule-based and deep learning natural language processing algorithms for detecting and predicting the total EDSS score and EDSS functional system subscores from the electronic health records of patients with MS.

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Objective: The number, unpredictability, and severity of seizures experienced by patients with Dravet syndrome (DS) negatively impact quality of life (QOL) for patients, caregivers, and families. Metrics are needed to assess whether patients with residual seizures have moved meaningfully toward seizure freedom after treatment with new antiseizure medications.

Methods: We evaluated the time required postrandomization for each patient to experience the same number of seizures experienced during baseline (i.

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Aim: To predict the risk of hypoglycaemia using machine-learning techniques in hospitalized patients.

Methods: We conducted a retrospective cohort study of patients hospitalized under general internal medicine (GIM) and cardiovascular surgery (CV) at a tertiary care teaching hospital in Toronto, Ontario. Three models were generated using supervised machine learning: least absolute shrinkage and selection operator (LASSO) logistic regression; gradient-boosted trees; and a recurrent neural network.

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Tuberous sclerosis protein complex (pTSC) nucleates a proteinaceous signaling hub that integrates information about the internal and external energy status of the cell in the regulation of growth and energy consumption. Biochemical and cryo-electron microscopy studies of recombinant pTSC have revealed its structure and stoichiometry and hinted at the possibility that the complex may form large oligomers. Here, we have partially purified endogenous pTSC from fasted mammalian brains of rat and pig by leveraging a recombinant antigen binding fragment (F) specific for the TSC2 subunit of pTSC.

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At the beginning of 2020, to stop the spread of the coronavirus disease (COVID-19) to the campus, the Ministry of Education of China launched a policy "Suspension of classes without suspending schooling" for the spring semester of 2020. However, the drawbacks of online teaching (e.g.

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Background: Optimal antithrombotic management of patients with preexisting atrial fibrillation undergoing transcatheter aortic valve replacement is challenging given the need to balance the risk of bleeding and thromboembolism. We aimed to examine variation in care and association of antithrombotic therapies with 1-year outcomes of stroke, bleeding, and mortality in patients undergoing transcatheter aortic valve replacement with concomitant atrial fibrillation in the United States.

Methods: Patients who underwent transcatheter aortic valve replacement with preexisting atrial fibrillation from November 2011 through September 2015 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry linked to the Medicare database were examined according to receipt of oral anticoagulants (OACs) or antiplatelet therapies (APTs) or a combination of these (OAC+APT) at discharge.

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