Mechanistic modeling of cell viability assays with lineage tracing.

Data from cell viability assays, which measure cumulative division and death events in a population and reflect substantial cellular heterogeneity, are widely available. However, interpreting such data with mechanistic computational models is hindered because direct model/data comparison is often muddled. We developed an algorithm that tracks simulated division and death events in mechanistically detailed single-cell lineages to enable such a model/data comparison and suggest causes of cell-cell drug response variability.

Needlessly Treated: Evaluation of Prehospital Needle Thoracostomy.

Background: Needle thoracostomy is a potentially life-saving intervention for tension pneumothorax but may be overused, potentially leading to unnecessary morbidity.

Objective: To review prehospital needle thoracostomy indications, effectiveness, and adverse outcomes.

Methods: A retrospective cohort study was conducted based on registry data for a United States Midwestern Level I trauma center for a 7.

Multimodal framework to resolve variants of uncertain significance in .

Efforts to resolve the functional impact of variants of uncertain significance (VUS) have lagged behind the identification of new VUS; as such, there is a critical need for scalable VUS resolution technologies. Computational variant effect predictors (VEPs), once trained, can predict pathogenicity for all missense variants in a gene, set of genes, or the exome. Existing tools have employed information on known pathogenic and benign variants throughout the genome to predict pathogenicity of VUS.

The Perspectives of Advanced Practice Provider Directors on Acute Care Nurse Practitioner Alignment and Hiring.

Demand for acute care is forecasted to grow in the United States. To meet this demand, nurse practitioners (NPs) are increasingly employed in acute care settings. Yet, there is concern about an adequate supply of acute care NPs given demand.

Electron microscopy mapping of the DNA-binding sites of monomeric, dimeric, and multimeric KSHV RTA protein.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human herpesvirus associated with several human cancers, typically in patients with compromised immune systems. Herpesviruses establish lifelong infections in hosts in part due to the two phases of infection: the dormant and active phases. Effective antiviral treatments to prevent the production of new viruses are needed to treat KSHV.

Evolution of Pediatric Critical Care Nursing.

Pediatric critical care nursing is a key pillar in patient care and outcomes for children who are ill and injured. Tremendous advances have occurred in pediatric critical care and nursing. This article provides an overview of the key advances in pediatric critical care nursing through the decades.

Electron microscopy mapping of the DNA-binding sites of monomeric, dimeric, and multimeric KSHV RTA protein.

Unlabelled: Molecular interactions between viral DNA and viral-encoded protein are a prerequisite for successful herpesvirus replication and production of new infectious virions. Here, we examined how the essential Kaposi's sarcoma-associated herpesvirus (KSHV) protein, RTA, binds to viral DNA using transmission electron microscopy (TEM). Previous studies using gel-based approaches to characterize RTA binding are important for studying the predominant form(s) of RTA within a population and identifying the DNA sequences that RTA binds with high affinity.

Long-read sequencing and profiling of RNA-binding proteins reveals the pathogenic mechanism of aberrant splicing of an poison exon in epilepsy.

Pathogenic loss-of-function variants cause a spectrum of seizure disorders. We previously identified variants in individuals with -related epilepsy that fall in or near a poison exon (PE) in intron 20 (20N). We hypothesized these variants lead to increased PE inclusion, which introduces a premature stop codon, and, therefore, reduced abundance of the full-length transcript and Na 1.

Increased dietary fiber is associated with weight loss among Full Plate Living program participants.

Introduction: Prior studies have demonstrated that an intake of foods rich in dietary fiber is associated with a favorable impact on health status and body weight. However, the association between fiber intake and weight loss has not been well-studied in employer settings. This research aimed to assess the relationship between dietary fiber and weight loss among individuals participating in the Full Plate Living (FPL) program.

Resolving two centuries of mistaken identity: Reinterpretation of Papilio marcus Fabricius, 1787 (Lepidoptera: Nymphalidae, Hesperiidae).

Here, we untangle an oversight surrounding the application of the name Papilio marcus Fabricius, 1787 (Hesperiidae: Hesperiinae), currently in Troyus Warren & Turland, 2012, which has eluded taxonomists for nearly two centuries. First, we note that P. marcus is a junior primary homonym of Papilio marcus Schaller, 1785, a species currently in Morpho Fabricius, 1807 (Nymphalidae: Satyrinae).

Development and content validation of the checklist for assessing placement of a small-bore chest tube (CAPS) for small-bore chest tube placement.

Background: Small-bore chest tube (SBCT) placement via modified Seldinger technique is a commonly performed invasive procedure for treatment of pleural effusion and pneumothorax. When performed suboptimally, it may lead to serious complications. Validated checklists are central to teaching and assessing procedural skills and may result in improved health care quality.

8-Hydroxyquinoline derivatives suppress GLI1-mediated transcription through multiple mechanisms.

Aberrant activation of the Hedgehog (Hh) signaling pathway has been observed in various human malignancies. Glioma-associated oncogene transcription factor 1 (GLI1) is the ultimate effector of the canonical Hh pathway and has also been identified as a common regulator of several tumorigenic pathways prevalent in Hh-independent cancers. The anti-cancer potential of GLI1 antagonism with small molecule inhibitors has demonstrated initial promise; however, the continued development of GLI1 inhibitors is still needed.

Precision medicine for developmental and epileptic encephalopathies in Africa-strategies for a resource-limited setting.

Purpose: Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes.

Enhancing a Rehabilitation Pathway for Pediatric Heart Transplant Recipients: An Improvement Project to Increase Adherence, Satisfaction, and Outcomes.

Aims: To refine a cardiac rehabilitation pathway for pediatric heart transplant recipients; assess clinician knowledge and adherence to the program; and evaluate patient outcomes.

Methods: The center has utilized a rehabilitation pathway for pediatric heart transplant recipients. Challenges in practice include access to centers, lack of data tracing, and adherence to the pathway.

Uses and Gratifications of Music in Bereavement: A Qualitative Inquiry.

This study investigates the role of music during bereavement. Music plays a role in peoples' bereavement experiences and gets associated with numerous memories. Despite widespread recognition of the importance of music, little research has considered what bereaved individuals "gain" through their musical selections.

Health Benefits of a 16-Week Whole Food, High Fiber, Plant Predominant Diet among U.S. Employees.

Purpose: To assess improvements in eating behaviors and health measures among adults participating in a whole food plant predominant diet, Full Plate Living (FPL) program.

Design: Retrospective, post hoc analysis of self-reported 16-week pre-post participant data obtained over a 3 year program period (2017-19).

Setting: Wellness offering for employees in Southwest U.

Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.

Aim: To identify additional genes associated with infantile spasms using a cohort with defined infantile spasms.

Method: Whole-exome sequencing (WES) was performed on 21 consented individuals with infantile spasms and their unaffected parents (a trio-based study). Clinical history and imaging were reviewed.

mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion.

Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTORC1 signalling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions, but these variants are increasingly detected and reported by clinical genetic testing in individuals with epilepsy.

DNA Sequence Specificity Reveals a Role of the HLTF HIRAN Domain in the Recognition of Trinucleotide Repeats.

DNA damage tolerance (DDT) pathways enable cells to cope with a variety of replication blocks that threaten their ability to complete DNA replication. Helicase-like transcription factor (HLTF) plays a central role in the error-free DDT pathway, template switching (TS), by serving as a ubiquitin ligase to polyubiquitinate the DNA sliding clamp PCNA, which promotes TS initiation. HLTF also serves as an ATP-dependent DNA translocase facilitating replication fork remodeling.

Lenvatinib Plus Anti-PD-1 Combination Therapy for Advanced Cancers: Defining Mechanisms of Resistance in an Inducible Transgenic Model of Thyroid Cancer.

Combination therapy with lenvatinib plus programmed death-1 (PD-1) immune checkpoint blockades (ICBs) is under investigation in many solid tumors, including thyroid cancer. Lenvatinib is known to reduce angiogenesis and may overturn the immunosuppressive effects of vascular endothelial growth factor in the tumor microenvironment. Previous studies investigating the effects of VEGF receptor inhibition on the immune response were performed in rapidly growing tumor models where immune equilibrium is not established before treatment.

Orthogonal pre-use and post-use efficiency testing for single-use anion exchange chromatography.

Three efficiency tests for single-use AEX chromatography devices have been developed and applied to six capsule formats of a new, salt tolerant, single-use AEX product. All the tests have been designed to be performed with simple equipment and common reagents. By performing each of the three tests on undamaged capsules and capsules intentionally damaged with small defects, in tandem with Phi-X174 challenges in a high-salt buffer, relationships between test results and viral clearance have been obtained.

A tyrosine kinase inhibitor-induced interferon response positively associates with clinical response in EGFR-mutant lung cancer.

Tyrosine kinase inhibitors (TKIs) targeting EGFR-mutant lung cancers promote a range of tumor regression responses to yield variable residual disease, a likely incubator for acquired resistance. Herein, rapid transcriptional responses induced by TKIs early in treatment that associate with the range of patient responses were explored. RNAseq was performed on EGFR mutant cell lines treated in vitro with osimertinib and on tumor biopsies of eight EGFR mutant lung cancer patients before and after 2 weeks of TKI treatment.