Tolerability and Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists in Lung Transplant Recipients: A Single Center Report.

Introduction: Diabetes and obesity increase risk of death after lung transplantation. Optimal treatment of diabetes and obesity may improve post-transplant outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are FDA-approved to treat diabetes and obesity and demonstrate improvement in renal and cardiovascular outcomes in the general population.

Views of Aging and Subjective Cognition in Middle-Aged and Older Adults: A Systematic Review.

Introduction: Views of aging have been linked with many important outcomes in older adults. Subjective cognition, or one's perception of their cognitive functioning, may be a valuable indicator of cognitive changes as individuals age, but is known to be impacted by a variety of factors. The aim of this systematic review was to synthesize the evidence on relationships between views of aging and subjective cognition, including whether and how these relationships may differ based on age.

Continuous multiplexed phage genome editing using recombitrons.

Bacteriophage genome editing can enhance the efficacy of phages to eliminate pathogenic bacteria in patients and in the environment. However, current methods for editing phage genomes require laborious screening, counterselection or in vitro construction of modified genomes. Here, we present a scalable approach that uses modified bacterial retrons called recombitrons to generate recombineering donor DNA paired with single-stranded binding and annealing proteins for integration into phage genomes.

A bacterial TIR-based immune system senses viral capsids to initiate defense.

Toll/interleukin-1 receptor (TIR) domains are present in immune systems that protect prokaryotes from viral (phage) attack. In response to infection, TIRs can produce a cyclic adenosine diphosphate-ribose (ADPR) signaling molecule, which activates an effector that depletes the host of the essential metabolite NAD+ to limit phage propagation. How bacterial TIRs recognize phage infection is not known.

Simultaneous multi-site editing of individual genomes using retron arrays.

During recent years, the use of libraries-scale genomic manipulations scaffolded on CRISPR guide RNAs have been transformative. However, these existing approaches are typically multiplexed across genomes. Unfortunately, building cells with multiple, nonadjacent precise mutations remains a laborious cycle of editing, isolating an edited cell and editing again.

Investigating the impact of antibiotic-induced dysbiosis on protection from colitis by mouse colonic innate lymphoid cells.

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota.

Efficacy of therapeutically administered gepotidacin in a rabbit model of inhalational anthrax.

is a Gram-positive Centers for Disease Control and Prevention category "A" biothreat pathogen. Without early treatment, inhalation of anthrax spores with progression to inhalational anthrax disease is associated with high fatality rates. Gepotidacin is a novel first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is being evaluated for use against biothreat and conventional pathogens.

Simultaneous multi-site editing of individual genomes using retron arrays.

Our understanding of genomics is limited by the scale of our genomic technologies. While libraries of genomic manipulations scaffolded on CRISPR gRNAs have been transformative, these existing approaches are typically multiplexed across genomes. Yet much of the complexity of real genomes is encoded within a genome across sites.

A phase I, first-in-human study investigating the safety, tolerability, and pharmacokinetics of the maturation inhibitor GSK3739937.

We report the safety and pharmacokinetic properties of the HIV-1 maturation inhibitor GSK3739937 (GSK'937) in healthy participants. This was a phase I, first-in-human, double-blind, randomized, placebo-controlled, single- (part 1) and multiple- (part 2) dose escalation study with an additional open-label relative bioavailability and food effect study (part 3). Participants received oral ascending single doses (10-800 mg) in part 1, up to 18 once-daily 25- to 100-mg or 3 once-weekly 500-mg doses in part 2, and single 100-mg doses as powder-in-bottle or tablet (in fed and fasted states) formulations in part 3.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F.

Continuous Multiplexed Phage Genome Editing Using Recombitrons.

Bacteriophages, which naturally shape bacterial communities, can be co-opted as a biological technology to help eliminate pathogenic bacteria from our bodies and food supply. Phage genome editing is a critical tool to engineer more effective phage technologies. However, editing phage genomes has traditionally been a low efficiency process that requires laborious screening, counter selection, or construction of modified genomes.

Metagenome-Assembled Genome of a Putative Chemoheterotroph from Volcanic Terrain in Hawaii.

Here, we present the draft genome for a new putative species, Gaiellasilicea maunaloa, most closely related to Gaiella occulta, within the phylum This group contains Gram-negative, aerobic mesophilic species. This metagenome-assembled genome (MAG) contributes to knowledge of life in volcanic environments and may inform investigations of life beyond Earth.

Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats.

Fluoroquinolone use in children is limited due to its potential toxicity and negative effects on skeletal development, but the actual effects/risks of fluoroquinolones on bone growth and the mechanisms behind fluoroquinolone-driven arthropathy remain unknown. Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic with a unique mechanism of action that is not anticipated to have the same risks to bone growth as those of fluoroquinolones. Gepotidacin is in phase III clinical development for uncomplicated urinary tract infections (ClinicalTrials.

Basaltic Lava Tube Hosts a Putative Novel Genus in the Family .

We report the draft genome sequence of a putative new genus and species, Siliceabacter maunaloa, in the family . The members of this family of are generally Gram positive and mesophilic. Found within a Hawaiian lava tube, this microbe illuminates the types of prokaryotes inhabiting secondary minerals in subsurface basaltic environments.

Recording gene expression order in DNA by CRISPR addition of retron barcodes.

Biological processes depend on the differential expression of genes over time, but methods to make physical recordings of these processes are limited. Here we report a molecular system for making time-ordered recordings of transcriptional events into living genomes. We do this through engineered RNA barcodes, based on prokaryotic retrons, that are reverse transcribed into DNA and integrated into the genome using the CRISPR-Cas system.

Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague.

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by depends on the U.S.

Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.

Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533).

Retron reverse transcriptase termination and phage defense are dependent on host RNase H1.

Retrons are bacterial retroelements that produce single-stranded, reverse-transcribed DNA (RT-DNA) that is a critical part of a newly discovered phage defense system. Short retron RT-DNAs are produced from larger, structured RNAs via a unique 2'-5' initiation and a mechanism for precise termination that is not yet understood. Interestingly, retron reverse transcriptases (RTs) typically lack an RNase H domain and, therefore, depend on endogenous RNase H1 to remove RNA templates from RT-DNA.

Use of the ZDF rat to model dietary fat induced hypercoagulability is limited by progressive and fatal nephropathy.

Introduction: Zucker diabetic fatty (ZDF) rats are used widely as an animal model of metabolic syndrome and insulin resistance. Our study focused on the effects of high versus low dietary fat on the development of Type 2 diabetes in obese male ZDF rats (fa/fa), including biomarkers to detect early signs of hypercoagulability and vascular injury in the absence of overt thrombosis.

Methods: In this study, male (5/group) 10-week-old CRL:ZDF370(obese) rats were fed low (LFD, 16.

Provider visual attention on a respiratory function monitor during neonatal resuscitation.

Background: A respiratory function monitor (RFM) provides real-time positive pressure ventilation feedback. Whether providers use RFM during neonatal resuscitation is unknown.

Methods: Ancillary study to the MONITOR(NCT03256578) randomised controlled trial.

Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates.

Despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. Many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. One of those exceptions is CCL20, which exclusively pairs to CCR6 and is associated with several immunologic conditions, thus providing a promising therapeutic target.

Visual attention patterns of team leaders during delivery room resuscitation.

Aim: To assess visual attention of neonatal team leaders during delivery room resuscitation of preterm infants using eye tracking glasses.

Methods: Prospective observational eye tracking study. Gaze fixations and sequences were captured, categorized, and mapped during the first 5 min of the resuscitations.

Genome-Wide Study Updates in the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN).

The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients.

Accuracy of real-time delivery room resuscitation documentation.

Objective: To assess the accuracy of real-time delivery room resuscitation documentation.

Design: Retrospective observational study.

Setting: Level 3 academic neonatal intensive care unit.