Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials.

Objective: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials.

Methods: Efficacy and safety of semaglutide 2.

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer.

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.

Iroquois homeobox 4 (IRX4) derived micropeptide promotes prostate cancer progression and chemoresistance through Wnt signalling dysregulation.

Background: Prostate cancer (PCa) is a commonly diagnosed cancer. Genome-wide association studies have implicated Iroquois homeobox 4 (IRX4) in PCa susceptibility, yet its functional roles remain unclear. We discovered a 78-amino acid micropeptide (miPEP, IRX4_PEP1), encoded from the alternative start site within the IRX4 gene.

Intact HIV reservoir in monocytes is associated with cognitive function in virally suppressed women with HIV.

Background: Monocytes are susceptible to HIV infection, form HIV reservoirs, and contribute to central nervous system complications (e.g., cognitive impairment) in virally suppressed women with HIV(vsWWH).

Glycolysis, the sweet appetite of the tumor microenvironment.

Cancer cells display an altered metabolic phenotype, characterised by increased glycolysis and lactate production, even in the presence of sufficient oxygen - a phenomenon known as the Warburg effect. This metabolic reprogramming is a crucial adaptation that enables cancer cells to meet their elevated energy and biosynthetic demands. Importantly, the tumor microenvironment plays a pivotal role in shaping and sustaining this metabolic shift in cancer cells.

Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology.

Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Escape mutants that alleviate this burden can rapidly evolve and take over cell populations, making genetic engineering less reliable and predictable. Synthetic biologists often use genetic parts encoded on plasmids, but their burden is rarely characterized.

Unique Idea: Using the KliniTray "Breast Board" for Immobilization of Digital Amputates During Replantation.

The KliniTray "breast board" used by many oncological breast surgeons is an innovative idea to succor microsurgical digital replantation. This piece of sterile equipment is readily available and provides excellent immobilization and retraction of the skin of digital amputates with minimal trauma. The fine metal pins are the key to its efficacy.

Management of Pilon Fractures.

Pilon fractures are complex injuries that can be difficult to treat and lead to severe complications if not managed appropriately. A thorough examination for polytraumatic injuries, neurovascular status, and skin condition should be done. A variety of approaches can be chosen based on fracture pattern, including staging, incisional approach, and no-touch technique.

Retrospective Analysis of Once-Daily Versus Twice-Daily Insulin Glargine Dosing in Noncritically Ill Individuals.

Background: Insulin is the treatment of choice for diabetes care in the hospital. There is some debate regarding the efficacy and safety of once-daily versus twice-daily insulin glargine in the hospital, particularly in the critically ill population.

Objective: The purpose of this pilot study was to evaluate the efficacy and safety of insulin glargine administered as a once-daily versus twice-daily regimen in the noncritically ill population.

Connectome-driven neural inventory of a complete visual system.

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brain's volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing.

Measuring the burden of hundreds of BioBricks defines an evolutionary limit on constructability in synthetic biology.

Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Populations of engineered cells can rapidly become dominated by "escape mutants" that evolve to alleviate this burden by inactivating the intended function. Synthetic biologists working with bacteria rely on genetic parts and devices encoded on plasmids, but the burden of different engineered DNA sequences is rarely characterized.

Interlaboratory validation of the ToxTracker assay: An in vitro reporter assay for mechanistic genotoxicity assessment.

ToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode-of-action (MoA), thereby supporting discrimination of direct-acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non-genotoxic compounds.

NeuronBridge: an intuitive web application for neuronal morphology search across large data sets.

Background: Neuroscience research in Drosophila is benefiting from large-scale connectomics efforts using electron microscopy (EM) to reveal all the neurons in a brain and their connections. To exploit this knowledge base, researchers relate a connectome's structure to neuronal function, often by studying individual neuron cell types. Vast libraries of fly driver lines expressing fluorescent reporter genes in sets of neurons have been created and imaged using confocal light microscopy (LM), enabling the targeting of neurons for experimentation.

The cell-type-specific spatial organization of the anterior thalamic nuclei of the mouse brain.

Understanding the cell-type composition and spatial organization of brain regions is crucial for interpreting brain computation and function. In the thalamus, the anterior thalamic nuclei (ATN) are involved in a wide variety of functions, yet the cell-type composition of the ATN remains unmapped at a single-cell and spatial resolution. Combining single-cell RNA sequencing, spatial transcriptomics, and multiplexed fluorescent in situ hybridization, we identify three discrete excitatory cell-type clusters that correspond to the known nuclei of the ATN and uncover marker genes, molecular pathways, and putative functions of these cell types.

HIV-1 Myeloid Reservoirs - Contributors to Viral Persistence and Pathogenesis.

Purpose Of Review: HIV reservoirs are the main barrier to cure. CD4+ T cells have been extensively studied as the primary HIV-1 reservoir. However, there is substantial evidence that HIV-1-infected myeloid cells (monocytes/macrophages) also contribute to viral persistence and pathogenesis.

[Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Novel immune-activating therapeutics for the treatment of glioblastoma multiforme (GBM) have shown potential for tumor regression and increased survival over standard therapies. However, immunotherapy efficacy remains inconsistent with response assessment being complicated by early treatment-induced apparent radiological tumor progression and slow downstream effects. This inability to determine early immunotherapeutic benefit results in a drastically decreased window for alternative, and potentially more effective, treatment options.

The role of the clinical pharmacist in the respiratory or sleep multidisciplinary team.

The role of the pharmacist has evolved significantly, not least over the last 20 years. It delivers a skilled profession with a vital role in medicines optimisation and the management of patients with a respiratory or sleep disorder. While pharmacists are capable of acting as independent practitioners delivering direct patient care, this article explores their contribution to multidisciplinary teams within asthma, COPD, cystic fibrosis, tuberculosis, interstitial lung disease and sleep medicine.

Key Challenges for Testing of Tobacco Products for Regulatory Applications: Recommendations for the Mouse Lymphoma Assay.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting assays to assess potential toxicity within and across traditional tobacco and various tobacco and nicotine next-generation products (NGPs), including Heated Tobacco Products (HTPs) and Electronic Nicotine Delivery Systems (ENDS). This report was developed by a working group composed of attendees of the seventh IIVS workshop, 'Approaches and recommendations for conducting the mouse lymphoma gene mutation assay (MLA) and introduction to disease models', which was held virtually on 21-23 June 2022. This publication provides a background overview of the MLA, and includes the description of assay conduct and data interpretation, key challenges and recommended best practices for evaluating tobacco and nicotine products, with a focus on the evaluation of NGPs, and a summary of how the assay has been used to evaluate and compare tobacco and nicotine products.

Supporting families with complex early parenting needs through a virtual residential parenting service: An investigation of outcomes, facilitators and barriers.

Aim: To investigate clients' perspectives about outcomes of a telehealth residential unit (RU) program for families experiencing complex early parenting issues, and to explore facilitators and barriers to positive client outcomes.

Design: Qualitative study using semi-structured interviews.

Methods: Semi-structured interviews were conducted with mothers (n = 18) admitted to a telehealth RU program.