Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene.

Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5'- and 3'-direction from its genomic context.

Location Preferences for Accessing Long-Acting Injectable Pre-Exposure Prophylaxis (LA-PrEP) Among Men Who Have Sex With Men (MSM) Currently on Daily Oral PrEP.

We investigated men who have sex with men's (MSM) location preferences for long-acting injectable pre-exposure prophylaxis (LA-PrEP). MSM ( = 1076) who completed the 2021 American Men's Internet Survey, were currently prescribed oral PrEP, and expressed LA-PrEP interest reported location preferences for receiving LA-PrEP: healthcare provider (HCP) setting, pharmacy, or at-home. HCP settings were preferred by 60% of participants; 26% preferred home and 14% preferred pharmacy.

Cumulative anticholinergic exposure and white matter hyperintensity burden in community-dwelling older adults.

Background: Anticholinergic exposure is associated with dementia risk; however, the mechanisms for this association remain unclear. The objective of this study was to examine the association between anticholinergic exposure and white matter hyperintensity (WMH) burden.

Methods: This was a retrospective analysis of data from the Adult Changes in Thought (ACT) study, a prospective cohort study among adults aged ≥65 years on dementia risk factors.

Quantification of PD-L1 expression and tumor mutational burden in biologically distinct advanced pancreatic cancers responding to pembrolizumab: case reports.

Background: The advent of checkpoint therapy is one of the most important recent advancements in cancer therapy. Though checkpoint therapy is a mainstay in some cancers, it has been largely ineffective in treating cancers of the pancreas. Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are seldom responsive to checkpoint inhibition.

Linear ubiquitination mediates coronavirus NSP14-induced NF-κB activation.

Human coronaviruses exhibit a spectrum of symptoms, ranging from mild seasonal colds to severe respiratory manifestations. Despite progress in understanding the host's innate defense mechanisms against coronaviruses, how these viruses manipulate the immune response to promote inflammation remains elusive. In this study, we unveil the role of the coronavirus nonstructural protein 14 (NSP14) in leveraging the host's linear ubiquitin chain assembly complex (LUBAC) to instigate NF-κB activation, thereby triggering proinflammatory responses.

Outcomes in Randomized Clinical Trials Testing Changes in Daily Water Intake: A Systematic Review.

Importance: Several public recommendations exist regarding the amount of daily water intake, yet the supporting evidence is not clear, and benefits of increasing water consumption are not well-established.

Objective: To summarize evidence from randomized clinical trials (RCTs) pertaining to the health-related outcomes associated with increased or decreased daily water consumption.

Evidence Review: A systematic search of PubMed, Web of Science, and Embase was performed up to April 6, 2023.

Cohesin distribution alone predicts chromatin organization in yeast via conserved-current loop extrusion.

Background: Inhomogeneous patterns of chromatin-chromatin contacts within 10-100-kb-sized regions of the genome are a generic feature of chromatin spatial organization. These features, termed topologically associating domains (TADs), have led to the loop extrusion factor (LEF) model. Currently, our ability to model TADs relies on the observation that in vertebrates TAD boundaries are correlated with DNA sequences that bind CTCF, which therefore is inferred to block loop extrusion.

Micellar solubility and co-solubilization of fragrance raw materials in sodium dodecyl sulfate and polysorbate 20 surfactant systems.

Objective: The aim of this work was to investigate the solubility and co-solubilization of fragrance raw materials (FRMs) in sodium dodecyl sulfate (SDS) and polysorbate 20 (P20) surfactant micellar systems, which can advance our knowledge of multi-solute micellar solubilization and fragrance olfactory performance from product matrices containing the surfactants.

Methods: The transfer of individual FRMs and binary FRM mixtures into micellar phases was quantified by UV-VIS differential spectroscopy and evaluated in terms of the standard Gibbs free energy change and micelle-water partition coefficient. Co-solubilization effects were further evaluated by the deviation ratio.

Consumer product-related female genital injuries in the USA from 2013 to 2022.

Background: Consumer product-related genital injuries in females across all age groups are understudied. Existing research focuses primarily on paediatric populations. We aimed to determine characteristics, trends and predictors of hospitalisation.

Molecular characterization of Streptococcus suis isolates recovered from diseased pigs in Europe.

Streptococcus suis is a major swine pathogen and zoonotic agent, causing important economic losses to the porcine industry. Here, we used genomics approaches to characterize 251 S. suis isolates recovered from diseased pigs across Belgium, France, Germany, Hungary, the Netherlands, Spain, and the United Kingdom.

Ejaculatory function after radiotherapy for prostate cancer: a systematic review and meta-analysis.

Background: Scant data exists on the impacts of prostate radiation on ejaculatory function. We performed a systematic review and meta-analysis to assess ejaculatory outcomes in men after prostate radiation.

Methods: We queried PubMed, Embase, and Web of Science to identify 17 articles assessing ejaculatory function post-radiation.

Immunometabolic effects of lactate on humoral immunity in healthy individuals of different ages.

Aging is characterized by chronic systemic inflammation and metabolic changes. We compare the metabolic status of B cells from young and elderly donors and found that aging is associated with higher oxygen consumption rates, and especially higher extracellular acidification rates, measures of oxidative phosphorylation and of anaerobic glycolysis, respectively. Importantly, this higher metabolic status, which reflects age-associated expansion of pro-inflammatory B cells, is found associated with higher secretion of lactate and autoimmune antibodies after in vitro stimulation.

Comparing GPT-4 and Human Researchers in Health Care Data Analysis: Qualitative Description Study.

Background: Large language models including GPT-4 (OpenAI) have opened new avenues in health care and qualitative research. Traditional qualitative methods are time-consuming and require expertise to capture nuance. Although large language models have demonstrated enhanced contextual understanding and inferencing compared with traditional natural language processing, their performance in qualitative analysis versus that of humans remains unexplored.

Fast depressive symptoms improvement in bipolar I disorder after Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT): A two-site feasibility and safety open-label trial.

Background: Although there are a few first-line treatment options for bipolar depression, none are rapid-acting. A new rTMS protocol, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT®), has been shown to have a rapid antidepressant effect in major depressive disorder (MDD). We examined the preliminary safety, tolerability, and efficacy of SAINT for the treatment of depression in a small sample of persons with treatment-resistant bipolar I disorder.

Inhibition of SUMOylation Induces Adaptive Antitumor Immunity against Pancreatic Cancer through Multiple Effects on the Tumor Microenvironment.

Improvement of outcome in patients with pancreatic ductal adenocarcinoma (PDAC) requires exploration of novel therapeutic targets. Thus far, most studies of PDAC therapies, including those inhibiting small ubiquitin-like modifications (SUMOylation), have focused on PDAC epithelial cell biology, yet SUMOylation occurs in a variety of cell types. The mechanisms by which SUMOylation impacts PDAC in the context of its tumor microenvironment are poorly understood.

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty: A Trauma and Urologic Reconstructive Network of Surgeons Analysis.

Purpose: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty.

Injuries With Electric vs Conventional Scooters and Bicycles.

Importance: Micromobility, the use of small vehicles (primarily scooters and bicycles), has become a standard transportation method in the US. Despite broad adoption of electric micromobility vehicles, there is a paucity of data regarding the injury profiles of these vehicles, particularly in the US.

Objective: To characterize micromobility injury trends in the US, identify demographic characteristic differences in users of electric and conventional vehicles, and identify factors associated with hospitalization.

Renal Autotransplantation: Association Between Preoperative Disease Duration and Surgical Outcomes.

Objective: To determine whether early versus delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation.

Methods: Patients who underwent renal autotransplantation from June 2012 to September 2022 were divided into 2 groups based on timing of autotransplant in relation to initial intervention or diagnosis (early cohort: ≤1-year; delayed cohort: >1-year). Primary outcomes were perioperative complications, aborted surgery, renal function (glomerular filtration rate [GFR]), and postoperative complications at most recent follow-up.

Patient Perception of Physician Reimbursement by Medicare for Artificial Urinary Sphincter Placement.

Introduction: Patient perceptions of physician reimbursement commonly differ from actual reimbursement. This study aims to improve health care cost transparency and trust between patients, physicians, and the health care system by evaluating patient perceptions of Medicare reimbursement for artificial urinary sphincter (AUS) placement.

Methods: We identified patients who underwent AUS placement at a single institution from 2014 to 2023.