Humphries

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum...

No abstract text is available yet for this article.

Single cancer cells within a tumor exhibit variable levels of resistance to drugs, ultimately leading to treatment failures. While tumor heterogeneity is recognized as a major obstacle to cancer therapy, standard dose-response measurements for the potency of targeted kinase inhibitors aggregate populations of cells, obscuring intercellular variations in responses. In this work, we develop an analytical and experimental framework to quantify and model dose responses of individual cancer cells to drugs. We first explore the connection between population and single-cell dose responses using a computational model, revealing that multiple heterogeneous populations can yield nearly identical population dose responses...

OBJECTIVE: To describe the incidence and management of vaginal stricture after uterus transplants (UTx) in the United States, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation. DESIGN: Prospective cohort study. SUBJECTS: Recipients undergoing UTx from 2016 to 2023 at Baylor University Medical Center at Dallas, Cleveland Clinic, University of Pennsylvania, and University of Alabama at Birmingham were monitored postoperatively with regular pelvic exams...

The neuropeptide Y (NPY) Y4 receptor (Y4 R), a member of the family of NPY receptors, is physiologically activated by the linear 36-amino acid peptide pancreatic polypeptide (PP). The Y4 R is involved in the regulation of various biological processes, most importantly pancreatic secretion, gastrointestinal motility, and regulation of food intake. So far, Y4 R binding affinities have been mostly studied in radiochemical binding assays. Except for a few fluorescently labeled PP derivatives, fluorescence-tagged Y4 R ligands with high affinity have not been reported...

PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT...

Pectobacterium atrosepticum (Pba) is a gram-negative bacterium that causes blackleg and tuber soft rot of potato but can also asymptomatically colonise other (non-host) plant species. The aim of this study was to investigate the molecular processes and responses involved in Pba-host (potato) and Pba-non-host (radish) interactions, under laboratory conditions. To achieve this, we used total mRNA-sequencing to measure the gene expression patterns from all three species: Pba, potato and radish. We employed an end-point dual transcriptome approach...

Y chromosomes are thought to undergo progressive degeneration due to stepwise loss of recombination and subsequent reduction in selection efficiency. However, the timescales and evolutionary forces driving degeneration remain unclear. To investigate the evolution of sex chromosomes on multiple timescales, we generated a high-quality phased genome assembly of the massive older (<10MYA) and neo (<200,000 years) sex chromosomes in the XYY cytotype of the dioecious plant Rumex hastatulus and a hermaphroditic outgroup R...

PURPOSE: The most prevalent method of carbon monoxide (CO) suicide is inhalation of vehicle exhaust (VE). However, a new method of CO suicide has recently emerged involving charcoal burning (CB) in a confined space to produce fatal CO levels. This method has been reported from countries in Asia, associated with economic instability and media reporting of high-profile celebrity cases. The current study was undertaken to analyze rates and characteristics of CB suicides in South Australia (SA) for comparison with respect to their characteristics and scene, autopsy and toxicology findings...

PURPOSE OF REVIEW: Lottery incentives are an innovative approach to encouraging HIV prevention, treatment initiation, and adherence behaviours. This paper reviews the latest research on lottery incentives' impact on HIV-related services, and their effectiveness for motivating behaviours to improve HIV service engagement and HIV health outcomes. RECENT FINDINGS: Our review of ten articles, related to lottery incentives, published between 2018 and 2023 (inclusive) shows that lottery incentives have promise for promoting HIV-related target behaviours...

Antimicrobial resistance (AMR) affects 2.8 million Americans annually. AMR is identified through antimicrobial susceptibility testing (AST), but current and proposed regulatory policies from the United States Food and Drug Administration (FDA) jeopardize the future availability of AST for many microorganisms. Devices that perform AST must be cleared by the FDA using their susceptibility test interpretive criteria, also known as breakpoints. The FDA list of breakpoints is relatively short. Today, laboratories supplement FDA breakpoints using breakpoints published by the Clinical and Laboratory Standards Institute, using legacy devices and laboratory-developed tests (LDTs)...

PURPOSE: The graduate medical education community implemented virtual residency interviews in response to travel restrictions during the COVID-19 pandemic, and this approach has persisted. Although many residency applicants wish to visit in person prospective training sites, such opportunities could bias programs toward those who are able to meet this financial burden, exacerbating equity concerns. One proposed solution is to offer applicants the opportunity to visit only after a program's rank list is "locked," avoiding favoritism to applicants who visit, but allowing applicants to experience some of the camaraderie, geography, and local effects of an in-person visit...

No abstract text is available yet for this article.

OBJECTIVES: Critics of quality-adjusted life years (QALYs) argue that it discriminates against older individuals. However, little empirical evidence has been produced to inform this debate. To compare published cost effectiveness analyses (CEAs) on patients aged ≥65 years and those aged <65 years. METHODS: We used the Tufts Cost-Effectiveness Analysis Registry to identify CEAs published in Medline between 1976 and 2021. Eligible CEAs were categorized according to age (≥65 years versus <65 years)...

BACKGROUND: Despite the existence of American Cleft Palate and Craniofacial Association (ACPA)-approved Cleft and Craniofacial Teams, access to multidisciplinary team-based care remains challenging for patients from rural areas, leading to disparities in care. We investigated the geospatial relationship between U.S. counties and ACPA-approved centers. METHODS: The geographic location of all ACPA-approved cleft and craniofacial centers in the U.S. was identified...

The vertebrate basal ganglia play an important role in action selection-the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement...

BACKGROUND: Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function. METHODS AND RESULTS: To address this, we have generated a mouse model with a cardiomyocyte-specific knockout of PFKFB2 (cKO)...

OBJECTIVE: The COVID-19 pandemic has drastically altered the medical landscape. Various strategies have been employed to preserve hospital beds, personal protective equipment, and other resources to accommodate the surges of COVID-19 positive patients, hospital overcapacities, and staffing shortages. This has had a dramatic effect on vascular surgical practice. The objective of this study is to analyze the impact of the COVID-19 pandemic on surgical delays and adverse outcomes for patients with chronic venous disease scheduled to undergo elective operations...

AIMS: While elevated levels of anxiety are associated with worse prognosis of cardiovascular disease (CVD), this association may vary between different aspects of anxiety. The aim of this study was to analyse self-reported behavioural, physiological, affective, and cognitive aspects of anxiety and their relation to the risk of recurrent CV events. METHODS AND RESULTS: This prospective cohort study utilized data from the U-CARE Heart trial. Participants (N = 935, post myocardial infarction) answered the Hospital Anxiety and Depression Scale (HADS: Anxiety subscale) and the Cardiac Anxiety Questionnaire (CAQ: Fear, Avoidance & Attention subscales)...

No abstract text is available yet for this article.