Expanding the CRISPR base editing toolbox in Drosophila melanogaster.

CRISPR base editors can introduce point mutations into DNA precisely, and cytosine base editors (CBEs) catalyze C to T transitions. While CBEs have been thoroughly explored in cell culture and organisms such as mice, little is known about DNA base editing in insects. In this study, we evaluated germline editing rates of three different CBEs expressed under actin (ubiquitous) or nanos (germline) promoters utilizing Drosophila melanogaster.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Introduction: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs.

How environmental impact is considered in economic evaluations of critical care: a scoping review.

Purpose: Health care is a major contributor to climate change, and critical care is one of the sector's highest carbon emitters. Health economic evaluations form an important component of critical care and may be useful in identifying economically efficient and environmentally sustainable strategies. The purpose of this scoping review was to synthesise available literature on whether and how environmental impact is considered in health economic evaluations of critical care.

Next-generation CRISPR gene-drive systems using Cas12a nuclease.

One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects.

Organization of Cancer Specialists in US Physician Practices and Health Systems.

Purpose: To describe the supply of cancer specialists, the organization of cancer care within versus outside of health systems, and the distance to multispecialty cancer centers.

Methods: Using the 2018 Health Systems and Provider Database from the National Bureau of Economic Research and 2018 Medicare data, we identified 46,341 unique physicians providing cancer care. We stratified physicians by discipline (adult/pediatric medical oncologists, radiation oncologists, surgical/gynecologic oncologists, other surgeons performing cancer surgeries, or palliative care physicians), system type (National Cancer Institute [NCI] Cancer Center system, non-NCI academic system, nonacademic system, or nonsystem/independent practice), practice size, and composition (single disciplinary oncology, multidisciplinary oncology, or multispecialty).

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys.

Distinct association between chronic Epstein-Barr virus infection and T cell compartments from pediatric heart, kidney, and liver transplant recipients.

Chronic Epstein-Barr virus (EBV) infection after pediatric organ transplantation (Tx) accounts for significant morbidity and mortality. The risk of complications, such as posttransplant lymphoproliferative disorders, in high viral load (HVL) carriers is the highest in heart Tx recipients. However, the immunologic signatures of such a risk have been insufficiently defined.

Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice.

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids.

Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations.

Purpose: The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non-small cell lung cancer harboring L747_A750>P and other uncommon ex19dels is not known.

Experimental Design: The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multicenter retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L).

The Three W's of Acetaminophen In Children: Who, Why, and Which Administration Mode.

Acetaminophen is one of the oldest medications commonly administered in children. Its efficacy in treating fever and pain is well accepted among clinicians. However, the available evidence supporting the use of acetaminophen's different modes of administration remains relatively scarce and poorly known.

Phytochrome F mediates red light responsiveness additively with phytochromes B1 and B2 in tomato.

Phytochromes are red light and far-red light sensitive, plant-specific light receptors that allow plants to orient themselves in space and time. Tomato (Solanum lycopersicum) contains a small family of five phytochrome genes, for which to date stable knockout mutants are only available for three of them. Using CRISPR technology, we created multiple alleles of SlPHYTOCHROME F (phyF) mutants to determine the function of this understudied phytochrome.

'Advocacy groups are the connectors': Experiences and contributions of rare disease patient organization leaders in advanced neurotherapeutics.

Introduction: Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic cell and other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectations and promote health literacy.

Capsaicin 8% Patch for Spinal Cord Injury Focal Neuropathic Pain, a Randomized Controlled Trial.

Background: Neuropathic pain (NP) after spinal cord injury (SCI) exacerbates disability, decreases quality of life (QOL), and is often refractory to available therapies. Patients report willingness to trade potential recovery of strength, bowel, bladder, or sexual function for pain relief. One proposed mechanism causing NP is up-regulation of transient receptor potential vanilloid 1 (TRPV 1) proteins in uninjured C fibers and dorsal root ganglia causing neuronal excitability.

The involvement of rare disease patient organisations in therapeutic innovation across rare paediatric neurological conditions: a narrative review.

Background: The patient voice is becoming increasingly prominent across all stages of therapeutic innovation. It pervades research domains from funding and recruitment, to translation, care, and support. Advances in genomic technologies have facilitated novel breakthrough therapies, whose global developments, regulatory approvals, and confined governmental subsidisations have stimulated renewed hope amongst rare disease patient organisations (RDPOs).

Serine, N-acetylaspartate differentiate adolescents with juvenile idiopathic arthritis compared with healthy controls: a metabolomics cross-sectional study.

Background: In comparison with the general population, adolescents with juvenile idiopathic arthritis (JIA) are at higher risk for morbidity and mortality. However, limited evidence is available about this condition's underlying metabolic profile in adolescents with JIA relative to healthy controls. In this untargeted, cross-sectional metabolomics study, we explore the plasma metabolites in this population.

Geriatric Pharmacology Case Series: Direct Oral Anticoagulants for Older People With Cancer.

This case study focuses on the treatment of a patient with cancer-associated venous thromboembolism (VTE). This is a common complication of cancer that can result in substantial morbidity and mortality. The case reviews the approach of analyzing older people with cancer-associated VTE and its treatment options.

Development of a Bamlanivimab Infusion Process in the Emergency Department for Outpatient COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) pandemic has prompted the creation of new therapies to help fight against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Bamlanivimab is a SARS-CoV-2 monoclonal antibody that is administered as an intravenous infusion to ambulatory patients with mild or moderate COVID-19, but a concern that arose was deciding the optimal location for patients to receive the medication. This report describes the development and implementation of a bamlanivimab infusion center in the emergency department of three hospitals in Orange County, California, shortly after bamlanivimab received emergency use authorization.

Best practices for recruitment of adolescents for biobanking and precision health research: a retrospective analysis comparing juvenile idiopathic arthritis cases with healthy controls.

Background: Precision health in adolescents relies on the successful collection of data and biospecimens from an adequately sized sample of cases and comparison group(s), often healthy controls, to answer the research question. This research report describes the recruitment strategy, enrollment rates, and approach utilized in a successful biobehavioral research study. The study was designed to examine key health indicators in adolescents (13-17 years of age) with juvenile idiopathic arthritis (JIA) compared to a control group of healthy adolescents.

Harnessing Digital Health to Objectively Assess Functional Performance in Veterans with Chronic Obstructive Pulmonary Disease.

Introduction: An early detection of impaired functional performance is critical to enhance symptom management for patients with chronic obstructive pulmonary disease (COPD). However, conventional functional measures based on walking assessments are often impractical for small clinics where the available space to administrate gait-based test is limited. This study examined the feasibility and effectiveness of an upper-extremity frailty meter (FM) in identifying digital measures of functional performance and assessing frailty in COPD patients.

Effect of voluntary exercise upon the metabolic syndrome and gut microbiome composition in mice.

The metabolic syndrome is a cluster of conditions that increase an individual's risk of developing diseases. Being physically active throughout life is known to reduce the prevalence and onset of some aspects of the metabolic syndrome. Furthermore, previous studies have demonstrated that an individual's gut microbiome composition has a large influence on several aspects of the metabolic syndrome.

Using Consistently Low Performance to Identify Low-Quality Physician Groups.

Importance: There has been a growth in the use of performance-based payment models in the past decade, but inherently noisy and stochastic quality measures complicate the assessment of the quality of physician groups. Examining consistently low performance across multiple measures or multiple years could potentially identify a subset of low-quality physician groups.

Objective: To identify low-performing physician groups based on consistently low performance after adjusting for patient characteristics across multiple measures or multiple years for 10 commonly used quality measures for diabetes and cardiovascular disease (CVD).

Digital Biomarker Representing Frailty Phenotypes: The Use of Machine Learning and Sensor-Based Sit-to-Stand Test.

Since conventional screening tools for assessing frailty phenotypes are resource intensive and unsuitable for routine application, efforts are underway to simplify and shorten the frailty screening protocol by using sensor-based technologies. This study explores whether machine learning combined with frailty modeling could determine the least sensor-derived features required to identify physical frailty and three key frailty phenotypes (slowness, weakness, and exhaustion). Older participants (n = 102, age = 76.

Integrating a Pharmacy Student into a Marriage and Family Therapy Counseling Course: A Pilot.

The Problem: Interprofessional educational experiences are a requirement in pharmacy and counseling curricula. However, scheduling conflicts between professional programs and lack of administrative support create barriers for students who want to take a course in another healthcare program.

Innovation: This pilot enabled a pharmacy student to participate in a counseling course for 8 weeks.

Bladder Agenesis and Bilateral Ectopic Ureters in an Infant Male With Cystic Renal Dysplasia, Imperforate Anus, and Penoscrotal Transposition.

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients. Commonly associated with other fatal malformations, the condition is often incompatible with life. Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.