Pharmacogenetics: Opportunities for the Research Program and Other Large Data Sets to Advance the Field.

Pharmacogenetic variation is common and an established driver of response for many drugs. There has been tremendous progress in pharmacogenetics knowledge over the last 30 years and in clinical implementation of that knowledge over the last 15 years. But there have also been many examples where translation has stalled because of the lack of available data sets for discovery or validation research.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Fully Atomistic Molecular Dynamics Simulation of Ice Nucleation Near an Antifreeze Protein.

Heterogeneous ice nucleation is a widespread phenomenon in nature. Despite extensive research on ice nucleation near biological antifreeze proteins, a probe for ice nucleation and growth processes at the atomic level is still lacking. Herein, we present simulation evidence of the heterogeneous ice nucleation process on the ice-binding surface (IBS) of the antifreeze protein (TmAFP).

Third Proceedings of The North American Airway Collaborative (NoAAC): Consensus Statement on Trial Design for Airway Stenosis.

Importance: Airway stenosis is a rare but debilitating disorder that significantly degrades the quality of life in affected patients. Treatments are primarily surgical, and disease management lacks established medical therapies. The North American Airway Collaborative held its third symposium at The Johns Hopkins Hospital in Baltimore, Maryland, on April 15, 2024, focused on strategies to advance the care of these patients.

Use of Intraoperative Frozen Section to Assess Surgical Margins in HPV-Related Oropharyngeal Carcinoma.

Importance: Given the favorable overall prognosis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and the morbidity of increased adjuvant therapy associated with positive surgical margins, large-scale studies on the accuracy of frozen sections in predicting final surgical margin status in HPV-related OPSCC are imperative. Final surgical margin status is the definitive assessment of tumor clearance as determined through surgeon-pathologist collaboration based on permanent analysis of frozen section margins, main specimens, and supplemental resections.

Objectives: To assess the accuracy and testing properties of intraoperative frozen section histology (IFSH) in assessing final surgical margin status in patients undergoing transoral surgery for HPV-related OPSCC.

Behavioral nudges prevent loan delinquencies at scale: A 13-million-person field experiment.

Americans collectively hold over $1.6 trillion in student loan debt, and over the last decade millions of borrowers have defaulted on loans, with serious consequences for their financial health. In a 13-million-person field experiment with the U.

Expert navigators deploy rational complexity-based decision precaching for large-scale real-world planning.

Efficient planning is a distinctive hallmark of intelligence in humans, who routinely make rapid inferences over complex world contexts. However, studies investigating how humans accomplish this tend to focus on naive participants engaged in simplistic tasks with small state spaces, which do not reflect the intricacy, ecological validity, and human specialization in real-world planning. In this study, we examine the street-by-street route planning of London taxi drivers navigating across more than 26,000 streets in London (United Kingdom).

A carnitine transporter at the blood-brain barrier modulates sleep via glial lipid metabolism in .

To regulate brain function, peripheral compounds must traverse the blood-brain barrier (BBB), an interface between the brain and the circulatory system. To determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen for genes affecting sleep in . We observed reduced sleep with knockdown of solute carrier , a carnitine transporter, as determined by isotope flux.

A Narrative Review of Cardiometabolic Profiles among U.S. Adults: Temporal Trends and Implications.

Purpose Of Review: To provide a narrative overview of trends and disparities in the cardiometabolic profiles of U.S. adults by synthesizing findings from nationally representative studies conducted between 1999 and 2020.

The Multifactorial Relationship Between Bone Tissue Water and Stiffness at the Proximal Femur.

Bone mechanical function is determined by multiple factors, some of which are still being elucidated. Here, we present a multivariate analysis of the role of bone tissue composition in the proximal femur stiffness of cadaver bones (n = 12, age 44-93). Stiffness was assessed by testing under loading conditions simulating a sideways fall onto the hip.

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Sleep, coparenting, and parenting among mothers and fathers prior to kindergarten transition.

The identification of family-level and modifiable factors that are influential determinants of parenting is of critical importance. The present study of mothers and fathers investigated within- and across-parent linkages between sleep duration and variability, the coparenting relationship, and parenting quality, as well as the moderating effect of coparenting in a sample of families with children making the transition to kindergarten using a family systems perspective. Mothers and fathers from 225 families participated in the late summer before their child started kindergarten.

Intrapericardial Corticosteroids and Colchicine Prevent Pericarditis and Atrial Fibrillation After Epicardial Ablation of Ventricular Arrhythmias.

Background: Postprocedural pericarditis (PP) can occur in up to 29.4% of patients undergoing epicardial catheter ablation of ventricular tachycardia (VT). Despite several proposed strategies to mitigate this adverse outcome, rates of PP and pericarditic pain remain high.

Atrial Fibrillation and Flutter in a Contemporary Cohort of Patients With Myotonic Muscular Dystrophy.

Background: Literature on the prevalence and management of atrial arrhythmias in patients with myotonic muscular dystrophy type 1 (MMD1) or myotonic muscular dystrophy type 2 (MMD2) is limited.

Objectives: This study sought to describe incidence, prevalence, and predictors of atrial fibrillation (AF) and atrial flutter (AFL) in a contemporary cohort of patients with myotonic muscular dystrophy (MMD).

Methods: Associations between patient factors and incident AF/AFL were analyzed in patients with MMD referred for routine electrophysiology evaluation between January 2013 and September 2023.

Transesophageal echocardiography monitoring for liver transplantation: where are we now?

Intraoperative hemodynamic monitoring is crucial for managing patients with end-stage liver disease (ESLD) undergoing orthotopic liver transplantation (OLT) due to their complex cardiovascular and pulmonary abnormalities. Traditionally, pulmonary artery catheterization (PAC) has been the standard for hemodynamic monitoring during OLT. However, the use of transesophageal echocardiography (TEE) has increased due to its real-time visualization of cardiac and vascular structures, which aids in managing hemodynamic instability during the three surgical phases of OLT: pre-anhepatic, anhepatic, and neo-hepatic.

Opportunities for More Tailored Approaches to Genotoxicity Testing and Carcinogenicity Strategy for Oligonucleotide Therapeutics: Outcome of an Industry Survey.

The Oligonucleotide Nonclinical Working Group (WG) of the European Federation of Pharmaceutical Industries and Associations conducted an industry survey to understand current practices and regulatory expectations for genotoxicity and carcinogenicity assessment of oligonucleotide therapeutics (ONTs), along with historical genotoxicity testing results. The survey, involving 29 pharmaceutical and biotechnology companies, revealed a consistent absence of genotoxicity across a diverse range of oligonucleotide classes and chemistries, consistent with previous observations. Despite the lack of genotoxicity, companies continue to follow standard testing guidelines, with only limited divergence.

Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.

Background: Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.

Methods: The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Inflammation in atherosclerosis: a Big Idea that has underperformed so far.

Purpose Of Review: For many years, inflammation has been a major concept in basic research on atherosclerosis and in the development of potential diagnostic tools and treatments. The purpose of this review is to assess the performance of this concept with an emphasis on recent clinical trials. In addition, contemporary literature may help identify new therapeutic targets, particularly in the context of the treatment of early, rather than end-stage, arterial disease.

Synergistic Effects of Extra X Chromosome on Development of Systemic Lupus Erythematosus and Sjögren Disease in Klinefelter and Triple X Syndrome: A Retrospective Cohort Study.

Objective: Systemic lupus erythematosus (SLE) and Sjögren disease (SjD) are autoimmune diseases with significant female predominance. The prevalence of SLE is increased in Klinefelter syndrome (KS) compared with the general male population. Our study investigates the dose effects of extra X chromosomes on the development of SLE and SjD in KS and triple X syndrome compared with the general population.

Concurrent Perioperative Benzodiazepine and Opioid Utilization in Opioid-Naive Patients Undergoing Soft Tissue Hand Surgery.

Background: While concomitant opioid and benzodiazepine use is discouraged due to an increased risk of sedation/overdose, the extent of perioperative opioid utilization in hand surgery patients already using benzodiazepines is unknown.

Methods: Using an administrative claims database, we identified adults undergoing carpal tunnel, DeQuervain, or trigger finger release, palmar fasciectomies, ganglion/mucoid cyst removals, and hand/wrist soft tissue mass excisions from 2011 to 2021. We identified opioid-naive patients with a benzodiazepine prescription within 90 days before surgery.

Exploring the presence and roles of humility when experiencing situations of uncertainty.

Background: Uncertainty is a pervasive challenge in clinical practice. Whereas the importance of humility in navigating uncertainty has been discussed, empirical research on how humility is practiced or expressed (i.e.