Long term latency of highly mutated cells in normal mouse skin is reversed by exposure to tumor promoters and chronic tissue damage.

Historical studies performed nearly a century ago using mouse skin models identified two key steps in cancer evolution: initiation, a likely mutational event, and promotion, driven by inflammation and cell proliferation. Initiation was proposed to be permanent, with promotion as the critical rate-limiting step for cancer development. Here, we carried out whole genome sequencing to demonstrate that initiated cells with thousands of mutagen-induced mutations can persist for long periods and are not removed by cell competition or by immune intervention, thus mimicking the persistence of cells with cancer driver mutations in normal human tissues.

Assessment of Fraud Deterrence and Detection Procedures Used in a Web-Based Survey Study With Adult Black Cisgender Women: Description of Lessons Learned and Recommendations.

Background: Online research studies enable engagement with more Black cisgender women in health-related research. However, fraudulent data collection responses in online studies raise important concerns about data integrity, particularly when incentives are involved.

Objective: The purpose of this study was to assess the strengths and limitations of fraud deterrence and detection procedures implemented in an incentivized, cross-sectional, online study about HIV prevention and sexual health with Black cisgender women living in Texas.

Frequency of Culture-proven Bacterial Infection and Radiographic Pneumonia in Pediatric Heart Transplant Recipients.

Background: Infection is a leading cause of death after pediatric heart transplants (PHTs). Understanding of common pathogens is needed to guide testing strategies and empiric antibiotic use.

Methods: We conducted a 3-center retrospective study of PHT recipients ≤18 years old presenting to cardiology clinics or emergency departments (EDs) from 2010 to 2018 for evaluation of suspected infections within 2 years of transplant.

Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients.

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology.

Targeting IL-23 in Psoriatic Arthritis: A Review of Guselkumab's Efficacy and Utilization.

Psoriatic arthritis (PsA) is a chronic, inflammatory disease with heterogeneous clinical features. The pathogenesis of PsA involves a complex interplay of genetic, immunologic, and environmental factors, leading to the activation of the immune system and subsequent inflammation. Over the past decade, the understanding of the immune mechanisms underlying PsA has advanced significantly, particularly regarding the role of the interleukin-23/T helper 17 pathway in the disease process.

Seizures, Driver Licensure, and Medical Reporting Update: An AAN Position Statement.

This consensus position statement of the American Academy of Neurology, American Epilepsy Society, and Epilepsy Foundation of America updates prior 1994 and 2007 position statements on seizures, driver licensure, and medical reporting. Key consensus positions include the following: (1) in the United States, national driving standards promulgated through a system such as the Uniform Law Commission would reduce confusion and improve adherence with state driving standards; (2) state licensing criteria for medical conditions should be promulgated by regulations and guidelines based on enabling legislation rather than in statutes themselves and should be developed by medical advisory boards working in collaboration with departments of motor vehicles; (3) licensing criteria should be equitable, nondiscriminatory, objective, and compatible with comparable risks in other populations; (4) a minimum seizure-free interval of 3 months should ordinarily be required before driving in all cases and should be extended in individual cases based on review of favorable and unfavorable features by medical advisory boards; (5) individuals with exclusively provoked seizures attributable to provoking factors that are unlikely to reoccur in the future may not require a seizure-free interval before resuming driving; (6) individuals with previously well-controlled epilepsy who experience seizures due to short-term interruptions of antiseizure medications in the setting of hospitalization or practitioner-directed medication-titration may not require a seizure-free interval before driving once previously effective levels of antiseizure medications have been resumed; (7) patients and practitioners should pause driving during tapering and following discontinuation of an antiseizure medication if another such medication is not introduced; (8) individuals whose cognition or coordination is impaired due to medications used to prevent seizures should refrain from driving; (9) health care practitioners should be allowed but not mandated to report drivers who pose an elevated risk; but (10) neither a decision to report a patient suspected of being at elevated risk nor a decision declining to report a patient suspected of being at elevated risk should be subject to legal liability; (11) nations, states, and municipalities should provide alternative methods of transportation and accommodations for individuals whose driving privileges are restricted due to medical conditions.

Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair.

Lung cancer exhibits altered metabolism, influencing its response to radiation. To investigate the metabolic regulation of radiation response, we conducted a comprehensive, metabolic-wide CRISPR-Cas9 loss-of-function screen using radiation as selection pressure in human non-small cell lung cancer. Lipoylation emerged as a key metabolic target for radiosensitization, with lipoyltransferase 1 (LIPT1) identified as a top hit.

Shear flow patterns antimicrobial gradients across bacterial populations.

Bacterial populations experience chemical gradients in nature. However, most experimental systems either ignore gradients or fail to capture gradients in mechanically relevant contexts. Here, we use microfluidic experiments and biophysical simulations to explore how host-relevant shear flow affects antimicrobial gradients across communities of the highly resistant pathogen .

In vivo antibody labeling route and fluorophore dictate labeling efficiency, sensitivity, and longevity.

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration.

Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, pannus formation, and progressive joint destruction. The inflammatory milieu in RA drives endothelial cell activation and upregulation of adhesion molecules, thus facilitating leukocyte infiltration into the synovium. Reelin, a circulating glycoprotein previously implicated in endothelial activation and leukocyte recruitment in diseases such as atherosclerosis and multiple sclerosis, has emerged as a potential upstream regulator of these processes.

Deciphering the structural consequences of R83 and R152 methylation on DNA polymerase β using molecular modeling.

DNA polymerase β, a member of the X-family of DNA polymerases, undergoes complex regulations both in vitro and in vivo through various posttranslational modifications, including phosphorylation and methylation. The impact of these modifications varies depending on the specific amino acid undergoing alterations. In vitro, methylation of DNA polymerase β with the enzyme protein arginine methyltransferase 6 (PRMT6) at R83 and R152 enhances polymerase activity by improving DNA binding and processivity.

Effects of mental fatigue on isometric mid-thigh pull performance and muscle activities.

This study investigated the effects of mental fatigue on rate of force development (RFD) and peak force during an isometric mid-thigh pull (IMTP), as well as its impact on muscle activation measured by electromyography (EMG) median frequency. Sixteen healthy, resistance-trained males completed two sessions: a control condition and a mentally fatigued state induced by a 30-minute modified Stroop task. IMTP performance and muscle activation were assessed before and after the mental fatigue task.

Eficacia y seguridad del ácido hipocloroso pH 5,5 en el manejo de heridas complejas en usuarios pediátricos.

Serie de casos que sugieren los beneficios de la implementación de una solución limpiadora no citotóxica de pH ácido en el tratamiento de heridas complejas en usuarios pediátricos en dos centros de salud de Santiago, Chile. Se propone como tratamiento adicional al manejo etiológico el uso de una solución limpiadora compuesta de ácido hipocloroso (HOCl) en una concentración de 330 ppm y pH 5,5 (Vashe® Wound Solution, Urgo Medical, Texas, Estados Unidos) la cual ha demostrado ser segura y efectiva en el manejo de heridas en usuarios pediátricos. Se evidencian beneficios significativos en términos de cicatrización acelerada y reducción del dolor en los casos tratados.

Phase 2, Randomized, Double-blind, Placebo-controlled Study of Fiztasovimab (NPC-21) for Kidney Transplant Recipients at High Risk of Cytomegalovirus Infection (LionHeart21).

Background: Kidney transplantation (KT) has dramatically improved the quality of life of patients with end-stage kidney disease. However, the incidence of opportunistic infections has also increased because of immunosuppression. A common infection after KT is cytomegalovirus (CMV).

Nurses, Chaplains, Clergy and Measurement Scales.

Much of the research in this issue relates to the long-standing profession of nursing and, secondly, the even longer established professions of chaplaincy and the clergy. This issue also provides evidence of the ever-increasing number of religious and spirituality measurement scales, as well as various other forms of religious and/or spiritual evaluations and the associated psychometric properties. Several articles researching religiosity/spirituality, however, identify common research limitations, in particular the error of using contaminated scales and the need to avoid tautological and uninterpretable results.

Guanfacine Use in the ICU for Management of Sedation Weaning.

Recent evidence highlights the increasing utilization of guanfacine in the intensive care unit. While dexmedetomidine is a widely used sedative and anti-anxiety agent in the intensive care unit, prolonged use can lead to withdrawal effects when attempting to reduce the dosage. This has generated interest in using guanfacine to manage agitation in patients being weaned off dexmedetomidine.

The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway.

Artificial intelligence-based automated surgical workflow recognition in esophageal endoscopic submucosal dissection: an international multicenter study (with video).

Background: Endoscopic submucosal dissection (ESD) is a crucial yet challenging multi-phase procedure for treating early gastrointestinal cancers. This study developed an artificial intelligence (AI)-based automated surgical workflow recognition model for esophageal ESD and proposed an innovative training program based on esophageal ESD videos with or without AI labels to evaluate its effectiveness for trainees.

Methods: We retrospectively analyzed complete ESD videos collected from seven hospitals worldwide between 2016 and 2024.

MR imaging of pediatric meniscal retears: pearls and pitfalls - a pictorial review.

Differentiating expected pediatric knee MRI post-operative changes and meniscal retear after primary repair or debridement may be challenging. This pictorial essay reviews treatment strategies for meniscal tears with or without underlying discoid morphology. MRI pearls and pitfalls to identify meniscal retears and differentiate them from normal post-treatment findings will be shown, geared toward pediatric musculoskeletal radiologists.

Plant-Based Diets Across the Spectrum of Kidney Disease.

Diet is gaining traction as a major chronic kidney disease (CKD)-related risk factor for death and disability. Furthermore, a "healthy" diet in patients with CKD is associated with reduced mortality. The data to be discussed support diet as the foundational, "food integrated with pharmacologic therapy," approach to management of individuals with CKD and those at risk for it.

Investigation of surficial seabed heterogeneity and geoacoustic variability in the New England Mud Patcha).

Benthic biological processes influence seabed heterogeneity and contribute to variability in geoacoustic properties. To investigate these relationships, measurements were conducted to quantify spatial variability in the upper few decimeters of sediment near the water-seabed interface within a fine-grained sediment deposit on the New England continental shelf. At each measurement location, an acoustic multicorer was deployed to sample the seabed.

Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial.

Importance: Excess body fat plays a pivotal role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). HU6 is a novel, controlled metabolic accelerator that enhances mitochondrial uncoupling resulting in increased metabolism and fat-specific weight loss.

Objective: To assess efficacy and safety of HU6 in reducing body weight, improving peak volume of oxygen consumption (VO2) and body composition among patients with obesity-related HFpEF.