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.

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.

Atrial fibrillation burden in clinical practice, research, and technology development: a clinical consensus statement of the European Society of Cardiology Council on Stroke and the European Heart Rhythm Association.

Atrial fibrillation (AF) is one of the most common cardiac diseases and a complicating comorbidity for multiple associated diseases. Many clinical decisions regarding AF are currently based on the binary recognition of AF being present or absent with the categorical appraisal of AF as continued or intermittent. Assessment of AF in clinical trials is largely limited to the time to (first) detection of an AF episode.

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.

Data Obfuscation Through Latent Space Projection for Privacy-Preserving AI Governance: Case Studies in Medical Diagnosis and Finance Fraud Detection.

Background: The increasing integration of artificial intelligence (AI) systems into critical societal sectors has created an urgent demand for robust privacy-preserving methods. Traditional approaches such as differential privacy and homomorphic encryption often struggle to maintain an effective balance between protecting sensitive information and preserving data utility for AI applications. This challenge has become particularly acute as organizations must comply with evolving AI governance frameworks while maintaining the effectiveness of their AI systems.

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.

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.

Enhanced Hot/Free Electron Effect for Photocatalytic Hydrogen Evolution Based on 3D/2D Graphene/MXene Composite.

Photocatalytic hydrogen production through water splitting represents a promising strategy to store solar energy as chemical energy. Current photocatalysts primarily focus on traditional semiconductor materials, such as metal oxides, sulfides, nitrides, g-CN, etc. However, these materials often suffer from large bandgap and fast charge recombination, which limit sunlight utilization and result in unsatisfactory photon conversion efficiency.

Update on Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition condition characterized by a high lifetime risk for a wide spectrum of malignancies associated with germline pathogenic/likely pathogenic (P/LP) variants in the TP53 tumor suppressor gene. Secondary malignant neoplasms are particularly common. Early cancer detection through surveillance enables early intervention and leads to improved clinical outcomes with reduced tumor-related mortality and treatment-related morbidity.

Stretchable, Patterned Carbon Nanotube Array Enhanced by TiCT/Graphene for Electromagnetic Interference Shielding.

Stretchability and flexibility are essential characteristics for high-performance electromagnetic interference (EMI) shielding materials in wearable and smart devices. However, achieving these mechanical properties while also maintaining high EMI shielding effectiveness (SE) for shielding materials remains a significant challenge. Here, a stretchable patterned carbon nanotube (CNT) array composite film, reinforced with two-dimensional (2D) nanomaterials (TiCT and graphene), is fabricated using a straightforward scraping method.

Extracellular Signaling Molecules from Adipose-Derived Stem Cells and Ovarian Cancer Cells Induce a Hybrid Epithelial-Mesenchymal Phenotype in a Bidirectional Interaction.

Ovarian cancer (OC) is characterized by high mortality rates due to late diagnosis, recurrence, and metastasis. Here, we show that extracellular signaling molecules secreted by adipose-derived mesenchymal stem cells (ASCs) and OC cells-either in the conditioned medium (CM) or within small extracellular vesicles (sEVs)-modulate cellular responses and drive OC progression. ASC-derived sEVs and CM secretome promoted OC cell colony formation, invasion, and migration while upregulating tumor-associated signaling pathways, including TGFβ/Smad, p38MAPK/ERK1/2, Wnt/β-catenin, and MMP-9.

Defining the Protein Phosphatase 2A (PP2A) Subcomplexes That Regulate FoxO Transcription Factor Localization.

The family of forkhead box O (FoxO) transcription factors regulate cellular processes involved in glucose metabolism, stress resistance, DNA damage repair, and tumor suppression. FoxO transactivation activity is tightly regulated by a complex network of signaling pathways and post-translational modifications. While it has been well established that phosphorylation promotes FoxO cytoplasmic retention and inactivation, the mechanism underlying dephosphorylation and nuclear translocation is less clear.

In-device Battery Failure Analysis.

Lithium-ion batteries are indispensable power sources for a wide range of modern electronic devices. However, battery lifespan remains a critical limitation, directly affecting the sustainability and user experience. Conventional battery failure analysis in controlled lab settings may not capture the complex interactions and environmental factors encountered in real-world, in-device operating conditions.

Penile prosthesis for erectile dysfunction: recommendations from the 5th International Consultation on Sexual Medicine.

Introduction: Penile prosthesis (PP) is one of the main approved therapies for erectile dysfunction (ED). Greater than 50 years of clinical use has led to considerable innovation in PP surgery and patient care.

Objectives: To summarize the current literature and provide updated clinical evidence to inform healthcare providers on best practices with PP.

Multi-level barriers to equitable postpartum permanent contraception.

Background: There are several barriers to fulfillment of desired postpartum permanent contraception (PC). Prior research has primarily focused on the federal Medicaid sterilization policy as a barrier to PC; however, other barriers need to be examined.

Objectives: To explore the levels and intersections of barriers to postpartum PC that exist external to the Medicaid policy.

Cutaneous lupus erythematosus presenting as a nonhealing ulcer in an African American woman: A case report.

Objective: Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disorder of the skin.

Methods: In this report, we describe the case of an African American woman with CLE who had an ulcer on her posterior thigh. Despite this, initial biopsy specimen of the lesion revealed no evidence of CLE until a repeat biopsy 5 months later.