First relapse in older adults with multiple myeloma: Creating new pathways in uncharted territory.

Treatment options for older adults with relapsed multiple myeloma are constrained by the toxicities of existing treatments, the ageing-associated vulnerabilities that may increase the risk of poor treatment tolerance and patient preferences for treatments that do not impair their function or cognition. The study by Toussea et al. epitomizes approaches to designing trials specifically for more vulnerable older adults and moves the field forward with a regimen of great interest for older adults experiencing their first relapse.

Chromoanagenesis Is Frequently Associated With Highly Complex Karyotypes, Extensive Clonal Heterogeneity, and Treatment Refractoriness in Acute Myeloid Leukemia.

Chromoanagenesis (CAG) encompasses a spectrum of catastrophic genomic events, including chromothripsis, chromoanasynthesis, and chromoplexy. We studied CAG in 410 patients with a diagnosis of acute myeloid leukemia (AML), 292 newly diagnosed (ND), and 118 refractory/relapsed, using optical genome mapping. CAG was identified by the presence of clusters (with 10 or more breakpoints) of structural abnormalities and/or segmental copy number alterations within one or more chromosomal regions.

Small molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.

Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.

Critical Incident Stress in Healthcare Education: An Integrative Review.

Background: Healthcare professionals' repeated exposure to critical incidents can cause various physical and psychological symptoms with potentially severe personal and professional consequences. Healthcare students' exposure to critical incidents begins during their clinical education. Despite known consequences, healthcare education has yet to implement a standardized approach for preparing students for critical incidents.

Use of digital image analysis to improve rigor and efficiency of physeal bone growth measurements.

In larger, translational animal models, manual measurements of longitudinal bone growth using fluorochrome labels is tedious and may be prone to less rigor due to variations in reader experience, sampling differences, and photobleaching that limits the repeatability of measurements. This study assesses the reliability of three different digital methods to assist in measurement of distance between pulsed fluorochrome labels. Forty-five tibial physes from skeletally immature New Zealand White rabbits were pulsed with fluorochrome labels and measured using Fully Manual Technique (FMT), Manual Digital Measurement (MDM), Computer Assisted Image Processing (AIP), and Fully Automated Measurement (FAM).

The PIKASO trial (Preventing Injured Knees from Osteoarthritis: Severity Outcomes): Rationale and design features for a randomized controlled trial.

Objective: Given the high burden and increasing prevalence of post-traumatic osteoarthritis (PTOA), identifying clinically beneficial strategies to prevent or delay its onset could improve the quality of life of those at high risk of developing the disease.

Methods: Preventing Injured Knees from OsteoArthritis: Severity Outcomes (PIKASO) is a multicenter blinded, parallel, two-arm randomized controlled trial of 512 individuals aged 18-45 years undergoing anterior cruciate ligament reconstruction (ACLR). This study is designed to evaluate the efficacy of a 12-month intervention of oral metformin vs.

Utilizing whole genome sequencing to characterize central line-associated bloodstream infections due to .

Whole genome sequencing (WGS) and clinical review were used to characterize 14 cases of central line-associated bloodstream infection (CLABSI) due to . WGS, which demonstrated disparate strains, suggested that 42.9% of CLABSI cases were due to contamination, while clinical review suggested that 57.

Digital Surveillance of Mental Health Care Services in Saudi Arabia: Cross-Sectional Study of National e-Referral System Data.

Background: Mental illness affects an estimated 25% of the global population, with treatment gaps persisting worldwide. The COVID-19 pandemic has exacerbated these challenges, leading to a significant increase in mental health issues globally. In Saudi Arabia, the lifetime prevalence of mental disorders is estimated at 34.

Evaluating Older Adults' Engagement and Usability With AI-Driven Interventions: Randomized Pilot Study.

Background: Technologies that serve as assistants are growing more popular for entertainment and aiding in daily tasks. Artificial intelligence (AI) in these technologies could also be helpful to deliver interventions that assist older adults with symptoms or self-management. Personality traits may play a role in how older adults engage with AI technologies.

Spatial Localization of Collagen Hydroxylated Proline Site Variation as an Ancestral Trait in the Breast Cancer Microenvironment.

Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment.

Data Collection Variability Across Neonatal Hypoxic-Ischemic Encephalopathy Registries.

Objective: To assess variability among data elements collected among existing neonatal hypoxic-ischemic encephalopathy (HIE) data registries worldwide and to determine the need for future harmonization of standard common data elements.

Study Design: This was a cross-sectional study of data elements collected from current or recently employed HIE registry data forms. Registries were identified by literature search and email inquiries to investigators worldwide.

Cross-Sectional Study Gender Pay Gap in Industry General Payments to U.S. General and Fellowship-Trained Surgeons.

Introduction: Gender disparities exist in nonresearch industry payments to U.S. physicians, but detailed analyses specific to surgeons are limited.

Single-Cell RNA-Seq Uncovers Robust Glial Cell Transcriptional Changes in Methamphetamine-Administered Mice.

Methamphetamine is a highly addictive stimulant known to cause neurotoxicity, cognitive deficits, and immune dysregulation in the brain. Despite significant research, the molecular mechanisms driving methamphetamine-induced neurotoxicity and glial cell dysfunction remain poorly understood. This study investigates how methamphetamine disrupts glial cell function and contributes to neurodevelopmental and neurodegenerative processes.

Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes.

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes.

Pediatric Non-Alcoholic Fatty Liver Disease (NAFLD): Trends, Mortality, and Socioeconomic Disparities in the U.S., 1998-2020.

Background/objectives: We aim to describe the changing inpatient epidemiology of NAFLD in the U.S. and identify major risk factors associated with mortality in the disease among hospitalized pediatric patients.

Body Composition in Preterm Infants: Current Insights and Emerging Perspectives.

In recent years, significant advancements in respiratory and nutritional care have markedly improved the survival rates of preterm infants and enhanced long-term health outcomes. Despite these improvements, emerging research highlights the lasting impacts of early growth patterns on an individual's health trajectory. Adults born prematurely face a higher incidence of health issues related to their early birth.

Advances in Fluorescence Techniques for the Detection of Hydroxyl Radicals near DNA and Within Organelles and Membranes.

Hydroxyl radicals (OH), the most potent oxidants among reactive oxygen species (ROS), are a major contributor to oxidative damage of biomacromolecules, including DNA, lipids, and proteins. The overproduction of OH is implicated in the pathogenesis of numerous diseases such as cancer, neurodegenerative disorders, and some cardiovascular pathologies. Given the localized nature of OH-induced damage, detecting OH, specifically near DNA and within organelles, is crucial for understanding their pathological roles.

Exploiting novel placental homing peptides for targeted drug delivery in breast Cancer.

More effective drug formulations are needed to increase the selectivity and efficacy of available chemotherapeutics. We have previously shown that nanoparticles decorated with the tumour homing peptide CGKRK can selectively deliver payloads to the placenta. In this study, we investigated whether two novel placental homing peptides NKGLRNK (NKG) and RSGVAKS (RSG) can be utilized to selectively deliver doxorubicin (DOX) to breast cancer cells.

Non-Parametric Estimation for Semi-Competing Risks Data With Event Misascertainment.

The semi-competing risks data model is a special type of disease-state model that focuses on studying the association between an intermediate event and a terminal event and proves to be a useful tool in modeling disease progression. The study of the semi-competing risk data model not only allows us to evaluate whether a disease episode is related to death but also provides a toolkit to predict death, given that the episode occurred at a certain time. However, the computation of the semi-competing risk models is a numerically challenging task.

Microlipophagy from Simple to Complex Eukaryotes.

Lipophagy is a selective degradation of lipid droplets in lysosomes or vacuoles. Apart from its role in generating energy and free fatty acids for membrane repair, growth, and the formation of new membranes, lipophagy emerges as a key player in other cellular processes and disease pathogenesis. While fungal, plant, and algal cells use microlipophagy, the most prominent form of lipophagy in animal cells is macrolipophagy.

Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.

Background And Aims: Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.

Mechanisms of lipid homeostasis in the Coxiella Containing Vacuole.

Coxiella burnetii, the causative agent of human Q fever, is an obligate intracellular bacterial pathogen that replicates in a large, membrane-bound vacuole known as the Coxiella Containing Vacuole (CCV). The CCV is a unique, phagolysosome-derived vacuole with a sterol-rich membrane containing host and bacterial proteins. The CCV membrane itself serves as a barrier to protect the bacteria from the host's innate immune response, and the lipid and protein content directly influence both the CCV luminal environment and interactions between the CCV and host trafficking pathways.

A health security-based framework for prioritizing regions for digital learning in complex health emergencies.

Digital health and learning have expanded significantly in recent decades though their use in settings of acute health emergencies has only recently begun. Growing experience among organizations working in the digital health and learning space suggest that virtual communities of practice in these areas may have value in response to health emergencies. Evaluation of recent virtual programs applied in acute health emergencies suggest that a pre-established digital learning network can serve as a valuable resource when an acute health emergency strikes.