Molecular Basis of Oncogenic PI3K Proteins.

The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers.

Metabolic Adaptation and Its Determinants in Adolescents Two Years After Sleeve Gastrectomy.

Weight loss is associated with reductions in resting energy expenditure (REE), which are impacted by changes in body composition following sleeve gastrectomy (SG). Current data regarding changes in measured REE (mREE) and metabolic adaptation in adolescents after SG are limited. We evaluated changes in mREE, metabolic adaptation, and body composition in youths after SG vs.

Dual Roles of miR-10a-5p and miR-10b-5p as Tumor Suppressors and Oncogenes in Diverse Cancers.

Cancer is a complex genetic disorder characterized by abnormalities in both coding and regulatory non-coding RNAs. microRNAs (miRNAs) are key regulatory non-coding RNAs that modulate cancer development, functioning as both tumor suppressors and oncogenes. miRNAs play critical roles in cancer progression, influencing key processes such as initiation, promotion, and metastasis.

Integrating Bacteriocins and Biofilm-Degrading Enzymes to Eliminate Persistence.

is a Gram-positive bacterium causing listeriosis, a severe infection responsible for significant morbidity and mortality globally. Its persistence on food processing surfaces via biofilm formation presents a major challenge, as conventional sanitizers and antimicrobials exhibit limited efficacy against biofilm-embedded cells. This study investigates a novel approach combining an engineered polysaccharide-degrading enzyme (CAase) with a bacteriocin (thermophilin 110) produced by .

Administration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN.

An Overview of Zika Virus and Zika Virus Induced Neuropathies.

Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms.

Microvascular decompression: a contemporary update.

Background: Microvascular decompression (MVD) is the gold-standard surgical treatment for cranial nerve compression disorders, including trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GPN). This review synthesizes historical milestones, recent advances, and evolving techniques in MVD, with a primary focus on these conditions.

Methods: A comprehensive literature review was conducted using databases such as PubMed, SpringerLink, Google Scholar, BioMed Central, Scopus, and ScienceDirect.

Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Beyond dyslipidemia, inflammation contributes to the development of atherosclerosis. However, intrinsic factors that counteract vascular inflammation and atherosclerosis remain scarce. Here we identify insulin-like growth factor binding protein 6 (IGFBP6) as a homeostasis-associated molecule that restrains endothelial inflammation and atherosclerosis.

Home Visitation as an Intervention Opportunity to Prevent Childhood Obesity Within the First 2000 Days: A Scoping Review.

Background: Home visitation programs are uniquely positioned to reach young children during the first 2000 days of life (ages 0 to 5 years), a critical time period to prevent childhood obesity.

Objective: This scoping review aimed to identify early childhood obesity prevention interventions implemented within home visitation during the first 2000 days of life, summarize outcomes assessed, and examine if and how nonmaternal caregivers and technology were included.

Methods: Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, three databases (PubMed, Web of Science, CINAHL) were searched from January 1980 to June 2023 for obesity prevention interventions that utilized home visitation as a treatment modality, targeted children ≤5 years old, reported on child weight outcomes, were experimental or quasi-experimental designs with a control or comparison arm, and had full-text available in English.

Selective lead ion sensing via cotton pad-based NaEDTA capped AuNPs: A smartphone-assisted colorimetric method.

Herein, NaEDTA-capped AuNPs specifically designed for selective smartphone-assisted colorimetric detection are synthesized and characterized. NaEDTA-capped AuNPs was synthesized and characterized by UV-Visible spectroscopy, ATR, Raman, XRD, SEM and EDX. The calculated activation energy of the produced nanoparticles was 0.

Substrate adaptors are flexible tethering modules that enhance substrate methylation by the arginine methyltransferase PRMT5.

Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.

Illicit drug use among adolescents and young adults with impairments in the US: A cross-sectional analysis of the National Survey on Drug Use And Health.

Objective: The purpose of this cross-sectional analysis is to compare the degree to which adolescents and adults with and without impairments in the US engage in illicit drug use.

Methods: This cross-sectional study utilized data from the 2022 National Survey of Drug Use and Health. Impairment status (mobility, cognitive, hearing, vision, self-care, and communication impairments), illicit drug use (cocaine, crack, heroin, hallucinogens, LSD, ecstasy and molly, inhalants, and methamphetamine), and demographic variables were measured using self-report.

Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.

Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis.

Cognitive restraint and body dissatisfaction are more strongly related to muscle building behaviors for men than women.

Muscle building behaviors are an understudied eating disorder (ED) symptom increasing in prevalence, especially among men. However, little is known about the cognitive ED correlates that may underlie muscle building behaviors and whether these associations differ by gender. We examined associations between cognitive ED symptoms and muscle building behaviors, and whether these associations differ between men and women.

The Paradigm Shift From Patient to Health Consumer: 20 Years of Value Assessment in Health.

Health care is undergoing a "revolution," where patients are becoming consumers and armed with apps, consumer review scores, and, in some countries, high out-of-pocket costs. Although economic analyses and health technology assessment (HTA) have come a long way in their evaluation of the clinical, economic, ethical, legal, and societal perspectives that may be impacted by new technologies and procedures, these approaches do not reflect underlying patient preferences that may be important in the assessment of "value" in the current value-based health care transition. The major challenges that come with the transformation to a value-based health care system lead to questions such as "How are economic analyses, often the basis for policy and reimbursement decisions, going to switch from a societal to an individual perspective?" and "How do we then assess (economic) value, considering individual preference heterogeneity, as well as varying heuristics and decision rules?" These challenges, related to including the individual perspective in cost-effectiveness analysis (CEA), have been widely debated.

Patient-reported outcome trajectories the first 24 months after surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

Objective: Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations.

Quantitative LC-MS/MS Analysis of Endogenous Isomeric Metabolites Biliverdin IX Alpha, Beta, and Delta in Cell Culture Supernatant, Cell Pellet, and Lung Tissue.

() utilizes heme as an iron source from the host during infection. Biliverdin beta and delta (BVIXβ and BVIXδ) are generated by HemO, specific to , while biliverdin alpha is generated from the bacterial BphO system and by mammalian heme oxygenases. Here, we have developed and characterized a quantitative LC-MS/MS assay for the separation of three endogenous isomers, BVIXα, BVIXβ, and BVIXδ.

The advantages of lexicon-based sentiment analysis in an age of machine learning.

Assessing whether texts are positive or negative-sentiment analysis-has wide-ranging applications across many disciplines. Automated approaches make it possible to code near unlimited quantities of texts rapidly, replicably, and with high accuracy. Compared to machine learning and large language model (LLM) approaches, lexicon-based methods may sacrifice some in performance, but in exchange they provide generalizability and domain independence, while crucially offering the possibility of identifying gradations in sentiment.

Ten simple rules for good model-sharing practices.

Computational models are complex scientific constructs that have become essential for us to better understand the world. Many models are valuable for peers within and beyond disciplinary boundaries. However, there are no widely agreed-upon standards for sharing models.

Neonatal and Home-Based PT Improves Neurodevelopmental Outcomes of Preterm Infants-A Randomized Clinical Trial.

Purpose: Investigate the effect of structured neonatal physical therapy program (SNP) on neurodevelopmental outcomes of moderate and late preterm (MLP) infants.

Methods: Sixty MLP infants were randomly allocated to usual care (UC) or SNP. A previous publication reported the effect of neonatal component of SNP at hospital discharge.

Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.