Real World Data in Stage III Melanoma in Latino Low Middle Income Country: Prognostic Factors and Outcomes.

Introduction: Malignant melanoma is a heterogeneous disease, with varying outcomes depending on the patient's race and ethnicity. Advanced stages can be tackled by novel targeted therapies and immunotherapy. We aimed to investigate the real-world data in Latino-Hispanic patients diagnosed with Stage III melanoma residing in Peru, a region marked by limited resources and healthcare infrastructure.

Risk Profile and Prognostic Implications of Premature Advanced Coronary Atherosclerotic Disease Among Young to Early Middle-aged Adults: The Coronary Artery Calcium Consortium.

Introduction: Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized.

Methods: We used data from 44,047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium.

The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.

Voltage-gated sodium (Nav) channels are pivotal for cellular signaling, and mutations in Nav channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function, loss-of-function effects, or both. However, the mechanism behind this functional diversity of mutations at equivalent positions remains elusive.

Mercury toxicity resulting from enzyme alterations- minireview.

Mercury is widely known for its detrimental effects on living organisms, whether in its elemental or bonded states. Recent comparative studies have shed light on the biochemical implications of mercury ingestion, both in low, persistent concentrations and in elevated acute dosages. Studies have presented models that elucidate how mercury disrupts healthy cells.

1-Methylxanthine enhances memory and neurotransmitter levels.

1-Methylxanthine (1-MX) is the major metabolite of caffeine and paraxanthine and might contribute to their activity. 1-MX is an adenosine receptor antagonist and increases the release and survivability of neurotransmitters; however, no study has addressed the potential physiological effects of 1-MX ingestion. The aim of this study was to compare the effect of 1-MX on memory and related biomarkers in rats compared to control.

Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2.

Action of the Euclidean versus projective group on an agent's internal space in curiosity driven exploration.

According to the Projective Consciousness Model (PCM), in human spatial awareness, 3-dimensional projective geometry structures information integration and action planning through perspective taking within an internal representation space. The way different perspectives are related to and transform a world model defines a specific perception and imagination scheme. In mathematics, such a collection of transformations corresponds to a 'group', whose 'actions' characterize the geometry of a space.

Vibrational weak and strong coupling modify a chemical reaction via cavity-mediated radiative energy transfer.

Controlling reaction outcomes through external influences is a central goal in chemistry. Vibrational coupling between molecular vibrations and cavity modes is rapidly emerging as a distinct strategy compared with conventional thermochemical and photochemical methods; however, insight into the fundamental mechanisms remains limited. Here we investigate how vibrational weak and strong coupling in plasmonic nanocavities modifies the thermal dehydration of copper sulfate pentahydrate.

Hepcidin, Incident Heart Failure and Cardiac Dysfunction in Older Adults: the ARIC Study.

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study who were free from prevalent anemia and HF at Visit 5 (2011-2013) and had available hepcidin and covariate data.

PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function.

Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.

An exosome-based liquid biopsy predicts depth of response and survival outcomes to cetuximab and panitumumab in metastatic colorectal cancer: The EXONERATE Study.

PURPOSE EXONERATE (EXOsome and cell-free micro-RNAs of anti-EGFR ResistAnce) was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC). PATIENTS AND METHODS Patients with newly diagnosed RAS-WT, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in 2-nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRC to predict PFS, OS, and ORR.

A Lambda-evo (λ) phage platform for Zika virus E protein display.

One of the most significant bacteriophage technologies is phage display, in which heterologous peptides are exhibited on the virion surface. This work describes the display of λ decorative protein D linked to the E protein domain III of Zika virus (D-ZE), to the GFP protein (D-GFP), or to different domain III epitopes of the E protein (D-TD), exhibited on the surface of an in vitro evolved lambda phage (λ). This phage harbors a gene D deletion and was subjected to directed evolution using Escherichia coli W3110/pD-ZE as background.

Stroke Prevention in Hispanic Children with Sickle Cell Anemia: the SACRED trial.

Sickle cell anemia (SCA) is recognized globally, but little is known about affected Hispanic populations. In partnership with Dominican Republic, a Hispanic Caribbean Island with a large SCA population, a TCD screening program provided hydroxyurea to children with conditional velocities. Building local capacity, ten Dominican medical graduates were certified in TCD examinations and trained in hydroxyurea management.

Torsion-Induced Traumatic Optic Neuropathy (TITON): A physiologically relevant animal model of traumatic optic neuropathy.

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone.

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.

Aims/hypothesis: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications.

Methods: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions.

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.

Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.

Development, review, and activation of thoracic oncology investigator-initiated trials.

Background: Investigator-initiated trials (IITs) may address important biological and clinical questions that may not be prioritized by pharmaceutical sponsors. However, little is known about the process by which IIT proposals are evaluated and activated.

Methods: We performed a retrospective study of IIT concepts submitted through the Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC), which comprises 13 institutions in the U.

Functional test of a naturally occurred tumor modifier gene provides insights to melanoma development.

Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness in most animal systems. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction, and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids.

Digital humanistic program to manage premature frailty in young breast cancer survivors with gender perspective.

Premature frailty is a critical challenge for young breast cancer survivors (YBCSs), impacting their health and perpetuating gender inequality through heightened vulnerability and marginalization. While digital health shows promise in frailty screening, its effectiveness for comprehensively managing frailty remains inconclusive. This randomized controlled trial, registered at the Chinese Clinical Trial Registry (ChiCTR2200058823), tests the "AI-TA" program's efficacy on premature frailty and quality of life in YBCSs.

Early Versus Late Atrial Fibrillation Recurrence After Pulsed Field Ablation: Insights From the admIRE Trial.

Background And Aims: Studies have shown correlations between early recurrence (ER) and late recurrence (LR) of atrial arrhythmia after ablation with thermal technologies. This admIRE trial (NCT05293639) subanalysis aims to analyze ER versus LR in patients with paroxysmal atrial fibrillation (PAF) undergoing pulsed field ablation (PFA).

Methods: Patients with symptomatic paroxysmal atrial fibrillation and ≥1 transtelephonic monitoring transmission during the blanking period were included (n=169).

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.

Utility of Papilledema for Detection of Elevated Intracranial Pressure in Craniosynostosis.

Papilledema is swelling of the optic disk due to fluid accumulation around the optic nerve and is commonly used to detect increased intracranial (ICP) in craniosynostosis. This study aimed to assess the prevalence and utility of papilledema detection in patients with single-suture, multi-suture, and syndromic craniosynostosis and the differences before and after surgical intervention. A retrospective review of ophthalmology examinations of patients diagnosed with craniosynostosis treated between 2008 and 2023 was performed.