Jun, an Oncological Foe or Friend?

Jun/JUN is a basic leucine zipper (bZIP) protein and a prototypic member of the activator protein-1 (AP-1) family of transcription factors that can act as homo- or heterodimers, interact with DNA elements and co-factors, and regulate gene transcription. Jun is expressed by both immune and inflammatory cells. Jun is traditionally seen as an oncoprotein that regulates processes involved in transformation and oncogenesis in human tumours.

Outcomes following deep hypothermic circulatory arrest versus antegrade cerebral perfusion during aortic arch reconstruction.

Objective: The optimal method for cerebral protection during aortic arch reconstruction in neonates and infants is unknown. We compare the outcomes of deep hypothermic circulatory arrest and selective antegrade cerebral perfusion strategies in neonatal and infant cardiac surgery.

Methods: We retrospectively identified all patients aged less than 1 year who underwent aortic arch reconstruction from 2012 to 2023.

Interplay between CD28 and PD-1 in T cell immunotherapy.

Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionised the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and vice versa).

Cardiac dysfunction and altered gene expression in acid ceramidase-deficient mice.

Farber disease (FD) is an ultrarare, autosomal-recessive, lysosomal storage disorder attributed to gene mutations. FD is characterized by acid ceramidase (ACDase) deficiency and the accumulation of ceramide in various tissues. Classical FD patients typically manifest symptoms including lipogranulomatosis, respiratory complications, and neurological deficits, often leading to mortality during infancy.

Microvascular Free Flap Practice Management and Career Development.

Microvascular free flap surgery has become the gold standard for head and neck reconstruction. There is significant variability in the technical aspects of this type of surgery, but commonalities can be found regarding general workflow and practice setup. This text will highlight several strategies to help the reconstructive head and neck surgeon improve efficiency, outcomes, and surgeon wellness.

Physiological role and mechanisms of action for a long noncoding haplotype region.

Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles and mechanisms of action for these noncoding variants, particularly large haplotypes containing multiple variants, is both critical and challenging. To address this challenge, we developed an approach that integrates physiological studies in genetically engineered and phenotypically permissive animal models, precise editing of large haplotypes in human induced pluripotent stem cells (hiPSCs), and targeted chromatin conformation analysis.

A broadly applicable method for quantifying cardiomyocyte cell division identifies proliferative events following myocardial infarction.

Cardiomyocyte proliferation is a challenging metric to assess. Current methodologies have limitations in detecting the generation of new cardiomyocytes and technical challenges that reduce widespread applicability. Here, we describe an improved cell suspension and imaging-based methodology that can be broadly employed to assess cardiomyocyte cell division in standard laboratories across a multitude of model organisms and experimental conditions.

Data and Process Harmonisation of Multi-National, Multi-Site Research Data.

To achieve a single fully harmonised research data set suitable for analysis from data collected at multiple sites requires not only semantic integration of collection concepts and convergence onto single collection units, but harmonisation of data collection processes. We describe our experience of identifying harmonisation challenges in the Precision ALS project, with particular focus on process alignment challenges in a multi-site multi-national research data collection project.

Novel Insights into Post-Myocardial Infarction Cardiac Remodeling through Algorithmic Detection of Cell-Type Composition Shifts.

Background: Recent advances in single cell sequencing have led to an increased focus on the role of cell-type composition in phenotypic presentation and disease progression. Cell-type composition research in the heart is challenging due to large, frequently multinucleated cardiomyocytes that preclude most single cell approaches from obtaining accurate measurements of cell composition. Our studies reveal that ignoring cell type composition when calculating differentially expressed genes (DEGs) can have significant consequences.

is sufficient but not required for cardiomyocyte cell-cycle activation.

Factors responsible for cardiomyocyte proliferation could serve as potential therapeutics to stimulate endogenous myocardial regeneration following insult, such as ischemic injury. A previously published forward genetics approach on cardiomyocyte cell cycle and ploidy led us to the transcription factor, . Here, we examine the effect of on cardiomyocyte cell cycle during postnatal development and cardiac regeneration using cardiomyocyte-specific gain- and loss-of-function mouse models.

PLASMA DYNAMICS OF NEUTROPHIL EXTRACELLULAR TRAPS AND CELL-FREE DNA IN SEPTIC AND NONSEPTIC VASOPLEGIC SHOCK: A PROSPECTIVE COMPARATIVE OBSERVATIONAL COHORT STUDY.

Background: The association between neutrophil extracellular traps (NETs) and the requirement for vasopressor and inotropic support in vasoplegic shock is unclear. This study aimed to investigate the dynamics of plasma levels of NETs and cell-free DNA (cfDNA) up to 48 h after the admission to the intensive care unit (ICU) for management of vasoplegic shock of infectious (SEPSIS) or noninfectious (following cardiac surgery, CARDIAC) origin. Methods: This is a prospective, observational study of NETs and cfDNA plasma levels at 0H (admission) and then at 12H, 24H, and 48H in SEPSIS and CARDIAC patients.

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives.

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPVOPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPVOPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPVOPSCC.

IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8 T cell responses.

Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown.

Global IL4Rα blockade exacerbates heart failure after an ischemic event in mice and humans.

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating disease progression. The literature suggests an important role for the activation of interleukin-13 or interleukin-4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans.

Evaluating the Appropriateness of Podcasts to Improve the Knowledge and Awareness of Selected Health Topics Among Undergraduate General Nursing Students: Protocol for an International Feasibility Study.

Background: Podcasts have proven to be a successful alternative source of educational material for students. Given the ability to listen to podcasts 24/7 and while on the go, this technology has the potential to provide informative and educational material to a large number of people at any given time. Podcasts are usually freely available on commonly used mobile devices, such as smartphones, laptops, and tablets.

Targeted therapy, immunotherapy, and small molecules and peptidomimetics as emerging immunoregulatory agents for melanoma.

Primary cutaneous melanoma is the most lethal of all skin neoplasms and its incidence is increasing. Clinical management of advanced melanoma in the last decade has been revolutionised by the availability of immunotherapies and targeted therapies, used alone and in combination. This article summarizes advances in the treatment of late-stage melanoma including use of protein kinase inhibitors, antibody-based immune checkpoint inhibitors, adoptive immunotherapy, vaccines and more recently, small molecules and peptidomimetics as emerging immunoregulatory agents.

Personalised Medicine and the Potential Role of Electrospinning for Targeted Immunotherapeutics in Head and Neck Cancer.

Advanced head and neck cancer (HNC) is functionally and aesthetically destructive, and despite significant advances in therapy, overall survival is poor, financial toxicity is high, and treatment commonly exacerbates tissue damage. Although response and durability concerns remain, antibody-based immunotherapies have heralded a paradigm shift in systemic treatment. To overcome limitations associated with antibody-based immunotherapies, exploration into de novo and repurposed small molecule immunotherapies is expanding at a rapid rate.

Antagonistic interactions safeguard mitotic propagation of genetic and epigenetic information in zebrafish.

The stability of cellular phenotypes in developing organisms depends on error-free transmission of epigenetic and genetic information during mitosis. Methylation of cytosine residues in genomic DNA is a key epigenetic mark that modulates gene expression and prevents genome instability. Here, we report on a genetic test of the relationship between DNA replication and methylation in the context of the developing vertebrate organism instead of cell lines.

IL-13 promotes functional recovery after myocardial infarction via direct signaling to macrophages.

There is great interest in identifying signaling pathways that promote cardiac repair after myocardial infarction (MI). Prior studies suggest a beneficial role for IL-13 signaling in neonatal heart regeneration; however, the cell types mediating cardiac regeneration and the extent of IL-13 signaling in the adult heart after injury are unknown. We identified an abundant source of IL-13 and the related cytokine, IL-4, in neonatal cardiac type 2 innate lymphoid cells, but this phenomenon declined precipitously in adult hearts.

Central Extracorporeal Membrane Oxygenation Support Following Calcium Channel Blocker Overdose in Children.

Refractory vasodilatory shock (RVS) following massive calcium channel blocker (CCB) overdose remains a challenging clinical entity. Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) has proven useful in several cases of CCB intoxication, however, its use in the pediatric population poses unique challenges given the generally small size of pediatric peripheral vasculature in comparison to the high flow rates necessary for adequate mechanical circulatory support. As a result of these challenges, our group has adopted a "primary" central ECMO cannulation approach to the treatment of children and adolescents admitted to our center with profound RVS after CCB ingestion.

Adenylate kinase 9 is essential for sperm function and male fertility in mammals.

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out.

Lymphocyte pathway analysis using naturally lymphocyte-deficient fish.

Comparative phylogenetic analyses are of potential value to establish the essential components of genetic networks underlying physiological traits. For species that naturally lack particular lymphocyte lineages, we show here that this strategy readily distinguishes trait-specific actors from pleiotropic components of the genetic network governing lymphocyte differentiation. Previously, three of the four members of the DNA polymerase X family have been implicated in the junctional diversification process during the somatic assembly of antigen receptors.