Breakdown of blood-brain barrier, astrocytic endfeet swelling, and abnormal behaviors by blockade of TROY signaling in TROY-Fc transgenic mice.

An orphan receptor of tumor necrosis factor receptor superfamily (TNFRSF), TROY (TNFRSF19), forms the receptor complex with Nogo-66 receptor/LINGO-1 and DR6 in neurons and cerebral endothelial cells, respectively. Although TROY is expressed in astrocytes of the brain under normal conditions, its function is still unknown. Here, we demonstrated that TROY was strongly expressed in astrocytes rather than in neurons and endothelial cells in the adult mouse brain under normal conditions.

Machine Learning-Based Predictive Modeling Maximizes the Efficacy of mTOR/p53 Co-Targeting Therapy Against AML.

Although mTOR signaling plays a key role in acute myeloid leukemia (AML), mTOR inhibitors have shown limited efficacy against AML in clinical trials. In this study, we found that the anti-leukemic effect of mTOR inhibition was mediated in part through the TP53 pathway. mTOR inhibition by rapamycin and TP53 activation by DS-5272 collaboratively induced the downregulation of MYC and MCL1 partly through miR-34a, thereby inducing cell cycle arrest and apoptosis in AML cells.

Neurodevelopmental and social determinants of school support received by children born preterm.

Background: Children born preterm face higher risks of neurodevelopmental difficulties that, with social vulnerabilities, may impair school performance. We described and assessed determinants of receiving school support in preterm-born children in France.

Methods: We used data from the prospective population-based cohort of births before 35 weeks' gestation in France, EPIPAGE-2, to estimate crude rates and adjusted relative risks (using multivariable, mixed-effects generalized linear models) of receiving school support at age five, by children's neurodevelopment at five, sociodemographic characteristics, and region.

Analysis of the Italian cohort of late-onset Pompe disease (LOPD) patients after 10 and 15 years of therapy with alglucosidase alfa.

Background And Objectives: Late-onset Pompe disease (LOPD) is the first genetic neuromuscular disease treated with enzyme replacement therapy (ERT) in 2006, with variable results over time. This study aimed to assess therapeutic efficacy and safety in a large national cohort of patients after 10 and 15 years of treatment with alglucosidase alfa, all of them regularly evaluated in expert Centers.

Methods: This retrospective study analyzed data from 15 Italian Centers, examining clinical-genetic features and motor and respiratory outcomes at baseline, 10 years (T10, n = 85), and 15 years (T15, n = 42) after ERT initiation.

Identification and validation of clinical phenotypes in bloodstream infection and their association with mortality (FEN-AUREUS study).

Background: bacteraemia (SAB) is heterogeneous in patients and infection-related features. The aim of the study was to identify clinical phenotypes among patients with SAB, to evaluate their association with mortality, and to derive and validate a simplified probabilistic model for phenotypes assignment.

Methods: Phenotypes were derived using two-stage cluster analysis of 2128 patients from the ISAC cohort (recruited between 2013 and 2015), analysing 62 variables.

RXR agonist S169 inhibits HBV/HDV entry in vitro by disrupting KIF4-dependent NTCP trafficking.

Chronic hepatitis B (HBV) and hepatitis D (HDV) viral infections pose serious global health challenges, and the lack of curative therapies calls for the development of new antiviral approaches. Recently, we have identified the Kinesin Family Member 4 (KIF4) as a crucial regulator of the surface transport for NTCP (HBV/HDV entry receptor). Our research has shown that the pan-RXR agonist, Bexarotene, suppresses KIF4 expression and inhibits HBV/HDV infections.

Herpes simplex virus 1 evades APOBEC1-mediated immunity via its uracil-DNA glycosylase in mice.

Herpes simplex virus 1 (HSV-1) is the most common cause of viral encephalitis, which can be lethal or result in severe neurological defects despite antiviral therapy. The apolipoprotein B messenger-RNA editing enzyme, catalytic polypeptide-like (APOBEC) group of proteins can act as viral restriction factors. How HSV-1 evades this intrinsic immune mechanism is unclear.

Prominent and fast response to eculizumab in myasthenic crisis: the potential as rescue therapy in refractory myasthenia gravis.

Introduction: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease caused by antibodies against the postsynaptic membrane at the neuromuscular junction, leading to muscle weakness, fatigue, and respiratory failure in severe cases. Myasthenic crisis (MC) is a life-threatening condition which requires hospitalization and treatments with intravenous immunoglobulin, plasma exchange and high dose steroids. We report a case of a patient with refractory MC and anti-AChR antibodies positivity who started Eculizumab as rescue therapy, leading to a complete resolution of the acute neuromuscular condition.

In-depth functional analysis of BRD9 in fetal hematopoiesis reveals context-dependent roles.

The hierarchical organization of hematopoietic stem cells (HSCs) governing adult hematopoiesis has been extensively investigated. However, the dynamic epigenomic transition from fetal to adult hematopoiesis remains incompletely understood, particularly regarding the involvement of epigenetic factors. In this study, we investigate the roles of BRD9, an essential component of the non-canonical BAF (ncBAF) complex known to govern the fate of adult HSCs, in fetal hematopoiesis.

Multiple respiratory assessment and thresholds for noninvasive ventilation in adult patients with spinal muscular atrophy.

This study aimed to examine feasibility of inspiratory muscle strength tests, such as maximal inspiratory pressure (MIP) and sniff nasal inspiratory pressure (SNIP) in adult patients affected by spinal muscular atrophy (SMA), as well as their ability, along with forced vital capacity (FVC), to predict noninvasive ventilation (NIV) needs. Additionally, we evaluated feasibility and effectiveness of respiratory oscillometric measurements in the same patients. Twenty patients were retrospectively evaluated.

ENO1/Hsp70 Interaction Domains: In Silico and In Vitro Insight for a Putative Therapeutic Target in Cancer.

Alpha-enolase (ENO1) is a multifunctional protein with oncogenic roles. First described as a glycolytic enzyme, the protein performs different functions according to its cellular localization, post-translational modifications, and binding partners. Cell surface-localized ENO1 serves as a plasminogen-binding receptor, and it has been detected in several cell types, including various tumor cells.

Differentiation, reduction, and proliferation of pancreatic β-cells and their regulatory factors.

The prevalence of diabetes has increased rapidly in recent years, and many types of therapeutic agents have been developed. However, the main purpose of these drugs is to lower blood glucose levels, and they are not fundamental solutions. In contrast, our research has been aimed at stimulating and inducing β-cell proliferation in vivo and replenishing β-cells.

Selenoprotein-mediated redox regulation shapes the cell fate of HSCs and mature lineages.

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of messenger RNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we used selenocysteine transfer RNA (tRNASec) gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis.

Attitudes and Beliefs of Primary Care Physicians and Nurses in Spain Toward Vegan Diets.

Background: As dietary habits shift in response to environmental concerns and health awareness, understanding healthcare professionals' perceptions of vegan diets is crucial.

Objectives: This study aimed to identify the beliefs and attitudes of primary care doctors and nurses in Spain towards vegan diets.

Methods: A questionnaire-based, observational, cross-sectional study was conducted among 208 healthcare professionals.

A decision-making tool for navigating extracellular vesicle research and product development.

Due to their intercellular communication properties and involvement in a wide range of biological processes, extracellular vesicles (EVs) are increasingly being studied and exploited for different applications. Nevertheless, their complex nature and heterogeneity, as well as the challenges related to their purification and characterization procedures, require a cautious assessment of the qualitative and quantitative parameters that need to be monitored. This translates into a multitude of choices and putative solutions that any EV researcher must confront in both research and translational environments.

Clonal hematopoiesis-related mutant ASXL1 promotes atherosclerosis in mice via dysregulated innate immunity.

Certain somatic mutations provide a fitness advantage to hematopoietic stem cells and lead to clonal expansion of mutant blood cells, known as clonal hematopoiesis (CH). Among the most common CH mutations, ASXL1 mutations pose the highest risk for cardiovascular diseases (CVDs), yet the mechanisms by which they contribute to CVDs are unclear. Here we show that hematopoietic cells harboring C-terminally truncated ASXL1 mutant (ASXL1-MT) accelerate the development of atherosclerosis in Ldlr mice.

The Influence of Job Crafting on Nurses' Intent to Stay: A Cross-Sectional Study.

: The increasing rates of nurse turnover pose significant challenges to healthcare systems, negatively impacting patient outcomes and increasing operational costs. Despite the recognized importance of retaining nursing staff, factors contributing to turnover intentions, such as job dissatisfaction and burnout, remain inadequately addressed. Developing job crafting skills among nurses can be a proactive strategy to mitigate these issues, leading to a more engaged and committed workforce.

Prostaglandin E-EP2/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells.

While prostaglandin E (PGE) is produced in human tumor microenvironment (TME), its role therein remains poorly understood. Here, we examine this issue by comparative single-cell RNA sequencing of immune cells infiltrating human cancers and syngeneic tumors in female mice. PGE receptors EP4 and EP2 are expressed in lymphocytes and myeloid cells, and their expression is associated with the downregulation of oxidative phosphorylation (OXPHOS) and MYC targets, glycolysis and ribosomal proteins (RPs).

NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation.

Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift mutations in exon12 (NPM1c), previous studies have identified NPM1 gene rearrangements leading to the expression of NPM1-fusion proteins in pediatric AML. However, whether the NPM1-fusions are indeed oncogenic and how the NPM1-fusions cause AML have been largely unknown.

Space Analogs and Behavioral Health Performance Research review and recommendations checklist from ESA Topical Team.

Space analog research has increased over the last few years with new analogs appearing every year. Research in this field is very important for future real mission planning, selection and training of astronauts. Analog environments offer specific characteristics that resemble to some extent the environment of a real space mission.

Structural and functional brain markers of cognitive impairment in healthcare workers following mild SARS-CoV-2 infection during the original stream.

Severe acute respiratory syndrome coronavirus 2 infection often involves the nervous system, leading to cognitive dysfunctions, fatigue and many other neurological signs that are becoming increasingly recognized. Despite mild forms of the disease accounting for most cases worldwide, research on the pathophysiology driving mild coronavirus disease 2019 (COVID-19) has received little attention. In this respect, recent evidence has pointed out that around 30-40% of non-critical, mild-to-moderate severity COVID-19 survivors may display cognitive disturbances several months post-illness.

Reinforcement Learning: A Paradigm Shift in Personalized Blood Glucose Management for Diabetes.

Managing blood glucose levels effectively remains a significant challenge for individuals with diabetes. Traditional methods often lack the flexibility needed for personalized care. This study explores the potential of reinforcement learning-based approaches, which mimic human learning and adapt strategies through ongoing interactions, in creating dynamic and personalized blood glucose management plans.

Effectiveness of a nurse-led mHealth approach in preventing obesity in adolescents: an intervention study.

Background: Obesity prevention in adolescents is a public health priority given its increasing prevalence and health impact of obesity.

Aim: To evaluate the effectiveness of an educational intervention in overweight and obesity using a mHealth app in improving nutritional and sports knowledge, adherence to the Mediterranean diet, physical activity and anthropometric measurements in adolescents.

Methods: A randomised controlled trial with parallel groups that included 305 adolescents.