A non-conditioned bone marrow transplantation mouse model to study clonal hematopoiesis and myeloid malignancies.

Clonal hematopoiesis of indeterminate potential (CHIP) is a condition where blood or bone marrow cells carry mutations associated with hematological malignancies. Individuals with CHIP have an increased risk of developing hematological malignancies, atherosclerotic cardiovascular disease, and all-cause mortality. Bone marrow transplantation (BMT) of cells carrying CHIP mutations into irradiated mice are useful procedures to investigate the dynamics of clonal expansion and potential therapeutic strategies, but myeloablative conditioning can induce confounding effects.

Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.

Background: HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete response remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for the management of dyslipidemia by enhancing the clearance of low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 and cancer cells.

Diagnostic performance of optical spectral transmission compared to magnetic resonance imaging in patients with inflammatory arthritis.

Background: Optical spectral transmission (OST) is a modern diagnostic method capable of quantifying inflammation in the finger and wrist joints of arthritis patients by assessing the blood-specific absorption of light transmitted through a tissue. The diagnostic performance of this modality has not been adequately examined and data regarding OST associations with magnetic resonance imaging (MRI) are limited. Aim of this study was therefore to investigate the performance of OST in assessing joint inflammation as compared to MRI in patients with inflammatory arthritis (IA).

Cytotoxicity and genotoxicity of orthodontic bands after aging: an in-vitro study.

Background: This investigation sought to evaluate cytotoxic and genotoxic effects of two different types of orthodontic bands after aging in acidic and neutral artificial saliva using human gingival fibroblast-like (HGF1-PI 1) cell lines.

Methods: Two commercial brands of orthodontic molar bands (American orthodontic (AO) and 3 S-dental bands), commonly used by orthodontists, were tested. These bands were divided into four groups to examine the effects of aging following thermocycling, and pH variations (pH = 4.

Enhancing individual glomerular filtration rate assessment: can we trust the equation? Development and validation of machine learning models to assess the trustworthiness of estimated GFR compared to measured GFR.

Background: Creatinine-based estimated glomerular filtration rate (eGFR) equations are widely used in clinical practice but exhibit inherent limitations. On the other side, measuring GFR is time consuming and not available in routine clinical practice. We developed and validated machine learning models to assess the trustworthiness (i.

Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.

Cyclin-dependent kinases (CDKs) 4 and 6 (CDK4/6) are important regulators of the cell cycle. Selective CDK4/6 small-molecule inhibitors have shown clinical activity in hormonal receptor-positive (HR) metastatic breast cancer, but their effectiveness remains limited in other cancer types. CDK4/6 degradation and improved selectivity across CDK paralogs are approaches that could expand the effectiveness of CDK4/6 targeting.

Kidney immunology from pathophysiology to clinical translation.

Kidney diseases are widespread and represent a considerable medical, social and economic burden. However, there has been marked progress in understanding the immunological aspects of kidney disease. This includes the identification of distinct intrarenal immunological niches and characterization of kidney disease endotypes according to the underlying molecular immunopathology, as well as a better understanding of the pathological roles for T cells, mononuclear phagocytes and B cells and the renal elements they target.

Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes.

Cell death mediated by executioner caspases is essential during organ development and for organismal homeostasis. The mechanistic role of activated executioner caspases in antibacterial defense during infections with intracellular bacteria, such as Listeria monocytogenes, remains elusive. Cell death upon intracellular bacterial infections is considered altruistic to deprive the pathogens of their protective niche.

Rhesus Cytomegalovirus-encoded Fcγ-binding glycoproteins facilitate viral evasion from IgG-mediated humoral immunity.

Human cytomegalovirus (HCMV) encodes four viral Fc-gamma receptors (vFcγRs) that counteract antibody-mediated activation in vitro, but their role in infection and pathogenesis is unknown. To examine their in vivo function in an animal model evolutionarily closely related to humans, we identified and characterized Rh05, Rh152/151 and Rh173 as the complete set of vFcγRs encoded by rhesus CMV (RhCMV). Each one of these proteins displays functional similarities to their prospective HCMV orthologs with respect to antagonizing host FcγR activation in vitro.

Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.

Oncolytic reprogramming of tumor microenvironment shapes CD4 T-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma.

Oncolytic viruses (OVs) emerge as a promising cancer immunotherapy. However, the temporal impact on tumor cells and the tumor microenvironment, and the nature of anti-tumor immunity post-therapy remain largely unclear. Here we report that CD4 T cells are required for durable tumor control in syngeneic murine models of glioblastoma multiforme after treatment with an oncolytic herpes simplex virus (oHSV) engineered to express IL-12.

Sensory neurotransmission and pain in solid tumor progression.

Sensory nerves form a crucial component of the tumor microenvironment (TME) that relays vital information to the central nervous system and modulates tumor progression via immunosurveillance. Afferent activity processed by the brain can sensitize brain circuitry and influence host behaviors. Peripheral sensory signaling (e.

Xanthomatous hypophysitis relapsing and remitting over two decades.

Inflammation of the pituitary gland can be primary (without another underlying cause) or secondary (associated with a systemic inflammatory condition). Primary hypophysitis is very rare, among which xanthomatous hypophysitis as a histological type is extremely unusual. A woman in her late 50s presented with recurrent pituitary lesions over 20 years.

Blocking the CD39/CD73 pathway synergizes with anti-CD20 bispecific antibody in nodal B-cell lymphoma.

Bispecific antibodies (BsAb) have emerged as a leading treatment modality in patients suffering from B-cell non-Hodgkin's lymphoma (B-NHL). However, treatment failure is common and may potentially be attributed to pre-existing or emerging T-cell exhaustion. CD39 catalyzes-together with CD73-the hydrolysis of immunogenic ATP into immunosuppressive adenosine and thus actively promotes an immunosuppressive micromilieu.

Severe pulmonary arterial hypertension and cardiogenic shock in acute systemic lupus erythematosus.

We describe a woman in her late 20s with newly diagnosed systemic lupus erythematosus (SLE), who presented with fulminant pulmonary arterial hypertension (PAH) requiring inotropic and extracorporeal support. She was established on triple pulmonary vasodilator therapy with concurrent aggressive immunosuppression; however, treatment was complicated by infection and diffuse alveolar haemorrhage, necessitating delays in immunosuppression and withdrawal of epoprostenol. Despite this, with ongoing suppression of her SLE, her pulmonary haemodynamics improved, with normal pressures on right heart catheterisation several months later allowing stepdown to sildenafil monotherapy.

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study.

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol.

Conflicts of interest in the International Agency for Research on Cancer process of identifying carcinogenic hazards to humans.

Managing conflicts of interest (COIs) in scientific decision-making is important for minimizing bias and fostering public trust in science. Proper management of COIs has added significance when scientists are making decisions that impact public policy, such as assessing substances for carcinogenicity. The International Agency for Research on Cancer (IARC) organizes expert working groups to identify putative carcinogens and determine whether or not the hazard is likely to present significant potential harm to humans.

Sp3 ameliorated experimental autoimmune encephalomyelitis by triggering Socs3 in Th17 cells.

Introduction: Although it is believed that chronic inflammatory and degenerative diseases of the central nervous system are mediated by autoimmune Th17 cells, the underlying mechanisms remain largely unexplored. Recent studies and our research have revealed that Sp3 was blocked in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE). However, it remained unclear why it is silent and how it regulates Th17 cell differentiation in MS.

COMPARING MESH AND COMPRESSOR NEBULIZERS IN PULMONARY FUNCTION TEST IN PEDIATRIC ASTHMA ATTACKS: A DOUBLE-BLIND RANDOMIZED COMPARATIVE CLINICAL TRIAL.

Objective: Asthma is a prevalent global health issue, especially affecting children in numerous countries. Our study aimed to determine the most effective nebulizer type by comparing the effects of mesh nebulizers (MNs) and compressor nebulizers (CNs) on spirometry tests in pediatric asthma attacks.

Methods: The prospective, double-blind, randomized comparative study was conducted with patients aged 7-15 presenting with asthma attacks.

Interferon-γ signaling in eosinophilic esophagitis affects epithelial barrier function and programmed cell death.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disorder characterized by eosinophil-rich mucosal inflammation and tissue remodeling. Prior research has revealed the upregulation of interferon (IFN) response signature genes (ISGs) in biopsy tissue from EoE patients, but the specific cell types that contribute to this IFN response and the effect of interferons on the esophageal epithelium remain incompletely understood. Here, we use scRNA-seq to examine the expression of IFN and ISGs during EoE and explore how IFN-α and IFN-γ treatments affect epithelial function.

Prenatal Per- and Polyfluoroalkyl Substances in Relation to Antibody Titers and Infections in Childhood.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals posing environmental and health risks. Impact on the human immune system is of particular concern, especially during fetal immune development. Alterations to fetal immune development can impact immunity later in life, e.

Assessing the Utilization of HIV Genotype Resistance Testing: Insight from Italian Infectious Diseases Units.

Purpose: We aimed to assess the utilization of Genotype Resistance Testing (GRT) by Infectious Diseases Units across Italy.

Methods: A cross-sectional study was conducted involving a questionnaire distributed to the Infectious Diseases Unit in Italy. A web-based survey using Google Forms software was utilized and spread via email or cellphone.