Transcription Factor 21 Regulates Cardiac Myofibroblast Formation and Fibrosis.

Background: TCF21 (transcription factor 21) is a bHLH (basic helix-loop-helix) protein required for the developmental specification of cardiac fibroblasts (CFs) from epicardial progenitor cells that surround the embryonic heart. In the adult heart, TCF21 is expressed in tissue-resident fibroblasts and is downregulated in response to injury or stimuli leading to myofibroblast differentiation. These findings led to the hypothesis that TCF21 regulates fibroblast differentiation in the adult mammalian heart to affect fibrosis.

Differentiating erythroblasts adapt to mechanical stimulation by upregulation of cholesterol biosynthesis via S1P/SREBP-induced HMGCR expression.

Understanding how mechanical stress affects erythropoiesis is crucial to produce transfusable erythrocytes in fluid-turbulent bioreactors. We investigated the effects of shear-stress on differentiating CD49dCD235a primary human erythroblasts (EBL) at molecular, cellular, and functional level. Shear-stress, at differentiation onset, enhanced EBL maturation and induced upregulation of genes regulating cholesterol/lipids biosynthesis, causing changes in cell lipid composition.

Development and validation of electronic health record-based, machine learning algorithms to predict quality of life among family practice patients.

Health-related quality of life (HRQol) is a crucial dimension of care outcomes. Many HRQoL measures exist, but methodological and implementation challenges impede primary care (PC) use. We aim to develop and evaluate a novel machine learning (ML) algorithm that predicts binary risk levels among PC patients by combining validated elements from existing measures with demographic data from patient electronic health records (eHR) to increase predictive accuracy while reducing prospectively-collected data required to generate valid risk estimates.

Every bite counts to achieve oral health: a scoping review on diet and oral health preventive practices.

Objective: To examine the landscape of preventive strategies and interventions directed to achieve oral health equity, with particular emphasis on the interplay between dental caries prevention, individual behaviors, and population-level strategies across various demographic and geographic regions.

Methods: This scoping review was guided by Peters et al.'s framework, which incorporates four key concepts aimed at reducing caries: education for individuals and healthcare providers, behavioral modifications, addressing broader social determinants of health, and extending oral health education programs beyond traditional dental settings.

Dynll1-PI31 Interaction Enhances Proteolysis via the Proteasome, Representing a Novel Therapeutic Target for INF2-Related FSGS.

Background: The p.Arg218Gln (R218Q) mutation in the inverted formin 2 (INF2) gene causes podocytopathy prone to focal segmental glomerulosclerosis (FSGS). This mutation disrupts the ability of INF2 to sequester DYNLL1, thus promoting dynein-mediated mistrafficking of the slit diaphragm protein, nephrin, to proteolytic pathways.

Mast cell sarcoma with KIT p.D816V mutation and concurrent systemic mastocytosis.

Mast cell sarcoma (MCS) is an extremely rare and aggressive form of mastocytosis characterized by highly atypical mast cells with local invasion, metastatic potential, and poor prognosis. MCS is predominantly a de novo process without recurrent molecular findings or predisposing lesions including various myeloid neoplasms. However, there have been rare case reports of MCS with preceding or concurrent systemic mastocytosis (SM) or cutaneous mastocytosis (CM), which is suggestive of an uncommon progression from SM/CM to MCS.

Exercising and immuno-oncology treatment (ExIO): a prospective pilot study for patients with solid tumors.

Purpose: Despite exercise's known benefits for cancer patients, little is understood about combining it with immune checkpoint inhibitors (ICI). This study aims to assess the feasibility and acceptability of a personalized physical activity program for cancer patients on ICI treatment and to investigate its effects on quality of life, ICI-related side effects, fatigue, and emotional symptoms.

Methods: This prospective study was conducted across eight cancer practices in a joint network in Brazil.

Analyzing the relationships among psychosocial variables associated with resilience.

Potentially Traumatic Events (PTEs) are common in current society, including college life. When exposed to PTE, stress reactions are greatly heterogeneous, and what contributes to psychological resilience is not well known. The purpose of the present study is to investigate the relationships among the antecedents, defining attributes, and consequences of resilience in a sample of 450 college students.

Prenatal exposure to environmental bisphenols over time and their association with childhood asthma, allergic rhinitis and atopic dermatitis in the ECHO consortium.

Concerns persist about the potential impact of prenatal exposure to bisphenols (BP) and their replacement analogues on childhood asthma and allergies. Previous studies on single and small cohorts had limited statistical power, few investigated analogues BPF and BPS, and even fewer examined atopic outcomes. Our objective was to assess whether prenatal exposures to individual environmental bisphenols (BPA, BPF, BPS) influence risk of childhood asthma, allergic rhinitis, and atopic dermatitis.

Building capacity in dissemination and implementation research: the presence and impact of advice networks.

Background: As dissemination and implementation (D&I) research increases, we must continue to expand training capacity and research networks. Documenting, understanding, and enhancing advice networks identifies key connectors and areas where networks are less established. In 2012 Norton et al.

Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity.

Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden.

Representativeness and adverse event reporting in late-phase clinical trials for rifampin-susceptible tuberculosis: a systematic review.

We did a systematic review and meta-analysis of trials of treatment for rifampicin-susceptible tuberculosis to evaluate the representativeness of participants compared with characteristics of the global population of people with tuberculosis, and the adequacy of adverse event reporting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from Jan 1, 2000, to Dec 10, 2023, for trials that had greater than or equal to 50 participants per arm and had follow-up to at least treatment completion. Studies were excluded if they compared different formulations of standard drugs (eg, fixed-dose combination tablets); aimed to primarily enrol participants with isoniazid-resistant or rifampicin-resistant tuberculosis; evaluated treatment to prevent tuberculosis infection; tested dietary or vitamin supplementation; tested vaccines or other immune-based interventions; tested adherence support or system-related mechanisms; or enrolled participants with tuberculosis, but tuberculosis treatment itself was not randomised (ie, trials of the timing of antiretroviral therapy initiation).

The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation.

During persistent antigen stimulation, exhausted CD8 T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway.

Difficult Intubation Alert Is Associated With a Reduced Incidence of Difficult Intubation.

Introduction: Difficult or failed intubation significantly increases the risk of morbidity and mortality. Documentation of a prior difficult or failed tracheal intubation is a strong predictor of future difficult intubation.

Methods: We undertook a quality improvement project to create a redesigned difficult intubation alert with increased visibility in our electronic health record.

Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus-Exposed Uninfected Children.

Background: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines.

Methods: In a pooled analysis of clinical trials of 7 live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed, uninfected (HUU) children.

Structure and function of the human mitochondrial MRS2 channel.

The human mitochondrial RNA splicing 2 protein (MRS2) has been implicated in Mg transport across mitochondrial inner membranes, thus having an important role in Mg homeostasis critical for mitochondrial integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity and regulation remain unclear. Here we present a structural and functional investigation of MRS2.

Host DNA depletion on frozen human respiratory samples enables successful metagenomic sequencing for microbiome studies.

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients.

Exploiting a type III interferon response to improve chemotherapeutic safety and efficacy.

Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying 1) which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans.