CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML.

CD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based CAR. However, here, we identify in vivo CD70 antigen escape as a limitation of single antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity.

Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state.

T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression.

Update to the Neonatal Early-Onset Sepsis Calculator Utilizing a Contemporary Cohort.

Background And Objectives: The Kaiser Permanente Neonatal Early-Onset Sepsis (EOS) Calculator has been an effective tool for risk stratification to safely reduce newborn antibiotic exposure. The calculator was derived from data on infants born between 1993 and 2007. Since that time, US obstetric practice has adopted universal antepartum screening for group B Streptococcus and intrapartum antibiotic prophylaxis guidance has changed.

Burnout is not associated with trainee performance on the Vascular Surgery In-Training Exam.

Objective: The Vascular Surgery In-Training Examination (VSITE) is a yearly exam evaluating vascular trainees' knowledge base. Although multiple studies have evaluated variables associated with exam outcomes, few have incorporated training program-specific metrics. The purpose of this study is to evaluate the impact of the learning environment and burnout on VSITE performance.

Edentulism and quality of life in the Salvadoran population: a cross-sectional study.

Introduction: Edentulism is the partial or total loss of teeth, it is irreversible and disabling due to its sequelae in the masticatory, phonetic and aesthetic function that affect the quality of life.

Objective: To establish the impact of edentulism and sociodemographic factors on the quality of life of the Salvadoran population.

Materials And Methods: Secondary cross-sectional analysis of data in 3322 users of the Public Health System of El Salvador, aged 15 to > 60 years.

Pan-cancer mapping of single CD8 T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.

CD8 T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8 T cells from 132 patients with seven human cancers.

Gender gaps in research: a systematic review.

Background: Despite significant advancements in closing the global gender gap, there is still much progress to be made, particularly in the field of science and scientific research. Numerous studies have addressed this issue and identified a variety of factors that contribute to gender asymmetries in research.

Methods: This study aimed to identify the determinants of gender gaps in scientific research present in the most cited studies of the past ten years as a first step towards closing these differences.

Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis.

Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules.

Experience with the use of intravitreal bevacizumab in cases with type I retinopathy of prematurity in a Latin American country.

In retinopathy of prematurity (ROP) type I, the use of intravitreal bevacizumab (IVB), which is an inhibitor of endothelial growth factor (VEGF), has become popular despite not being a therapy approved by regulatory agencies. However, IVB has shown positive effects in halting disease progression at lower costs compared to other anti-VEGF therapies (ranibizumab or aflibercept). In this report, we present the experience during the treatment with IVB of 102 Colombian children with ROP type I, with a success rate of 98% (100).

Personalized Infant Risk Prediction for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Requiring Intensive Care Unit Admission.

Background: Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission.

Methods: We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life.

Default Palliative Care Consultation for Seriously Ill Hospitalized Patients: A Pragmatic Cluster Randomized Trial.

Importance: Increasing inpatient palliative care delivery is prioritized, but large-scale, experimental evidence of its effectiveness is lacking.

Objective: To determine whether ordering palliative care consultation by default for seriously ill hospitalized patients without requiring greater palliative care staffing increased consultations and improved outcomes.

Design, Setting, And Participants: A pragmatic, stepped-wedge, cluster randomized trial was conducted among patients 65 years or older with advanced chronic obstructive pulmonary disease, dementia, or kidney failure admitted from March 21, 2016, through November 14, 2018, to 11 US hospitals.

Reported pain at work is a risk factor for vascular surgery trainee burnout.

Background: Work-related pain is a known risk factor for vascular surgeon burnout. It risks early attrition from our workforce and is a recognized threat to the specialty. Our study aimed to understand whether work-related pain similarly contributed to vascular surgery trainee well-being.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study.

Objectives: In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients' referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme.

Sound-based cough peak flow estimation in patients with neuromuscular disorders.

Introduction/aims: Cough impairment is common in individuals with neuromuscular disorders and is associated with respiratory infections and shorter survival. Cough strength is assessed by measuring cough peak flow (CPF) using a flow meter, but this method requires a complex device setup and trained staff. The aim of the study is to evaluate the reliability of a smartphone app to estimate CPF based on cough sounds in a cohort of individuals with neuromuscular disorders.

First Argentine database for the accurate identification of Brucella to species level by MALDI-TOF MS.

MALDI-TOF mass spectrometry (MS) has proven to be a fast and reliable method for the identification of a large number of taxonomic groups. It offers the advantage of being able to incorporate protein spectra of microorganisms that are absent or poorly represented in commercial databases, such as the genus Brucella. The aim of the study was to build the first database of protein spectra of local biological variants of Brucella in Argentina and of standard strains.

Tumor immunogenicity dictates reliance on TCF1 in CD8 T cells for response to immunotherapy.

Stem-like CD8 T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1CD8 T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8 T cells and ICB response in poorly immunogenic tumors that accumulate TOX dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors.

If You're Not Confused, You're Not Paying Attention: Is Not Brucella.

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related spp. in the genus Brucella.

Combined lineage tracing and scRNA-seq reveals unexpected first heart field predominance of human iPSC differentiation.

During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as the first and second heart fields, respectively. While these populations have been extensively studied in non-human model systems, their identification and study in vivo human tissues have been limited due to the ethical and technical limitations of accessing gastrulation-stage human embryos. Human-induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling early human embryogenesis due to their well-established ability to differentiate into all embryonic germ layers.

Higher diversity of Brucella canis in Latin America, according to an MLVA_13 Bc analysis.

Brucella canis is the main causative agent of canine brucellosis, which affects domestic and wild canids and leads to clinical signs and symptoms of the reproductive and locomotor systems. Owing to the scarce information on this pathogen, here we addressed the genetic diversity of the circulating strains of this species in Argentina by following an MVLA_13 Bc scheme. The analyzed sample set consisted of 101 strains of B.

Deep Gluteal Pain Syndrome: Endoscopic Technique and Medium-Term Functional Outcomes.

Background: Sciatic nerve entrapment is an entity that generates disabling pain, mainly when the patient is sitting on the involved side. According to some studies, the presence of fibrovascular bands has been described as the main cause of this pathology, and the sciatic nerve's decompression by endoscopic release has been described as an effective treatment generally associated with a piriformis tenotomy. The aim of this study was to present the medium-term functional results of endoscopic release of the sciatic nerve without resection of the piriformis tendon.

Parent Perception of School Meals in the San Joaquin Valley during COVID-19: A Photovoice Project.

School-based nutrition programs are crucial to reducing food insecurity. The COVID-19 pandemic adversely impacted students' school meal participation. This study seeks to understand parent views of school meals during COVID-19 to inform efforts to improve participation in school meal programs.