knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors.

Introduction: Natural Killer (NK) cells hold the potential to shift cell therapy from a complex autologous option to a universal off-the-shelf one. Although NK cells have demonstrated efficacy and safety in the treatment of leukemia, the limited efficacy of NK cell-based immunotherapies against solid tumors still represents a major hurdle. In the immunosuppressive tumor microenvironment (TME), inhibitory interactions between cancer and immune cells impair antitumoral immunity.

Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1 epileptic encephalopathy.

Dynamin-1 is a large GTPase with an obligatory role in synaptic vesicle endocytosis at mammalian nerve terminals. Heterozygous missense mutations in the dynamin-1 gene (DNM1) cause a novel form of epileptic encephalopathy, with pathogenic mutations clustering within regions required for its essential GTPase activity. We reveal the most prevalent pathogenic DNM1 mutation, R237W, disrupts dynamin-1 enzyme activity and endocytosis when overexpressed in central neurons.

Mental Illness Following Physical Assault Among Children.

Importance: Physical assault during childhood is common and can lead to lasting mental health problems. Yet, there are few studies on the patterns of mental illness (ie, timing of onset, type, and acuity) in survivors of physical assault.

Objective: To determine the risk of incident health record diagnoses of mental illness among children who experienced assault compared with children who did not.

Prevention of COVID-19 with oral vitamin D supplemental therapy in essential healthcare teams (PROTECT): protocol for a multicentre, triple-blind, randomised, placebo-controlled trial.

Introduction: In the COVID-19 pandemic, healthcare workers (HCWs) were at high risk of infection due to their exposure to COVID infections. HCWs were the backbone of our healthcare response to this pandemic; every HCW withdrawn or lost due to infection had a substantial impact on our capacity to deliver care. Primary prevention was a key approach to reduce infection.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.

Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months.

Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis.

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma.

Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience.

Background: ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein.

Objective: To determine the real-life long-term benefits of REVCOVI in ADA-SCID.

Factors Determining the Success of the Chronically Instrumented Non-anesthetized Fetal Sheep Model of Human Development: A Retrospective Cohort Study.

Background The chronically instrumented non-anesthetized fetal sheep (CINAFS) model has been a mainstay of human fetal development research for the past 60 years. As a large "two for one" animal model, involving the instrumentation of the ewe and her fetus, the model poses challenges to implement de novo and maintain overtime at the highest standards of operating procedures to ensure ongoing performance. A common yet conventionally underreported issue researchers face is a high rate of animal loss.

Impaired muscle stem cell function and abnormal myogenesis in acquired myopathies.

Skeletal muscle possesses a high plasticity and a remarkable regenerative capacity that relies mainly on muscle stem cells (MuSCs). Molecular and cellular components of the MuSC niche, such as immune cells, play key roles to coordinate MuSC function and to orchestrate muscle regeneration. An abnormal infiltration of immune cells and/or imbalance of pro- and anti-inflammatory cytokines could lead to MuSC dysfunctions that could have long lasting effects on muscle function.

Molecular basis for antiviral activity of two pediatric neutralizing antibodies targeting SARS-CoV-2 Spike RBD.

Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity.

Guilt and Regret Experienced by Parents of Children Born Extremely Preterm.

Objectives: To explore decisional regret of parents of babies born extremely preterm and analyze neonatal, pediatric, and parental factors associated with regret.

Study Design: Parents of infants born <29 weeks of gestational age, aged between 18 months and 7 years, attending neonatal follow-up were enrolled. Hospital records were reviewed to examine morbidities and conversations with parents about levels of care.

Lyme borreliosis in pregnancy and associations with parent and offspring health outcomes: An international cross-sectional survey.

Background: Lyme disease (LD) is a complex tick-borne pathology caused by sensu lato bacteria. Currently, there are limited data regarding the health outcomes of people infected during pregnancy, the potential for perinatal transmission to their fetus, and the long-term effects on these children. Therefore, the primary objective of this survey study was to investigate the impact of LD in pregnancy on both the parent and their offspring.

When the clock ticks wrong with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID-19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes.

Type 2 autoimmune hepatitis: Genetic susceptibility.

Two types of autoimmune hepatitis (AIH) are recognized; AIH-1 is characterized by the presence of anti-nuclear and/or anti-smooth muscle autoantibodies, while AIH-2 is associated with the presence of anti-Liver kidney microsome and/or anti-Liver Cytosol antibodies. The autoantigens targeted by AIH-2 autoantibodies are the cytochrome P450 2D6 and Formiminotransferase-cyclodeaminase for anti-LKM1 and anti-LC1 respectively. Both autoantigens are expressed in hepatocytes at higher levels than in any other cell type.

Proinflammatory changes in the maternal circulation, maternal-fetal interface, and placental transcriptome in preterm birth.

Background: Preterm birth remains a leading obstetrical complication because of the incomplete understanding of its multifaceted etiology. It is known that immune alterations toward a proinflammatory profile are observed in women with preterm birth, but therapeutic interventions are still lacking because of scarcity of evidence in the integration of maternal and placental interrelated compartments.

Objective: This study aimed to obtain an integrated view of the maternal and placental contribution to preterm birth compared with normal term pregnancies for an in-depth understanding of the immune/inflammatory involvement, intending to identify novel strategies to mitigate the negative impact of inflammation.

A Shifting Relationship Between Sex Hormone-Binding Globulin and Total Testosterone Across Puberty in Boys.

Context: Sex hormone-binding globulin (SHBG) is associated with levels of total testosterone (total-T), and both total-T and SHBG are associated with obesity.

Objective: We aimed to clarify the nature of the relationship between testosterone and SHBG and improve our understanding of their relationships with obesity. We hypothesize that the hypothalamic-pituitary-gonadal axis contributes to the homeostasis of testosterone by increasing the production of gonadal testosterone through a feedback mechanism that might operate differently at different pubertal stages.

Long-term outcomes of type 1 retinopathy of prematurity following monotherapy with bevacizumab: a Canadian experience.

Objective: To report long-term structural, visual, and refractive outcomes after monotherapy with intravitreal bevacizumab injection.

Design: Cohort retrospective chart review.

Participants: A total of 56 premature infants with type 1 retinopathy of prematurity.

Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis.

Unlabelled: Compositional analysis of the intestinal microbiome in pre-schoolers is understudied. Effects of probiotics on the gut microbiota were evaluated in children under 4-years-old presenting to an emergency department with acute gastroenteritis. Included were 70 study participants (n=32 placebo, n=38 probiotics) with stool specimens at baseline (day 0), day 5, and after a washout period (day 28).