Expectation-driven sensory adaptations support enhanced acuity during categorical perception.

Expectations can influence perception in seemingly contradictory ways, either by directing attention to expected stimuli and enhancing perceptual acuity or by stabilizing perception and diminishing acuity within expected stimulus categories. The neural mechanisms supporting these dual roles of expectation are not well understood. Here, we trained European starlings to classify ambiguous song syllables in both expected and unexpected acoustic contexts.

Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers.

CIZ1 is part of the RNA-dependent supramolecular assemblies that form around the inactive X-chromosome (Xi) in female cells and smaller assemblies throughout the nucleus in both sexes. Here, we show that CIZ1 C-terminal anchor domain (AD) is elevated in human breast tumor transcriptomes, even at stage I. Elevation correlates with deprotection of chromatin and upregulation of lncRNA-containing gene clusters in ∼10 Mb regions enriched in cancer-associated genes.

Primary atopic disorders: inborn errors of immunity causing severe allergic disease.

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and food allergies, are driven by dysregulated immune responses, often involving IgE-mediated mast cell and basophil activation, Th2 inflammation, and epithelial dysfunction. While environmental factors are well-known contributors, the genetic components underpinning these conditions are increasingly understood. Traditionally viewed as polygenic multifactorial disorders, allergic diseases can also be caused by single-gene defects affecting the immune system and skin epithelial barrier, leading to profoundly dysregulated allergic responses.

Long-Term Outcomes of Children Born to Anti-Ro Antibody-Positive Mothers With and Without Rheumatic Disease.

Objective: The objective of this study was to estimate the prevalence of allergy, and/or neurodevelopmental and autoimmune diagnoses in children born to anti-Ro antibody-positive mothers.

Methods: We conducted a cohort study of children born to anti-Ro antibody-positive mothers observed in the neonatal lupus erythematosus (NLE) clinic at The Hospital for Sick Children. Participants one year of age or older were invited to complete a health status questionnaire.

Gut microbiota metabolites, secretory immunoglobulin A and Bayley-III cognitive scores in children from the CHILD Cohort Study.

Background: Dysbiosis of the gut microbiota has been demonstrated in neurodevelopmental disorders but the underlying mechanisms that may explain these associations are poorly understood. Gut secretory immunoglobulin A (SIgA) binds pathogenic microbes, preventing mucosal penetration. Gut microbes also influence SIgA production and its binding characteristics through short-chain fatty acid (SCFA) metabolites, allowing them to regulate the immune response.

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study.

Objective: Lower respiratory tract infections (LRTIs) in early life are one of the strongest risk factors for childhood asthma and are often treated with systemic antibiotics (IV or oral). We aimed to explore the association between early-life LRTIs and systemic antibiotics on asthma development and the potential mediating role of antibiotics in this relationship.

Methods: Data were collected as part of the longitudinal, general Canadian population CHILD Study.

Ultraprocessed Food Consumption and Obesity Development in Canadian Children.

Importance: Ultraprocessed foods (UPF), characterized as shelf-stable but nutritionally imbalanced foods, pose a public health crisis worldwide. In adults, UPF consumption is associated with increased obesity risk, but findings among children are inconsistent.

Objectives: To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children.

Recurrent Diffuse Tenosynovial Giant Cell Tumor of the Temporomandibular Joint.

Purpose: Recurrent diffuse-type tenosynovial giant cell tumor: Clinical presentation, Diagnosis, and Management.

Background: Tenosynovial giant cell tumor (TGCT), is a neoplasm arising from synovial joints, bursae, or tendon sheaths. The initial clinical symptoms are vague and non-diagnostic.

Impact analysis of infant antibiotic exposure on the burden of asthma: a simulation modeling study.

Background: Infant antibiotic use is associated with increased risk of asthma. We examined the population impact of antibiotic exposure in the first year of life on the burden of pediatric asthma in British Columbia, Canada, using simulation modeling.

Methods: We performed a Bayesian meta-analysis of empirical studies to construct dose-response equations between antibiotic exposure in the first year of life and pediatric (<19 years of age) asthma.

Human disease-causing missense genetic variants are enriched in the evolutionarily ancient domains of the cytosolic aminoacyl-tRNA synthetase proteins.

All life depends on accurate and efficient protein synthesis. The aminoacyl-tRNA synthetases (aaRSs) are a family of proteins that play an essential role in protein translation, as they catalyze the esterification reaction that charges a transfer RNA (tRNA) with its cognate amino acid. However, new domains added to the aaRSs over the course of evolution in eukaryotes confer novel functions unrelated to protein translation.

Pets and related allergens modify the association between early life DEHP exposure and respiratory outcomes in children.

Introduction: Throughout the perinatal period children are exposed to complex mixtures, including indoor chemicals such as phthalates, and biological agents. However, few studies focus on interactions between early-life co-exposures to shed light on how co-exposures modify their individual effects. Therefore, our study aims to assess whether early-life exposure to pets and related biological agents, namely pet allergens and endotoxin, modifies the association between di-(2-ethylhexyl) phthalate (DEHP) and asthma and wheeze in preschoolers to gain insight into interactions.

How the early life microbiome shapes immune programming in childhood asthma and allergies.

Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome.

The effectiveness of integrating making every contact count into an undergraduate medical curriculum.

Objective: To evaluate the feasibility and effectiveness of integrating Making Every Contact Count (MECC) using Healthy Conversation Skills (HCS) into an undergraduate medical curriculum and test the performance of an associated assessment.

Methods: Concepts were introduced to second year students through lectures, small group seminars, role-plays and a new Objective Structured Clinical Examination (OSCE).station.

Impact of postpartum hospital length of stay on infant gut microbiota: a comprehensive analysis of vaginal and caesarean birth.

Background: The primary concern with prolonged hospitalization following birth is the risk of acquiring hospital-acquired infections (HAIs) caused by opportunistic bacteria, which can alter the early establishment of gut microbiota.

Objective: To assess the association between postpartum hospital length of stay (LOS) and the composition of gut microbiota at 3 and 12 months of age according to birth mode.

Methods: In total, 1313 Canadian infants from the CHILD Cohort Study were involved in this study.

Reduce, reinforce, and replenish: safeguarding the early-life microbiota to reduce intergenerational health disparities.

Socioeconomic (SE) disparity and health inequity are closely intertwined and associated with cross-generational increases in the rates of multiple chronic non-communicable diseases (NCDs) in North America and beyond. Coinciding with this social trend is an observed loss of biodiversity within the community of colonizing microbes that live in and on our bodies. Researchers have rightfully pointed to the microbiota as a key modifiable factor with the potential to ease existing health inequities.

Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells.

Objectives: The insulin receptor (IR) and insulin like growth factor-1 receptor (IGF-1R) are heterodimers consisting of two extracellular α-subunits and two transmembrane β -subunits. Insulin αβ and insulin like growth factor-1 αβ hemi-receptors can heterodimerize to form hybrids composed of one IR αβ and one IGF-1R αβ. The function of hybrids in the endothelium is unclear.

Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.

Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL.

Prenatal vitamin C and fish oil supplement use are associated with human milk microbiota composition in the Canadian CHILD Cohort Study.

Maternal diet may modulate human milk microbiota, but the effects of nutritional supplements are unknown. We examined the associations of prenatal diet and supplement use with milk microbiota composition. Mothers reported prenatal diet intake and supplement use using self-administered food frequency and standardised questionnaires, respectively.