A Phase 1 Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients With Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors.

Purpose: FHD-609, a potent, selective, heterobifunctional degrader of bromodomain-containing protein 9 (BRD9), was evaluated for treatment of patients with advanced synovial sarcoma (SS) or SMARCB1-deficient tumors.

Patients And Methods: In this multinational, open-label, phase 1 study (NCT04965753), patients received FHD609 intravenously at escalating doses either twice weekly (BIW) (5 to 80 mg; n=40) or once weekly (QW) (40 to 120 mg; n=15).

Results: Fifty-five patients received FHD-609 for a median of 43 days.

Kinematic signature of high risk labored breathing revealed by novel signal analysis.

Breathing patterns (respiratory kinematics) contain vital prognostic information. This dimension of physiology is not captured by conventional vital signs. We sought to determine the feasibility and utility of quantifying respiratory kinematics.

Chromatin profiling and state predictions reveal insights into epigenetic regulation during early porcine development.

Background: Given their physiological similarities to humans, pigs are increasingly used as model organisms in human-oriented biomedical studies. Additionally, their value to animal agriculture across the globe has led to the development of numerous studies to investigate how to improve livestock welfare and production efficiency. As such, pigs are uniquely poised as compelling models that can yield findings with potential implications in both human and animal contexts.

Identification of SWI/SNF Subcomplex GBAF Presence, Intra-Complex Interactions, and Transcriptional Dynamics during Early Porcine Development.

Understanding the complex interplay between genetics and environmental factors is vital for enhancing livestock production efficiency while safeguarding animal health. Despite extensive studies on production-specific genes in livestock, exploring how epigenetic mechanisms and heritable modifications govern animal growth and development remains an under-explored frontier with potential implications across all life stages. This study focuses on the GBAF chromatin remodeling complex and evaluates its presence during embryonic and fetal development in swine.

Children Aged 5-6 Years in Vancouver, Canada Meet Dietary Recommendations for Folate and Vitamin B12 but not Choline.

Background: Choline, folate, and vitamin B12 are required for growth and development, but there is limited information on the intakes and relationships to biomarkers of status in children.

Objectives: The objective of this study was to determine the choline and B-vitamin intakes and relationship to biomarkers of status in children.

Methods: A cross-sectional study was conducted in children (n = 285, aged 5-6 y) recruited from Metro Vancouver, Canada.

Complexity of understanding the role of dietary and erythrocyte docosahexaenoic acid (DHA) on the cognitive performance of school-age children.

Background: Early childhood is a period of rapid brain development, with increases in synapses rich in the omega-3 (ω-3) fatty acid, DHA (22:6ω-3) continuing well beyond infancy. Despite the importance of DHA to neural phospholipids, the requirement of dietary DHA for neurodevelopment remains unclear.

Objectives: The aim was to assess the dietary DHA and DHA status of young children, and determine the association with cognitive performance.

Analysis of respiratory kinematics: a method to characterize breaths from motion signals.

Breathing motion (respiratory kinematics) can be characterized by the interval and depth of each breath, and by magnitude-synchrony relationships between locations. Such characteristics and their breath-by-breath variability might be useful indicators of respiratory health. To enable breath-by-breath characterization of respiratory kinematics, we developed a method to detect breaths using motion sensors.

GSEAplot: A Package for Customizing Gene Set Enrichment Analysis in R.

Gene Set Enrichment Analysis (GSEA) is used to identify differentially expressed gene sets that are enriched for annotated biological functions. The existing GSEA R code is not in the form of a flexible package with analysis and plotting customization options, and the results produced are not generated in the form of R objects. In this study, we introduce the GSEAplot R package with novel functionality for saving relevant information from the analysis to the current R workspace, and we introduce the ability to customize plots and databases.

GBAF, a small BAF sub-complex with big implications: a systematic review.

ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development.

Sex differences in human adipose tissue gene expression and genetic regulation involve adipogenesis.

Sex differences in adipose tissue distribution and function are associated with sex differences in cardiometabolic disease. While many studies have revealed sex differences in adipocyte cell signaling and physiology, there is a relative dearth of information regarding sex differences in transcript abundance and regulation. We investigated sex differences in subcutaneous adipose tissue transcriptional regulation using omic-scale data from ∼3000 geographically and ethnically diverse human samples.

Variability of Water-Soluble Forms of Choline Concentrations in Human Milk during Storage, after Pasteurization, and among Women.

Choline is critical for infant development and mother's milk is the sole source of choline for fully breastfed infants until six months of age. Human milk choline consists to 85% of water-soluble forms of choline including free choline (FC), phosphocholine (PhosC), and glycerophosphocholine (GPC). Donor milk requires safe handling procedures such as cold storage and pasteurization.

Biomarkers of Docosahexaenoic Acid but Not Arachidonic Acid Reflect Dietary Intakes in Toddlers at Ages 1 and 2 Years Who Are Not Meeting Dietary Recommendations.

Background: Long-chain n-6 and n-3 PUFAs are important for growth and development. However, little is known about requirements and current dietary intakes of these fatty acids in toddlers.

Objectives: This study assessed dietary intakes of n-6 and n-3 PUFAs and determined the relation to circulating PUFAs in toddlers at ages 1 and 2 y.

New anthropometric classification scheme of preoperative nutritional status in children: a retrospective observational cohort study.

Objective: WHO uses anthropometric classification scheme of childhood acute and chronic malnutrition based on low body mass index (BMI) ('wasting') and height for age ('stunting'), respectively. The goal of this study was to describe a novel two-axis nutritional classification scheme to (1) characterise nutritional profiles in children undergoing abdominal surgery and (2) characterise relationships between preoperative nutritional status and postoperative morbidity.

Design: This was a retrospective observational cohort study.

Dietary Choline Intake: Current State of Knowledge Across the Life Cycle.

Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g.

Milk Fat Globule Membrane Supplementation in Formula-fed Rat Pups Improves Reflex Development and May Alter Brain Lipid Composition.

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas.

Evaluation of A Concentrated Preterm Formula as a Liquid Human Milk Fortifier in Preterm Babies at Increased Risk of Feed Intolerance.

There are concerns around safety and tolerance of powder human milk fortifiers to optimize nutrition in preterm infants. The purpose of this study was to evaluate the tolerance and safety of a concentrated preterm formula (CPF) as a liquid human milk fortifier (HMF) for premature infants at increased risk of feeding intolerance. We prospectively enrolled preterm infants over an 18-month period, for whom a clinical decision had been made to add CPF to human milk due to concerns regarding tolerance of powder HMF.

-α-Tocopherol Is the Predominant Stereoisomer of α-Tocopherol in Human Milk.

Background: The naturally occurring α-tocopherol (α-T) stereoisomer, -α-tocopherol (-α-T), is known to be more bioactive than -α-tocopherol (-α-T), a synthetic racemic mixture of 8 stereoisomers. There is widespread use of -α-T in maternal supplements.

Objective: The aim of the study was to thoroughly describe the α-T stereoisomer profile of human milk.

Variations in plasma choline and metabolite concentrations in healthy adults.

Background: Plasma concentrations of choline and its metabolites might serve as biomarkers for the health outcomes of several pathological states such as cardiovascular disease and cancer. However, information about the reliability of biomarkers of choline status is limited. We investigated biological variations in repeated measures of choline and metabolites in healthy adults to assess them as biomarkers.

Plasma Betaine Is Positively Associated with Developmental Outcomes in Healthy Toddlers at Age 2 Years Who Are Not Meeting the Recommended Adequate Intake for Dietary Choline.

Background: Choline is an important nutrient during development. However, there are limited data on dietary choline intake and status in toddlers and the relation to neurodevelopmental outcomes.

Objective: This study assessed dietary choline intake and status in healthy toddlers at ages 1 and 2 y and determined the relation to neurodevelopmental outcomes.

Concentrations of Water-Soluble Forms of Choline in Human Milk from Lactating Women in Canada and Cambodia.

Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin.

Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy.

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood.

Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial.

Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers ( = 133) age 13.4 ± 0.

Relationships among Different Water-Soluble Choline Compounds Differ between Human Preterm and Donor Milk.

Choline is essential for infant development. Human milk choline is predominately present in three water-soluble choline (WSC) forms: free choline (FC), phosphocholine (PhosC), and glycerophosphocholine (GPC). It is unclear whether mother's own preterm milk and pooled donor milk differ in WSC composition and whether WSC compounds are interrelated.

Sex Hormone-Binding Globulin Reduction in Metabolic Disorders May Play a Role in NAFLD Development.

Low plasma sex hormone-binding globulin (SHBG) levels are a hallmark in chronic metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), which represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The functional link between altered SHBG production and NAFLD development and progression remains unclear. We investigated the effects of overexpressing human SHBG in 2 mouse models of NAFLD: a genetically induced double transgenic mouse and a diet-induced model.

Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition.