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Furthermore, convergent arrays of CTCF sites separate the left and right sections of TADs that harbour internal CTCF sites, resulting in unequal TAD 'halves'.

The orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome.

The orientation-based CTCF binding site cluster classification that we present reconciles TAD boundaries and CTCF site clusters in a mechanistically elegant fashion. This model suggests that the emergent structure of nuclear chromatin in the form of TADs relies on the obligate alternation of divergent and convergent CTCF site clusters that occur at different length scales along the genome.

Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.

We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBmary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

One reason that asthma remains poorly controlled in children is poor inhaler technique. Current guidelines recommend checking inhaler technique at each clinical visit. However, they do not specify how best to train children to mastery of correct inhaler technique. Currently, many children are simply shown how to use inhalers (brief intervention) which results in less than 50% with correct inhaler technique. The aim of this scoping review is to explore published literature on teaching methods used to train children to master correct inhaler technique.

This scoping review will follow the Arksey and O'Malley framework and the Joanna Briggs Institute guidelines. We will search (from inception onwards) MEDLINE, Embase, Scopus, Web of Science, CINAHL and the Cochrane library. We will include quantitative studies (e.g. Eganelisib supplier randomised controlled trials, cohort studies and case-control studies), published from the year 1956 to present, on teaching the skill of inhaler technique to children with asthma. Two reviewers will complete all screening and data abstraction independently. Data will be extracted onto a data charting table to create a descriptive summary of the results. Data will then be synthesised with descriptive statistics and visual mapping.

This scoping review will provide a broad overview of currently used educational methods to improve inhaler technique in children with asthma. The analysis will allow us to refine future research in this area by focusing on the most effective methods and optimising them.

Open Science Framework ( osf.io/n7kcw ).

Open Science Framework ( osf.io/n7kcw ).

Indigenous communities are often portrayed from a deficit-based lens; however, Indigenous communities have self-determined perspectives of health and well-being that are strength based. The objective of this study will be to systematically map the literature on perspectives, concepts, and constructs of wellness and well-being in Indigenous communities in Canada.

A scoping review protocol was designed following the Arksey and O'Malley framework. We will search the following electronic databases (from inception onwards) MEDLINE, EMBASE, Web of Science, CINAHL, Academic Search Complete, Anthropology Plus, Bibliography of Native North Americans, Canadian Business and Current Affairs, and Circumpolar Health Bibliographic Database. Grey literature will be identified through searching dissertation databases, Google Scholar, and conference abstracts. We will include all types of literature in English, published and unpublished, including any study design, reviews and meta-analyses, dissertations, reports, and boo Canada. We anticipate the study will contribute to improve our understanding of how Indigenous communities conceptualize and embody wellness. Our findings will provide a basis for engaging Indigenous stakeholders in future health research and informing future interpretations of how wellness is conceptualized, whether written or unwritten.

There is a promising outlook regarding the potential effect of spinach-derived thylakoids in the management of obesity and its associated metabolic disturbances. This research aimed to evaluate the effects of spinach-derived thylakoids supplementation combined with a calorie-restricted diet on anthropometric and metabolic profiles in obese women with the polycystic ovary syndrome (PCOS).

In a 12-week double-blind placebo-controlled randomized clinical trial, 48 females with obesity and PCOS were randomly allocated into either intervention (5 g/day thylakoid) or placebo (5 g/day cornstarch) groups along with calorie-restricted diets. Anthropometric measures, physical activity levels, dietary intakes, insulin resistance markers, as well as serum levels of insulin, fasting blood glucose (FBG), non-esterified fatty acids (NEFA), and sex hormones including dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and free androgen index (FAI) were evaluated pre-and post-intervention.

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