Disentangling the temporal relationship between alcohol-related attitudes and heavy episodic drinking in adolescents within a randomized controlled trial.

Background And Aims: Within many alcohol prevention interventions, changes in alcohol-related attitudes (ARA) are often proposed as precursors to changes in drinking behaviour. This study aimed to measure the longitudinal relationship between ARA and behaviour during the implementation of a large-scale prevention trial.

Design And Setting: This study was a two-arm school-based clustered randomized controlled trial.

Suspended Tissue Open Microfluidic Patterning (STOMP).

Cell-laden hydrogel constructs suspended between pillars are powerful tools for modeling tissue structure and physiology, though current fabrication techniques often limit them to uniform compositions. In contrast, tissues are complex in nature with spatial arrangements of cell types and extracellular matrices. Thus, we present Suspended Tissue Open Microfluidic Patterning (STOMP), which utilizes a removable, open microfluidic patterning channel to pattern multiple spatial regions across a single suspended tissue.

Engineered Heart Tissues for Standard 96-Well Tissue Culture Plates.

Engineered heart tissues (EHTs) have been shown to be a valuable platform for disease investigation and therapeutic testing by increasing human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) maturity and better recreating the native cardiac environment. The protocol detailed in this chapter describes the generation of miniaturized EHTs (mEHTs) incorporating hiPSC-CMs and human stromal cells in a fibrin hydrogel. This platform utilizes an array of silicone posts designed to fit in a standard 96-well tissue culture plate.

Targeted CRISPR activation is functional in engineered human pluripotent stem cells but undergoes silencing after differentiation into cardiomyocytes and endothelium.

Human induced pluripotent stem cells (hiPSCs) offer opportunities to study human biology where primary cell types are limited. CRISPR technology allows forward genetic screens using engineered Cas9-expressing cells. Here, we sought to generate a CRISPR activation (CRISPRa) hiPSC line to activate endogenous genes during pluripotency and differentiation.

Reliability and Validity of a Multidimensional Measure of Subjective Community Well-Being.

An individual's flourishing is sustained by and dependent on their community's well-being. We provide one of the first studies of a measure of communal subjective well-being, focusing on individuals' relationships with their community. Using two samples from the Greater Columbus, Ohio region, we provide evidence of the reliability and validity of the Subjective Community Well-being (SCWB) assessment.

Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation.

Integrating marine debris into socioeconomic monitoring: Informing local actions in Minicoy Island, India and charting a new global approach.

In 2019, the authors introduced the topic of anthropogenic marine debris into the Global Socioeconomic Monitoring Initiative for Coastal Management (SocMon) during an assessment conducted at Minicoy Island in India. SocMon is a process-based approach and set of tools for conducting community-based socio-economic monitoring of changes in coastal communities that has been adopted and adapted worldwide through the Global SocMon network. It provides an experiential learning opportunity that often leads to community driven action.

A multimodal analysis of genomic and RNA splicing features in myeloid malignancies.

RNA splicing dysfunctions are more widespread than what is believed by only estimating the effects resulting by splicing factor mutations (SF) in myeloid neoplasia (MN). The genetic complexity of MN is amenable to machine learning (ML) strategies. We applied an integrative ML approach to identify co-varying features by combining genomic lesions (mutations, deletions, and copy number), exon-inclusion ratio as measure of RNA splicing (percent spliced in, PSI), and gene expression (GE) of 1,258 MN and 63 normal controls.

Full-length dystrophin deficiency leads to contractile and calcium transient defects in human engineered heart tissues.

Cardiomyopathy is currently the leading cause of death for patients with Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys. Animal models have provided insight into the mechanisms by which dystrophin protein deficiency causes cardiomyopathy, but there remains a need to develop human models of DMD to validate pathogenic mechanisms and identify therapeutic targets. Here, we have developed human engineered heart tissues (EHTs) from CRISPR-edited, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) expressing a truncated dystrophin protein lacking part of the actin-binding domain.

Antiplatelet Therapy in Acute Myocardial Infarction and Cardiogenic Shock: Insights From the National Cardiogenic Shock Initiative.

Background: Patients presenting with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) are at high risk for impaired antiplatelet activity secondary to malabsorption, systemic hypoperfusion, hypothermia, need for mechanical ventilation, and high use of analgesics. The use of antiplatelet therapy in these high-risk patients is not well studied.

Methods: Using the National Cardiogenic Shock Initiative database, we analyzed patients who presented with AMI-CS at 60 hospitals from March 2018 to December 2020.

Intervention impact on alcohol use, alcohol harms, and a combination of both: A latent class, secondary analysis of results from a randomized controlled trial.

Background: Alcohol use and alcohol-related harm (ARH) among adolescents places a substantial burden on health, and public services more generally. To date, attempts to intervene at a universal level have yielded results varying from iatrogenic to null, although some skill-enhancing universal interventions have successfully impacted drinking behaviors. One such intervention is SHAHRP.

Germline DDX41 mutations cause ineffective hematopoiesis and myelodysplasia.

DDX41 mutations are the most common germline alterations in adult myelodysplastic syndromes (MDSs). The majority of affected individuals harbor germline monoallelic frameshift DDX41 mutations and subsequently acquire somatic mutations in their other DDX41 allele, typically missense R525H. Hematopoietic progenitor cells (HPCs) with biallelic frameshift and R525H mutations undergo cell cycle arrest and apoptosis, causing bone marrow failure in mice.

Exploration of Diet Quality by Obesity Severity in Association with Gestational Weight Gain and Distal Gut Microbiota in Pregnant African American Women: Opportunities for Intervention.

Objective: To conduct an exploratory examination of dietary patterns and quality during pregnancy in African-American women who were class I, II, or III obese, and those women with normal pre-pregnancy body mass index (pBMI), as well to identify dietary factors associated with GWG, and changes in the distal gut microbiome. African American women represent the largest group affected by pre-pregnancy obesity, a risk factor for several adverse birth outcomes.

Methods: This prospective study investigated the association between diet, distal gut microbiome, and GWG among African-American women (n = 21) with obesity (n = 15) compared to women with a normal pre-pregnancy body mass index (pBMI) (n = 6) at two time points, 27-29 and 37-39 weeks gestation.

Body image and antiretroviral therapy adherence among people living with HIV: a protocol for a systematic review and meta-analysis.

Introduction: Adherence to antiretroviral therapy (ART) remains a key challenge to achieving the fast-track goal of ending the HIV epidemic by 2030. To provide a more comprehensive indication of whether interventions designed to promote ART adherence might benefit from targeting body image perceptions, we aim to conduct a systematic review to synthesise existing evidence on the association between body image and ART adherence.

Methods And Analysis: A systematic review of peer-reviewed observational studies and randomised controlled trials that have investigated the association between body image and adherence to ART will be performed.

Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms.

Vertebrates have evolved three paralogs, termed LUC7L, LUC7L2, and LUC7L3, of the essential yeast U1 small nuclear RNA (snRNA)-associated splicing factor Luc7p. We investigated the mechanistic and regulatory functions of these putative splicing factors, of which one (LUC7L2) is mutated or deleted in myeloid neoplasms. Protein interaction data show that all three proteins bind similar core but distinct regulatory splicing factors, probably mediated through their divergent arginine-serine-rich domains, which are not present in Luc7p.

Excessive R-loops trigger an inflammatory cascade leading to increased HSPC production.

Hematopoietic stem and progenitor cells (HSPCs) arise during embryonic development and are essential for sustaining the blood and immune systems throughout life. Tight regulation of HSPC numbers is critical for hematopoietic homeostasis. Here, we identified DEAD-box helicase 41 (Ddx41) as a gatekeeper of HSPC production.

Metabolic Health, Obesity, and Cardiovascular Disease: 2015-2016 National Health and Nutrition Examination Survey.

Background: The metabolically unhealthy normal weight (MUN) and metabolically healthy obese (MHO) phenotypes are abnormal metabolic states. The purpose of this study was to report the frequency of the strictly defined MHO and MUN phenotypes and the association between metabolic phenotype and 10-year Framingham cardiovascular disease (CVD) risk score using a sample taken from the 2015-2016 National Health and Nutrition Examination Survey.

Methods: A cross-sectional sample of 2,316 participants age 18-79 years with complete metabolic health information were selected from the 2015-2016 dataset and included in the present analysis.

Complex landscape of alternative splicing in myeloid neoplasms.

Myeloid neoplasms are characterized by frequent mutations in at least seven components of the spliceosome that have distinct roles in the process of pre-mRNA splicing. Hotspot mutations in SF3B1, SRSF2, U2AF1 and loss of function mutations in ZRSR2 have revealed widely different aberrant splicing signatures with little overlap. However, previous studies lacked the power necessary to identify commonly mis-spliced transcripts in heterogeneous patient cohorts.

Culturally Relevant Resilience: A Psychometric Meta-Analysis of the Child and Youth Resilience Measure (CYRM).

Measuring key components of resilience is vital for understanding cross-cultural dynamics among youth and the environment. The Child and Youth Resilience Measure (CYRM-28) was developed as a cross-cultural measure of resilience and has been used globally. To examine the cross-cultural utility of the CYRM-28, we conducted a systematic review of the literature reporting on the psychometric properties of the measure.

Clinical interpretation of variants identified in RNU4ATAC, a non-coding spliceosomal gene.

Biallelic variants in RNU4ATAC, a non-coding gene transcribed into the minor spliceosome component U4atac snRNA, are responsible for three rare recessive developmental diseases, namely Taybi-Linder/MOPD1, Roifman and Lowry-Wood syndromes. Next-generation sequencing of clinically heterogeneous cohorts (children with either a suspected genetic disorder or a congenital microcephaly) recently identified mutations in this gene, illustrating how profoundly these technologies are modifying genetic testing and assessment. As RNU4ATAC has a single non-coding exon, the bioinformatic prediction algorithms assessing the effect of sequence variants on splicing or protein function are irrelevant, which makes variant interpretation challenging to molecular diagnostic laboratories.

Developing and training mental toughness in sport: a systematic review and meta-analysis of observational studies and pre-test and post-test experiments.

Objective: To investigate the efficacy of interventions designed to train and develop mental toughness (MT) in sport.

Design: Systematic review and meta-analysis.

Data Sources: Journal articles, conference papers and doctoral theses indexed in Embase, Scopus, PubMed and SPORTDiscus from inception to 22 November 2019.

Comprehensive database and evolutionary dynamics of U12-type introns.

During nuclear maturation of most eukaryotic pre-messenger RNAs and long non-coding RNAs, introns are removed through the process of RNA splicing. Different classes of introns are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucleoprotein particles and associated proteins. We created intronIC, a program for assigning intron class to all introns in a given genome, and used it on 24 eukaryotic genomes to create the Intron Annotation and Orthology Database (IAOD).

An Examination of Sensitivity to Measurement Error in Rasch Residual-based Fit Statistics.

The purpose of this paper is to examine the sensitivity of commonly used Rasch fit measures to different distributions of error in item responses. Using Monte Carlo methods, we generated 10 different measurement error conditions within the Rasch rating scale model or partial credit model, and we recorded the estimates of INFIT MNSQ, OUTFIT MNSQ, and person separation reliability for each error distribution condition. INFIT MNSQ and OUTFIT MNSQ were not sensitive to error distributions when the distribution was the same across items.