Comparative Analysis of NCLEX-RN Questions: A Duel Between ChatGPT and Human Expertise.

BACKGROUND: Artificial intelligence (AI) has the potential to revolutionize nursing education. This study compared NCLEX-RN questions generated by AI and those created by nurse educators. METHOD: Faculty of accredited baccalaureate programs were invited to participate. Likert-scale items for grammar and clarity of the item stem and distractors were compared using Mann-Whitney U, and yes/no questions about clinical relevance and complex terminology were analyzed using chi-square. A one-sample binomial test with confidence intervals evaluated participants' question preference (AI-generated or educator-written). Qualitative responses identified themes across faculty. RESULTS: Item clarity, grammar, and difficulty were similar for AI and educator-created questions. Clinical relevance and use of complex terminology was similar for all question pairs. Of the four sets with preference for one item, three were generated by AI. CONCLUSION: AI can assist faculty with item generation to prepare nursing students for the NCLEX-RN examination. Faculty expertise is necessary to refine questions written using both methods. [J Nurs Educ. 2023;62(12):679-687.].

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Social Justice in Nursing Education: A Way Forward.

BACKGROUND: Systemic racism and inequity are embedded in higher education, especially in nursing. By disregarding health disparities and inequities, a hidden curriculum is endorsed, implicitly letting both instructors and students know that not addressing these subjects is acceptable. METHOD: Needs assessments were performed to assess faculty and student attitudes about the needs for justice, equity, diversity, and inclusion (JEDI) concepts. Using the Plan-Do-Study-Act model, the School of Nursing leadership, faculty, and students created taskforces to implement anti-oppression curricula throughout prelicensure courses. RESULTS: Anti-oppression curricula and workshops were piloted successfully in the first semester of prelicensure nursing. Student feedback was positive with constructive suggestions. JEDI curriculum mapping was completed across the prelicensure nursing curriculum. CONCLUSION: JEDI concepts must be integrated across nursing curricula to identify gaps. Forming a collaboration between leadership, faculty, and students is an optimal way to proceed as they all are invested and accountable for change. [J Nurs Educ. 2022;61(8):447-454.].

Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.

Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids.

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.

The power of genetic diversity in genome-wide association studies of lipids.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.

Fine-scale population structure and demographic history of British Pakistanis.

Previous genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genotype chip data from 2,200 British Pakistanis. We reveal strong recent population structure driven by the biraderi social stratification system. We find that all subgroups have had low recent effective population sizes (Ne), with some showing a decrease 15‒20 generations ago that has resulted in extensive identity-by-descent sharing and homozygosity, increasing the risk of recessive disorders. Our results from two orthogonal methods (one using machine learning and the other coalescent-based) suggest that the detailed reporting of parental relatedness for mothers in the cohort under-represents the true levels of consanguinity. These results demonstrate the impact of cultural practices on population structure and genomic diversity in Pakistanis, and have important implications for medical genetic studies.

Implementation and Evaluation of an Acute Care Multicomponent Intervention for Dementia-Related Behavioral Expressions.

Despite the high prevalence and negative outcomes associated with poorly managed dementia-related behavioral expressions (BE) during hospitalization, evidence-based interventions for BE management in acute care environments are lacking. To address this gap, we designed, implemented, and evaluated feasibility, utility, and exploratory nurse and patient outcomes associated with a low-cost, nurse-led multicomponent decision support intervention-the Personalized Approach and Targeted Interventions (PROACTIVE) Treatment Approach-which was implemented as a quality improvement program and evaluated with a historical matched comparison group. The intervention was feasibly implemented and improved nurse-sensitive outcomes (stress, confidence), practices (use of nonpharmacological approaches) for BE management, and perceived utility of intervention resources. Patients receiving the PROACTIVE Treatment Approach (N = 40) had higher rates of acetaminophen use, and shorter lengths of stay (N = 40). More rigorous evaluation is needed to better determine optimal implementation strategies and intervention impact. [Journal of Gerontological Nursing, 47(9), 21-30.].

Nursing student experiences of remote learning during the COVID-19 pandemic.

BACKGROUND: The emergence of the COVID-19 pandemic resulted in a sudden transition to remote learning. These circumstances presented many challenges for higher education faculty and students around the world but especially for nursing education programs which are traditionally conducted in a face-to-face learning environment that includes hands-on experiential learning. METHODS: Guided by Meleis' Transition Theory, a qualitative descriptive design was utilized to explore prelicensure nursing students' experiences of the transition to remote learning during the Spring 2020 semester. Participants were recruited from one baccalaureate program in the Pacific Northwestern United States. Interviews were conducted and transcribed using a web conferencing platform. Data were analyzed using Colaizzi's phenomenological reduction. RESULTS: Eleven students participated. Interviews revealed four overarching themes: technological challenges, academic relationship changes, role stress and strain, and resilience. CONCLUSION: The sudden transition to remote learning resulted in a number of challenges for nursing students. Despite these challenges, students demonstrated a remarkable sense of resilience and perseverance. Faculty have an opportunity to address student stressors and design remote courses in such a way to facilitate student engagement and community building.

Pulsed-Field Gel Electrophoresis (PFGE) Analysis of Listeria monocytogenes.

PFGE is a valuable tool for assessing L. monocytogenes strain interrelatedness. It is based on the study of total bacterial DNA restriction patterns. Cells are embedded in agarose plugs before being lysed. The released DNA is then digested into large fragments by restriction enzymes. As DNA fragments are too large to be separated by traditional electrophoresis in an agarose gel, changes in the direction of the electrical current are periodically applied in order to allow the proper migration of large DNA fragments. Strains are characterized by the obtained DNA fragment patterns or pulsotypes which vary depending on the number and size of bands.

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

Characterising a healthy adult with a rare HAO1 knockout to support a therapeutic strategy for primary hyperoxaluria.

By sequencing autozygous human populations, we identified a healthy adult woman with lifelong complete knockout of HAO1 (expected ~1 in 30 million outbred people). HAO1 (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n = 67). Plasma metabolomics and lipidomics (1871 biochemicals) revealed 18 markedly elevated biochemicals (>5 sd outliers versus n = 25 controls) suggesting additional HAO1 effects. Comparison with lumasiran preclinical and clinical trial data suggested she has <2% residual glycolate oxidase activity. Cell line p.Leu333SerfsTer4 expression showed markedly reduced HAO1 protein levels and cellular protein mis-localisation. In this woman, lifelong HAO1 knockout is safe and without clinical phenotype, de-risking a therapeutic approach and informing therapeutic mechanisms. Unlocking evidence from the diversity of human genetic variation can facilitate drug development.

Challenge Studies to Determine the Ability of Foods to Support the Growth of Listeria monocytogenes.

: Listeria monocytogenes is a foodborne pathogen that causes listeriosis, a relatively rare, but potentially fatal, disease, with a mortality rate of 20⁻30%. In general, European Regulations require the absence of L. monocytogenes in five samples of 25 g before the food has left the producer, but if the food has been demonstrated not to support the growth of L. monocytogenes, up to 100 cfu g-1 are allowed in the food (except for foods for infants or medical purposes) during its shelf-life under reasonably foreseeable storage conditions. It is important for food producers to determine if their food supports the growth of L. monocytogenes. The European Union Reference Laboratory for L. monocytogenes published a Technical Guidance document for conducting shelf-life studies on L. monocytogenes in ready-to-eat foods in June 2014. Primarily based on the EURL guidance document for conducting challenge studies, the ability of cheese (feta and soft goat's milk cheese), cold-smoked salmon, coleslaw, and pork pate to support the growth of L. monocytogenes was determined using a starting inoculum of approximately 100 cfu g-¹. The cheese and pork pate were incubated at 8 °C for 14 days; the smoked salmon was incubated at 6 °C for 5 days and 8°C for 9 days; and the coleslaw was incubated at 8 °C for 7 days and 12 °C for 14 days. The results showed that the smoked salmon and pork pate supported growth, while coleslaw and cheese did not. From this study, it is evident that there are factors in food other than pH, water activity, and total bacterial count (TBC) that can inhibit the ability of L. monocytogenes to grow in food.

A 3-year multi-food study of the presence and persistence of Listeria monocytogenes in 54 small food businesses in Ireland.

The problem of assessing the occurrence of the food-borne pathogen Listeria monocytogenes in the food chain, and therefore the risk of exposure of the human population, is often challenging because of the limited scope of some studies. In this study the occurrence of L. monocytogenes in food from four major food groups, dairy products, meats, seafood and vegetables, and associated food processing environments in Ireland was studied over a three-year period. Fifty-four small food businesses participated in the study and sent both food and environmental samples every 2months between 2013 and 2015. L. monocytogenes was isolated using the ISO11290 standard method. Confirmation of L. monocytogenes and identification of serogroups were achieved using a multiplex PCR assay, and for some isolates serotype was determined using commercial antisera. Pulsed- field gel electrophoresis (PFGE) analysis was performed on all isolates allowing the relatedness of isolates from different food businesses to be compared nationwide. In total, 86 distinct pulsotypes were identified. The overall occurrence of L. monocytogenes in food samples was 4.2%, while in environmental samples it was 3.8%. In general, the occurrence of L. monocytogenes in food businesses decreased over the course of the study, presumably reflecting increased awareness and vigilance. The majority of the pulsotypes detected were unique to a particular food group (63/86), while only three pulsotypes were found in all four food groups investigated. The highest occurrence in food was found in the meat category (7.5%) while seafood had the lowest rate of occurrence (1.8%). Seventeen of the pulsotypes detected in the study were persistent, where persistence was defined as repeated isolation from a single facility with a minimum time interval of 6months. Using PFGE, 11 of the pulsotypes identified in this study were indistinguishable from those of 11 clinical isolates obtained from patients in Ireland over the last 4years, highlighting the fact that these pulsotypes are capable of causing disease. Overall, the study shows the diversity of L. monocytogenes strains in the Irish food chain and highlights the ability of many of these strains to persist in food processing environments. The finding that a significant proportion of these pulsotypes are also found in clinical settings highlights the need for continued vigilance by food producers, including frequent sampling and typing of isolates detected.

Health and population effects of rare gene knockouts in adult humans with related parents.

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.

Complete Genome Sequence of Listeria monocytogenes Strain DPC6895, a Serotype 1/2b Isolate from Bovine Raw Milk.

Listeria monocytogenes is a foodborne pathogen and is the causative agent of listeriosis among humans and animals. The draft genome sequence of L. monocytogenes DPC6895, a serotype 1/2b strain isolated from the raw milk of a cow with subclinical bovine mastitis, is reported.