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Molecular vaccines comprising antigen peptides and inflammatory cues make up a class of therapeutics that promote immunity against cancer and pathogenic diseases but often exhibit limited efficacy. Here, we engineered an antigen peptide delivery system to enhance vaccine efficacy by targeting dendritic cells and mediating cytosolic delivery. The delivery system consists of the nontoxic anthrax protein, protective antigen (PA), and a single-chain variable fragment (scFv) that recognizes the XCR1 receptor on dendritic cells (DCs). Combining these proteins enabled selective delivery of the N-terminus of lethal factor (LFN) into XCR1-positive cross-presenting DCs. Incorporating immunogenic epitope sequences into LFN showed selective protein translocation in vitro and enhanced the priming of antigen-specific T cells in vivo. Administering DC-targeted constructs with tumor antigens (Trp1/gp100) into mice bearing aggressive B16–F10 melanomas improved mouse outcomes when compared to free antigen, including suppressed tumor growth up to 58% at 16 days post tumor induction (P < 0.0001) and increased survival (P = 0.03). These studies demonstrate that harnessing DC-targeting anthrax proteins for cytosolic antigen delivery significantly enhances the immunogenicity and antitumor efficacy of cancer vaccines.

As the complexity of products and their development processes increases, a trend emerged where companies try to manage the complexity through implementing agile practices on all or on some levels of the development process. It is not yet clear if an agile approach is the solution or under which circumstances it can be most effective in the development of physical products. This paper aims to compile the information from existing empirical and meta-studies to give an overview of the strengths and weaknesses of conventional, agile and hybrid paradigms.

Background Diatoms, a keystone phylum in Earth’s ecosystems, are responsible for substantial oxygen production and the fixation of carbon dioxide in the form of carbohydrates that fuel global food webs. They host diverse prokaryotes, yet how diatoms preferentially recruit those with complementary metabolic traits remains unknown. Results We discovered that diatoms exude a C6-sulfated α-1,3-mannan that serves as a selective carbon source for adapted Polaribacter . Its structure was resolved using NMR spectroscopy, chromatography, chemical synthesis, and enzymatic dissection. Biochemical, physiological, and structural analyses demonstrated, that specialized Bacteroidota employ a four-enzyme pathway to metabolize this glycan. Metagenomic and transcriptomic data revealed that sulfated mannan utilization loci are globally abundant and actively expressed in surface ocean bacterioplankton. Because this mannan provides only carbon, oxygen, sulfur, and hydrogen, bacteria must obtain other essential elements elsewhere, reinforcing metabolic interdependence. Conclusions Together, these results define a chemically specific interaction between diatoms and specialized bacteria that is mediated by a single sulfated polysaccharide and a dedicated four-enzyme degradation pathway. Presence of this pathway in marine metagenomes and transcriptomes indicates that a sulfated mannan from diatoms exerts selection pressure in the sunlit ocean microbiome. 5kCwS6BEacZCaPFxt1T7DN Video Abstract

Abstract Alternative splicing is a major contributor to transcriptome and proteome diversity in health and disease. A plethora of tools have been developed for studying alternative splicing in RNA-seq data. Previous benchmarks focused on isoform quantification and mapping. They neglected event detection tools, which arguably provide the most detailed insights into the alternative splicing process. DICAST offers a modular and extensible framework for analysing alternative splicing integrating eleven splice-aware mapping and eight event detection tools. We benchmark all tools extensively on simulated as well as whole blood RNA-seq data. STAR and HISAT2 demonstrated the best balance between performance and run time. The performance of event detection tools varies widely with no tool outperforming all others. DICAST allows researchers to employ a consensus approach to consider the most successful tools jointly for robust event detection. Furthermore, we propose the first reporting standard to unify existing formats and to guide future tool development.

Background: Recommendations for health care institutions to evaluate the effectiveness of nurse internship programs in facilitating the acquisition of an interprofessional collaborative practice exist. This pilot project explored the effectiveness of simulation-based education compared with online education on inter-professional socialization and collaboration among newly licensed RNs transitioning into medical-surgical practice. Method: An experimental repeated-measures design examined professional nursing practice attributes of values, attitudes, and behaviors along with interprofessional collaboration core competencies. Participants (n = 29) were randomized into either a control group (nurse internship with online interprofessional education) or an experimental group (nurse internship with simulation-based interprofessional education). Results: Changes in interprofessional role socialization and valuing occurred as measured by the Interprofessional Socialization and Valuing Scale. Interprofessional Collaborative Competency Attainment Survey data demonstrated a change in interprofessional collaboration. Conclusion: Findings support how educators in the health care setting can consider the integration of interprofessional education teaching methodologies into nurse internship programs. [J Contin Educ Nurs. 2020;51(7):331–337.]

This article reports how one pilot project explored prelicensure baccalaureate nursing students' perceptions of peer-assisted learning combined with simulation-based education to prepare for and enhance readiness for programmatic exit and national examinations. A convergent parallel mixed-methods study design was used to address the research questions. A nonprobability convenience purposive sample of 17 prelicensure baccalaureate nursing students enrolled in a programmatic synthesis course participated. Findings demonstrate how prelicensure nursing students, despite experiencing varied levels of anxiety, are ready to engage in peer-assisted learning strategies that incorporate simulation-based education to gain additional preparation for both programmatic and licensure examinations. In an era where hospitals are onboarding newly licensed nurses with simulation, hospital educators and specialists in the health care industry can look to the literature on anxiety and teaching preferences to determine opportunities to integrate peer learning and simulation within transition into practice programs. [ J Contin Educ Nurs. 2019;50(3):115–120.]

Background Aicardi-Goutières syndrome (AGS) is a severe familial, mostly autosomal recessive encephalopathy, first described in 1984. The clinical picture and genetic abnormalities are heterogeneous. US findings in AGS have thus far not been systematically described. Objective The purpose of this study was to analyse sonographic features in AGS and to compare them to CT/MRI. Materials and methods Four male infants with AGS, two brothers, underwent imaging between the ages of 4 weeks and 6 months. Results Sonographically isolated mineralization of lenticulostriate vessels, dilatation of the lateral ventricles, subependymal cysts, and diffuse and focal hyperechogenicity of the periventricular white matter and basal ganglia, respectively, were the abnormal findings, that may be present even before the development of major neurological symptoms. Conclusion Early cranial US is able to visualize the whole spectrum of cerebral anomalies in AGS: calcifying microangiopathy, white matter disease and unusual subependymal cysts. The imaging pattern is similar to that of congenital viral infection of the central nervous system, which may mislead the genetic counseling.

The Patient Protection and Affordable Care Act increased numbers of insured individuals and demands for health care cost reductions. A national call for nursing education to focus on health promotion activities exists. Nurse educators can address this shift in health care by including motivational interviewing (MI), a health promotion technique, in the curriculum. This exploratory descriptive pilot survey examined postlicensure nursing students' perceptions and self-reported behaviors following an online synchronous telehealth simulation-based experience in which they practiced MI. The survey yielded a 45% (n = 10) response rate. All participants agreed the experience was beneficial to their learning and provided insights on a new clinical practice environment. Eighty percent of participants would have liked to have learned MI in their prelicensure program, and 50% of participants have integrated it in their current practice. This tele-health simulation-based experience positively affected the learning and behaviors of postlicensure nursing students. [J Nurs Educ. 2019;58(4):221-224.].

•Transition into practice with simulation-based education was explored.•Themes of Gaining Comfort with Relationships and Talking It Out were evident.•Newly licensed registered nurses need guidance with role socialization.•The simulated environment encouraged the development of collective competence.

This paper aims to describe how the Nominal Group Technique was applied to obtain focused content to develop medication administration error scenarios for future use to educate practicing RNs with immersive virtual reality simulation. In the United States, medication errors account for up to $46 million in daily loss to hospital operational budgets. Each phase of prescribing, dispensing, administration, monitoring, and reconciliation is crucial in reducing potentially life-threatening outcomes associated with medication errors. Registered Nurses are responsible for safely administering diverse classifications of medications to patients in various healthcare settings. However, human and system factors can contribute to the exposure of hospitalized patients to a medication error. Virtual reality simulation-based education can be a methodology to educate practicing Registered Nurses on safe medication practices. A Nominal Group Technique process was used to generate consensus from participating Registered Nurses on human and system factors that can contribute to medication administration errors. The process consisted of (a) preparation, (b) running the group with an introduction of the subject, (c) generation of ideas, (d) listing of ideas, (e) discussion of ideas, (f) ranking of top ideas, (g) voting on top ideas, (h) discussion of the vote outcome, and (i) re-ranking and rating the top items. Human and system factor idea items encompassed medication errors during ordering, prescribing, or administering medications. Both novice and experienced Registered Nurses rank-ordered these factors as those most likely to encounter or which would most likely occur during one working shift. Descriptive statistics of frequencies and percentages were used to analyze the findings when grouped by human and system factor categories. Non-parametric testing with a Kruskal-Wallis test was conducted to compare the human and system factors by categories and years of Registered Nurse experience. Findings revealed that the factors of Time Management: getting behind, hurried, urgent (KW-H 11.2, df 4, p = .025) and Right Medication: medications have similar look and sound-alike names (KW-H 11.1, df 4, p = .025) impacted safe medication administration for both the novice and experienced nurse. The NGT process identified human and system factors contributing to errors and impacting safe medication administration practices. Findings will support the creation of medication administration scenarios for use with immersive virtual reality simulation. •Training to improve the practice of medication administration safety is warranted.•Registered nurses can use a Nominal Group Technique for generating consensus.•Topics to teach medication administration with virtual reality were identified.