Everyday Needs Assessment for Cognitive Tasks: Challenges for Persons With Cognitive Impairment

ENACT (Everyday Needs Assessment for Cognitive Tasks) is an exploration and discovery project to gather information on challenges in daily and community living experienced by individuals aging with compromised cognition due to mild cognitive impairment, traumatic brain injury, or post-stroke. We are exploring their challenges through a longitudinal needs assessment study involving interviews with older adults with cognitive impairment and their care partners. We will describe the study development process wherein we interviewed subject matter experts, including persons with professional (neurology, rehabilitation, gerontology) or personal experience with individuals who have cognitive impairment. Based on their collective insights, we selected the following categories of activities for the ENACT in-depth interviews: health, social engagement, transportation, domestic life, and leisure/recreation. The ENACT longitudinal data will provide insights to guide development of adaptive, context-sensitive technology-based supports for the AUGMENT, DREAM, and STRUMM projects described in this symposium, as well as other initiatives.

HLA-A*03:01 is associated with increased risk of fever, chills, and more severe reaction to Pfizer-BioNTech COVID-19 vaccination

COVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the US have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination. Our GWAS identifies an association between severe vaccine side effects and HLA-A*03:01. This association was statistically significant only for those who received the Pfizer-BioNTech vaccine (BNT162b2; p=4.70E-11), but showed a trending association in those who received the Moderna vaccine (mRNA-1273; p=0.005) despite similar sample sizes for study. In Pfizer-BioNTech recipients, HLA-A*03:01 was associated with a two-fold increase in risk of severe vaccine side effects. The effect was consistent across ages, sexes, and whether the person had previously had a COVID-19 infection. The reactions experienced by HLA-A*03:01 carriers were driven by associations with chills, fever, fatigue, and in general feeling unwell.

The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae

Neisseria gonorrhoeae infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus Neisseria also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic Neisseria species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the N. mucosa species group displayed activity against other Neisseria in delayed antagonism assays; three of these were active against N. gonorrhoeae. The antimicrobial compound secreted by N. mucosa NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of N. gonorrhoeae. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown N. mucosa NRL 9300. These data suggest N. mucosa produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.

grünifai: interactive multiparameter optimization of molecules in a continuous vector space

Summary Optimizing small molecules in a drug discovery project is a notoriously difficult task as multiple molecular properties have to be considered and balanced at the same time. In this work, we present our novel interactive in silico compound optimization platform termed grünifai to support the ideation of the next generation of compounds under the constraints of a multiparameter objective. grünifai integrates adjustable in silico models, a continuous representation of the chemical space, a scalable particle swarm optimization algorithm and the possibility to actively steer the compound optimization through providing feedback on generated intermediate structures. Availability and implementation Source code and documentation are freely available under an MIT license and are openly available on GitHub (https://github.com/jrwnter/gruenifai). The backend, including the optimization method and distribution on multiple GPU nodes is written in Python 3. The frontend is written in ReactJS.

COVID-19: A Brief Overview of the Discovery Clinical Trial

The outbreak of COVID-19 is leading to a tremendous search for curative treatments. The urgency of the situation favors a repurposing of active drugs but not only antivirals. This short communication focuses on four treatments recommended by WHO and included in the first clinical trial of the European Discovery project.

Why African Americans Say “No”: A Study of Pharmacogenomic Research Participation

Objective: To identify reasons for nonpar­ticipation by African Americans in cardio­vascular pharmacogenomic research.Design: Prospective, open-ended, qualita­tive survey.Setting: Research staff approached patients eligible for the Discovery Project of The African American Cardiovascular pharma­cogenomics CONsorTium in the inpatient or outpatient setting at four different institu­tions during September and October 2018.Participants: Potential Discovery Proj­ect participants self-identified as African American, aged >18 years, were on one of five cardiovascular drugs of interest, and de­clined enrollment in the Discovery Project.Methods: After declining participation in the Discovery Project, patients were asked, “What are your reasons for not participat­ing?” We analyzed their responses using a directed content analytic approach. Ultimately, responses were coded into one of nine categories and analyzed using descriptive statistics.Main Outcome Measures: Reasons for nonparticipation.Results: Of the 194 people approached for the Discovery Project during an eight-week period, 82 declined participation and provided information for this study. The most common reason for refusal was concern about the amount of blood drawn (19.5%). The next most common reasons for refusal to participate included concerns about genetic testing (14.6%) and mistrust of research (12.2%). Across study sites, significantly more patients enrolled in the inpatient than outpatient setting (P<.001). Significantly more women and younger individuals declined participation due to concerns about genetic testing and too little compensation (P<.05).Conclusions: Collection of blood samples and concerns about genetic testing are ob­stacles for the recruitment of African Ameri­cans to pharmacogenomics studies. Efforts to overcome these barriers to participation are needed to improve representation of minorities in pharmacogenomic research. Enrolling participants from inpatient populations may be a solution to bolster recruitment efforts.Ethn Dis. 2020;30(Suppl 1):159-166; doi:10.18865/ed.30.S1.159