Molecular cartooning with knowledge graphs.

Molecular "cartoons," such as pathway diagrams, provide a visual summary of biomedical research results and hypotheses. Their ubiquitous appearance within the literature indicates their universal application in mechanistic communication. A recent survey of pathway diagrams identified 64,643 pathway figures published between 1995 and 2019 with 1,112,551 mentions of 13,464 unique human genes participating in a wide variety of biological processes. Researchers generally create these diagrams using generic diagram editing software that does not itself embody any biomedical knowledge. Biomedical knowledge graphs (KGs) integrate and represent knowledge in a semantically consistent way, systematically capturing biomedical knowledge similar to that in molecular cartoons. KGs have the potential to provide context and precise details useful in drawing such figures. However, KGs cannot generally be translated directly into figures. They include substantial material irrelevant to the scientific point of a given figure and are often more detailed than is appropriate. How could KGs be used to facilitate the creation of molecular diagrams? Here we present a new approach towards cartoon image creation that utilizes the semantic structure of knowledge graphs to aid the production of molecular diagrams. We introduce a set of "semantic graphical actions" that select and transform the relational information between heterogeneous entities (e.g., genes, proteins, pathways, diseases) in a KG to produce diagram schematics that meet the scientific communication needs of the user. These semantic actions search, select, filter, transform, group, arrange, connect and extract relevant subgraphs from KGs based on meaning in biological terms, e.g., a protein upstream of a target in a pathway. To demonstrate the utility of this approach, we show how semantic graphical actions on KGs could have been used to produce three existing pathway diagrams in diverse biomedical domains: Down Syndrome, COVID-19, and neuroinflammation. Our focus is on recapitulating the semantic content of the figures, not the layout, glyphs, or other aesthetic aspects. Our results suggest that the use of KGs and semantic graphical actions to produce biomedical diagrams will reduce the effort required and improve the quality of this visual form of scientific communication.

Transitioning from Direct to Video Laryngoscopy during the COVID-19 Pandemic Was Associated with a Higher Endotracheal Intubation Success Rate.

OBJECTIVE: The objective of this study was to determine the effect of transitioning from direct laryngoscopy (DL) to video laryngoscopy (VL) on endotracheal intubation success overall and with enhanced precautions implemented during the COVID-19 pandemic. METHODS: We examined electronic transport records from Mayo Clinic Ambulance Service, a large advanced life support (ALS) provider serving rural, suburban, and urban areas in Minnesota and Wisconsin, USA. We determined the success of intubation attempts when using DL (March 10, 2018 to December 19, 2019), VL (December 20, 2019 to September 29, 2021), and VL with an enhanced COVID-19 guideline that restricted intubation to one attempt, performed by the most experienced clinician, who wore enhanced personal protective equipment (April 1 to December 18, 2020). Success rates at first attempt and after any attempt were assessed for association with type of laryngoscopy (VL vs DL) after adjusting for patient age group, patient weight, use of enhanced COVID-19 guideline, medical vs trauma patient, and ALS vs critical care clinician. A secondary analysis further adjusted for degree of glottic visualization. RESULTS: We identified 895 intubation attempts using DL and 893 intubation attempts using VL, which included 382 VL intubation attempts using the enhanced COVID-19 guideline. Success on first intubation attempt was 69.2% for encounters with DL, 82.9% overall with VL, and 83.2% with VL and enhanced COVID-19 protocols (DL vs overall VL: p < 0.001; COVID-19 vs non-COVID VL: p = 0.86). In multivariable analysis, use of VL was associate with higher odds of successful intubation on first attempt (odds ratio, 2.28; 95%CI, 1.73-3.01; p < 0.001) and on any attempt (odds ratio, 2.16; 95%CI, 1.58-2.96; p < 0.001) compared with DL. Inclusion of glottic visualization in the model resulted in a nonsignificant association between laryngoscopy type and successful first intubation (p = 0.41) and a significant association with the degree of glottic visualization (p < 0.001). CONCLUSIONS: VL is designed to improve glottic visualization. The use of VL by a large, U.S. multistate ALS ambulance service was associated with increased odds of successful first-pass and overall attempted intubation, which was mediated by better visualization of the glottis. COVID-19 protocols were not associated with success rates.

Emotional Appetite Questionnaire: psychometric properties in Brazilian adult samples before and after the COVID-19 pandemic onset.

Background: Appetite represents a desire of a person to eat specific food in order to reach satisfaction and pleasure states. This desire may be associated with the experience of negative or positive emotions (emotional appetite). Emotional appetite can influence eating behavior, and its investigation is relevant to avoid possible damage to health resulting from a disordered eating. Objectives: To adapt the Emotional Appetite Questionnaire (EMAQ) to the Portuguese language; to assess the validity and reliability of the data; and to assess emotional appetite in three samples of adults collected before and after the outbreak of the COVID-19 pandemic. Methods: This is a cross-sectional study with non-probabilistic convenience sampling. The Portuguese version of the EMAQ was presented after translation, back-translation, and content analysis. Two studies were conducted, the first before and the second after the pandemic onset. Three samples were formed (2019: Sample 1 (age = 19.7 ± 1.5 years) n = 323; 2020: Sample 2 (age = 21.3 ± 1.8 years) n = 1,011; and Sample 3 (age = 28.9 ± 3.1 years) n = 909). An exploratory strategy with parallel analysis was performed. The analyses were conducted in FACTOR and R (lavaan and semTools packages) software. After determining the best-fit model for the data, emotional appetite was examined considering decrease, non-alteration, and increase in appetite in the face of positive and negative emotions/situations. The profile of emotional appetite was determined using a circumplex model. Results: The two-factor model described by the valence of emotions/situations fitted the samples (Comparative Fit Indexminimum-maximum = 0.95-0.98; Tucker-Lewis Index = 0.94-0.98; Root Mean Square Error of Approximation = 0.03-0.08; αord = 0.78-0.88). Increases in appetite were more frequent for positive emotions/situations (52.0-57.5%), and both decreases (35.4-44.5%) and increases (50.0-56.2%) in appetite were observed for negative emotions/situations. Emotions with negative valence and activation were more relevant to appetite reduction, while a significant increase in appetite was observed with anxiety (negative valence and positive activation). Conclusion: Different emotions and situations may influence appetite in people, and such an investigation may be useful in preparing eating protocols.

Antiviral potential of diminazene aceturate against SARS-CoV-2 proteases using computational and in vitro approaches.

Diminazene aceturate (DIZE), an antiparasitic, is an ACE2 activator, and studies show that activators of this enzyme may be beneficial for COVID-19, disease caused by SARS-CoV-2. Thus, the objective was to evaluate the in silico and in vitro affinity of diminazene aceturate against molecular targets of SARS-CoV-2. 3D structures from DIZE and the proteases from SARS-CoV-2, obtained through the Protein Data Bank and Drug Database (Drubank), and processed in computer programs like AutodockTools, LigPlot, Pymol for molecular docking and visualization and GROMACS was used to perform molecular dynamics. The results demonstrate that DIZE could interact with all tested targets, and the best binding energies were obtained from the interaction of Protein S (closed conformation -7.87 kcal/mol) and Mpro (-6.23 kcal/mol), indicating that it can act both by preventing entry and viral replication. The results of molecular dynamics demonstrate that DIZE was able to promote a change in stability at the cleavage sites between S1 and S2, which could prevent binding to ACE2 and fusion with the membrane. In addition, in vitro tests confirm the in silico results showing that DIZE could inhibit the binding between the spike receptor-binding domain protein and ACE2, which could promote a reduction in the virus infection. However, tests in other experimental models with in vivo approaches are needed.

Disparities in distribution of COVID-19 vaccines across US counties: A geographic information system-based cross-sectional study.

BACKGROUND: The US Centers for Disease Control and Prevention has repeatedly called for Coronavirus Disease 2019 (COVID-19) vaccine equity. The objective our study was to measure equity in the early distribution of COVID-19 vaccines to healthcare facilities across the US. Specifically, we tested whether the likelihood of a healthcare facility administering COVID-19 vaccines in May 2021 differed by county-level racial composition and degree of urbanicity. METHODS AND FINDINGS: The outcome was whether an eligible vaccination facility actually administered COVID-19 vaccines as of May 2021, and was defined by spatially matching locations of eligible and actual COVID-19 vaccine administration locations. The outcome was regressed against county-level measures for racial/ethnic composition, urbanicity, income, social vulnerability index, COVID-19 mortality, 2020 election results, and availability of nontraditional vaccination locations using generalized estimating equations. Across the US, 61.4% of eligible healthcare facilities and 76.0% of eligible pharmacies provided COVID-19 vaccinations as of May 2021. Facilities in counties with >42.2% non-Hispanic Black population (i.e., > 95th county percentile of Black race composition) were less likely to serve as COVID-19 vaccine administration locations compared to facilities in counties with <12.5% non-Hispanic Black population (i.e., lower than US average), with OR 0.83; 95% CI, 0.70 to 0.98, p = 0.030. Location of a facility in a rural county (OR 0.82; 95% CI, 0.75 to 0.90, p < 0.001, versus metropolitan county) or in a county in the top quintile of COVID-19 mortality (OR 0.83; 95% CI, 0.75 to 0.93, p = 0.001, versus bottom 4 quintiles) was associated with decreased odds of serving as a COVID-19 vaccine administration location. There was a significant interaction of urbanicity and racial/ethnic composition: In metropolitan counties, facilities in counties with >42.2% non-Hispanic Black population (i.e., >95th county percentile of Black race composition) had 32% (95% CI 14% to 47%, p = 0.001) lower odds of serving as COVID administration facility compared to facilities in counties with below US average Black population. This association between Black composition and odds of a facility serving as vaccine administration facility was not observed in rural or suburban counties. In rural counties, facilities in counties with above US average Hispanic population had 26% (95% CI 11% to 38%, p = 0.002) lower odds of serving as vaccine administration facility compared to facilities in counties with below US average Hispanic population. This association between Hispanic ethnicity and odds of a facility serving as vaccine administration facility was not observed in metropolitan or suburban counties. Our analyses did not include nontraditional vaccination sites and are based on data as of May 2021, thus they represent the early distribution of COVID-19 vaccines. Our results based on this cross-sectional analysis may not be generalizable to later phases of the COVID-19 vaccine distribution process. CONCLUSIONS: Healthcare facilities in counties with higher Black composition, in rural areas, and in hardest-hit communities were less likely to serve as COVID-19 vaccine administration locations in May 2021. The lower uptake of COVID-19 vaccinations among minority populations and rural areas has been attributed to vaccine hesitancy; however, decreased access to vaccination sites may be an additional overlooked barrier.

Evaluating the management timeline of tracheoesophageal fistulas secondary to button batteries: A systematic review.

INTRODUCTION: During the SARS-CoV-2 pandemic, the incidence of pediatric button battery (BB) ingestions has risen. Children have spent more time at home from school, while many parents try to balance working from home and childcare. Additionally, the amount of electronics powered by BB has increased. Tracheoesophageal fistula (TEF) secondary to a retained aerodigestive BB is a devastating development. Management is challenging, and the clinical timeline of watchful waiting versus surgical intervention for TEF is poorly defined in the literature. METHODS: In accordance with PRISMA guidelines, databases searched include PubMed, Scopus, and CINAHL from database date of inception through August 13, 2021. All study designs were included, and no language, publication date, or other restrictions were applied. Case series and reports of TEFs secondary to BBs were included. Clinical risk factors and outcomes were compared between the spontaneous closure and surgical repair groups. RESULTS: A total of 79 studies with 105 total patients were included. Mortality was 11.4%. There were 23 (21.9%) TEFs that spontaneously closed and 71 (67.6%) that underwent surgical repair. Median time to spontaneous closure compared to surgical repair was significantly different (8.0 weeks [IQR 4.0-18.4] vs. 2.0 weeks [IQR 0.1-3.3], p<0.001). Smaller TEFs were more likely to spontaneously close versus being surgically repaired (9.3 mm ± 3.5 vs. 14.9 mm ± 8.3, p=0.022). Duration of symptoms before BB discovery, BB size, time between BB removal and TEF discovery, and location of the TEF were not statistically different between the spontaneous closure and surgical repair groups. CONCLUSION: A TEF secondary to BB ingestion is a potentially deadly complication. Timing of reported TEF spontaneous closure varies significantly. While smaller TEFs may be amenable to healing without surgical repair, no other significant factors were identified that may be associated with spontaneous closure. If clinical status permits, these data suggest a period of observation of at least 8 weeks prior to surgical intervention may be practical for many BB-induced TEFs.

A Thermostable Oral SARS-CoV-2 Vaccine Induces Mucosal and Protective Immunity.

An ideal protective vaccine against SARS-CoV-2 should not only be effective in preventing disease, but also in preventing virus transmission. It should also be well accepted by the population and have a simple logistic chain. To fulfill these criteria, we developed a thermostable, orally administered vaccine that can induce a robust mucosal neutralizing immune response. We used our platform based on retrovirus-derived enveloped virus-like particles (eVLPs) harnessed with variable surface proteins (VSPs) from the intestinal parasite Giardia lamblia, affording them resistance to degradation and the triggering of robust mucosal cellular and antibody immune responses after oral administration. We made eVLPs expressing various forms of the SARS-CoV-2 Spike protein (S), with or without membrane protein (M) expression. We found that prime-boost administration of VSP-decorated eVLPs expressing a pre-fusion stabilized form of S and M triggers robust mucosal responses against SARS-CoV-2 in mice and hamsters, which translate into complete protection from a viral challenge. Moreover, they dramatically boosted the IgA mucosal response of intramuscularly injected vaccines. We conclude that our thermostable orally administered eVLP vaccine could be a valuable addition to the current arsenal against SARS-CoV-2, in a stand-alone prime-boost vaccination strategy or as a boost for existing vaccines.