| 11. |
- Lawniczak, Mara K. N., et al.
(author)
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Standards recommendations for the Earth BioGenome Project
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Journal article (peer-reviewed)abstract
- A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met.
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| 12. |
- Lewin, Harris A., et al.
(author)
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The Earth BioGenome Project 2020 : Starting the clock
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Journal article (other academic/artistic)
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| 13. |
- McMahon, J. H., et al.
(author)
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Neurotoxicity with high-dose disulfiram and vorinostat used for HIV latency reversal
- 2022
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In: Aids. - : Ovid Technologies (Wolters Kluwer Health). - 0269-9370 .- 1473-5571. ; 36:1, s. 75-82
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is well tolerated and can enhance HIV latency reversal. Design: Vorinostat and disulfiram can increase HIV transcription in PWH on ART. Together, these agents may lead to significant HIV latency reversal. Methods: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated unspliced RNA as a marker of latency reversal, HIV DNA in CD4(+) T-cells, plasma HIV RNA, and plasma concentrations of ART, vorinostat, and disulfiram. Results: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia, and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4-fold and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8 to 37 (peak 81 copies ml(-1)) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. Conclusion: The combination of prolonged high-dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal.
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| 14. |
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| 15. |
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| 16. |
- Sousa, Ronaldo, et al.
(author)
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The role of anthropogenic habitats in freshwater mussel conservation
- 2021
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In: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 27, s. 2298-2314
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Journal article (peer-reviewed)abstract
- Anthropogenic freshwater habitats may provide undervalued prospects for long-term conservation as part of species conservation planning. This fundamental, but overlooked, issue requires attention considering the pace that humans have been altering natural freshwater ecosystems and the accelerated levels of biodiversity decline in recent decades. We compiled 709 records of freshwater mussels (Bivalvia, Unionida) inhabiting a broad variety of anthropogenic habitat types (from small ponds to large reservoirs and canals) and reviewed their importance as refuges for this faunal group. Most records came from Europe and North America, with a clear dominance of canals and reservoirs. The dataset covered 228 species, including 34 threatened species on the IUCN Red List. We discuss the conservation importance and provide guidance on how these anthropogenic habitats could be managed to provide optimal conservation value to freshwater mussels. This review also shows that some of these habitats may function as ecological traps owing to conflicting management practices or because they act as a sink for some populations. Therefore, anthropogenic habitats should not be seen as a panacea to resolve conservation problems. More information is necessary to better understand the trade-offs between human use and the conservation of freshwater mussels (and other biota) within anthropogenic habitats, given the low number of quantitative studies and the strong biogeographic knowledge bias that persists.
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| 17. |
- Steadman, Randolph H., et al.
(author)
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Screen-Based Simulation for Training and Automated Assessment of Teamwork Skills Comparing 2 Modes With Different Interactivity
- 2021
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In: Simulation in Healthcare. - : LIPPINCOTT WILLIAMS & WILKINS. - 1559-2332 .- 1559-713X. ; 16:5, s. 318-326
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Journal article (peer-reviewed)abstract
- Introduction: The need for teamwork training is well documented; however, teaching these skills is challenging given the logistics of assembling individual team members together to train in person. We designed 2 modes of screen-based simulation for training teamwork skills to assess whether interactivity with nonplayer characters was necessary for in-game performance gains or for player satisfaction with the experience. Methods: Mixed, randomized, repeated measures study with licensed healthcare providers block-stratified and randomized to evaluation-participant observes and evaluates the team player in 3 scenarios-and game play-participant is immersed as the leader in the same 3 scenarios. Teamwork construct scores (leadership, communication, situation monitoring, mutual support) from an ontology-based, Bayesian network assessment model were analyzed using mixed randomized repeated measures analyses of variance to compare performance, across scenarios and modes. Learning was measured by pretest and posttest quiz scores. User experience was evaluated using chi(2) analyses. Results: Among 166 recruited and randomized participants, 120 enrolled in the study and 109 had complete data for analysis. Mean composite teamwork Bayesian network scores improved for successive scenarios in both modes, with evaluation scores statistically higher than game play for every teamwork construct and scenario (r = 0.73, P = 0.000). Quiz scores improved from pretest to posttest (P = 0.004), but differences between modes were not significant. Conclusions: For training teamwork skills using screen-based simulation, interactivity of the player with the nonplayer characters is not necessary for in-game performance gains or for player satisfaction with the experience.
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| 18. |
- Stokowska, Anna, et al.
(author)
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Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity
- 2023
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In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:10
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Journal article (peer-reviewed)abstract
- Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.
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