| 1. |
- Gaziano, Liam, et al.
(författare)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 2. |
- Liopyris, Konstantinos, et al.
(författare)
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Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy.
- 2023
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Ingår i: The Journal of investigative dermatology. - 1523-1747. ; 144:3
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Tidskriftsartikel (refereegranskat)abstract
- Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.
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| 3. |
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Avian Behavioral and Physiological Responses to Challenging Thermal Environments and Extreme Weather Events
- 2022
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Birds occupy habitats ranging from Antarctic ice shelves and Arctic tundra to low-latitude deserts and lowland rainforests, and so are exposed to the full range of climates present on Earth. Cold, hot, or variable (on a variety of temporal scales) thermal conditions can present significant thermoregulatory challenges to birds, which typically must maintain body temperatures within narrow physiological tolerance limits. Such challenges may occur in all stages of the annual cycle and in all life stages of birds, so the ability to adjust to these conditions is required to maintain stable populations through time. For this Research Topic, we broadly define a challenging thermal environment as one necessitating behavioral or physiological adjustments to maintain body temperatures at levels appropriate for continued physiological function.Avian abilities to respond to extreme cold and heat are defined by thermoregulatory capacities for heat production or dissipation, respectively. Behavioral responses to temperature challenges can reduce the necessity for and magnitude of physiological adjustments, so together, physiological capacities and behavioral responses determine the probability of survival in thermally challenging situations. Moreover, thermal conditions experienced during reproduction can affect parental investment in the nesting effort and, independently, alter the course of nestling development, with potentially long-term consequences. Behavioral responses to these conditions as well as physiological responses at multiple levels of organization, from organisms to molecules, allow birds to tolerate thermal challenges. Our knowledge of the mechanisms by which birds respond, the time course for such responses, and the impacts on fitness, however, remain incompletely understood. Studies examining behavioral and physiological responses of birds to extreme and/or seasonally variable climates have been a research focus for decades, but recent advances in methods of measurement and analyses of physiological and behavioral traits have led to novel findings regarding the patterns and mechanisms by which birds adjust to challenging thermal environments.This Research Topic examines how thermal conditions in the environment pose challenges to birds and the physiological and behavioral adjustments that birds employ to meet them. Articles for this Research Topic may be original research papers, reviews, or perspectives. Specific themes that we believe are suitable for this Research Topic include, but are not limited to:• Integrative mechanisms underlying bird thermoregulatory capacities contributing to a tolerance of challenging thermal environments and their links to fitness• Influence of thermal conditions during reproduction on parental investment or nestling development• Behavioral responses to challenging thermal conditions and their mechanistic underpinnings• Time courses for physiological adjustments to environmental temperature variation• Physiological and behavioral flexibility associated with daily or seasonal temperature variation• Physiological and behavioral responses and tolerance limits during extreme weather events• Body temperature regulation under challenging thermal conditions and energy or water restrictions, including real-time field measurements and thermal imaging• Body temperature regulation and environmental or ecological drivers of hypometabolic strategies• Physiological consequences of exceeding thermoregulatory capacities
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| 4. |
- Evans, David A.D., et al.
(författare)
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An expanding list of reliable paleomagnetic poles for Precambrian tectonic reconstructions
- 2021
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Ingår i: Ancient Supercontinents and the Paleogeography of Earth. - : Elsevier. ; , s. 605-639
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Bokkapitel (refereegranskat)abstract
- We present a compilation of reliable Precambrian paleomagnetic poles from three successive international workshops (in years 2009, 2014, 2017), comprising paleomagnetists specializing in Precambrian tectonic reconstructions. The working groups compiled lists of two global classes of poles, published through the end of 2017. “Grade-A” results are judged to provide essential constraints on tectonic reconstructions; “Grade-B” poles are judged to be suggestive of high-quality, but not yet demonstrated to be primary, or perhaps lacking precise geochronologic or other constraints. Our catalog documents a resurgence of high-quality data acquisition in recent years, and highlights specific cratons and time intervals that are most lacking in the data needed to reconstruct those blocks through supercontinental cycles.
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