| 1. |
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 6. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 7. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 8. |
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| 9. |
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| 10. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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| 11. |
- Crous, P. W., et al.
(författare)
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Fungal Planet description sheets: 1478-1549
- 2023
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Ingår i: Persoonia. - 0031-5850. ; 50, s. 158-310
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Tidskriftsartikel (refereegranskat)abstract
- Novel species of fungi described in this study include those from various countries as follows: Australia, Aschersonia mackerrasiae on whitefly, Cladosporium corticola on bark of Melaleuca quinquenervia, Penicillium nudgee from soil under Melaleuca quinquenervia, Pseudocercospora blackwoodiae on leaf spot of Persoonia fal- cata, and Pseudocercospora dalyelliae on leaf spot of Senna alata. Bolivia, Aspicilia lutzoniana on fully submersed siliceous schist in high-mountain streams, and Niesslia parviseta on the lower part and apothecial discs of Erioderma barbellatum on a twig. Brazil, Cyathus bonsai on decaying wood, Geastrum albofibrosum from moist soil with leaf litter, Laetiporus pratigiensis on a trunk of a living unknown hardwood tree species, and Scytalidium synnematicum on dead twigs of unidentified plant. Bulgaria, Amanita abscondita on sandy soil in a plantation of Quercus suber. Canada, Penicillium acericola on dead bark of Acer saccharum, and Penicillium corticola on dead bark of Acer saccharum. China, Colletotrichum qingyuanense on fruit lesion of Capsicum annuum. Denmark, Helminthosphaeria leptospora on corticioid Neohypochnicium cremicolor. Ecuador (Galapagos), Phaeosphaeria scalesiae on Scalesia sp. Finland, Inocybe jacobssonii on calcareous soils in dry forests and park habitats. France, Cortinarius rufomyr- rheus on sandy soil under Pinus pinaster, and Periconia neominutissima on leaves of Poaceae. India, Coprinopsis fragilis on decaying bark of logs, Filoboletus keralensis on unidentified woody substrate, Penicillium sankaranii from soil, Physisporinus tamilnaduensis on the trunk of Azadirachta indica, and Poronia nagaraholensis on elephant dung. Iran, Neosetophoma fici on infected leaves of Ficus elastica. Israel, Cnidariophoma eilatica (incl. Cnidario- phoma gen. nov.) from Stylophora pistillata. Italy, Lyophyllum obscurum on acidic soil. Namibia, Aureobasidium faidherbiae on dead leaf of Faidherbia albida, and Aureobasidium welwitschiae on dead leaves of Welwitschia mirabilis. Netherlands, Gaeumannomycella caricigena on dead culms of Carex elongata, Houtenomyces caricicola (incl. Houtenomyces gen. nov.) on culms of Carex disticha, Neodacampia ulmea (incl. Neodacampia gen. nov.) on branch of Ulmus laevis, Niesslia phragmiticola on dead standing culms of Phragmites australis, Pseudopyricularia caricicola on culms of Carex disticha, and Rhodoveronaea nieuwwulvenica on dead bamboo sticks. Norway, Arrhenia similis half-buried and moss-covered pieces of rotting wood in grass-grown path. Pakistan, Mallocybe ahmadii on soil. Poland, Beskidomyces laricis (incl. Beskidomyces gen. nov.) from resin of Larix decidua ssp. polonica, Lapi- domyces epipinicola from sooty mould community on Pinus nigra, and Leptographium granulatum from a gallery of Dendroctonus micans on Picea abies. Portugal, Geoglossum azoricum on mossy areas of laurel forest areas planted with Cryptomeria japonica, and Lunasporangiospora lusitanica from a biofilm covering a biodeteriorated limestone wall. Qatar, Alternaria halotolerans from hypersaline sea water, and Alternaria qatarensis from water sample collected from hypersaline lagoon. South Africa, Alfaria thamnochorti on culm of Thamnochortus fraternus, Knufia aloeicola on Aloe gariepensis, Muriseptatomyces restionacearum (incl. Muriseptatomyces gen. nov. ) on culms of Restionaceae, Neocladosporium arctotis on nest of cases of bag worm moths (Lepidoptera, Psychidae) on Arctotis auriculata, Neodevriesia scadoxi on leaves of Scadoxus puniceus, Paraloratospora schoenoplecti on stems of Schoenoplectus lacustris, Tulasnella epidendrea from the roots of Epidendrum x obrienianum, and Xenoidriella cinnamomi (incl. Xenoidriella gen. nov.) on leaf of Cinnamomum camphora. South Korea, Lemonniera fraxinea on decaying leaves of Fraxinus sp. from pond. Spain, Atheniella lauri on the bark of fallen trees of Laurus nobilis, Halocryptovalsa endophytica from surface-sterilised, asymptomatic roots of Salicornia patula, Inocybe amygda- liolens on soil in mixed forest, Inocybe pityusarum on calcareous soil in mixed forest, Inocybe roseobulbipes on acidic soils, Neonectria borealis from roots of Vitis berlandieri x Vitis rupestris, Sympoventuria eucalyptorum on leaves of Eucalyptus sp., and Tuber conchae from soil. Sweden, Inocybe bidumensis on calcareous soil. Thailand, Cordyceps sandindaengensis on Lepidoptera pupa, buried in soil, Ophiocordyceps kuchinaraiensis on Coleoptera larva, buried in soil, and Samsoniella winandae on Lepidoptera pupa, buried in soil. Taiwan region (China), Neo- phaeosphaeria livistonae on dead leaf of Livistona rotundifolia. Turkiye, Melanogaster anatolicus on clay loamy soils. UK, Basingstokeomyces allii (incl. Basingstokeomyces gen. nov.) on leaves of Allium schoenoprasum. Ukraine, Xenosphaeropsis corni on recently dead stem of Cornus alba. USA, Nothotrichosporon aquaticum (incl. Nothotrichosporon gen. nov.) from water, and Periconia philadelphiana from swab of coil surface. Morphological and culture characteristics for these new taxa are supported by DNA barcodes.
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| 12. |
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| 13. |
- Correa, D. F., et al.
(författare)
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Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates
- 2023
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:1, s. 49-69
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period Tree-inventory plots established between 1934 and 2019. Major taxa studied Trees with a diameter at breast height (DBH) >= 9.55 cm. Location Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types.
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| 14. |
- Sabatini, F. M., et al.
(författare)
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sPlotOpen - An environmentally balanced, open-access, global dataset of vegetation plots
- 2021
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238.
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Tidskriftsartikel (refereegranskat)abstract
- Motivation Assessing biodiversity status and trends in plant communities is critical for understanding, quantifying and predicting the effects of global change on ecosystems. Vegetation plots record the occurrence or abundance of all plant species co-occurring within delimited local areas. This allows species absences to be inferred, information seldom provided by existing global plant datasets. Although many vegetation plots have been recorded, most are not available to the global research community. A recent initiative, called 'sPlot', compiled the first global vegetation plot database, and continues to grow and curate it. The sPlot database, however, is extremely unbalanced spatially and environmentally, and is not open-access. Here, we address both these issues by (a) resampling the vegetation plots using several environmental variables as sampling strata and (b) securing permission from data holders of 105 local-to-regional datasets to openly release data. We thus present sPlotOpen, the largest open-access dataset of vegetation plots ever released. sPlotOpen can be used to explore global diversity at the plant community level, as ground truth data in remote sensing applications, or as a baseline for biodiversity monitoring. Main types of variable contained Vegetation plots (n = 95,104) recording cover or abundance of naturally co-occurring vascular plant species within delimited areas. sPlotOpen contains three partially overlapping resampled datasets (c. 50,000 plots each), to be used as replicates in global analyses. Besides geographical location, date, plot size, biome, elevation, slope, aspect, vegetation type, naturalness, coverage of various vegetation layers, and source dataset, plot-level data also include community-weighted means and variances of 18 plant functional traits from the TRY Plant Trait Database. Spatial location and grain Global, 0.01-40,000 m(2). Time period and grain 1888-2015, recording dates. Major taxa and level of measurement 42,677 vascular plant taxa, plot-level records. Software format Three main matrices (.csv), relationally linked.
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| 15. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 16. |
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| 17. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 18. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 19. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 20. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 21. |
- Ibanez, L., et al.
(författare)
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Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2394-2406
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Tidskriftsartikel (refereegranskat)abstract
- During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.
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| 22. |
- Heitsch, L., et al.
(författare)
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Early Neurological Change After Ischemic Stroke Is Associated With 90-Day Outcome
- 2021
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 52:1, s. 132-141
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSSbaseline - NIHSS24hours = Delta NIHSS6-24h), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced Delta NIHSS6-24h. In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on Delta NIHSS6-24h was examined. Finally, the association of Delta NIHSS6-24h with 90-day favorable outcomes (modified Rankin Scale score 0-2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4-16), and median Delta NIHSS6-24h was 2 (interquartile range, 0-5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted Delta NIHSS6-24h (R-2=0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R-2=0.27), but much of the variance remained unexplained. Delta NIHSS6-24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, Delta NIHSS3-24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, Delta NIHSS6-24h, captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, Delta NIHSS6-24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.
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