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1.
  • Niemi, MEK, et al. (author)
  • 2021
  • swepub:Mat__t
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2.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
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3.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
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4.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
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5.
  • Aad, G., et al. (author)
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :8
  • Journal article (peer-reviewed)
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6.
  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)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.
  • Correa, D. F., et al. (author)
  • Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates
  • 2023
  • In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:1, s. 49-69
  • Journal article (peer-reviewed)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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8.
  • Crous, Pedro W., et al. (author)
  • Fungal Planet description sheets: 1383–1435
  • 2022
  • In: Persoonia: Molecular Phylogeny and Evolution of Fungi. - : Naturalis Biodiversity Center. - 0031-5850 .- 1878-9080. ; 48, s. 261-371
  • Journal article (peer-reviewed)abstract
    • Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum laurisilvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes.
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9.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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10.
  • Turcot, Valerie, et al. (author)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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11.
  • Householder, John Ethan, et al. (author)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • In: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
  • Journal article (peer-reviewed)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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12.
  • Justice, Anne E., et al. (author)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Journal article (peer-reviewed)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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13.
  • Luize, Bruno Garcia, et al. (author)
  • Geography and ecology shape the phylogenetic composition of Amazonian tree communities
  • 2024
  • In: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
  • Journal article (peer-reviewed)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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14.
  • ter Steege, Hans, et al. (author)
  • Mapping density, diversity and species-richness of the Amazon tree flora
  • 2023
  • In: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
  • Journal article (peer-reviewed)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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15.
  • Carlsson, Sigrid, 1982, et al. (author)
  • Long-Term Outcomes of Active Surveillance for Prostate Cancer: The Memorial Sloan Kettering Cancer Center Experience
  • 2020
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 203:6, s. 1122-1127
  • Journal article (peer-reviewed)abstract
    • Purpose: We report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center. Materials and Methods: A total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis. Results: Median patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years. Conclusions: Active surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.
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16.
  • Carlsson, Sigrid, 1982, et al. (author)
  • Risk of Metastasis in Men with Grade Group 2 Prostate Cancer Managed with Active Surveillance at a Tertiary Cancer Center
  • 2020
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 203:6, s. 1117-1121
  • Journal article (peer-reviewed)abstract
    • Purpose: We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center. Materials and Methods: A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. Results: Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9). Conclusions: Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.
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17.
  • Fleshner, K., et al. (author)
  • Clinical Findings and Treatment Outcomes in Patients with Extraprostatic Extension Identified on Prostate Biopsy
  • 2016
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 196:3, s. 703-708
  • Journal article (peer-reviewed)abstract
    • Purpose: We describe histopathological, clinical and imaging findings among men with extraprostatic extension on prostate biopsy. Materials and Methods: We searched our institutional pathology database between 2004 and 2015 for pathology reports detailing extraprostatic extension on prostate biopsy in untreated patients. Patient characteristics, biopsy features, imaging interpretations and outcomes were examined. Results: Of 19,950 patients with prostate cancer on biopsy 112 had extraprostatic extension for a prevalence of 0.6% (95% CI 0.5-0.7). Most of the 112 patients had palpable, high grade (Gleason score 9), high volume disease, which was classified as high risk in 34 (30%), locally advanced in 17 (15%) and metastatic in 39 (35%). Most patients had 1 or 2 cores with extraprostatic extension, typically at the base and with concomitant perineural invasion. Extraprostatic extension was identified by magnetic resonance imaging in 32 of 40 patients (80%). Median followup in those who did not die was 1.3 years (IQR 0.3-4.2). Outcomes in the subgroup of 24 men treated with radical prostatectomy were consistent with high risk disease, including positive margins in 14 (58%), seminal vesicle invasion in 10 (42%) and lymph node invasion in 11 (46%). In the entire cohort the 3-year risks of metastasis and overall mortality were 32% (95% CI 22-44) and 37% (95% CI 27-50), respectively. We did not find evidence to suggest that the proportion of cores with cancer that also had extraprostatic extension was associated with overall mortality (p = 0.09). Conclusions: Extraprostatic extension is a rare finding on prostate biopsy. It is strongly associated with other features of aggressive prostate cancer.
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20.
  • Levi, L, et al. (author)
  • Legal and legislative issues
  • 2000
  • In: Occupational medicine (Philadelphia, Pa.). - 0885-114X. ; 15:1, s. 269-292
  • Journal article (peer-reviewed)
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21.
  • Licht, S. de Fine, et al. (author)
  • Hepatoblastoma in the Nordic countries
  • 2012
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:4, s. E555-E561
  • Journal article (peer-reviewed)abstract
    • Little is known about the etiology of hepatoblastoma. Because of the young age at diagnosis, several studies have looked at various birth characteristics. The purpose of our study was to investigate the incidence of hepatoblastoma in the Nordic countries and the association between selected birth characteristics and hepatoblastoma. Data from national cancer registries and birth registries in Denmark, Sweden, Norway and Finland 19852006 was used. Overall, 155 children with hepatoblastoma aged 0-14 years were included and individually matched to five controls drawn randomly from national population registries. The incidence rate of hepatoblastoma was 1.7 per million person-years with a predominance of boys (1.5:1). Incidence rate was highest before the age of 1 year (8.3 per million person-years). A higher risk of hepatoblastoma was found in children with birth weight <1,500 g [odds ratio (OR) = 9.5; 95% confidence interval (CI): 2.338.2], born preterm in week 22-32 (OR = 4.5; CI: 1.811.5) and Apgar scores <7 after 1 min (OR = 3.1; CI: 1.37.1) and 5 min (OR = 7.5; CI: 1.832.4). A doubling in risk was found in children who were large for gestational age (OR = 2.3; CI: 1.05.3). No associations were found with birth order, maternal age or maternal smoking. Our study indicates that intrauterine and/or neonatal factors are associated with increased risk of hepatoblastoma. These may include low birth weight and asphyxia leading to neonatal intensive care. Alternatively, the factors may be a consequence of hepatoblastoma developing in utero.
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23.
  • Melén, Erik, et al. (author)
  • Short-acting β2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.
  • 2022
  • In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038 .- 0905-6157. ; 33:11
  • Journal article (peer-reviewed)abstract
    • In adults and adolescents with asthma, use of ≥3 short-acting β2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population.This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression.Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups).High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.
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24.
  • Muus, Christoph, et al. (author)
  • Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
  • 2021
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 546-559
  • Journal article (peer-reviewed)abstract
    • Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.
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25.
  • Perera, M., et al. (author)
  • Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer
  • 2022
  • In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 208:2, s. 309-316
  • Journal article (peer-reviewed)abstract
    • Purpose: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. Materials and Methods: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. Results: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum % GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. Conclusions: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.
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