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- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 9. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 12. |
- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 15. |
- Yaqub, S., et al.
(författare)
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Aspirin as secondary prevention in colorectal cancer liver metastasis (ASAC trial): study protocol for a multicentre randomized placebo-controlled trial
- 2021
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Ingår i: Trials. - London, United Kingdom : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Colorectal cancer is one the most common cancers in the western world with increasing incidence. Approximately 50% of the patients develop liver metastases. Resection of liver metastases is the treatment of choice although almost half of the resected patients get recurrence in the liver. Methods The ASAC trial is a Scandinavian, multicentre, double-blinded, randomized, placebo-controlled study to determine whether adjuvant treatment with low-dose aspirin (acetylsalicylic acid (ASA)) can improve disease-free survival in patients treated for colorectal cancer liver metastases (CRCLM). Up to 800 patients operated for CRCLM will be randomized to Arm#1 ASA 160 mg once daily or Arm#2 Placebo, for a period of 3 years or until disease recurrence. The patients will be recruited at all major hepatobiliary surgical units in Norway, Sweden and Denmark and have follow-up according to standard of care and the National Guidelines. Discussion The ASAC trial will be the first clinical interventional trial to assess the potential beneficial role of ASA in recurrence of CRCLM and survival. ASA is an inexpensive, well-tolerated and easily accessible drug that will be highly potential as adjuvant drug in secondary prevention of CRCLM if the study shows a beneficial effect. We will also determine the effect of ASA as adjuvant treatment on Health-Related Quality of Life and the cost-effectiveness.
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| 16. |
- Soust-Verdaguer, B., et al.
(författare)
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Implications of using systematic decomposition structures to organize building LCA information: A comparative analysis of national standards and guidelines- IEA EBC ANNEX 72
- 2020
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Ingår i: IOP Conference Series: Earth and Environmental Science. - : IOP Publishing. - 1755-1307 .- 1755-1315. ; 588:2
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Konferensbidrag (refereegranskat)abstract
- Introduction: The application of the Life Cycle Assessment (LCA) technique to a building requires the collection and organization of a large amount of data over its life cycle. The systematic decomposition method can be used to classify building components, elements and materials, overcome specific difficulties that are encountered when attempting to complete the life cycle inventory and increase the reliability and transparency of results. In this paper, which was developed in the context of the research project IEA EBC Annex 72, we demonstrate the implications of taking such approach and describe the results of a comparison among different national standards/guidelines that are used to conduct LCA for building decomposition. Methods: We initially identified the main characteristics of the standards/guidelines used by Annex participant countries. The “be2226” reference office building was used as a reference to apply the different national standards/guidelines related to building decomposition. It served as a basis of comparison, allowing us to identify the implications of using different systems/standards in the LCA practice, in terms of how these differences affect the LCI structures, LCA databases and the methods used to communicate results. We also analyzed the implications of integrating these standards/guidelines into Building Information Modelling (BIM) to support LCA. Results: Twelve national classification systems/ standards/guidelines for the building decomposition were compared. Differences were identified among the levels of decomposition and grouping principles, as well as the consequences of these differences that were related to the LCI organization. In addition, differences were observed among the LCA databases and the structures of the results. Conclusions: The findings of this study summarize and provide an overview of the most relevant aspects of using a standardized building decomposition structure to conduct LCA. Recommendations are formulated on the basis of these findings.
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| 21. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 22. |
- Eriksson, Mats E., et al.
(författare)
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A review of ichthyosaur (Reptilia, Ichthyopterygia) soft tissues with implications for life reconstructions
- 2022
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Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252. ; 226
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Forskningsöversikt (refereegranskat)abstract
- The dolphin-like ichthyosaurs – also known as ‘fish lizards’ – are extinct marine reptiles that roamed the Mesozoic oceans for some 160 million years. As for most ancient vertebrates, our knowledge of these iconic animals largely derives from biomineralized hard parts (teeth and bones). However, soft tissues are also known from a number of Lagerstätte specimens, and have opened up new avenues for deciphering their biology and ecology. Herein, we present a review of ichthyosaur research and life style iconography with particular focus on soft-tissue structures and inferences made from these, including aspects of coloration and thermoregulation. We then distill novel insights on ichthyosaur anatomy and physiology gained from an exceptionally preserved, sub-adult specimen of the parvipelvian Stenopterygius from the Jurassic Posidonia Shale in Germany, and describe the process in which a detailed, three-dimensional reconstruction in scale 1:1 was produced. Our new sculpture is based on empirical evidence obtained directly from the fossil record, including uniquely preserved soft-tissue structures (e.g., original pigments and blubber), resulting in the scientifically most up-to-date reconstruction of an ichthyosaur currently available.
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| 23. |
- Erséus, Christer, 1951, et al.
(författare)
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Phylogenomic analyses reveal a Palaeozoic radiation and support a freshwater origin for clitellate annelids
- 2020
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Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 49:5, s. 614-640
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Tidskriftsartikel (refereegranskat)abstract
- Clitellata is a major clade of Annelida comprising nearly all freshwater and terrestrial annelids as well as several marine species. We investigated clitellate phylogenetic relationships using transcriptomes sampled from 74 taxa (64 clitellates and 10 polychaetes), including multiple representatives of nearly all major clitellate higher taxa (Branchiobdellida, Capilloventridae, Crassiclitellata, Enchytraeidae, Haplotaxidae, Hirudinida, Lumbriculida, Moniligastridae, Naididae, Parvidrilidae, Phreodrilidae, Propappidae and Randiellidae). We used a number of filtered data matrices and phylogenetic analyses to examine the effects of data partitioning, missing data and compositional and branch-length heterogeneity and used the resulting phylogenies for divergence time estimation and ancestral habitat reconstructions. All analyses and filtering methods produced a consistent, strongly supported topology in which (a) Enchytraeidae, Hirudinida, Hirudinea (here, Branchiobdellida plus Hirudinida), Lumbriculida, Lumbriculata (Lumbriculida plus Hirudinea), Phreodrilidae and Naididae are monophyletic, (b) a Parvidrilidae + Randiellidae clade is sister to the rest of Clitellata, (c) Phreodrilidae is sister to Naididae, (d) Haplotaxidae is non-monophyletic, with some haplotaxids grouping with Crassiclitellata + Moniligastridae, (e) the Phreodrilidae + Naididae clade is sister to all other clitellates except Parvidrilidae + Randiellidae and Capilloventridae, and (f) Lumbriculata is sister to the Crassiclitellata + Moniligastridae + Haplotaxidae (in part) clade. Ancestral habitat reconstructions and divergence time analysis suggested that the most recent common ancestor of Clitellata lived in freshwater during the Devonian (419-359 million years ago) and that all major extant clitellate lineages arose over the next similar to 150 million years, with multiple lineages subsequently returning to marine habitats or invading land. This study provides a phylogenetic framework for further investigation of the geological, environmental and biotic forces and genomic changes that may have impacted clitellate evolution and enabled several major habitat transitions within this group.
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| 24. |
- Glas, Gerie J., et al.
(författare)
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Ventilation practices in burn patients-an international prospective observational cohort study
- 2021
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Ingår i: BURNS & TRAUMA. - : Oxford University Press. - 2321-3868 .- 2321-3876. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). Methods: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V-T) was defined as V-T <= 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V-T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. Results: A total of 160 patients from 28 ICUs in 16 countries were included. Low V-T was used in 74% of patients, median V-T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p= 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V-T (p= 0.98). All patients were ventilated with PEEP levels >= 5 cmH(2)O; 80% of patients had maximum airway pressures <30 cmH(2)O. Conclusion: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V-T was not associated with a reduction in VFD-28.
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| 25. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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