| 1. |
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 7. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 8. |
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| 9. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 10. |
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| 11. |
- 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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| 12. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 14. |
- Sun, M. D., et al.
(författare)
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New short-lived isotope 223Np and the absence of the Z = 92 subshell closure near N = 126
- 2017
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 771, s. 303-308
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Tidskriftsartikel (refereegranskat)abstract
- The N=130 short-lived isotope 223Np was produced as evaporation residue (ER) in the fusion reaction 40Ar + 187Re at the gas-filled recoil separator Spectrometer for Heavy Atom and Nuclear Structure (SHANS). It was identified through temporal and spatial correlations with α decays of 215Ac and/or 211Fr, the third and fourth members of the α-decay chain starting from 223Np. The pileup signals of ER(223Np)–α(223Np)–α(219Pa) were resolved by using the digital pulse processing technique. An α decay with half-life of T1/2=2.15(52100) μs and energy of Eα=9477(44) keV was attributed to 223Np. Spin and parity of 9/2− were tentatively proposed for the ground state of 223Np by combining the reduced α-decay width and large-scale shell-model calculations. This assignment together with the proton separation energy disprove the existence of a Z=92 subshell closure.
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| 15. |
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| 16. |
- Li, Hongjie J., et al.
(författare)
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Collective band structures in the Tc-99 nucleus
- 2015
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:5
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in Tc-99 with energies up to 6 MeV have been populated using the Zr-96(Li-7, 4n)Tc-99 reaction with a laboratory beam energy of 35 MeV. Coincident gamma rays from excited nuclei produced in the reactions were detected using an array of coaxial, planar, and clover-type high-purity germanium detectors. A total of 60 new gamma-ray transitions and 21 new levels are identified and placed into a new level scheme. Two collective bands assigned to be built on the pi g(9/2)[422]5/2(+) and pi p(1/2)[301]1/2(-) Nilsson configurations have been extended with spins up to 35/2 and 33/2 h, respectively. Backbending and signature inversion have been observed in the yrast band. The large signature splitting of the positive-parity band in Tc-99 may be caused by a triaxial deformation, which agrees well with the electromagnetic properties, theoretical calculations based on total Routhian surface, and triaxial particle-rotor model calculations.
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| 17. |
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| 18. |
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| 19. |
- Huang, Y., et al.
(författare)
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High-spin structures in the Xe-129 nucleus
- 2016
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985. ; 93:6
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states in the Xe-129 nucleus are studied with the reaction Sn-124(Be-9,4n) at a beam energy of 36 MeV. The level scheme is extended significantly. For the positive-parity band, the alpha = +1/2 and the alpha = -1/2 signature components are combined to form a complete band structure based on the 3/2(+) state with spin and parity up to 21/2(+). For the negative-parity band based on the 11/2(-) state, the alpha = +1/2 signature component is newly established and both the alpha = +1/2 and the alpha = -1/2 signature components also form a complete band structure up to the 35/2(-) state. The positive-and negative-parity bands are proposed to originate from nu d(3/2) 3/2(+)[402] and nu h(11/2)11/2(-)[505] Nilsson configurations, respectively. A backbending is observed in the negative-parity band, which originates from the alignments of two h(11/2) protons according to crank shell model calculations. Based on the total Routhian surface and quasiparticle triaxial rotor model calculations, the negative-parity band is interpreted as a triaxially deformed shape with gamma approximate to -30 degrees, while the positive-parity band is associated with. softness, in accordance with previous studies. In the high-spin states, three decoupled bands and one oblate band with gamma approximate to -60 degrees are newly identified. The systematics and other characteristics of these bands are discussed.
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| 20. |
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| 21. |
- Xu, Q., et al.
(författare)
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Investigation of high spin states in Cs-133
- 2018
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Ingår i: European Physical Journal A. - : SPRINGER. - 1434-6001 .- 1434-601X. ; 54:5
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Tidskriftsartikel (refereegranskat)abstract
- High spin states in Cs-133 nucleus have been studied with the reaction Te-130 (Li-7, 4n) at a beam energy of 38 MeV. The level scheme has been expanded with spin up to 31/2 (h) over bar. Compared with a recent paper, ground state band and other two collective band structures at lower spin states have been confirmed. Another collective band structure at higher spin states as well as some levels and transitions are updated. Compared with the experimental data, large-scale shell model and tilted axis cranking model calculations have been carried out. The results show that the band-head configuration of yrast band based on 7/2(+) ground state and the side band built on the 5/2(+) state are a pair of pseudospin partner states with pi (f) over tilde 7/2,5/2. The negative parity band based on 1071.5 keV level originates from pi h(11/2) orbital. Another band built on 2642.9 keV level at high spin states has been proposed with oblate deformation. Other characteristics for these bands were also discussed.
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| 22. |
- Aktas, Özge, et al.
(författare)
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Single-particle structures in 85,87Ge
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X.
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray transitions have been identified for the first time in the extremely neutron-rich (N =Z + 25) nucleus 87 Ge following nucleon knockout reactions studied at the RIBF, RIKEN, Japan.New γ-ray transitions from excited states in 85 Ge were also observed and placed in a tentative levelscheme. The exclusive parallel momentum distribution was measured for the 1/2 + state for theneutron knockout reaction leading to 85 Ge which is compared with calculated distorted wave impulseapproximation (DWIA) distributions. The 85,87 Ge results are compared with large-scale shell-modelcalculations and potential energy surface calculations based on the total Routhian surface formalism.
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| 23. |
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| 24. |
- Li, Hongjie, et al.
(författare)
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Reinvestigation of the collective band structures in odd-odd Pm-138 nucleus
- 2015
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:5
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Tidskriftsartikel (refereegranskat)abstract
- The high-spin states in the odd-odd Pm-138 nucleus have been reinvestigated via the Te-124(F-19, 5n) reaction at the beam energy of 103MeV. Most of the known transitions and levels are confirmed. A number of bands are revised and one new band has been established. For the yrast pi h(11/2) circle times nu h(11/2) band based on 8(+) state, no evidence supporting the occurence of signature inversion is found. The experimental and theoretical B(M1)/B(E2) ratios have been calculated for band (2), which support the pi g(7/2)[413]5/2(+) circle times nu h(11/2)[514]9/2(-) Nilsson configuration assignment. Four bands with Delta I = 2 transitions are tentatively assigned as doubly decoupled bands. The other three bands are proposed as oblate-triaxial bands. The possible configuration assignments for these bands are also discussed under the calculations of total Routhian surface and particle-rotor model.
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| 25. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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