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| 2. |
- 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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| 3. |
- Andersson, Mats, et al.
(författare)
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Use of celite-immobilised chloroperoxidase in predominantly organic media
- 1999
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Ingår i: Biocatalysis and Biotransformation. - : Informa UK Limited. - 1024-2422 .- 1029-2446. ; 17:4, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- It is possible to use the chloroperoxidase from Caldariomyces fumago to catalyse the oxidation of benzyl alcohol to benzaldehyde in predominantly organic media, even at water activities below 1.0, if the oxidant is tert-butyl hydroperoxide. The enzyme activity increased with increasing water activity and no enzyme activity was observed at water activities below 0.6. Hydrophobic solvents such as cyclohexane showed the highest initial activities. It was beneficial in terms of obtainable yield to use high concentrations of the peroxide due to the kinetics of the system. The apparent K(m) for benzyl alcohol in cyclohexane was estimated to be 13 mM while the initial reaction rate increased almost linearly up to 250 mM tert-butyl hydroperoxide.
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| 6. |
- Halle-Smith, James M., et al.
(författare)
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Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy : meta-analysis
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:9, s. 812-821
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.
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| 7. |
- Khan, Moien A. B., et al.
(författare)
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Systematic review of the effects of pandemic confinements on body weight and their determinants
- 2022
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 127:2, s. 298-317
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Forskningsöversikt (refereegranskat)abstract
- Pandemics and subsequent lifestyle restrictions such as 'lockdowns' may have unintended consequences, including alterations in body weight. This systematic review assesses the impact of pandemic confinement on body weight and identifies contributory factors. A comprehensive literature search was performed in seven electronic databases and in grey sources from their inception until 1 July 2020 with an update in PubMed and Scopus on 1 February 2021. In total, 2361 unique records were retrieved, of which forty-one studies were identified eligible: one case-control study, fourteen cohort and twenty-six cross-sectional studies (469, 362 total participants). The participants ranged in age from 6 to 86 years. The proportion of female participants ranged from 37 % to 100 %. Pandemic confinements were associated with weight gain in 7.2-724 % of participants and weight loss in 11.1-32.0 % of participants. Weight gain ranged from 0.6 (SD 1.3) to 3.0 (SD 2.4) kg, and weight loss ranged from 2.0 (SD 1.4) to 2.9 (SD 1.5) kg. Weight gain occurred predominantly in participants who were already overweight or obese. Associated factors included increased consumption of unhealthy food with changes in physical activity and altered sleep patterns. Weight loss during the pandemic was observed in individuals with previous low weight, and those who ate less and were more physically active before lockdown. Maintaining a stable weight was more difficult in populations with reduced income, particularly in individuals with lower educational attainment. The findings of this systematic review highlight the short-term effects of pandemic confinements.
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| 8. |
- Samra, Babinder K., et al.
(författare)
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Chloroperoxidase catalysed oxidation of benzyl alcohol using tert-butyl hydroperoxide oxidant in organic media
- 1999
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Ingår i: Biocatalysis and Biotransformation. - : Informa UK Limited. - 1024-2422 .- 1029-2446. ; 17:5, s. 381-391
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Tidskriftsartikel (refereegranskat)abstract
- The quantitative oxidation of benzyl alcohol to benzaldehyde using the enzyme chloroperoxidase (CPO) from Caldariomyces fumago as catalyst and tert-butyl hydroperoxide (t-BuOOH) as a cosubstrate for the enzyme, in organic solvent is demonstrated. The enzymatic transformation of primary alcohols to aldehydes has not previously been shown in predominantly organic solvent using CPO, and in aqueous media, has only been reported to have been effected in moderate yields. A simple procedure for this transformation was carried out using 10 μmol each of benzyl alcohol and t-BuOOH dissolved in water-saturated isooctane (1.5 ml), 0.5 μl CPO solution (10 units) in pH 4.0 acetate buffer. The reaction rates obtained in organic media were similar to that obtained in aqueous media, the enzyme was found to be significantly stabilised towards peroxide dependent inactivation and no continuous addition of the peroxide was necessary.
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| 10. |
- Samra, K, et al.
(författare)
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Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia
- 2023
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Ingår i: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 5:2, s. fcad036-
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Tidskriftsartikel (refereegranskat)abstract
- Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.
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