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- Bethlehem, RAI, et al.
(författare)
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Brain charts for the human lifespan
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Tidskriftsartikel (refereegranskat)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 4. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 5. |
- Dennis, J, et al.
(författare)
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Rare germline copy number variants (CNVs) and breast cancer risk
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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| 8. |
- Porru, E, et al.
(författare)
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Ventriculoperitoneal Shunt Treatment Increases 7 Alpha Hy-Droxy-3-Oxo-4-Cholestenoic Acid and 24-Hydroxycholesterol Concentrations in Idiopathic Normal Pressure Hydrocephalus
- 2022
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Ingår i: Brain sciences. - : MDPI AG. - 2076-3425. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- Idiopathic normal pressure hydrocephalus (iNPH) is the most common form of hydrocephalus in the adult population, and is often treated with cerebrospinal fluid (CSF) drainage using a ventriculoperitoneal (VP) shunt. Symptoms of iNPH include gait impairment, cognitive decline, and urinary incontinence. The pathophysiology behind the symptoms of iNPH is still unknown, and no reliable biomarkers have been established to date. The aim of this study was to investigate the possible use of the oxysterols as biomarkers in this disease. CSF levels of the oxysterols 24S- and 27-hydroxycholesterol, as well as the major metabolite of 27-hydroxycholesterol, 7 alpha hydroxy-3-oxo-4-cholestenoic acid (7HOCA), were measured in iNPH-patients before and after treatment with a VP-shunt. Corresponding measurements were also performed in healthy controls. VP-shunt treatment significantly increased the levels of 7HOCA and 24S-hydroxycholesterol in CSF (p = 0.014 and p = 0.037, respectively). The results are discussed in relation to the beneficial effects of VP-shunt treatment. Furthermore, the possibility that CSF drainage may reduce an inhibitory effect of transiently increased pressure on the metabolic capacity of neuronal cells in the brain is discussed. This capacity includes the elimination of cholesterol by the 24S-hydroxylase mechanisms.
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| 9. |
- El-Hajj, VG, et al.
(författare)
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Current Knowledge on Spinal Meningiomas Epidemiology, Tumor Characteristics and Non-Surgical Treatment Options: A Systematic Review and Pooled Analysis (Part 1)
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spinal meningiomas are the most common primary intradural spinal tumors. Although they are a separate entity, a large portion of the knowledge on spinal meningiomas is based on findings in intracranial meningiomas. Therefore, a comprehensive review of all the literature on spinal meningiomas was performed. Methods: Electronic databases were searched for all studies on spinal meningiomas dating from 2000 and onward. Findings of matching studies were pooled to strengthen the current body of evidence. Results: A total of 104 studies were included. The majority of patients were female (72.83%), elderly (peak decade: seventh), and had a world health organization (WHO) grade 1 tumor (95.7%). Interestingly, the minority of pediatric patients had a male overrepresentation (62.0% vs. 27.17%) and higher-grade tumors (33.3% vs. 4.3%). Sensory and motor dysfunction and pain were the most common presenting symptoms. Despite a handful of studies reporting promising findings associated with the use of non-surgical treatment options, the literature still suffers from contradictory results and limitations of study designs. Conclusions: Elderly females with WHO grade 1 tumors constituted the stereotypical type of patient. Compared to surgical alternatives, the evidence for the use of non-surgical treatments is still relatively weak.
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| 10. |
- El-Hajj, VG, et al.
(författare)
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Current Knowledge on Spinal Meningiomas-Surgical Treatment, Complications, and Outcomes: A Systematic Review and Meta-Analysis (Part 2)
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most of the knowledge on spinal meningiomas is extrapolated from their intracranial counterparts, even though they are considered separate entities. This review aimed to systematically summarize studies covering different aspects of spinal meningiomas and their management. Methods: Databases were searched for all studies concerning spinal meningiomas dating from 2000 and onwards. When possible, a meta-analysis was performed. Results: Neurological outcomes of surgery were consistently favorable across studies, with a complication rate of 7.9% and 78.9% of the patients demonstrating good postoperative neurological function (McCormick score 1–2). The most relevant predictors of unfavorable outcomes were poor preoperative status, longer time from diagnosis to surgery, and surgery of recurrent tumors. The recurrence rate after surgery was estimated at 6%. Meta-analysis and/or survival analysis revealed that higher WHO grade (p < 0.001), higher Simpson grade (p < 0.001), ventral tumor location (p = 0.02), and male sex (p = 0.014) were all associated with higher odds of recurrence. However, the meta-analysis did not show any difference between Simpson grade 1 and grade 2 with respect to the odds of recurrence (p = 0.94). Surgery provided immediate and durable health-related quality-of-life improvement, as well as a high frequency of return to work. Conclusion: Spinal meningioma surgery is a relatively safe procedure with a low risk of tumor recurrence and high likelihood of favorable postoperative outcomes.
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