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- 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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- Kang, JS, et al.
(författare)
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Risk prediction for malignant intraductal papillary mucinous neoplasm of the pancreas: logistic regression versus machine learning
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 20140-
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Tidskriftsartikel (refereegranskat)abstract
- Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.
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- Cheng, Q, et al.
(författare)
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Clinical features of patients with multiple sclerosis from a survey in Shanghai, China
- 2008
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 14:5, s. 671-678
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe clinical features of patients with multiple sclerosis (MS) in Shanghai, China. Methods Prevalent patients with MS were identified and investigated by a network of physicians in 11 districts of Shanghai during the period from 1 September 2004 to 31 August 2005. Admission registries of each hospital in the study area were checked systematically for patients with a diagnosis of MS, neuromyelitis optica or other demyelinating disorders. All patients with collected information were evaluated by four senior neurologists according to the McDonald criteria. Results There were 249 (146 female and 103 male) patients with a confirmed MS diagnosis, at a female-to-male ratio of 1.4. The mean age at onset of MS was 37.4 years for the 249 patients with MS and, on the prevalence day, 42.7 years. The most frequent location of clinical MS lesions in the central nervous system was the spinal cord (61%), followed by the cerebrum (55%) and optic nerves (41%). Nearly all (96%) of the patients with MS had been examined by magnetic resonance imaging, and 226 (94%) patients of those examined were suggestive of MS. No family history of MS was found in any of the patients. Most (86%) of the patients had no or mild disability on the prevalence day (31 December 2004). Almost all (96%) patients with MS had been treated with corticosteroids. Conclusion Clinical features of patients with MS are described based on the information from the largest case series reported among Chinese. Comparisons and discussions are made with findings from the other populations.
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- He, YQ, et al.
(författare)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- Lin, J, et al.
(författare)
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Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 224-
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Tidskriftsartikel (refereegranskat)abstract
- The advantage of oncolytic viruses (OV) in cancer therapy is their dual effect of directly killing tumours while prompting anti-tumour immune response. Oncolytic parapoxvirus ovis (ORFV) and other OVs are thought to induce apoptosis, but apoptosis, being the immunogenically inert compared to other types of cell death, does not explain the highly inflamed microenvironment in OV-challenged tumors. Here we show that ORFV and its recombinant therapeutic derivatives are able to trigger tumor cell pyroptosis via Gasdermin E (GSDME). This effect is especially prominent in GSDME-low tumor cells, in which ORFV-challenge pre-stabilizes GSDME by decreasing its ubiquitination and subsequently initiates pyroptosis. Consistently, GSDME depletion reduces the proportion of intratumoral cytotoxic T lymphocytes, pyroptotic cell death and the success of tumor ORFV virotherapy. In vivo, the OV preferentially accumulates in the tumour upon systemic delivery and elicits pyroptotic tumor killing. Consequentially, ORFV sensitizes immunologically ‘cold’ tumors to checkpoint blockade. This study thus highlights the critical role of GSDME-mediated pyroptosis in oncolytic ORFV-based antitumor immunity and identifies combinatorial cancer therapy strategies.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Song, YJ, et al.
(författare)
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The Microbiota in Hematologic Malignancies
- 2020
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Ingår i: Current treatment options in oncology. - : Springer Science and Business Media LLC. - 1534-6277 .- 1527-2729. ; 21:1, s. 2-
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Sun, C, et al.
(författare)
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Association of sleep behaviour and pattern with the risk of glaucoma: a prospective cohort study in the UK Biobank
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:11, s. e063676-
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Tidskriftsartikel (refereegranskat)abstract
- Given the role of intraocular pressure in glaucoma, the patient’s sleeping pattern might contribute to the development and progression of glaucoma. We performed a study to understand the association between sleep behaviours and glaucoma.DesignOur study was a prospective cohort study.SettingThis was a prospective cohort study in the UK Biobank. Self-reported data on five sleep behaviours were collected using a questionnaire at baseline. We identified four sleep patterns based on a cluster analysis of the sleep behaviours.ParticipantsIn the UK Biobank, 409 053 participants were recruited between 2006 and 2010 and followed for a diagnosis of glaucoma. We identified glaucoma as any hospital admission with a diagnosis of glaucoma, based on UK Biobank inpatient hospital data. Individuals who withdrew from the UK Biobank, or were diagnosed with glaucoma before recruitment, or had self-reported surgery or laser treatment for glaucoma, or had no information on sleep behaviors were excluded.Primary and secondary outcome measuresWe estimated hazard ratios (HRs) with 95% confidence intervals (CI) using Cox proportional hazards models to estimate the associations of different sleep behaviors, as well as identified sleep patterns, with the risk of glaucoma, adjusting for multiple confounders.ResultsCompared with individuals who had a healthy sleep pattern, an excess risk of any glaucoma was observed among individuals with snoring and daytime sleepiness (HR 1.11, 95% CI 1.03 to 1.19) or insomnia and short/long sleep duration (HR 1.13, 95% CI 1.06 to 1.20), but not late chronotype sleep pattern (HR 0.98, 95% CI 0.93 to 1.03).ConclusionSnoring, daytime sleepiness, insomnia, and short/long duration, individually or jointly, were all associated with the risk of glaucoma. These findings underscore the need for sleep intervention for individuals at high risk of glaucoma as well as potential ophthalmologic screening among individuals with chronic sleep problems for glaucoma prevention.
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- Wang, JR, et al.
(författare)
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Cardiovascular-related deaths at the beginning of the COVID-19 outbreak: a prospective analysis based on the UK Biobank
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:6, s. e046931-
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Tidskriftsartikel (refereegranskat)abstract
- To assess the impact of the COVID-19 outbreak on cardiovascular disease (CVD) related mortality and hospitalisation.DesignCommunity-based prospective cohort study.SettingThe UK Biobank.Participants421 372 UK Biobank participants who were registered in England and alive as of 1 January 2020.Primary and secondary outcome measuresThe primary outcome of interest was CVD-related death, which was defined as death with CVD as a cause in the death register. We retrieved information on hospitalisations with CVD as the primary diagnosis from the UK Biobank hospital inpatient data. The study period was 1 January 2020 to June 30 2020, and we used the same calendar period of the three preceding years as the reference period. In order to control for seasonal variations and ageing of the study population, standardised mortality/incidence ratios (SMRs/SIRs) with 95% CIs were used to estimate the relative risk of CVD outcomes during the study period, compared with the reference period.ResultsWe observed a distinct increase in CVD-related deaths in March and April 2020, compared with the corresponding months of the three preceding years. The observed number of CVD-related deaths (n=218) was almost double in April, compared with the expected number (n=120) (SMR=1.82, 95% CI 1.58 to 2.07). In addition, we observed a significant decline in CVD-related hospitalisations from March onwards, with the lowest SIR observed in April (0.45, 95% CI 0.41 to 0.49).ConclusionsThere was a distinct increase in the number of CVD-related deaths in the UK Biobank population at the beginning of the COVID-19 outbreak. The shortage of medical resources for hospital care and stress reactions to the pandemic might have partially contributed to the excess CVD-related mortality, underscoring the need of sufficient healthcare resources and improved instructions to the public about seeking healthcare in a timely way.
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- Wang, Y, et al.
(författare)
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Trends in incident diagnoses and drug prescriptions for anxiety and depression during the COVID-19 pandemic: an 18-month follow-up study based on the UK Biobank
- 2023
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 13:1, s. 12-
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Tidskriftsartikel (refereegranskat)abstract
- Serious concerns have been raised about the negative effects of the COVID-19 pandemic on population psychological well-being. However, limited data exist on the long-term effects of the pandemic on incident psychiatric morbidities among individuals with varying exposure to the pandemic. Leveraging prospective data from the community-based UK Biobank cohort, we included 308,400 participants free of diagnosis of anxiety or depression, as well as 213,757 participants free of anxiolytics or antidepressants prescriptions, to explore the trends in incident diagnoses and drug prescriptions for anxiety and depression from 16 March 2020 to 31 August 2021, compared to the pre-pandemic period (i.e., 1 January 2017 to 31 December 2019) and across populations with different exposure statuses (i.e., not tested for COVID-19, tested negative and tested positive). The age- and sex-standardized incidence ratios (SIRs) were calculated by month which indicated an increase in incident diagnoses of anxiety or depression among individuals who were tested for COVID-19 (tested negative: SIR 3.05 [95% confidence interval 2.88–3.22]; tested positive: 2.03 [1.76–2.34]), especially during the first six months of the pandemic (i.e., March-September 2020). Similar increases were also observed for incident prescriptions of anxiolytics or antidepressants (tested negative: 1.56 [1.47–1.67]; tested positive: 1.41 [1.22–1.62]). In contrast, individuals not tested for COVID-19 had consistently lower incidence rates of both diagnoses of anxiety or depression (0.70 [0.67–0.72]) and prescriptions of respective psychotropic medications (0.70 [0.68–0.72]) during the pandemic period. These data suggest a distinct rise in health care needs for anxiety and depression among individuals tested for COVID-19, regardless of the test result, in contrast to a reduction in health care consumption for these disorders among individuals not tested for and, presumably, not directly exposed to the disease.
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- Thomas, HS, et al.
(författare)
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- 2019
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