| 1. |
- Duffy, Stephen W., et al.
(författare)
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Mammography screening reduces rates of advanced and fatal breast cancers : Results in 549,091 women
- 2020
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Ingår i: Cancer. - : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 126:13, s. 2971-2979
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death.Methods: Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression.Results: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66‐0.84 [P < .001]).Conclusions: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.
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| 2. |
- Tabar, Laszlo, et al.
(författare)
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Early detection of breast cancer rectifies inequality of breast cancer outcomes
- 2021
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Ingår i: Journal of Medical Screening. - : Sage Publications. - 0969-1413 .- 1475-5793. ; 28:1, s. 34-38
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome.Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression.Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range.Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.
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| 3. |
- Chen, Sheng, et al.
(författare)
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On the First Observed Wave-Induced Stress Over the Global Ocean
- 2020
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Ingår i: Journal of Geophysical Research - Oceans. - : AMER GEOPHYSICAL UNION. - 2169-9275 .- 2169-9291. ; 125:12
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Tidskriftsartikel (refereegranskat)abstract
- Despite many investigations/studies on the surface wave-induced stress, the global feature of the wave-induced stress has not been obtained previously as that requires a simultaneous observation of wave spectra and wind on a global scale. The China France Oceanography Satellite (CFOSAT) provided an opportunity for the first time to evaluate the global wave-induced stress and its contribution to the total wind stress. In this study, the global spatial distributions of wave-induced stress and its correlated index for August to November in 2019 are presented using the simultaneous ocean surface winds and wave spectra from the CFOSAT. The main results show that the wave-induced stress is fundamentally dependent on the wind and wave fields on a global scale and shows significant temporal and spatial variations. Further analyses indicate that there is an upward momentum flux under strong swells and low wind speeds (below similar to 5 m/s), and an anticorrelation between the dimensionless wave-induced stress and the proportion of swell energy to the total. Finally, the variations of the surface wave induced wind stress are clear asymmetric between northern and southern hemispheres in late summer but symmetric in late fall, which are closely associated with the seasonal changes in large-scale atmospheric circulation.
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| 4. |
- Guo, Ying, et al.
(författare)
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A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation.
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| 5. |
- Liu, Jiale, et al.
(författare)
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STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs)
- 2024
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Ingår i: Cancer Letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 588
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy resistance in ovarian cancer hampers cure rates, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Despite their known impact on cancer progression and chemotherapy resistance, the specific mechanism by which CAFs regulate the tumor inflammatory environment remains unclear. This study reveals that cisplatin facilitates DNA transfer from ovarian cancer cells to CAFs, activating the CGAS-STING-IFNB1 pathway in CAFs and promoting IFNB1 release. Consequently, this reinforces cancer cell resistance to platinum drugs. High STING expression in the tumor stroma was associated with a poor prognosis, while inhibiting STING expression enhanced ovarian cancer sensitivity. Understanding the relevance of the CGAS-STING pathway in CAFs for platinum resistance suggests targeting STING as a promising combination therapy for ovarian cancer, providing potential avenues for improved treatment outcomes.
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| 6. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 7. |
- Tabár, László, et al.
(författare)
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Evaluation issues in the Swedish Two-County Trial of breast cancer screening : An historical review
- 2017
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Ingår i: Journal of Medical Screening. - : SAGE PUBLICATIONS LTD. - 0969-1413 .- 1475-5793. ; 24:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To summarize debate and research in the Swedish Two-County Trial of mammographic screening on key issues of trial design, endpoint evaluation, and overdiagnosis, and from these to infer promising directions for the future. Methods: A cluster-randomized controlled trial of the offer of breast cancer screening in Sweden, with a single screen of the control group at the end of the screening phase forms the setting for a historical review of investigations and debate on issues of design, analysis, and interpretation of results of the trial. Results: There has been considerable commentary on the closure screen of the control group, ascertainment of cause of death, and cluster randomization. The issues raised were researched in detail and the main questions answered in publications between 1989 and 2003. Overdiagnosis issues still remain, but methods of estimation taking full account of lead time and of nonscreening influences on incidence (taking place mainly before 2005) suggest that it is a minor phenomenon. Conclusion: Despite resolution of issues relating to this trial in peer-reviewed publications dating from years, or even decades ago, issues that already have been addressed continue to be raised. We suggest that it would be more profitable to concentrate efforts on current research issues in breast cancer diagnosis, treatment, and prevention.
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| 8. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 9. |
- Xue, Tian-Tian, et al.
(författare)
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Ignored Biodiversity in Acid Soil Islands in Karst Areas, South China : Impatiens longlinensis (Balsaminaceae), a New Critically Endangered Species
- 2020
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Ingår i: Systematic Botany. - 0363-6445 .- 1548-2324. ; 45:4, s. 891-899
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Tidskriftsartikel (refereegranskat)abstract
- The karst area in South China is notable for its fragile vegetation and unique flora with many narrow endemic species, and is one of the most threatened biodiversity hotspots in the world. However, the biodiversity of acid soil areas scattered in the karst area have previously been underestimated. With a recent increase of new discoveries of plants and animals, the conservation of biodiversity in these acid soil areas has become urgent. This study deals with a new species, Impatiens longlinensis . The new species is similar to I. yui and I. lasiophyton in having pubescence, two lateral sepals, funnelform lower sepal, and linear capsule. But it can be distinguished by having orbicular to obovate dorsal sepals and oblong to elliptic lower and upper lobes of lateral united petals. Moreover, molecular data and micro-morphological evidence also support that the species is new to science. The new species is only known from a valley near the summit of Mt. Jinzhongshan within an area of less than 5 km2. Based on the Red List categories and criteria developed by the International Union for Conservation of Nature, and the threat posed by exploitation for tourism development, we categorize it as Critically Endangered (CR).
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| 10. |
- Yuan, Shuai, et al.
(författare)
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Health effects of high serum calcium levels : Updated phenome-wide Mendelian randomisation investigation and review of Mendelian randomisation studies
- 2022
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 76
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Forskningsöversikt (refereegranskat)abstract
- BackgroundCalcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.MethodsOne-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.FindingsHigher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.InterpretationThis study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed
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