| 1. |
- Hu, Jinhong, et al.
(författare)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 2. |
- Li, Wenjing, et al.
(författare)
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Spatial variation in the effects of air pollution on cardiovascular mortality in Beijing, China
- 2019
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Ingår i: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499.
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Tidskriftsartikel (refereegranskat)abstract
- Due to lack of data from multiple air quality monitoring stations, studies about spatial association between concentrations of ambient pollutants and mortality in China are rare. To investigate the spatial variation of association between concentrations of particulate matter less than 10 μm in aerodynamic diameter (PM10) and nitrogen dioxide (NO2) and cardiovascular mortality in Beijing, China, we collected data including daily deaths, concentrations of PM10 and NO2, and meteorological factors from January 1, 2009, to December 31, 2010, in all 16 districts of Beijing. Generalized additive model (GAM) and generalized additive mixed model (GAMM) were used to examine the citywide and district-specific effects of PM10 and NO2 on cardiovascular mortality. The citywide effect derived from GAMM was lower than that derived from GAM and the strongest effects were identified for 2-day moving average lag 0–1. For every 10 μg/m3 increases in concentrations of PM10 and NO2, the corresponding daily cardiovascular mortality increases in 0.31% (95%CI 0.15%, 0.46%) and 1.63% (95%CI 1.11%, 2.13%), respectively. The death risk associated with air pollutants varied across different geographic districts in Beijing. We found spatially varied adverse effects of air pollution on cardiovascular deaths in Beijing. But there was insufficient evidence to show the significant spatial heterogeneity in mortality effects of PM10 and NO2 in this study.
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| 3. |
- Li, Yingming, et al.
(författare)
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Reduction of atmospheric polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during the 2008 Beijing Olympic games
- 2011
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 45:8, s. 3304-3309
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Tidskriftsartikel (refereegranskat)abstract
- A total of 120 air samples were collected at three urban and one rural location in Beijing, China in the summers of 2007-2010, and before, during, and after the Beijing 2008 Olympic Games (BOG), in order to assess the effectiveness of long-term and short-term emission-control measures in reducing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the atmosphere. During the BOG (August, 2008), the PCDD/Fs concentrations decreased to an average value of 1150 fg m−3 (63 fg I-TEQ m−3), which was reduced by approximately 70% from the average in 2007 and by 29% from that in July 2008, before the Olympic event began. Although 2009-2010 levels of PCDD/Fs were significantly higher than 2008, the overall temporal trend was decreasing for summer months during the sampling campaign period. The apparent half-lives of atmospheric PCDD/Fs were estimated to be 3.2-5.8 years by statistically regressing the logarithm PCDD/Fs concentrations versus the number of years passed since 2006. The air concentrations of total suspended particulates (TSP) during the BOG ranged between 135 and 183 μg m−3, showing a 52% reduction from 2007 and 26% decrease from those prior to the Olympic event. No significant relationships were found between meteorological parameters (temperature, humidity, and wind speed) and PCDD/Fs or TSP during the BOG, whereas the PCDD/Fs concentrations were significantly dependent on the air quality (p < 0.05, positive against TSP and negative against visibility). This work is one of few temporal trend studies of atmospheric PCDD/Fs in mainland China, and provides unique insight into the effects of large-scale control measures in improving air quality and reducing one of the most ubiquitous and toxic organic pollutants in the environment.
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| 4. |
- Li, Yunyun, et al.
(författare)
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Understanding Enhanced Microbial MeHg Production in Mining-Contaminated Paddy Soils under Sulfate Amendment : Changes in Hg Mobility or Microbial Methylators?
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:4, s. 1844-1852
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Tidskriftsartikel (refereegranskat)abstract
- Elevated methylmercury (MeHg) production in mining-contaminated paddy soils, despite the high fraction of refractory HgS(s), has been frequently reported, while the underlying mechanisms are not fully understood. Here, we hypothesized that sulfate input, via fertilization, rainfall, and irrigation, is critical in mobilizing refractory HgS(s) and thus enhancing Hg methylation in mining-contaminated paddy soils. To test this hypothesis, the effects of sulfate amendment on Hg methylation and MeHg bioaccumulation in mining-contaminated soil-rice systems were examined. The results indicated 28-61% higher net MeHg production in soils under sulfate amendment (50-1000 mg kg-1), which in turn increased grain MeHg levels by 22-55%. The enhancement of Hg methylation by Hg mobilization in sulfate-amended soils was supported by two observations: (1) the increased Hg(aq) release from HgS(s), the dominant Hg species in the paddy soils, in the presence of sulfide produced following sulfate reduction and (2) the decreases of refractory HgS(s) in soils under sulfate amendment. By contrast, changes in the abundances/activities of potential microbial Hg methylators in different Hg-contaminated soils were not significant following sulfate amendment. Our results highlight the importance to consider enhanced Hg mobility and thus methylation in soils under sulfate amendment.
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| 5. |
- Vos, T., et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 6. |
- Wang, Xiyan, et al.
(författare)
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Association of changes in self-reported sleep duration with mild cognitive impairment in the elderly : a longitudinal study
- 2021
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 13:11, s. 14816-14828
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Tidskriftsartikel (refereegranskat)abstract
- As a symptomatic predementia stage with progressive cognitive decline, mild cognitive impairment (MCI) is common with aging. How changes in self-reported sleep duration affect MCI risk in the older adults remains unclear. Participants aged ≥ 65 years and enrolled at least two waves in the Chinese Longitudinal Healthy Longevity Survey were included in present longitudinal study. Changes in sleep duration were calculated as the difference between two waves and categorized into five groups: decreased >2 h, decreased 0-2h, stable, increased 0-2 h, and increased >2 h. MCI was measured by the Chinese version of the Mini-Mental State Examination. Generalized estimating equation model and restricted cubic spline function was applied to investigate the association. Among 9,005 participants (mean age, 81.19 years; 4,391 male), 2,877 developed MCI. Comparing with individuals with stable sleep duration, MCI risk [odds ratio (95% confidence intervals)] was: 1.15 (0.99-1.34) for decreased >2 h, 0.99 (0.87-1.13) for decreased 0-2h, 1.09 (0.95-1.24) for increased 0-2 h, and 1.57 (1.36-1.81) for increased >2 h, respectively. Similar patterns were observed among subgroup analyses by sex, age, and sleep quality at baseline. For participants with long sleep duration at baseline (>8h), further increased >2 h was associated with higher MCI risk [2.23 (1.55-3.21)]. Either in the whole or subgroup population, a U-shaped association was observed (Pnon-linearity<0.05). In conclusion, changes in self-reported sleep duration were associated with MCI risk in a U-shaped pattern. Strategies that shifting sleep duration into normal range and keeping it stable are essential to prevent MCI in clinical practice.
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| 7. |
- Fan, Chuan-Wen, et al.
(författare)
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Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells
- 2021
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 13:8, s. 12067-12085
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
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| 8. |
- Hao, Yanfen, et al.
(författare)
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Air monitoring of polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides in West Antarctica during 2011-2017 : Concentrations, temporal trends and potential sources
- 2019
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 249, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Annual air samples were collected at various sites in the Fildes Peninsula, West Antarctica from December 2010 to January 2018 using XAD-2 resin passive air samplers to investigate concentrations, temporal trends and potential sources of persistent organic pollutants (POPs) in Antarctic air. Relatively low concentrations of polychlorinated biphenyls (PCBs) (Σ19PCBs: 1.5-29.7 pg/m3), polybrominated diphenyl ethers (PBDEs) (Σ12PBDEs: 0.2-2.9 pg/m3) and organochlorine pesticides (OCPs) (Σ13OCPs: 101-278 pg/m3) were found in the atmosphere of West Antarctica. PCB-11, BDE-47 and hexachlorobenzene (HCB) were the predominant compounds in the atmosphere. The concentrations of PCBs, HCHs, DDTs and endosulfans were found to show decreasing temporal trends, whereas uniform temporal trends were observed for HCB. The atmospheric half-life values for PCBs, HCHs, DDTs and endosulfans in Antarctic air were estimated for the first time, using regressions of the natural logarithm of the concentrations versus the number of years, obtaining the values of 2.0, 2.0, 2.4 and 1.2 year, respectively. An increasing ratio of α-HCH/γ-HCH indicated long residence time for α-HCH and possible transformation of γ-HCH to α-HCH in the atmosphere. The ratios of p,p'-DDT/p,p'-DDE were mostly lower than unity in this study, which could be attributed to aged sources. It was found that long-range atmospheric transport was still considered to be the main contributing factor to the atmospheric levels of the POPs in West Antarctica whereas the contribution of human activities at the Chinese Great Wall Station was minor. The results of this study give a view on the most recent temporal trends and provide new insights regarding the occurrence of various POPs in the Antarctic atmosphere.
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| 9. |
- Ho, Peh Joo, et al.
(författare)
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Comparison of self-reported and register-based hospital medical data on comorbidities in women
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer patients commonly present with comorbidities which are known to influence treatment decisions and survival. We aim to examine agreement between self-reported and register-based medical records (National Patient Register [NPR]). Ascertainment of nine conditions, using individually-linked data from 64,961 women enrolled in the Swedish KARolinska MAmmography Project for Risk Prediction of Breast Cancer (KARMA) study. Agreement was assessed using observed proportion of agreement (overall agreement), expected proportion of agreement, and Cohen's Kappa statistic. Two-stage logistic regression models taking into account chance agreement were used to identify potential predictors of overall agreement. High levels of overall agreement (i.e. ≥86.6%) were observed for all conditions. Substantial agreement (Cohen's Kappa) was observed for myocardial infarction (0.74), diabetes (0.71) and stroke (0.64) between self-reported and NPR data. Moderate agreement was observed for preeclampsia (0.51) and hypertension (0.46). Fair agreement was observed for heart failure (0.40) and polycystic ovaries or ovarian cysts (0.27). For hyperlipidemia (0.14) and angina (0.10), slight agreement was observed. In most subgroups we observed negative specific agreement of >90%. There is no clear reference data source for ascertainment of conditions. Negative specific agreement between NPR and self-reported data is consistently high across all conditions.
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| 10. |
- Li, Honghua, et al.
(författare)
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Levels and distribution of hexabromocyclododecane (HBCD) in environmental samples near manufacturing facilities in Laizhou Bay area, East China
- 2012
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Ingår i: Journal of Environmental Monitoring. - : Royal Society of Chemistry (RSC). - 1464-0325 .- 1464-0333. ; 14:10, s. 2591-2597
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Tidskriftsartikel (refereegranskat)abstract
- A total of 55 samples including soil, sediment, plants (cypress, reed and seepweed) and aquatic species were collected at locations around hexabromocyclododecane (HBCD) manufacturing facilities in Laizhou Bay area, East China. HBCD was determined at concentrations ranging between 0.88 and 6901 ng g(-1) dry weight (dw), 2.93-1029 ng g(-1) dw, 8.88-160241 ng g(-1) dw, and 7.09-815 ng g(-1) lipid weight (lw), respectively. Significant negative correlations (r(2) = 0.54, p = 0.006) were observed between HBCD concentrations in soils and the distance from the manufacturing facility, and the concentrations became constant when the distance was >4 km. The calculation results on the bioaccumulation factors (BAFs) suggested that HBCD may be accumulated in plants. Tissue-specific bioaccumulation of HBCD diastereoisomers was found in aquatic species. For example, in crabs the highest concentrations of HBCD (815 ng g(-1) lw for female and 446 ng g(-1) lw for male) were observed in the gill. Besides the gill, α-HBCD was more preferentially accumulated in the spermary and ovary, while β- and γ-HBCD were more accumulated in the muscle. A similar distribution was also observed in roe and muscle of goby fish.
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