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1.
  • Sbarra, AN, et al. (author)
  • Mapping routine measles vaccination in low- and middle-income countries
  • 2021
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 589:7842, s. 415-
  • Journal article (peer-reviewed)abstract
    • The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1–4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5–8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
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  • Bhattacharjee, Natalia V, et al. (author)
  • Global fertility in 204 countries and territories, 1950-2021, with forecasts to 2100 : a comprehensive demographic analysis for the Global Burden of Disease Study 2021.
  • 2024
  • In: The Lancet. - 0140-6736 .- 1474-547X.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios.METHODS: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline.FINDINGS: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction.INTERPRETATION: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world.FUNDING: Bill & Melinda Gates Foundation.
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  • Kinyoki, DK, et al. (author)
  • Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
  • 2020
  • In: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
  • Journal article (peer-reviewed)abstract
    • A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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  • Abdollahi, Maryam, et al. (author)
  • Anti-tumor effect of berberine on chronic lymphocytic leukemia cells
  • 2022
  • In: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 39:12
  • Journal article (peer-reviewed)abstract
    • Chronic lymphocytic leukemia (CLL) is a blood malignancy that is characterized by remarkable expression of CD69 and Ki67 in CLL cells. Elevated levels of Cleaved-Poly (ADP-ribose) polymerase-1 (PARP1) and microRNA-155 (MiR-155) are related to poor prognosis of disease. Berberine as a natural isoquinoline alkaloid, has shown an anti-tumor potential in tumor cells. The objective of present study was to explore some aspects of molecular mechanisms of berberine effect in CLL cells. To analyze the expression of CD69 and Ki67 using flow cytometry, 16 peripheral blood samples and seven bone marrow aspirates were collected from CLL patients. Isolated peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) were treated with 25 mu M of berberine for 24 h. The level of miR-155 expression was subsequently evaluated by real-time PCR. Furthermore, western blot was used for assessment of cleaved PARP1. Our results demonstrated a significant reduction in CD69 and Ki67 expression on CD19(+) cells when the cells were treated by berberine. Interestingly, the expression level of miR-155 was reduced after berberine treatment in compare to the control group. Furthermore, western blotting revealed an increased level of cleaved PARP1 in dose-dependently manner in CLL cells. The results confirmed the anti-tumor impact of berberine on CLL cells through reducing CD69, Ki67, and miR-155 expression and increasing cleaved PARP1 may be considered as an option for future clinical studies.
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  • Abdollahi, Meisam, et al. (author)
  • RAP-NoC : Reliability Assessment of Photonic Network-on-Chips, A simulator
  • 2021
  • In: Proceedings of the 8th ACM international conference on nanoscale computing and communication (ACM NANOCOM 2021). - New York, NY, USA : Association for Computing Machinery (ACM).
  • Conference paper (peer-reviewed)abstract
    • Nowadays, optical network-on-chip is accepted as a promising alternative solution for traditional electrical interconnects due to lower transmission delay and power consumption as well as considerable high data bandwidth. However, silicon photonics struggles with some particular challenges that threaten the reliability of the data transmission process.The most important challenges can be considered as temperature fluctuation, process variation, aging, crosstalk noise, and insertion loss. Although several attempts have been made to investigate the effect of these issues on the reliability of optical network-on-chip, none of them modeled the reliability of photonic network-on-chip in a system-level approach based on basic element failure rate. In this paper, an analytical model-based simulator, called Reliability Assessment of Photonic Network-on-Chips (RAP-NoC), is proposed to evaluate the reliability of different 2D optical network-on-chip architectures and data traffic. The experimental results show that, in general, Mesh topology is more reliable than Torus considering the same size. Increasing the reliability of Microring Resonator (MR) has a more significant impact on the reliability of an optical router rather than a network.
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  • Abdollahi, Sara, et al. (author)
  • A dose planning study for cardiac and lung dose sparing techniques in left breast cancer radiotherapy : Can free breathing helical tomotherapy be considered as an alternative for deep inspiration breath hold?
  • 2023
  • In: Technical Innovations and Patient Support in Radiation Oncology. - : Elsevier BV. - 2405-6324. ; 25
  • Journal article (peer-reviewed)abstract
    • Purpose: To investigate the possibility to be able to offer left sided breast cancer patients, not suitable for DIBH, an organ at risk saving treatment. Materials and Methods: Twenty patients receiving radiotherapy for left breast cancer in DIBH were enrolled in the study. Planning CT scans were acquired in the same supine treatment position in FB and DIBH. 3DCRT_DIBH plans were designed and optimized using two parallel opposed tangent beams (with some additional segments) for the breast and chest wall and anterior-posterior fields for regional lymph nodes irradiation. Additionally, FB helical tomotherapy plans were optimized to minimize heart and lung dose. All forty plans were optimized with at least 95% of the total CTV covered by the 95% of prescribed dose of 50 Gy in 25 fractions. Results: HT_FB plans showed significantly better dose homogeneity and conformity compared to the 3DCRT_DIBH specially for regional nodal irradiation. The heart mean dose was almost comparable in 3DCRT_DIBH and HT_FB while the volume (%) of the heart receiving 25 Gy had a statistically significant reduction from 7.90 ± 3.33 in 3DCRT_DIBH to 0.88 ± 0.66 in HT_FB. HT_FB was also more effective in left descending artery (LAD) mean dose reduction about 100% from 30.83 ± 9.2 Gy to 9.7 ± 3.1. The ipsilateral lung volume receiving 20 Gy has a further reduction of 43 % in HT_FB compared with 3DCRT_DIBH. For low dose comparison, 3DCRT_DIBH was superior for contralateral organ sparing compared to the HT_FB due to the limited angle for dose delivery. Conclusion: For patients who cannot be a candidate for DIBH for any reason, HT in free breathing may be a good alternative and provides heart and ipsilateral lung dose sparing, however with the cost of increased dose to contralateral breast and lung.
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  • Abdollahi, Sara, et al. (author)
  • Dynamic anthropomorphic thorax phantom for quality assurance of motion management in radiotherapy
  • 2024
  • In: Physics and imaging in radiation oncology. - 2405-6316. ; 30
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Motion management techniques are important to spare the healthy tissue adequately. However, they are complex and need dedicated quality assurance. The aim of this study was to create a dynamic phantom designed for quality assurance and to replicate a patient's size, anatomy, and tissue density. Materials and methods: A computed tomography (CT) scan of a cancer patient was used to create molds for the lungs, heart, ribs, and vertebral column via additive manufacturing. A pump system and software were developed to simulate respiratory dynamics. The extent of respiratory motion was quantified using a 4DCT scan. End-to-end tests were conducted to evaluate two motion management techniques for lung stereotactic body radiotherapy (SBRT). Results: The chest wall moved between 4 mm and 13 mm anteriorly and 2 mm to 7 mm laterally during the breathing. The diaphragm exhibited superior-inferior movement ranging from 5 mm to 16 mm in the left lung and 10 mm to 36 mm in the right lung. The left lung tumor displaced ± 7 mm superior-inferiorly and anterior-posteriorly. The CT numbers were for lung: −716 ± 108 HU (phantom) and −713 ± 70 HU (patient); bone: 460 ± 20 HU (phantom) and 458 ± 206 HU (patient); soft tissue: 92 ± 9 HU (phantom) and 60 ± 25 HU (patient). The end-to-end testing showed an excellent agreement between the measured and the calculated dose for ion chamber and film dosimetry. Conclusions: The phantom is recommended for quality assurance, evaluating the institution's specific planning and motion management strategies either through end-to-end testing or as an external audit phantom.
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  • Abdollahi, Sara, et al. (author)
  • Surface guided 3DCRT in deep-inspiration breath-hold for left sided breast cancer radiotherapy : implementation and first clinical experience in Iran
  • 2022
  • In: Reports of Practical Oncology and Radiotherapy. - 1507-1367. ; 27:5, s. 881-896
  • Journal article (peer-reviewed)abstract
    • Background: The aim of the study is to evaluate the overall accuracy of the surface-guided radiotherapy (SGRT) workflow through a comprehensive commissioning and quality assurance procedures and assess the potential benefits of deep-inspiration breath-hold (DIBH) radiotherapy as a cardiac and lung dose reduction approach for left-sided breast cancer irradiation. Materials and methods: Accuracy and reproducibility of the optical surface scanner used for DIBH treatment were evaluated using different phantoms. Patient positioning accuracy and reproducibility of DIBH treatment were evaluated. Twenty patients were studied for treatment plan quality in target dose coverage and healthy organ sparing for the two different treatment techniques. Results: Reproducibility tests for the surface scanner showed good stability within 1 mm in all directions. The maximum position variation between applied shifts on the couch and the scanner measured offsets is 1 mm in all directions. The clinical study of 200 fractions showed good agreement between the surface scanner and portal imaging with the isocenter position deviation of less than 3 mm in each lateral, longitudinal, and vertical direction. The standard deviation of the DIBH level showed a value of < 2 mm during all evaluated DIBHs. Compared to the free breathing (FB) technique, DIBH showed significant reduction of 48% for heart mean dose, 43% for heart V25, and 20% for ipsilateral lung V20. Conclusion: Surface-guided radiotherapy can be regarded as an accurate tool for patient positioning and monitoring in breast radiotherapy. DIBH treatment are considered to be effective techniques in heart and ipsilateral lung dose reductions for left breast radiotherapy.
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  • Bahrami, Ataallah, et al. (author)
  • Combined Effect of Operating Parameters on Separation Efficiency and Kinetics of Copper Flotation
  • 2019
  • In: Mining, metallurgy & exploration. - : Springer. - 2524-3462 .- 2524-3470. ; 36:2, s. 409-421
  • Journal article (peer-reviewed)abstract
    • This study aims to investigate the effects of operational variables on concentrate grade, recovery, separation efficiency, and kinetic parameters of the copper flotation process. For this purpose, the effects of the pulp solids content, collector and frother dosage, and preparation and concentrate collection time were studied using a Taguchi experimental design. The results of statistical analyses indicated that the concentrate collection time and pulp density were the most influential parameters on concentrate grade. Considering copper recovery, concentrate collection time, collector dosage, and pulp density were the most significant variables, in decreasing order of importance. Also, the separation efficiency was mostly influenced by the concentrate collection time. Furthermore, kinetic studies showed that the second-order rectangular distribution model perfectly matched the experimental flotation data. The highest kinetic constant of 0.0756 s−1 was obtained from the test, which was performed with 35% solids content and 40 and 20 g/t collector and frother, respectively. The highest predicted copper recovery of 99.57% was obtained from the test at 30% solids content, and the collector and frother dosages of 40 and 15 g/t, respectively.
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  • Brauer,, Michael, et al. (author)
  • Burden of disease scenarios for 204 countries and territories, 2022-2050 : a forecasting analysis for the Global Burden of Disease Study 2021.
  • 2024
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 403:10440, s. 2204-2256
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.METHODS: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.FINDINGS: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8-63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0-45·0] in 2050) and south Asia (31·7% [29·2-34·1] to 15·5% [13·7-17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4-40·3) to 41·1% (33·9-48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6-25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5-43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5-17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7-11·3) in the high-income super-region to 23·9% (20·7-27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5-6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2-26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [-0·6 to 3·6]).INTERPRETATION: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.FUNDING: Bill & Melinda Gates Foundation.
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  • Brauer,, Michael, et al. (author)
  • Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021 : a systematic analysis for the Global Burden of Disease Study 2021.
  • 2024
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 403:10440, s. 2162-2203
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.METHODS: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.FINDINGS: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).INTERPRETATION: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.FUNDING: Bill & Melinda Gates Foundation.
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16.
  • Bryazka, D., et al. (author)
  • Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
  • 2022
  • In: Lancet. - 0140-6736. ; 400:10347, s. 185-235
  • Journal article (peer-reviewed)abstract
    • Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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17.
  • Burstein, R., et al. (author)
  • Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
  • 2019
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
  • Journal article (peer-reviewed)abstract
    • Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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18.
  • GBD 2021 Risk Factors Collaborators,, et al. (author)
  • Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
  • 2024
  • In: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2162-2203
  • Journal article (peer-reviewed)abstract
    • Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.The GBD 2021 risk factor analysis used data from 54561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.Bill & Melinda Gates Foundation.
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19.
  • Ghazinour, Mehdi, 1967-, et al. (author)
  • Age and gender differences in the use of various poisoning methods for deliberate self-harm in individuals admitted to Loghman Hospital in Tehran (2000-2004)
  • 2008
  • In: Journal of Suicide and Life-threatening Behaviour. - : Wiley. - 0363-0234 .- 1943-278X. ; 39:2, s. 231-239
  • Journal article (peer-reviewed)abstract
    • Different methods of poisoning used by individuals with the diagnosis of parasuicide admitted to the Loghman Hospital, Tehran, from 2000 to 2004 were investigated, with particular focus on gender and age differences. Drugs, pesticides, and other agricultural chemicals (women: 12.7%, men: 9%) were the most commonly used methods. In males, the percentage of use of drugs increased with age, but the frequency of pesticides use decreased with age. In females, drugs were most often used in the youngest age group, whereas the use of pesticides was lowest in the youngest age category. Females outnumbered males, especially in the youngest age group of 10 to 19 years olds. Drugs and pesticides were the substances used most often for parasuicide in each age group regardless of gender.
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20.
  • Jafari, Mohammad, et al. (author)
  • A comparative study on the effect of flotation reagents on growth and iron oxidation activities of Leptospirillum ferrooxidans and Acidithiobacillus ferrooxidans
  • 2017
  • In: Minerals. - : MDPI. - 2075-163X. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Recently, extraction of metals from different resources using a simple, efficient, and low-cost technique-known as bioleaching-has been widely considered, and has turned out to be an important global technology. Leptospirillum ferrooxidans and Acidithiobacillus (Thiobacillus) ferrooxidans are ubiquitous bacteria in the biomining industry. To date, the effects of commercial flotation reagents on the biooxidation activities of these bacteria have not been thoroughly studied. This investigation, by using various systematic measurement methods, studied the effects of various collectors and frothers (collectors: potassium amylxanthate, potassium isobutyl-xanthate, sodium ethylxanthate, potassium isopropylxanthate, and dithiophosphate; and frothers: pine oil and methyl isobutyl carbinol) on L. ferrooxidans and A. ferrooxidans activities. In general, results indicate that in the presence of these collectors and frothers, L. ferrooxidans is less sensitive than T. ferrooxidans. In addition, the inhibition effect of collectors on both bacteria is recommended in the following order: for the collectors, potassium isobutyl-xanthate > dithiophosphate > sodium ethylxanthate > potassium isobutyl-xanthate > potassium amylxanthate; and for the frothers, methyl isobutyl carbinol > pine oil. These results can be used for the optimization of biometallurgical processes or in the early stage of a process design for selection of flotation reagents.
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21.
  • Jafari, Mohammad, et al. (author)
  • Effects of Conventional Flotation Frothers on the Population of Mesophilic Microorganisms in Different Cultures
  • 2019
  • In: Processes. - : MDPI. - 2227-9717. ; 7:10
  • Journal article (peer-reviewed)abstract
    • Bioleaching is an environment-friendly and low-investment process for the extraction of metals from flotation concentrate. Surfactants such as collectors and frothers are widely used in the flotation process. These chemical reagents may have inhibitory effects on the activity of microorganisms through a bioleaching process; however, there is no report indicating influences of reagents on the activity of microorganisms in the mixed culture which is mostly used in the industry. In this investigation, influences of typical flotation frothers (methyl isobutyl carbinol and pine oil) in different concentrations (0.01, 0.10, and 1.00 g/L) were examined on activates of bacteria in the mesophilic mixed culture (Acidithiobacillus ferrooxidans, Leptospirillum ferrooxidans, and Acidithiobacillus thiooxidans). For comparison purposes, experiments were repeated by pure cultures of Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans in the same conditions. Results indicated that increasing the dosage of frothers has a negative correlation with bacteria activities while the mixed culture showed a lower sensitivity to the toxicity of these frothers in comparison with examined pure cultures. Outcomes showed the toxicity of Pine oil is lower than methyl isobutyl carbinol (MIBC). These results can be used for designing flotation separation procedures and to produce cleaner products for bio extraction of metals.
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22.
  • Jafari, Mohammad, et al. (author)
  • Study effects of conventional flotation reagents on bioleaching of zinc sulfide
  • 2019
  • In: Journal of Industrial and Engineering Chemistry. - : Elsevier. - 1226-086X .- 1876-794X. ; 78, s. 364-371
  • Journal article (peer-reviewed)abstract
    • Although flotation and bio-extraction of metals from its products are extensively investigated, there are few studied which evaluated the effects of reagents on bioleaching process. Both structure and concentration of flotation reagents are effective factors on microorganism activities. In this study, Kendall’s tau (τ) as a statistical method was used to statistically access the effect of typical sulfide flotation surfactants (collectors: potassium amyl-xanthate, potassium isobutyl-xanthate, sodium ethyl-xanthate, potassium isopropyl-xanthate, and Dithiophosphate), and frothers: pine oil and methyl isobutyl carbinol) on the bioleaching of Zn sulfides in a mixed culture (Leptospirillum ferrooxidans, Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans). To consider both structure and concentration of these reagents, their molarities were used for the statistical evaluations. The Kendall assessments indicated that by increasing in the molarity of reagents, the pH value (the most effective factors of bioleaching) was increased (τ: 0.56) while the ORP value (τ: -0.54), Fe ratio (τ: -0.51) and numbers of oxidizing bacteria (τ: -0.38) in the solution were decreased. Therefore, as a result of these multi-interactions, by increasing the molarity of reagents, Zn recovery was decreased (τ: -0.45). These results potentially can be used for selection of flotation reagents when bioleaching would be the metallurgical metal extraction method.
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23.
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24.
  • Khan, Tauseef A., et al. (author)
  • Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke : Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals
  • 2013
  • In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 42:2, s. 475-492
  • Journal article (peer-reviewed)abstract
    • Background At the APOE gene, encoding apolipoprotein E, genotypes of the epsilon 2/epsilon 3/epsilon 4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk. Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT). Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for epsilon 2/epsilon 2; 0.85 (95% CrI: 0.78-0.92) for epsilon 2/epsilon 3; 1.05 (95% CrI: 0.89-1.24) for epsilon 2/epsilon 4; 1.05 (95% CrI: 0.99-1.12) for epsilon 3/epsilon 4; and 1.12 (95% CrI: 0.94-1.33) for epsilon 4/epsilon 4 using the epsilon 3/epsilon 3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 x 10(-152)), apolipoprotein B (P-trend: 8.7 x 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 x 10(-26)) and HDL-C (P-trend: 1.6 x 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear. Conclusions In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE epsilon 2/epsilon 2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
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25.
  • Kianersi, Farzad, et al. (author)
  • Biosynthesis of rutin changes in Capparis spinosa due to altered expression of its pathway genes under elicitors' supplementation
  • 2020
  • In: Plant Cell Tissue and Organ Culture. - : Springer Nature. - 0167-6857 .- 1573-5044. ; 141:3, s. 619-631
  • Journal article (peer-reviewed)abstract
    • Caper plant is (Capparis spinosa L.) a good source of rutin which plays a key role in the human diet. In this study, the effect of different concentrations of salicylic acid (SA) and methyl jasmonate (MeJA) on the weight of anther-derived calli and their rutin contents were assessed in caper plants. Also, we investigated the rutin content and expression pattern of some rutin related genes in leaves of caper plants at vegetative and fresh fruiting growth stages under SA and MeJA treatments. In the first experiment, the highest rutin contents were observed in anther-derived calli treated with 10 mu M MeJA and 100 mg L-1 SA after 2 weeks from initial treatments, which were 2.44 and 2.22-fold higher than control. Also, the treatment of caper plants with150 mu M MeJA and 100 mg L-1 SA resulted in a higher increase in the rutin content of leaves at the fresh fruiting stage (61.46 and 9.99 mg g(-1) DW, respectively), in the second experiment. Among the studied genes, the FLS gene showed the highest expression in the leaves of the MeJA- and SA-treated plants at vegetative growth stage, while in the fresh fruiting stage the highest expression was related to the RT gene. Use of 150 mu M MeJA and 100 mg L-1 SA enhanced the expression levels of the RT gene up to 7.36 and 2.89 times of the control, respectively. These results suggest that rutin content and the expression patterns of rutin biosynthesis genes in caper can be significantly enhanced by the SA and MeJA treatments in a growth stage-dependent manner. Key message Methyl jasmonate and salicylic acid treatments enhance the rutin contents of Capparis spinosa in vitro and in vivo and up-regulate the rutin biosynthetic related genes at two different growth stages.
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26.
  • Kianersi, Farzad, et al. (author)
  • Identification and tissue-specific expression of rutin biosynthetic pathway genes in Capparis spinosa elicited with salicylic acid and methyl jasmonate
  • 2020
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Capparis spinosa is an edible medicinal plant which is considered as an excellent source of rutin. Rutin is a glycoside of the flavonoid quercetin that has been reported to have a beneficial role in controlling various diseases such as hypertension, arteriosclerosis, diabetes, and obesity. In this study, the partial cDNA of four genes involved in the rutin biosynthetic pathway including 4-coumaroyl CoA ligase (4CL), flavonoid 3'-hydroxylase (F3'H), flavonol synthase (FLS) and flavonol-3-O-glucoside L-rhamnosyltransferase (RT) were identified in C.spinosa plants for the first time. The protein sequences of these genes shared high similarity with the same proteins in other plant species. Subsequently, the expression patterns of these genes as well as rutin accumulation in C.spinosa leaves treated with different concentrations of salicylic acid (SA) and methyl jasmonate (MeJA) and also in different tissues of Caper plants treated with 100 mgL(-1) SA and 150 mu M MeJA were evaluated. The expression of all four genes was clearly up-regulated and rutin contents increased in response to MeJA and SA treatments after 24 h. The highest rutin contents (5.30 mgg(-1) DW and 13.27 mgg(-1) DW), as well as the highest expression levels of all four genes, were obtained using 100 mgL(-1) SA and 150 mu M MeJA, respectively. Among the different tissues, the highest rutin content was observed in young leaves treated with 150 mu M MeJA, which corresponded to the expression of related genes, especially RT, as a key gene in the rutin biosynthetic pathway. These results suggest that rutin content in various tissues of C. spinosa can be enhanced to a significant extent by MeJA and SA treatments and the gene expression patterns of rutin-biosynthesis-related genes are regulated by these elicitors.
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27.
  • Mohammadlou, Maryam, et al. (author)
  • Apoptotic effect of berberine via Bcl-2, ROR1, and mir-21 in patients with B-chronic lymphocytic leukemia
  • 2021
  • In: Phytotherapy Research. - : John Wiley & Sons. - 0951-418X .- 1099-1573. ; 35:4, s. 2025-2033
  • Journal article (peer-reviewed)abstract
    • Berberine is a natural isoquinoline alkaloid that has been shown to inhibit the proliferation and induce apoptosis in a wide variety of tumor cells. However, the action mechanism of berberine in CLL cells is unknown. The previous study has shown that berberine leads to reduced viability and elevated levels of apoptosis in PBMCs of CLL patients. CLL cells are characterized by remarkable expression of Bcl-2 and ROR1 which leads to activation and survival and increases disease progression in patients. High-level expression of miR-21 in patients with CLL is associated with a higher risk of death. Here we investigated the anticancer effects of berberine upon peripheral blood mononuclear cells (PBMCs) of CLL patients. To evaluate the expression of anti-apoptotic proteins and ROR1 using flow cytometry and western blot, PBMCs were treated with 25 mu M of berberine for 24 hr. The expression levels of mir-21 were evaluated by real-time PCR. Examination of treated cells demonstrated that berberine decreased Bcl-2 and ROR1 levels. Although western blot results did not show any change in Bax as a pro-apoptotic protein, an increased Bax/Bcl-2 ratio indicated that mitochondrial pathway is involved in berberine-induced apoptosis of CLL cells. Interestingly, berberine could reduce the expression of miR-21 in comparison to the untreated group. Our findings describe some of the molecular mechanisms of berberine by decreasing Bcl-2, ROR1, and mir-21 which may be considered as a novel apoptosis inducer in CLL cells.
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28.
  • Schumacher, Austin E, et al. (author)
  • Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950-2021, and the impact of the COVID-19 pandemic : a comprehensive demographic analysis for the Global Burden of Disease Study 2021.
  • 2024
  • In: The Lancet. - 0140-6736 .- 1474-547X.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020-21 COVID-19 pandemic period.METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5-65·1] decline), and increased during the COVID-19 pandemic period (2020-21; 5·1% [0·9-9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98-5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50-6·01) in 2019. An estimated 131 million (126-137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7-17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8-24·8), from 49·0 years (46·7-51·3) to 71·7 years (70·9-72·5). Global life expectancy at birth declined by 1·6 years (1·0-2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67-8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4-52·7]) and south Asia (26·3% [9·0-44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic.FUNDING: Bill & Melinda Gates Foundation.
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