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- Bryazka, D., et al.
(author)
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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
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In: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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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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- James, SL, et al.
(author)
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Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017
- 2020
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In: Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention. - : BMJ. - 1475-5785. ; 26:SUPP_1Supp 1, s. 96-114
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Journal article (peer-reviewed)abstract
- Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries.MethodsWe reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs).FindingsIn 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505).InterpretationInjuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.
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- Haagsma, J. A., et al.
(author)
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The burden of injury in Central, Eastern, and Western European sub-region: a systematic analysis from the Global Burden of Disease 2019 Study
- 2022
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In: Archives of Public Health. - : Springer Science and Business Media LLC. - 0778-7367 .- 2049-3258. ; 80:1
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Journal article (peer-reviewed)abstract
- Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.
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- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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- Sattui, Sebastian E., et al.
(author)
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Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study
- 2021
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In: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864
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Journal article (peer-reviewed)abstract
- Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
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26. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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- Cole, Lorna J., et al.
(author)
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A critical analysis of the potential for EU Common Agricultural Policy measures to support wild pollinators on farmland
- 2020
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In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 57:4, s. 681-694
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Journal article (peer-reviewed)abstract
- Agricultural intensification and associated loss of high-quality habitats are key drivers of insect pollinator declines. With the aim of decreasing the environmental impact of agriculture, the 2014 EU Common Agricultural Policy (CAP) defined a set of habitat and landscape features (Ecological Focus Areas: EFAs) farmers could select from as a requirement to receive basic farm payments. To inform the post-2020 CAP, we performed a European-scale evaluation to determine how different EFA options vary in their potential to support insect pollinators under standard and pollinator-friendly management, as well as the extent of farmer uptake. A structured Delphi elicitation process engaged 22 experts from 18 European countries to evaluate EFAs options. By considering life cycle requirements of key pollinating taxa (i.e. bumble bees, solitary bees and hoverflies), each option was evaluated for its potential to provide forage, bee nesting sites and hoverfly larval resources. EFA options varied substantially in the resources they were perceived to provide and their effectiveness varied geographically and temporally. For example, field margins provide relatively good forage throughout the season in Southern and Eastern Europe but lacked early-season forage in Northern and Western Europe. Under standard management, no single EFA option achieved high scores across resource categories and a scarcity of late season forage was perceived. Experts identified substantial opportunities to improve habitat quality by adopting pollinator-friendly management. Improving management alone was, however, unlikely to ensure that all pollinator resource requirements were met. Our analyses suggest that a combination of poor management, differences in the inherent pollinator habitat quality and uptake bias towards catch crops and nitrogen-fixing crops severely limit the potential of EFAs to support pollinators in European agricultural landscapes. Policy Implications. To conserve pollinators and help protect pollination services, our expert elicitation highlights the need to create a variety of interconnected, well-managed habitats that complement each other in the resources they offer. To achieve this the Common Agricultural Policy post-2020 should take a holistic view to implementation that integrates the different delivery vehicles aimed at protecting biodiversity (e.g. enhanced conditionality, eco-schemes and agri-environment and climate measures). To improve habitat quality we recommend an effective monitoring framework with target-orientated indicators and to facilitate the spatial targeting of options collaboration between land managers should be incentivised.
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- Klenk, T., et al.
(author)
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Taking women on boards : a comparative analysis of public policies in higher education
- 2022
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In: Policy Reviews in Higher Education. - : Informa UK Limited. - 2332-2969 .- 2332-2950. ; 6:2, s. 128-152
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Journal article (peer-reviewed)abstract
- There is growing interest in the underlying mechanisms affecting female leaders in Higher Education (HE). This article compares four countries–Germany, Norway, Poland and Sweden to identify key structural conditions (enablers and barriers) for female representation in academia by studying the regulative framework of government policy. Two research questions are guiding the analysis: first, what (if any) policy instruments are chosen to increase the number of female leaders in HE? Second, to what extent does this choice of instruments mirror either sectorial logic (HE) or national policy styles? The empirical results of the article show that while processes of policy diffusion are observable at the sectoral level, gender equality policies and instrument choice differ considerably in the four countries under consideration. The article thus concludes that national policy styles need to be understood as enabling and disabling policy factors for gender equality in HE shaping the process of translating diffused models decisively.
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- Perez-Nadales, Elena, et al.
(author)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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In: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Journal article (peer-reviewed)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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32. |
- Pinheiro, T., et al.
(author)
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CUBIC-f : An optimized clearing method for cell tracing and evaluation of neurite density in the salamander brain
- 2021
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In: Journal of Neuroscience Methods. - : Elsevier B.V.. - 0165-0270 .- 1872-678X. ; 348
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Journal article (peer-reviewed)abstract
- Background: Although tissue clearing and subsequent whole-brain imaging is now possible, standard protocols need to be adjusted to the innate properties of each specific tissue for optimal results. This work modifies exiting protocols to clear fragile brain samples and documents a downstream pipeline for image processing and data analysis. New Method: We developed a clearing protocol, CUBIC-f, which we optimized for fragile samples, such as the salamander brain. We modified hydrophilic and aqueous’ tissue-clearing methods based on Advanced CUBIC by incorporating Omnipaque 350 for refractive index matching. Results: By combining CUBIC-f, light sheet microscopy and bioinformatic pipelines, we quantified neuronal cell density, traced genetically marked fluorescent cells over long distance, and performed high resolution characterization of neural progenitor cells in the salamander brain. We also found that CUBIC-f is suitable for conserving tissue integrity in embryonic mouse brains. Comparison with exiting methods: CUBIC-f shortens clearing and staining times, and requires less reagent use than Advanced CUBIC and Advanced CLARITY. Conclusion: CUBIC-f is suitable for conserving tissue integrity in embryonic mouse brains, larval and adult salamander brains which display considerable deformation using traditional CUBIC and CLARITY protocols.
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- Pinheiro, V. E., et al.
(author)
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Anaerobic digestion of cornmeal : the effect of crude enzyme extract and co-digestion with cow manure
- 2021
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In: Biofuels, Bioproducts and Biorefining. - : John Wiley and Sons Ltd. - 1932-104X .- 1932-1031.
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Journal article (peer-reviewed)abstract
- This study examined the effect of a crude enzyme extract, containing mainly starch-degrading enzymes, on cornmeal (Zea mays) hydrolysis. This was followed by an investigation of the effect of enzymatic treatment for the anaerobic digestion of this biomass. Cornmeal and cow manure were also co-digested, and both batch and semi-continuous experiments were performed. The enzymatic pretreatment of cornmeal resulted in a yield of 65 ± 5% reducing sugars, with 1:10 w/v (grams of dry substrate per mililiters of enzyme extract) enzyme load at 45 °C for 48 h. There was an 8% enhancement of methane production observed during the batch assays, both when cornmeal hydrolysate was digested and when enzymes were added directly to the digester. Synergetic effects were found when co-digesting cornmeal and cow manure, leading to higher methane yield (280 NmL gVS–1) than that (200 NmL gVS–1) calculated based on the methane potential of the individual substrates. Regarding long-term effects, the laboratory-scale semi-continuous experiments also demonstrated that the co-digestion of cornmeal and cow manure (1:1 volatile solid (VS) basis) led to a stable process reaching an organic loading rate of 3 g VS L day–1 and achieving a daily methane production of 1280.12 ± 99.4 NmL CH4/day. However, when cornmeal was investigated in mono-digestion, and the enzyme extract was directly added during semi-continuous digestion of cornmeal, volatile fatty acid (VFA) accumulation was observed, leading to a decrease in pH, and no significant enhancement of the conversion into methane was observed. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
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- Pinheiro, V. E., et al.
(author)
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Screening and cocktail optimization using experimental mixture design : enzymatic saccharification as a biological pretreatment strategy
- 2021
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In: Biofuels, Bioproducts and Biorefining. - : John Wiley & Sons. - 1932-104X .- 1932-1031.
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Journal article (peer-reviewed)abstract
- Biofuels contribute environment-friendly, renewable energy, minimizing dependence on fossil energy. The pretreatment of biomass is a practical step that accelerates and facilitates the hydrolysis of complex materials. This work aimed to screen, select, and study cocktail formulations for biomass hydrolysis, where the enzymes were provided both from a commercial source (Trichoderma reesei, Novozymes®) and through the cultivation of Aspergillus brasiliensis and Aspergillus tamarii Kita. Experimental mixture designs were used to optimize the enzymatic conversion of substrates into simple sugars. A crude extract rich in amylase (AAB) had a significant favorable influence on cornmeal hydrolysis by maximizing the yield of reducing sugars (RS) (173 μmol mL–1). Celluclast™, rich in cellulase, significantly affected the hydrolysis of banana peel, maximizing the RS yield (175 μmol mL–1). Variable degrees of enzyme synergism were evident from statistical analysis of the biomass hydrolysis.
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- Raghavan, Sukanya, 1974, et al.
(author)
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Conditional Deletion of Pdcd1 Identifies the Cell-Intrinsic Action of PD-1 on Functional CD8 T Cell Subsets for Antitumor Efficacy
- 2021
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Journal article (peer-reviewed)abstract
- Programmed cell death-1 (PD-1) blockade has a profound effect on the ability of the immune system to eliminate tumors, but many questions remain about the cell types involved and the underlying mechanisms of immune activation. To shed some light on this, the cellular and molecular events following inhibition of PD-1 signaling was investigated in the MC-38 colon carcinoma model using constitutive (PD-1 KO) and conditional (PD1cKO) mice and in wild-type mice treated with PD-1 antibody. The impact on both tumor growth and the development of tumor immunity was assessed. In the PD-1cKO mice, a complete deletion of Pdcd1 in tumor-infiltrating T cells (TILs) after tamoxifen treatment led to the inhibition of tumor growth of both small and large tumors. Extensive immune phenotypic analysis of the TILs by flow and mass cytometry identified 20-different T cell subsets of which specifically 5-CD8 positive ones expanded in all three models after PD-1 blockade. All five subsets expressed granzyme B and interferon gamma (IFN gamma). Gene expression analysis of the tumor further supported the phenotypic analysis in both PD-1cKO- and PD-1 Ab-treated mice and showed an upregulation of pathways related to CD4 and CD8 T-cell activation, enhanced signaling through costimulatory molecules and IFN gamma, and non-T-cell processes. Altogether, using PD-1cKO mice, we define the intrinsic nature of PD-1 suppression of CD8 T-cell responses in tumor immunity.
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- Serna-Sanchez, M. A., et al.
(author)
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Plastid phylogenomics resolves ambiguous relationships within the orchid family and provides a solid timeframe for biogeography and macroevolution
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Recent phylogenomic analyses based on the maternally inherited plastid organelle have enlightened evolutionary relationships between the subfamilies of Orchidaceae and most of the tribes. However, uncertainty remains within several subtribes and genera for which phylogenetic relationships have not ever been tested in a phylogenomic context. To address these knowledge-gaps, we here provide the most extensively sampled analysis of the orchid family to date, based on 78 plastid coding genes representing 264 species, 117 genera, 18 tribes and 28 subtribes. Divergence times are also provided as inferred from strict and relaxed molecular clocks and birth-death tree models. Our taxon sampling includes 51 newly sequenced plastid genomes produced by a genome skimming approach. We focus our sampling efforts on previously unplaced clades within tribes Cymbidieae and Epidendreae. Our results confirmed phylogenetic relationships in Orchidaceae as recovered in previous studies, most of which were recovered with maximum support (209 of the 262 tree branches). We provide for the first time a clear phylogenetic placement for Codonorchideae within subfamily Orchidoideae, and Podochilieae and Collabieae within subfamily Epidendroideae. We also identify relationships that have been persistently problematic across multiple studies, regardless of the different details of sampling and genomic datasets used for phylogenetic reconstructions. Our study provides an expanded, robust temporal phylogenomic framework of the Orchidaceae that paves the way for biogeographical and macroevolutionary studies.
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38. |
- Tan, Benedict, et al.
(author)
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The human mitochondrial genome contains a second light strand promoter
- 2022
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In: Molecular Cell. - : Elsevier BV. - 1097-2765. ; 82:19, s. 3646-3660
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Journal article (peer-reviewed)abstract
- The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which ex-pands our long-held understanding of mitochondrial gene expression in humans.
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39. |
- Tarnoki, Adam Domonkos, et al.
(author)
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Lumbar spine abnormalities in patients with obstructive sleep apnoea
- 2021
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland-Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0-3.5/ vs. 0/0-1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.
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