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- Blach, S., et al.
(författare)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Tidskriftsartikel (refereegranskat)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 4. |
- Peters, S., et al.
(författare)
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Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
- 2021
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Ingår i: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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| 5. |
- Athey, S. N., et al.
(författare)
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Unraveling Physical and Chemical Effects of Textile Microfibers
- 2022
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Ingår i: Water (Switzerland). - : MDPI AG. - 2073-4441. ; 14:23
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Forskningsöversikt (refereegranskat)abstract
- Microfibers are the most prevalent microplastics in most terrestrial, freshwater, and marine biota as well as in human tissues and have been collected from environmental compartments across most ecosystems and species sampled worldwide. These materials, made of diverse compound types, range from semi-synthetic and treated natural fibers to synthetic microfibers. Microfibers expose organisms across diverse taxa to an array of chemicals, both from the manufacturing process and from environmental adsorption, with effects on organisms at subcellular to population levels. Untangling the physical versus chemical effects of these compounds on organisms is challenging and requires further investigations that tease apart these mechanisms. Understanding how physical and chemical exposures affect organisms is essential to improving strategies to minimize harm.
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| 6. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 10. |
- Guath, Mona, et al.
(författare)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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