| 51. |
- Wang, Ying, et al.
(författare)
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Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:27, s. 15818-15826
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via the accumulation of cholesterol and inflammatory cells. However, recent evidence suggests that a substantial portion of the plaque may arise from a subset of "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in a clonal fashion. Herein we use multicolor lineage-tracing models to confirm that the mature SMC can give rise to a hyperproliferative cell which appears to promote inflammation via elaboration of complement-dependent anaphylatoxins. Despite being extensively opsonized with prophagocytic complement fragments, we find that this cell also escapes immune surveillance by neighboring macrophages, thereby exacerbating its relative survival advantage. Mechanistic studies indicate this phenomenon results from a generalized opsoninsensing defect acquired by macrophages during polarization. This defect coincides with the noncanonical up-regulation of so-called don't eat me molecules on inflamed phagocytes, which reduces their capacity for programmed cell removal (PrCR). Knockdown or knockout of the key antiphagocytic molecule CD47 restores the ability of macrophages to sense and clear opsonized targets in vitro, allowing for potent and targeted suppression of clonal SMC expansion in the plaque in vivo. Because integrated clinical and genomic analyses indicate that similar pathways are active in humans with cardiovascular disease, these studies suggest that the clonally expanding SMC may represent a translational target for treating atherosclerosis.
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| 52. |
- Molina-Montes, E, et al.
(författare)
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Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:2, s. 319-329
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Tidskriftsartikel (refereegranskat)abstract
- To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI).DesignInformation about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data. Multivariate logistic regression models were applied to derive ORs and 95% CIs. T2DM and PC-related single nucleotide polymorphism (SNP) were used as instrumental variables (IVs) in bidirectional MR analysis to test for two-way causal associations between PC, NODM and LSDM. Indirect and direct effects of the BMI-T2DM-PC association were further explored using mediation analysis.ResultsT2DM was associated with an increased PC risk when compared with non-T2DM (OR=2.50; 95% CI: 2.05 to 3.05), the risk being greater for NODM (OR=6.39; 95% CI: 4.18 to 9.78) and insulin users (OR=3.69; 95% CI: 2.80 to 4.86). The causal association between T2DM (57-SNP IV) and PC was not statistically significant (ORLSDM=1.08, 95% CI: 0.86 to 1.29, ORNODM=1.06, 95% CI: 0.95 to 1.17). In contrast, there was a causal association between PC (40-SNP IV) and NODM (OR=2.85; 95% CI: 2.04 to 3.98), although genetic pleiotropy was present (MR-Egger: p value=0.03). Potential mediating effects of BMI (125-SNPs as IV), particularly in terms of weight loss, were evidenced on the NODM-PC association (indirect effect for BMI in previous years=0.55).ConclusionFindings of this study do not support a causal effect of LSDM on PC, but suggest that PC causes NODM. The interplay between obesity, PC and T2DM is complex.
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| 53. |
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| 54. |
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| 55. |
- Blondel, A., et al.
(författare)
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The SuperFGD Prototype charged particle beam tests
- 2020
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221 .- 1748-0221. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- A novel scintillator detector, the SuperFGD, has been selected as the main neutrino target for an upgrade of the T2K experiment ND280 near detector. The detector design will allow nearly 47r coverage for neutrino interactions at the near detector and will provide lower energy thresholds, significantly reducing systematic errors for the experiment. The SuperFGD is made of optically-isolated scintillator cubes of size 10 x 10 x 10 mm(3), providing the required spatial and energy resolution to reduce systematic uncertainties for future T2K runs. The SuperFGD for T2K will have close to two million cubes in a 1920 x 560 x 1840 mm(3) volume. A prototype made of 24 x 8 x 48 cubes was tested at a charged particle beamline at the CERN PS facility. The SuperFGD Prototype was instrumented with readout electronics similar to the future implementation for T2K. Results on electronics and detector response are reported in this paper, along with a discussion of the 3D reconstruction capabilities of this type of detector. Several physics analyses with the prototype data are also discussed, including a study of stopping protons.
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| 56. |
- Burgman, A., et al.
(författare)
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Updated physics performance of the ESSnuSB experiment
- 2021
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Ingår i: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 81:12
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present the physics performance of the ESSnuSB experiment in the standard three flavor scenario using the updated neutrino flux calculated specifically for the ESSnuSB configuration and updated migration matrices for the far detector. Taking conservative systematic uncertainties corresponding to a normalization error of 5% for signal and 10% for background, we find that there is 10 sigma (13 sigma) CP violation discovery sensitivity for the baseline option of 540 km (360 km) at delta(CP) = +/- 90 degrees. The corresponding fraction of delta(CP )for which CP violation can be discovered at more than 5 sigma is 70%. Regarding CP precision measurements, the 1 sigma error associated with delta(CP )= 0 degrees is around 5 degrees and with delta(CP )= -90 degrees is around 14 degrees (7 degrees) for the baseline option of 540 km (360 km). For hierarchy sensitivity, one can have 3 sigma sensitivity for 540 km baseline except delta(CP) = +/- 90 degrees and 5 sigma sensitivity for 360 km baseline for all values of delta(CP). The octant of theta(23) can be determined at 30 for the values of: theta(23) > 51 degrees (theta(23) < 42 degrees and theta(23) > 49 degrees) for baseline of 540 km (360 km). Regarding measurement precision of the atmospheric mixing parameters, the allowed values at 3 sigma are: 40 degrees < theta(23) < 52 degrees (42 degrees < theta(23) < 51.5 degrees) and 2.485 x 10(-3) eV(2) < Delta(2)(m31) < 2.545 x 10(-3) eV(2) (2.49x 10(-3 ) eV(2) < Delta(2)(m31) < 2.54 x 10(-3) eV(2)) for the baseline of 540 km (360 km).
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| 57. |
- Chen, XD, et al.
(författare)
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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
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Tidskriftsartikel (refereegranskat)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
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| 58. |
- Fahimi, A., et al.
(författare)
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Poultry litter ash characterisation and recovery
- 2020
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Ingår i: Waste Management. - : Elsevier Ltd. - 0956-053X .- 1879-2456. ; 111, s. 10-21
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports a complete characterisation of poultry litter ash and its potential use as a heavy metal stabiliser. We propose a novel approach, in which the ashes deriving from municipal solid waste incineration (MSWI) are combined with poultry litter ash, rather than with coal combustion flue gas desulfurisation (FGD) residues. Heavy metals stabilisation was demonstrated by comparing the elemental concentrations in the leaching solutions of the starting raw and stabilised materials: leachable Pb and Zn showed a reduced solubility. The characterisation was conducted by total reflection X-ray fluorescence (TXRF), X-ray diffraction (XRD), micro-Raman spectroscopy and scanning electron microscopy combined with energy-dispersive X-ray spectrometry (SEM-EDX). The results showed that the poultry litter ash was Ca-, P-, K- and S-rich (>29 g/kg). It contained amorphous materials (i.e. fly ash economiser (FAECO) 73% and fly ash cyclone (FACYC) 61%) and soluble phases (e.g. arkanite and sylvite; up to 13% FAECO and 28% FACYC), as well as resilient crystalline (up to 2% of FAECO and FACYC) and amorphous phases (e.g. hydroxyapatite). After two months, the Pb and Zn concentrations in the leachate solutions were below the limit set by the European regulations for waste disposal (<0.2 mg/L and 1.5 mg/L, respectively). We propose a mechanism for the heavy metals stabilisation based on the carbonation process and high amounts of P, Ca and reactive amorphous phases. In conclusion, it is demonstrated that poultry litter ash can be an effective secondary source of heavy metals, allowing their immobilisation through P- and Ca-based reactive amorphous phases.
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| 59. |
- Hafdi, M, et al.
(författare)
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Design and Development of a Mobile Health (mHealth) Platform for Dementia Prevention in the Prevention of Dementia by Mobile Phone Applications (PRODEMOS) Project
- 2021
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 733878-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China.Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China.Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities.Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes.
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| 60. |
- Huang, C. Y., et al.
(författare)
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The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance
- 2021
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Ingår i: Cell Discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.
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