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2. |
- Casanova-Acebes, M, et al.
(författare)
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Neutrophils instruct homeostatic and pathological states in naive tissues
- 2018
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 215:11, s. 2778-2795
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Tidskriftsartikel (refereegranskat)abstract
- Immune protection relies on the capacity of neutrophils to infiltrate challenged tissues. Naive tissues, in contrast, are believed to remain free of these cells and protected from their toxic cargo. Here, we show that neutrophils are endowed with the capacity to infiltrate multiple tissues in the steady-state, a process that follows tissue-specific dynamics. By focusing in two particular tissues, the intestine and the lungs, we find that neutrophils infiltrating the intestine are engulfed by resident macrophages, resulting in repression of Il23 transcription, reduced G-CSF in plasma, and reinforced activity of distant bone marrow niches. In contrast, diurnal accumulation of neutrophils within the pulmonary vasculature influenced circadian transcription in the lungs. Neutrophil-influenced transcripts in this organ were associated with carcinogenesis and migration. Consistently, we found that neutrophils dictated the diurnal patterns of lung invasion by melanoma cells. Homeostatic infiltration of tissues unveils a facet of neutrophil biology that supports organ function, but can also instigate pathological states.
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3. |
- Maxwell, Tania L., et al.
(författare)
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Global dataset of soil organic carbon in tidal marshes
- 2023
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
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5. |
- Raccosta, L, et al.
(författare)
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The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
- 2013
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 210:9, s. 1711-1728
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs. We report that tumor-derived oxysterols recruit protumor neutrophils in a liver X receptor (LXR)–independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression. We demonstrate that interfering with the oxysterol–CXCR2 axis delays tumor growth and prolongs the overall survival of tumor-bearing mice. These results identify an unanticipated protumor function of the oxysterol–CXCR2 axis and a possible target for cancer therapy.
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7. |
- Conde, E, et al.
(författare)
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Effects of the COVID-19 Health Crisis on Sports Practice, Life Quality, and Emotional Status in Spanish High-Performance Athletes
- 2021
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Ingår i: Frontiers in psychology. - : Frontiers Media SA. - 1664-1078. ; 12, s. 736499-
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Tidskriftsartikel (refereegranskat)abstract
- Spain is one of the many countries highly affected by the COVID-19 crisis, establishing very restrictive measures with a complete lockdown for more than 3 months. This situation forced the complete closure of sport practice and national or international competitions, leading to a negative impact on physical and psychological health of high-performance athletes. Therefore, the objectives of this study were (a) to determine the effects of the COVID-19 health crisis on Spanish high-performance athletes in terms of sports practice, life quality, and emotional state and (b) to identify the profile with the greatest difficulties during and after the lockdown. A sample of 130 high-performance athletes aged between 18 and 34 years (67 women and 63 men) participated in this study (83.1% achieved a medal in National–International elite competitions; 86.9% were considered student-athletes). Measures included socio-demographic data through a 5-dimension ad hoc survey: physical activity and exercise using an adapted version from the International Physical Activity Questionnaire (IPAQ); health status and limitations using an adapted version of SF-12 Health Questionnaire; Perceived stress (Short-PSS); and Mood States (29-item POMS). All participants have shown a significant decrease pre–post-lockdown in both health and performance perception, especially in women, individual athletes, medalists, and student-athletes. Strong limitations of training, attention, and motivation as well as a moderate negative emotional state during lockdown were reported, in women, individual athletes, medalists, and student-athletes. Even with an improved emotional state and energy level in the post-lockdown period, moderate-to-high stress scores were reported by women and medalists. Our findings highlight the importance of paying attention to the physical and psychological health of elite athletes on three profiles: team athletes (due to social distance), student-athletes (dual-career issues), and women athletes (prevalence of implicit gender inequalities in sport).
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8. |
- Dahl, Martin, 1984-, et al.
(författare)
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A 2,000-Year Record of Eelgrass (Zostera marina L.) : Colonization Shows Substantial Gains in Blue Carbon Storage and Nutrient Retention
- 2024
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Ingår i: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 38:3
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Tidskriftsartikel (refereegranskat)abstract
- Assessing historical environmental conditions linked to habitat colonization is important for understanding long-term resilience and improving conservation and restoration efforts. Such information is lacking for the seagrass Zostera marina, an important foundation species across cold-temperate coastal areas of the Northern Hemisphere. Here, we reconstructed environmental conditions during the last 14,000 years from sediment cores in two eelgrass (Z. marina) meadows along the Swedish west coast, with the main aims to identify the time frame of seagrass colonization and describe subsequent biogeochemical changes following establishment. Based on vegetation proxies (lipid biomarkers), eelgrass colonization occurred about 2,000 years ago after geomorphological changes that resulted in a shallow, sheltered environment favoring seagrass growth. Seagrass establishment led to up to 20- and 24-fold increases in sedimentary carbon and nitrogen accumulation rates, respectively. This demonstrates the capacity of seagrasses as efficient ecosystem engineers and their role in global change mitigation and adaptation through CO2 removal, and nutrient and sediment retention. By combining regional climate projections and landscape models, we assessed potential climate change effects on seagrass growth, productivity and distribution until 2100. These predictions showed that seagrass meadows are mostly at risk from increased sedimentation and hydrodynamic changes, while the impact from sea level rise alone might be of less importance in the studied area. This study showcases the positive feedback between seagrass colonization and environmental conditions, which holds promise for successful conservation and restoration efforts aimed at supporting climate change mitigation and adaptation, and the provision of several other crucial ecosystem services. © 2024. The Authors.
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9. |
- Leiva, Claudio A., et al.
(författare)
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Design and Evaluation of an Expert System in a Crushing Plant
- 2018
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Ingår i: Minerals. - : MDPI. - 2075-163X. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- This document presents a proposal for designing an expert system in the Gabriela Mistral Division’s crushing plant belonging to Codelco (Chile) with the objective of maximizing stacked tonnage, allowing the improvement of operational variables that directly interact with the crushing process. In addition, this study considers the impact that occurs in both the process and operational continuity regarding the standardization of the system. In the first stage, a survey and analysis of historic operation data was carried out, which allowed the definition of benchmarking indicators. Subsequently, both modalities of operation were compared, monitoring processed tonnage and detentions related to operational failures. As a result, significant differences were observed in the performance of the critical line operating with expert control, with a 55% reduction in the detentions referred to operational failures. Added to this is the benefit of low cost and improved quality as the control provides an analysis of the variables in reduced time intervals, which is superior to human control.
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13. |
- Del Cura-González, Isabel, et al.
(författare)
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How to Improve Healthcare for Patients with Multimorbidity and Polypharmacy in Primary Care : A Pragmatic Cluster-Randomized Clinical Trial of the MULTIPAP Intervention
- 2022
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- (1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65-74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was -2.42 (95% CI from -4.27 to -0.59) and, between baseline and a 12-month follow-up was -3.40 (95% CI from -5.45 to -1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI.
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14. |
- Gentekaki, Eleni, et al.
(författare)
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Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis
- 2017
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Ingår i: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%-61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize alpha-glucans rather than beta-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease.
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15. |
- Leiva, R. A., et al.
(författare)
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High real-world effectiveness of 12-week elbasvir/grazoprevir without resistance testing in the treatment of patients with HCV genotype 1a infection in Norway
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:3, s. 264-268
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The recommended treatment duration of hepatitis C virus (HCV) genotype 1a (GT1a) infection with elbasvir/grazoprevir (EBR/GZR) in the presence of a high baseline viral load and resistance associated substitutions (RAS) is 16 weeks with ribavirin added. The objective of this study was to evaluate the real-world effectiveness of 12 weeks of EBR/GZR without ribavirin and regardless of baseline viral load and RAS testing. Method: This retrospective, observational cohort study was performed at five Norwegian hospitals that did not systematically utilize RAS testing. All adult patients with chronic HCV GT1a and compensated liver disease who had received 12 weeks of EBR/GZR without ribavirin and baseline RAS testing, were included. The primary endpoint was sustained virologic response at week 12 (SVR12), or if not available, at week 4 (SVR4). Results: We included 433 patients and attained SVR data on 388. The mean age was 45.7 years (22–73 years). 67.2% were male. HIV co-infection was present in 3.8% (16/424) and cirrhosis in 4% (17/424). The viral load was >800 000 IU/mL in 55.0% (235/427) of patients. Overall SVR was achieved in 97.2% (377/388). SVR was achieved in 98.3% (169/172) of those with viral load ≤800 000 IU/mL and in 96.2% (202/210) of those with viral load >800 000 IU/mL. Conclusion: We observed high SVR rates among patients with HCV GT1a infection treated with EBR/GZR for 12 weeks without ribavirin, with no regard to baseline viral load and no RAS testing. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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16. |
- Lozano-Hernández, Cristina M., et al.
(författare)
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Social support, social context and nonadherence to treatment in young senior patients with multimorbidity and polypharmacy followed-up in primary care. MULTIPAP Study
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo estimate the prevalence of nonadherence to treatment and its relationship with social support and social context in patients with multimorbidity and polypharmacy followed-up in primary care.MethodsThis was an observational, descriptive, cross-sectional, multicenter study with an analytical approach. A total of 593 patients between 65–74 years of age with multimorbidity (≥3 diseases) and polypharmacy (≥5 drugs) during the last three months and agreed to participate in the MULTIPAP Study. The main variable was adherence (Morisky-Green). The predictors were social support (structural support and functional support (DUFSS)); sociodemographic variables; indicators of urban objective vulnerability; health-related quality of life (EQ-5D-5L-VAS & QALY); and clinical variables. Descriptive, bivariate and multivariate analyses with logistic regression models and robust estimators were performed.ResultsFour out of ten patients were nonadherent, 47% had not completed primary education, 28.7% had an income ≤1050 €/month, 35% reported four or more IUVs, and the average perceived health-related quality of life (HRQOL) EQ-5D-5L-VAS was 65.5. The items that measure functional support, with significantly different means between nonadherent and adherent patients were receiving love and affection (-0.23; 95%CI: -0.40;-0.06), help when ill (-0.25; 95%CI: -0.42;-0.08), useful advice (-0.20; 95%CI: -0.37;-0.02), social invitations (-0.22; 95%CI:-0.44;-0.01), and recognition (-0.29; 95%CI:-0.50;-0.08). Factors associated with nonadherence were belonging to the medium vs. low tertile of functional support (0.62; 95%CI: 0.42;0.94), reporting less than four IUVs (0.69; 95%CI: 0.46;1.02) and higher HRQOL perception (0.98; 95%CI: 0.98;0.99).ConclusionsAmong patients 65–74 years of age with multimorbidity and polypharmacy, lower functional support was related to nonadherence to treatment. The nonadherence decreased in those patients with higher functional support, lower urban vulnerability and higher perceived health status according to the visual analog scale of health-related quality of life.
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17. |
- Lozano-Hernandez, CM, et al.
(författare)
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Sex differences in social support perceived by polymedicated older adults with multimorbidity. MULTIPAP study
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7, s. e0268218-
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Tidskriftsartikel (refereegranskat)abstract
- The beneficial effects of social support on morbidity, mortality, and quality of life are well known. Using the baseline data of the MULTIPAP study (n = 593), an observational, descriptive, cross-sectional study was carried out that analyzed the sex differences in the social support perceived by polymedicated adults aged 65 to 74 years with multimorbidity. The main outcome variable was social support measured through the Duke–UNC-11 Functional Social Support (DUFSS) questionnaire in its two dimensions (confident support and affective support). For both sexes, the perception of functional social support was correlated with being married or partnered and having a higher health-related quality of life utility index. In women, it was correlated with a higher level of education, living alone, and treatment adherence, and in men with higher monthly income, prescribed drugs and fewer diagnosed diseases.
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18. |
- Mendieta-Leiva, Glenda, et al.
(författare)
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EpIG-DB: A database of vascular epiphyte assemblages in the Neotropics
- 2020
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Ingår i: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 31, s. 518-528
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Tidskriftsartikel (refereegranskat)abstract
- Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil-rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large-scale distribution patterns. EpIG-DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG-DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG-DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up-to-date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG-DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG-DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes.
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19. |
- Nava, Veronica, et al.
(författare)
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Plastic debris in lakes and reservoirs
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 619:7969, s. 317-322
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Tidskriftsartikel (refereegranskat)abstract
- Plastic debris is thought to be widespread in freshwater ecosystems globally(1). However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging(2,3). Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 mu m) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris(4). Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.
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21. |
- Sabatine, M. S., et al.
(författare)
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Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 Trial
- 2005
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Ingår i: Circulation. - 1524-4539. ; 112:25, s. 3846-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low-molecular-weight heparin (LMWH) offers pharmacological and practical advantages over unfractionated heparin (UFH). Whether these advantages translate into greater infarct-related artery patency and fewer adverse clinical events in patients with ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy remains under study. METHODS AND RESULTS: We compared angiographic and clinical outcomes in patients treated with LMWH (n=1429) versus UFH (n=1431) in CLARITY-TIMI 28, a randomized trial of clopidogrel versus placebo in STEMI patients aged 18 to 75 years undergoing fibrinolysis. After comprehensive adjustment for baseline characteristics, therapeutic interventions, and a propensity score, treatment with LMWH was associated with a significantly lower rate of a closed infarct-related artery or death or myocardial infarction before angiography (13.5% versus 22.5%, adjusted OR 0.76, P=0.027). Treatment with LMWH was also associated with a significantly lower rate of cardiovascular death or recurrent myocardial infarction through 30 days (6.9% versus 11.5%, adjusted OR 0.68, P=0.030). The lower event rates were observed in patients allocated to clopidogrel and in those who underwent percutaneous coronary intervention. Rates of TIMI major bleeding through 30 days (1.6% versus 2.2%, P=0.27) and intracranial hemorrhage (0.6% versus 0.8%, P=0.37) were similar in the LMWH and UFH groups. Patients who received both clopidogrel and LMWH, in addition to a standard fibrinolytic and aspirin, had a particularly high rate of infarct-related artery patency (90.9%) and particularly low rates of cardiovascular death (3.2%), recurrent myocardial infarction (3.0%), and major bleeding (1.8%). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, use of LMWH with other standard therapies, including clopidogrel and aspirin, is associated with improved angiographic outcomes and lower rates of major adverse cardiovascular events.
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22. |
- Salas-Leiva, Dayana E., et al.
(författare)
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Genomic analysis finds no evidence of canonical eukaryotic DNA processing complexes in a free-living protist
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells replicate and segregate their DNA with precision. Previous studies showed that these regulated cell-cycle processes were present in the last eukaryotic common ancestor and that their core molecular parts are conserved across eukaryotes. However, some metamonad parasites have secondarily lost components of the DNA processing and segregation apparatuses. To clarify the evolutionary history of these systems in these unusual eukaryotes, we generated a genome assembly for the free-living metamonad Carpediemonas membranifera and carried out a comparative genomics analysis. Here, we show that parasitic and free-living metamonads harbor an incomplete set of proteins for processing and segregating DNA. Unexpectedly, Carpediemonas species are further streamlined, lacking the origin recognition complex, Cdc6 and most structural kinetochore subunits. Carpediemonas species are thus the first known eukaryotes that appear to lack this suite of conserved complexes, suggesting that they likely rely on yet-to-be-discovered or alternative mechanisms to carry out these fundamental processes.
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24. |
- Sasai, F, et al.
(författare)
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Inhaled silica nanoparticles cause chronic kidney disease in rats
- 2022
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 323:1, s. F48-F58
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Tidskriftsartikel (refereegranskat)abstract
- Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.
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27. |
- Alexander, John H., et al.
(författare)
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Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome
- 2011
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:8, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.Results: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.Conclusions: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events.
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28. |
- Castellvi Obiols, P, et al.
(författare)
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Physical and mental health impact of the COVID-19 pandemic at first year in a Spanish adult cohort
- 2023
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4547-
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic and the political and health measures have profoundly affected the health of our populations. However, very few studies have been published assessing its impact using a prospective cohort. The aim of this study is to describe the impact on physical and mental health due to the COVID-19 pandemic in the general population in Spain, and according to COVID-19 clinical status, during the first year of the pandemic. A longitudinal cohort study with two online surveys were performed on a representative sample of the adult Spanish population before (N = 2005, October/November 2019) and during the pandemic (N = 1357, November/December 2020). We assessed disability using the World Health Organisation Disability Assessment Schedule (WHODAS), major depressive episode (MDE) and suicidal thoughts and behaviours (STB), using an adapted version of the Composite International Diagnostic Interview (CIDI 3.0); generalised anxiety disorder (GAD) using the GAD-7 scale; post-traumatic stress disorder (PTSD) symptoms using the PTSD checklist for DSM-5 (PCL-5). For physical health, there was a statistically significant loss of weight (mean/SD) (T0, 73.22/15.56 vs. T1, 71.21/11.94), less use of tobacco (T0, 11.4% vs. T1, 9.0%) and decreased disability (mean/SD) (T0, 21.52/9.22 vs. T1, 19.03/7.32). For mental health, there was a significant increase in MDE (T0, 6.5% vs. T1, 8.8%) and in the prevalence of GAD (T0, 13.7% vs. T1, 17.7%). The prevalence of STB (T0, 15.1% vs. T1, 7.1%) significantly decreased. Individuals who declared they had been diagnosed with COVID-19 (3.6%) showed a worsening in physical health and an increase in mental health problems and PTSD symptoms. Although suicide risk during the first year of the pandemic was significantly less, many suicide risk factors increased: such as the incidence and persistence of MDE and GAD, the presence of PTSD symptoms in those diagnosed with COVID-19, and a worsening in self-assessed health status. We expect an increase in STB in the population in the long-term. Future research should gather information about the long-term impact of the pandemic.
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29. |
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30. |
- Cooper, Chris E., et al.
(författare)
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Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute
- 2019
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Ingår i: Free Radical Biology and Medicine. - : Elsevier BV. - 0891-5849. ; 134, s. 106-118
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb β subunit (βF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and β subunits of Hb to determine if this effect of βF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (βT84Y, αL91Y and βF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (< 100 μM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (βT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of βT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, βT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. βT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product.
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31. |
- García, Patricia, et al.
(författare)
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Functional and genomic characterization of three novel cell lines derived from a metastatic gallbladder cancer tumor
- 2020
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Ingår i: Biological Research. - : Springer Science and Business Media LLC. - 0716-9760 .- 0717-6287. ; 53
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Author(s). Background: Gallbladder cancer (GBC) is the most common tumor of the biliary tract. The incidence of GBC shows a large geographic variability, being particularly frequent in Native American populations. In Chile, GBC represents the second cause of cancer-related death among women. We describe here the establishment of three novel cell lines derived from the ascitic fluid of a Chilean GBC patient, who presented 46% European, 36% Mapuche, 12% Aymara and 6% African ancestry. Results: After immunocytochemical staining of the primary cell culture, we isolated and comprehensively characterized three independent clones (PUC-GBC1, PUC-GBC2 and PUC-GBC3) by short tandem repeat DNA profiling and RNA sequencing as well as karyotype, doubling time, chemosensitivity, in vitro migration capability and in vivo tumorigenicity assay. Primary culture cells showed high expression of CK7, CK19, CA 19-9, MUC1 and MUC16, and negative expression of mesothelial markers. The three isolated clones displayed an epithelial phenotype and an abnormal structure and number of chromosomes. RNA sequencing confirmed the increased expression of cytokeratin and mucin genes, and also of TP53 and ERBB2 with some differences among the three cells lines, and revealed a novel exonic mutation in NF1. The PUC-GBC3 clone was the most aggressive according to histopathological features and the tumorigenic capacity in NSG mice. Conclusions: The first cell lines established from a Chilean GBC patient represent a new model for studying GBC in patients of Native American descent.
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32. |
- Garre, Elena, 1978, et al.
(författare)
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Breast Cancer Patient-Derived Scaffolds Can Expose Unique Individual Cancer Progressing Properties of the Cancer Microenvironment Associated with Clinical Characteristics
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Despite huge progress in cancer diagnostics and medicine we still lack optimal cancer treatments for patients with aggressive diseases. This problem can be influenced by the biological heterogeneity of cancer cells as well as poorly understood cancer promoting effects of the cancer microenvironment being an important part of the cancer niche. In this study we have specifically monitored the activity of the cancer microenvironment in breast cancer patients using cell-free scaffolds repopulated with reporter cancer cells sensing the activity of the patient environment. The data show that scaffold induced changes in epithelial-mesenchymal transition and pluripotency markers were linked to clinical and prognostic properties of the original cancer and the information was even more precise when matching estrogen receptor status in our system. The findings highlight that patient-derived scaffolds uncover important information about varying malignant promoting properties in the cancer niche and can be used as a complementary diagnostic tool. Breast cancer is a heterogeneous disease in terms of cellular and structural composition, and besides acquired aggressive properties in the cancer cell population, the surrounding tumor microenvironment can affect disease progression and clinical behaviours. To specifically decode the clinical relevance of the cancer promoting effects of individual tumor microenvironments, we performed a comprehensive test of 110 breast cancer samples using a recently established in vivo-like 3D cell culture platform based on patient-derived scaffolds (PDSs). Cell-free PDSs were recellularized with three breast cancer cell lines and adaptation to the different patient-based microenvironments was monitored by quantitative PCR. Substantial variability in gene expression between individual PDS cultures from different patients was observed, as well as between different cell lines. Interestingly, specific gene expression changes in the PDS cultures were significantly linked to prognostic features and clinical information from the original cancer. This link was even more pronounced when ER alpha-status of cell lines and PDSs matched. The results support that PDSs cultures, including a cancer cell line of relevant origin, can monitor the activity of the tumor microenvironment and reveal unique information about the malignancy-inducing properties of the individual cancer niche and serve as a future complementary diagnostic tool for breast cancer.
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33. |
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34. |
- Jerlström-Hultqvist, Jon, 1982-, et al.
(författare)
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A unique symbiosome in an anaerobic single-celled eukaryote
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Symbiotic relationships drive evolutionary change and are important sources of novelty. Here we demonstrate a highly structured syntrophic symbiosis between species of the anaerobic protist Anaeramoeba (Anaeramoebae, Metamonada) and bacterial ectosymbionts. We dissected this symbiosis with long-read metagenomics, transcriptomics of host and symbiont cells coupled with fluorescent in situ hybridization (FISH), and microscopy. Genome sequencing, phylogenomic analyses and FISH show that the symbionts belong to the Desulfobacteraceae and were acquired independently in two different Anaeramoeba species. We show that ectosymbionts likely reside deep within cell surface invaginations in a symbiosomal membrane network that is tightly associated with cytoplasmic hydrogenosomes. Metabolic reconstructions based on the genomes and transcriptomes of the symbionts suggest a highly evolved syntrophic interaction. Host hydrogenosomes likely produce hydrogen, acetate, and propionate that are consumed by the symbionts dissimilatory sulfate reduction, Wood-Ljungdahl and methylmalonyl pathways, respectively. Because the host genome sequences encode several vitamin B12-dependent enzymes but appear to lack the ability to biosynthesize this vitamin, we hypothesize that the symbionts supply their hosts with B12. We detected numerous lateral gene transfers from diverse bacteria to Anaeramoeba, including genes involved in oxygen defense and anaerobic metabolism. Gene families encoding membrane-trafficking components that regulate the phagosomal maturation machinery are notably expanded in Anaeramoeba spp. and may be involved in organizing and/or stabilizing the symbiosomal membrane system. Overall, the Anaeramoebae have evolved a dynamic symbiosome comprised of a vacuolar system that facilitates positioning and maintenance of sulfate-reducing bacterial ectosymbionts.
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35. |
- Jokipii-Lukkari, Soile, et al.
(författare)
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Dual targeted poplar ferredoxin NADP+ oxidoreductase interacts with hemoglobin 1
- 2016
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Ingår i: Plant Science. - : Elsevier BV. - 0168-9452. ; 247, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports have connected non-symbiotic and truncated hemoglobins (Hbs) to metabolism of nitric oxide (NO), an important signalling molecule involved in wood formation. We have studied the capability of poplar (Populus tremula × tremuloides) Hbs PttHb1 and PttTrHb proteins alone or with a flavin-protein reductase to relieve NO cytotoxicity in living cells. Complementation tests in a Hb-deficient, NO-sensitive yeast (Saccharomyces cerevisiae) δyhb1 mutant showed that neither PttHb1 nor PttTrHb alone protected cells against NO. To study the ability of Hbs to interact with a reductase, ferredoxin NADP+ oxidoreductase PtthFNR was characterized by sequencing and proteomics. To date, by far the greatest number of the known dual-targeted plant proteins are directed to chloroplasts and mitochondria. We discovered a novel variant of hFNR that lacks the plastid presequence and resides in cytosol. The coexpression of PttHb1 and PtthFNR partially restored NO resistance of the yeast δyhb1 mutant, whereas PttTrHb coexpressed with PtthFNR failed to rescue growth. YFP fusion proteins confirmed the interaction between PttHb1 and PtthFNR in plant cells. The structural modelling results indicate that PttHb1 and PtthFNR are able to interact as NO dioxygenase. This is the first report on dual targeting of central plant enzyme FNR to plastids and cytosol.
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36. |
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37. |
- Llistosella, M, et al.
(författare)
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Low Resilience Was a Risk Factor of Mental Health Problems during the COVID-19 Pandemic but Not in Individuals Exposed to COVID-19: A Cohort Study in Spanish Adult General Population
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:22
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim is to analyze whether people with low resilience are at higher risk of mental health problems during the COVID-19 pandemic in Spanish adults. Methods: a longitudinal cohort study was carried out. Resilience was measured with the CD-RISC. Mental health problems that were assessed included: Major Depressive Episode (MDE), Generalized Anxiety Disorder (GAD), Suicidal Thoughts and Behaviors (STB), and Posttraumatic Stress Disorder (PTSD) symptoms. Results: we found statistically significant differences between groups and resilience scores in MDE [F (3; 48.40) = 19.55], GAD [F (3; 19.63) = 6.45] and STB [F (3; 111.74) = 31.94]. Multivariable analyses showed individuals with very low resilience were at a 5-fold risk of Incidence of MDE and a 4-fold risk of STB. Persistent group presented a 21-fold risk of MDE and 54-fold risk of STB. No evidence of higher risk was found for GAD. Individuals with low resilience and exposed to COVID-19 were not at higher risk. Individuals with low resilience were at higher risk of PTSD in general population [β(95% CI) = −3.25 (−3.969 to −2.54)], but not for individuals with COVID-19. Conclusion: in the general population, having low or very low resilience increases the risk of suffering MDE, STB, and PTSD, but not GAD during the COVID-19 pandemic, and not in the population with COVID-19.
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38. |
- Maquiling, Virmarie, et al.
(författare)
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V-ir-Net : A Novel Neural Network for Pupil and Corneal Reflection Detection trained on Simulated Light Distributions
- 2023
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Ingår i: MobileHCI '23 Companion : Proceedings of the 25th International Conference on Mobile Human-Computer Interaction - Proceedings of the 25th International Conference on Mobile Human-Computer Interaction. - 9781450399241 ; , s. 1-7
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Konferensbidrag (refereegranskat)abstract
- Deep learning has shown promise for gaze estimation in Virtual Reality (VR) and other head-mounted applications, but such models are hard to train due to lack of available data. Here we introduce a novel method to train neural networks for gaze estimation using synthetic images that model the light distributions captured in a P-CR setup. We tested our model on a dataset of real eye images from a VR setup, achieving 76% accuracy which is close to the state-of-the-art model which was trained on the dataset itself. The localization error for CRs was 1.56 pixels and 2.02 pixels for the pupil, which is on par with state-of-the-art. Our approach allowed inference on the whole dataset without sacrificing data for model training. Our method provides a cost-efficient and lightweight training alternative, eliminating the need for hand-labeled data. It offers flexible customization, e.g. adapting to different illuminator configurations, with minimal code changes.
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39. |
- Obiols, PC, et al.
(författare)
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Physical and mental health impact of the COVID-19 pandemic at first year in a Spanish adult cohort
- 2023
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1, s. 4547-
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic and the political and health measures have profoundly affected the health of our populations. However, very few studies have been published assessing its impact using a prospective cohort. The aim of this study is to describe the impact on physical and mental health due to the COVID-19 pandemic in the general population in Spain, and according to COVID-19 clinical status, during the first year of the pandemic. A longitudinal cohort study with two online surveys were performed on a representative sample of the adult Spanish population before (N = 2005, October/November 2019) and during the pandemic (N = 1357, November/December 2020). We assessed disability using the World Health Organisation Disability Assessment Schedule (WHODAS), major depressive episode (MDE) and suicidal thoughts and behaviours (STB), using an adapted version of the Composite International Diagnostic Interview (CIDI 3.0); generalised anxiety disorder (GAD) using the GAD-7 scale; post-traumatic stress disorder (PTSD) symptoms using the PTSD checklist for DSM-5 (PCL-5). For physical health, there was a statistically significant loss of weight (mean/SD) (T0, 73.22/15.56 vs. T1, 71.21/11.94), less use of tobacco (T0, 11.4% vs. T1, 9.0%) and decreased disability (mean/SD) (T0, 21.52/9.22 vs. T1, 19.03/7.32). For mental health, there was a significant increase in MDE (T0, 6.5% vs. T1, 8.8%) and in the prevalence of GAD (T0, 13.7% vs. T1, 17.7%). The prevalence of STB (T0, 15.1% vs. T1, 7.1%) significantly decreased. Individuals who declared they had been diagnosed with COVID-19 (3.6%) showed a worsening in physical health and an increase in mental health problems and PTSD symptoms. Although suicide risk during the first year of the pandemic was significantly less, many suicide risk factors increased: such as the incidence and persistence of MDE and GAD, the presence of PTSD symptoms in those diagnosed with COVID-19, and a worsening in self-assessed health status. We expect an increase in STB in the population in the long-term. Future research should gather information about the long-term impact of the pandemic.
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40. |
- Simons, Michelle, et al.
(författare)
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Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin : implications for the design of hemoglobin-based oxygen carriers
- 2018
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Ingår i: Bioscience Reports. - 0144-8463. ; 38:4
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been engineered to replace or augment the oxygen carrying capacity of erythrocytes. However, clinical results have generally been disappointing, in part due to the intrinsic oxidative toxicity of Hb. The most common HBOC starting material is adult human or bovine Hb. However, it has been suggested that fetal Hb may offer advantages due to decreased oxidative reactivity. Large-scale manufacturing of HBOC will likely and ultimately require recombinant sources of human proteins. We, therefore, directly compared the functional properties and oxidative reactivity of recombinant fetal (rHbF) and recombinant adult (rHbA) Hb. rHbA and rHbF produced similar yields of purified functional protein. No differences were seen in the two proteins in: autoxidation rate; the rate of hydrogen peroxide reaction; NO scavenging dioxygenase activity; and the NO producing nitrite reductase activity. The rHbF protein was: less damaged by low levels of hydrogen peroxide; less damaging when added to human umbilical vein endothelial cells (HUVEC) in the ferric form; and had a slower rate of intrinsic heme loss. The rHbA protein was: more readily reducible by plasma antioxidants such as ascorbate in both the reactive ferryl and ferric states; less readily damaged by lipid peroxides; and less damaging to phosphatidylcholine liposomes. In conclusion in terms of oxidative reactivity, there are advantages and disadvantages to the use of rHbA or rHbF as the basis for an effective HBOC.
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41. |
- Tawil, Rabi, et al.
(författare)
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Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial
- 2024
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Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 23:5, s. 477-486
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Tidskriftsartikel (refereegranskat)abstract
- Background Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38 alpha MAPK, a regulator of DUX4 expression, and p38 beta MAPK) for the treatment of facioscapulohumeral muscular dystrophy. Methods We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. Findings Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45<middle dot>7 (SD 12<middle dot>5) years. Least squares mean changes from baseline in DUX4driven gene expression did not differ significantly between the losmapimod (0<middle dot>83 [SE 0<middle dot>61]) and placebo (0<middle dot>40 [0<middle dot>65]) groups (difference 0<middle dot>43 [SE 0<middle dot>56; 95% CI -1<middle dot>04 to 1<middle dot>89]; p=0<middle dot>56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drugrelated) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. Interpretation Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy.
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42. |
- Valls, C, et al.
(författare)
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Safety and Efficacy of Ultrasound-Guided Radiofrequency Ablation of Recurrent Colorectal Cancer Liver Metastases after Hepatectomy
- 2015
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Ingår i: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1799-7267. ; 104:3, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- To assess the results and outcome of radiofrequency ablation in the treatment of recurrent colorectal liver metastases. Patients and Methods: Between January 2005 and September 2012, we treated 59 patients with recurrent colorectal metastases not amenable to surgery with 77 radiofrequency ablation procedures. Radiofrequency was indicated if oncologic resection was technically not possible or the patient was not fit for major surgery. A total of 91 lesions were treated. The mean number of liver tumors per patient was 1.5, and the mean tumor diameter was 2.3 cm. In 37.5% of the cases, lesions had a subcapsular location, and 34% were close to a vascular structure. Results: The morbidity rate was 18.7%, and there were no post-procedural deaths. Distant extrahepatic recurrence appeared in 50% of the patients. Local recurrence at the site of ablation appeared in 18% of the lesions. Local recurrence rate was 6% in lesions less than 3 cm and 52% in lesions larger than 3 cm. The size of the lesions (more than 3 cm) was an independent risk factor for local recurrence (p < 0.05). Survival rates at 1, 3, and 5 years were 94.5%, 65.3%, and 21.7%, respectively. Discussion: Radiofrequency ablation is a safe procedure and allows local tumor control in lesions less than 30 mm (local recurrence of 6%) and provides survival benefits in patients with recurrent colorectal liver metastases.
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