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Sökning: WFRF:(Lopez Ana) > (2020-2024)

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51.
  • Guisado-Clavero, Marina, et al. (författare)
  • The role of primary health care in long-term care facilities during the COVID-19 pandemic in 30 European countries : A retrospective descriptive study (Eurodata study)
  • 2023
  • Ingår i: Primary Health Care Research and Development. - 1463-4236. ; 24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aim: Primary health care (PHC) supported long-term care facilities (LTCFs) in attending COVID-19 patients. The aim of this study is to describe the role of PHC in LTCFs in Europe during the early phase of the pandemic. Methods: Retrospective descriptive study from 30 European countries using data from September 2020 collected with an ad hoc semi-structured questionnaire. Related variables are SARS-CoV-2 testing, contact tracing, follow-up, additional testing, and patient care. Results: Twenty-six out of the 30 European countries had PHC involvement in LTCFs during the COVID-19 pandemic. PHC participated in initial medical care in 22 countries, while, in 15, PHC was responsible for SARS-CoV-2 test along with other institutions. Supervision of individuals in isolation was carried out mostly by LTCF staff, but physical examination or symptom's follow-up was performed mainly by PHC. Conclusion: PHC has participated in COVID-19 pandemic assistance in LTCFs in coordination with LTCF staff, public health officers, and hospitals.
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52.
  • Gutic, Sanjin J., et al. (författare)
  • Hydrogen Evolution Reaction-From Single Crystal to Single Atom Catalysts
  • 2020
  • Ingår i: Catalysts. - : MDPI. - 2073-4344. ; 10:3
  • Forskningsöversikt (refereegranskat)abstract
    • Hydrogen evolution reaction (HER) is one of the most important reactions in electrochemistry. This is not only because it is the simplest way to produce high purity hydrogen and the fact that it is the side reaction in many other technologies. HER actually shaped current electrochemistry because it was in focus of active research for so many years (and it still is). The number of catalysts investigated for HER is immense, and it is not possible to overview them all. In fact, it seems that the complexity of the field overcomes the complexity of HER. The aim of this review is to point out some of the latest developments in HER catalysis, current directions and some of the missing links between a single crystal, nanosized supported catalysts and recently emerging, single-atom catalysts for HER.
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53.
  • Herreros-Montejano, Francisca, et al. (författare)
  • Outbreak of occupational allergic contact dermatitis from a smartphone screen protector glue
  • 2022
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 87:1, s. 53-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sensitization to acrylates is a concern in the occupational/environmental dermatology field. Objective: To describe an occupational allergic contact dermatitis (ACD) outbreak from a smartphone screen protector glue. Methods: Thirteen affected workers of a chain store selling phone screen protectors were investigated in five Spanish dermatology departments. The glue datasheet and label were assessed. A chemical analysis of the glue was performed. Based on this, some patients underwent additional testing. Results: All patients (all female, mean age: 25) had severe fingertip dermatitis. The datasheet/label indicated that the glue contained isobornyl acrylate (IBOA), a “photoinitiator” and polyurethane oligomer. The company informed us that the ingredients were polyurethane acrylate, “methacrylate” (unspecified), acrylic acid, hydroxyethyl methacrylate, propylmethoxy siloxane, and photoinitiator 184. Isobornyl acrylate (or IBOA) and N,N-dimethylacrylamide (DMAA) were patch tested in eight and two cases, respectively, with negative results. A chemical analysis revealed 4-acryloylmorpholine (ACMO); isobornyl methacrylate (IBMA), and lauryl acrylate in one glue sample. Seven patients were patch tested with dilutions of the identified substances and six of seven were positive for ACMO 0.5% pet. Conclusion: An outbreak of occupational ACD, likely from ACMO in a glue is described. Further investigations are needed to corroborate the role played by each compound identified in the chemical analyses.
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54.
  • Householder, John Ethan, et al. (författare)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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55.
  • Iguacel, Isabel, et al. (författare)
  • Evaluation of protein and amino acid intake estimates from the EPIC dietary questionnaires and 24-h dietary recalls using different food composition databases
  • 2022
  • Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier. - 0939-4753 .- 1590-3729. ; 32:1, s. 80-89
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: This study aimed to expand the European Prospective Investigation into Cancer and Nutrition (EPIC) nutrient database (ENDB) by adding amino acid (AA) values, using the U.S. nutrient database (USNDB). Additionally, we aimed to evaluate these new protein and AA intake estimates from the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR) using different matching procedures.METHODS AND RESULTS: Dietary energy, protein and AA intakes were assessed via DQ and 24-HDR by matching with the USNDB food composition table. Energy and protein intakes calculated using USNDB matching were compared with those calculated using ENDB, that uses country specific food composition tables. Pearson correlations, Cohen's weighted kappa statistic and Bland-Altman plots were used to compare data resulting from USNDB matching with our reference from ENDB matching. Very high correlations were found when comparing daily energy (r = 0.99) and dietary protein intakes (r = 0.97) assessed via USNDB with those obtained via ENDB (matching for DQ and 24-HDR). Significant positive correlations were also found with energy and protein intakes acquired via 24-HDRs in the EPIC calibration sample.CONCLUSION: Very high correlations between total energy and protein intake obtained via the USDA matching and those available in ENDB suggest accuracy in the food matching. Individual AA have been included in the extended EPIC Nutrient database that will allow important analyses on AA disease prospective associations in the EPIC study.
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56.
  • Insausti, Ricardo, et al. (författare)
  • Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
  • 2023
  • Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
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57.
  • Jayasekara, Harindra, et al. (författare)
  • Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer : A pooled analysis of data from two prospective cohort studies
  • 2021
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:11, s. 2759-2773
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity =.02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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58.
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59.
  • Kahsay, Abraha, et al. (författare)
  • Pax3 loss of function delays tumour progression in kRAS-induced zebrafish rhabdomyosarcoma models
  • 2022
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Rhabdomyosarcoma is a soft tissue cancer that arises in skeletal muscle due to mutations in myogenic progenitors that lead to ineffective differentiation and malignant transformation. The transcription factors Pax3 and Pax7 and their downstream target genes are tightly linked with the fusion positive alveolar subtype, whereas the RAS pathway is usually involved in the embryonal, fusion negative variant. Here, we analyse the role of Pax3 in a fusion negative context, by linking alterations in gene expression in pax3a/pax3b double mutant zebrafish with tumour progression in kRAS-induced rhabdomyosarcoma tumours. Several genes in the RAS/MAPK signalling pathway were significantly down-regulated in pax3a/pax3b double mutant zebrafish. Progression of rhabdomyosarcoma tumours was also delayed in the pax3a/pax3b double mutant zebrafish indicating that Pax3 transcription factors have an unappreciated role in mediating malignancy in fusion negative rhabdomyosarcoma.
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60.
  • Karakostis, Konstantinos, et al. (författare)
  • Molecular and Biochemical Techniques for Deciphering p53-MDM2 Regulatory Mechanisms
  • 2021
  • Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:1
  • Forskningsöversikt (refereegranskat)abstract
    • The p53 and Mouse double minute 2 (MDM2) proteins are hubs in extensive networks of interactions with multiple partners and functions. Intrinsically disordered regions help to adopt function-specific structural conformations in response to ligand binding and post-translational modifications. Different techniques have been used to dissect interactions of the p53-MDM2 pathway, in vitro, in vivo, and in situ each having its own advantages and disadvantages. This review uses the p53-MDM2 to show how different techniques can be employed, illustrating how a combination of in vitro and in vivo techniques is highly recommended to study the spatio-temporal location and dynamics of interactions, and to address their regulation mechanisms and functions. By using well-established techniques in combination with more recent advances, it is possible to rapidly decipher complex mechanisms, such as the p53 regulatory pathway, and to demonstrate how protein and nucleotide ligands in combination with post-translational modifications, result in inter-allosteric and intra-allosteric interactions that govern the activity of the protein complexes and their specific roles in oncogenesis. This promotes elegant therapeutic strategies that exploit protein dynamics to target specific interactions.
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61.
  • Kobialka, Piotr, et al. (författare)
  • The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib
  • 2022
  • Ingår i: EMBO Molecular Medicine. - : EMBO Press. - 1757-4676 .- 1757-4684. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-flow vascular malformations are congenital overgrowths composed of abnormal blood vessels potentially causing pain, bleeding and obstruction of different organs. These diseases are caused by oncogenic mutations in the endothelium, which result in overactivation of the PI3K/AKT pathway. Lack of robust in vivo preclinical data has prevented the development and translation into clinical trials of specific molecular therapies for these diseases. Here, we demonstrate that the Pik3caH1047R activating mutation in endothelial cells triggers a transcriptome rewiring that leads to enhanced cell proliferation. We describe a new reproducible preclinical in vivo model of PI3K-driven vascular malformations using the postnatal mouse retina. We show that active angiogenesis is required for the pathogenesis of vascular malformations caused by activating Pik3ca mutations. Using this model, we demonstrate that the AKT inhibitor miransertib both prevents and induces the regression of PI3K-driven vascular malformations. We confirmed the efficacy of miransertib in isolated human endothelial cells with genotypes spanning most of human low-flow vascular malformations.
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62.
  • López-Pérez, Ana R., et al. (författare)
  • Diet-induced rewiring of the Wnt gene regulatory network connects aberrant splicing to fatty liver and liver cancer in DIAMOND mice
  • 2023
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Several preclinical models have been recently developed for metabolic associated fatty liver disease (MAFLD) and associated hepatocellular carcinoma (HCC) but comprehensive analysis of the regulatory and transcriptional landscapes underlying disease in these models are still missing. We investigated the regulatory and transcriptional landscape in fatty livers and liver tumours from DIAMOND mice that faithfully mimic human HCC development in the context of MAFLD. RNA-sequencing and ChIP-sequencing revealed rewiring of the Wnt/β-catenin regulatory network in DIAMOND tumours, as manifested by chromatin remodelling and associated switching in the expression of the canonical TCF/LEF downstream effectors. We identified splicing as a major mechanism leading to constitutive oncogenic activation of β-catenin in a large subset of DIAMOND tumours, a mechanism that is independent on somatic mutations in the locus and that has not been previously shown. Similar splicing events were found in a fraction of human HCC and hepatoblastoma samples.
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63.
  • López-Pérez, Ana R., et al. (författare)
  • Identification of downstream effectors of retinoic acid specifying the zebrafish pancreas by integrative genomics
  • 2021
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinoic acid (RA) is a key signal for the specification of the pancreas. Still, the gene regulatory cascade triggered by RA in the endoderm remains poorly characterized. In this study, we investigated this regulatory network in zebrafish by combining RNA-seq, RAR ChIP-seq and ATAC-seq assays. By analysing the effect of RA and of the RA receptor (RAR) inverse-agonist BMS493 on the transcriptome and on the chromatin accessibility of endodermal cells, we identified a large set of genes and regulatory regions regulated by RA signalling. RAR ChIP-seq further defined the direct RAR target genes in zebrafish, including hox genes as well as several pancreatic regulators like mnx1, insm1b, hnf1ba and gata6. Comparison of zebrafish and murine RAR ChIP-seq data highlighted the conserved direct target genes and revealed that some RAR sites are under strong evolutionary constraints. Among them, a novel highly conserved RAR-induced enhancer was identified downstream of the HoxB locus and driving expression in the nervous system and in the gut in a RA-dependent manner. Finally, ATAC-seq data unveiled the role of the RAR-direct targets Hnf1ba and Gata6 in opening chromatin at many regulatory loci upon RA treatment.
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64.
  • López-Pérez, Ana R., et al. (författare)
  • Pan-AMPK activator O304 prevents gene expression changes and remobilisation of histone marks in islets of diet-induced obese mice
  • 2021
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AMP-activated protein kinase (AMPK) has an important role in cellular energy homeostasis and has emerged as a promising target for treatment of Type 2 Diabetes (T2D) due to its beneficial effects on insulin sensitivity and glucose homeostasis. O304 is a pan-AMPK activator that has been shown to improve glucose homeostasis in both mouse models of diabetes and in human T2D subjects. Here, we describe the genome-wide transcriptional profile and chromatin landscape of pancreatic islets following O304 treatment of mice fed high-fat diet (HFD). O304 largely prevented genome-wide gene expression changes associated with HFD feeding in CBA mice and these changes were associated with remodelling of active and repressive chromatin marks. In particular, the increased expression of the β-cell stress marker Aldh1a3 in islets from HFD-mice is completely abrogated following O304 treatment, which is accompanied by loss of active chromatin marks in the promoter as well as distant non-coding regions upstream of the Aldh1a3 gene. Moreover, O304 treatment restored dysfunctional glucose homeostasis as well as expression of key markers associated with β-cell function in mice with already established obesity. Our findings provide preclinical evidence that O304 is a promising therapeutic compound not only for T2D remission but also for restoration of β-cell function following remission of T2D diabetes.
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65.
  • Loughman, Tony, et al. (författare)
  • Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer
  • 2022
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 68:6, s. 837-847
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundOncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study.MethodsExpression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays.ResultsThe overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue.ConclusionThe OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.
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66.
  • Luize, Bruno Garcia, et al. (författare)
  • Geography and ecology shape the phylogenetic composition of Amazonian tree communities
  • 2024
  • Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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67.
  • Luquiens, Amandine, et al. (författare)
  • Pictograms to aid laypeople in identifying the addictiveness of gambling products (PictoGRRed study)
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The structural addictive characteristics of gambling products are important targets for prevention, but can be unintuitive to laypeople. In the PictoGRRed (Pictograms for Gambling Risk Reduction) study, we aimed to develop pictograms that illustrate the main addictive characteristics of gambling products and to assess their impact on identifying the addictiveness of gambling products by laypeople. We conducted a three-step study: (1) use of a Delphi consensus method among 56 experts from 13 countries to reach a consensus on the 10 structural addictive characteristics of gambling products to be illustrated by pictograms and their associated definitions, (2) development of 10 pictograms and their definitions, and (3) study in the general population to assess the impact of exposure to the pictograms and their definitions (n = 900). French-speaking experts from the panel assessed the addictiveness of gambling products (n = 25), in which the mean of expert’s ratings was considered as the true value. Participants were randomly provided with the pictograms and their definitions, or with a standard slogan, or with neither (control group). We considered the control group as representing the baseline ability of laypeople to assess the addictiveness of gambling products. Each group and the French-speaking experts rated the addictiveness of 14 gambling products. The judgment criterion was the intraclass coefficients (ICCs) between the mean ratings of each group and the experts, reflecting the level of agreement between each group and the experts. Exposure to the pictograms and their definition doubled the ability of laypeople to assess the addictiveness of gambling products compared with that of the group that read a slogan or the control group (ICC = 0.28 vs. 0.14 (Slogan) and 0.14 (Control)). Laypeople have limited awareness of the addictive characteristics of gambling products. The pictograms developed herein represent an innovative tool for universally empowering prevention and for selective prevention.
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68.
  • Mader, Sophie L., et al. (författare)
  • Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control the folding and activation of several client proteins in the eukaryotic cell. To elucidate how the local ATPase reaction in the active site couples to the global conformational dynamics of Hsp90, we integrate here large-scale molecular simulations with biophysical experiments. We show that the conformational switching of conserved ion pairs between the N-terminal domain, harbouring the active site, and the middle domain strongly modulates the catalytic barrier of the ATP-hydrolysis reaction by electrostatic forces. Our combined findings provide a mechanistic model for the coupling between catalysis and protein dynamics in Hsp90, and show how long-range coupling effects can modulate enzymatic activity.
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69.
  • Martínez-Pérez, Amparo, et al. (författare)
  • Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine : Short and Long-Term Post-immunization
  • 2021
  • Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Deciphering protection mechanisms against Mycobacterium tuberculosis (Mtb) remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose Mtb. We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) and long term (11 weeks) post-vaccination, and compared it to ineffective Nano-FP2 vaccine. We observed several changes in the mouse lung environment by both nanovaccines, which are lost shortly after boosting. Additional boosting at long-term (14 weeks) recovered partially cell populations and transcriptomic profile, but not enough to enhance protection to infection. An increase in both total and resident memory CD4 and CD8 T cells, but no pro-inflammatory cytokine levels, were correlated with better protection. A unique gene expression pattern with differentially expressed genes revealed potential pathways associated to the immune defense against Mtb. Our findings provide an insight into the critical immune responses that need to be considered when assessing the effectiveness of a novel TB vaccine.
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70.
  • Mayén, Ana-Lucia, et al. (författare)
  • Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers : a multinational cohort study
  • 2021
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:4, s. 854-864
  • Tidskriftsartikel (refereegranskat)abstract
    • Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their pro-inflammatory and pro-oxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer aetiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n=450,111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL), and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder, and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer, and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with risk of HCC (per 1 standard deviation [SD] increment, HR-CML =0.87, 95% CI: 0.76 to 0.99, HR-CEL =0.84, 95% CI: 0.74 to 0.96, and HR-MH-G1 = 0.84, 95% CI: 0.74 to 0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML =1.28, 95% CI: 1.05 to 1.56, HR-CEL =1.17; 95% CI: 0.96 to 1.40, HR-MH-G1 =1.27, 95% CI: 1.06 to 1.54). No associations were observed for cancers of the intra- and extra-hepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.
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71.
  • McWhinney, Sean R, et al. (författare)
  • Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
  • 2021
  • Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:11, s. 6806-6819
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediatedby BMI (Z=2.73, p=0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
  •  
72.
  • McWhinney, Sean R, et al. (författare)
  • Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.
  • 2022
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 24:5, s. 509-520
  • Tidskriftsartikel (refereegranskat)abstract
    • Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry.We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles.We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
  •  
73.
  • McWhinney, Sean R, et al. (författare)
  • Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.
  • 2023
  • Ingår i: Psychological medicine. - 1469-8978. ; 53:14, s. 6743-6753
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
  •  
74.
  • McWhinney, Sean R, et al. (författare)
  • Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.
  • 2024
  • Ingår i: Human brain mapping. - 1097-0193. ; 45:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.
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75.
  • Merbold, Lutz, et al. (författare)
  • Opportunities for an African greenhouse gas observation system
  • 2021
  • Ingår i: Regional Environmental Change. - : Springer Science and Business Media LLC. - 1436-3798 .- 1436-378X. ; 21:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Global population projections foresee the biggest increase to occur in Africa with most of the available uncultivated land to ensure food security remaining on the continent. Simultaneously, greenhouse gas emissions are expected to rise due to ongoing land use change, industrialisation, and transport amongst other reasons with Africa becoming a major emitter of greenhouse gases globally. However, distinct knowledge on greenhouse gas emissions sources and sinks as well as their variability remains largely unknown caused by its vast size and diversity and an according lack of observations across the continent. Thus, an environmental research infrastructure—as being setup in other regions—is more needed than ever. Here, we present the results of a design study that developed a blueprint for establishing such an environmental research infrastructure in Africa. The blueprint comprises an inventory of already existing observations, the spatial disaggregation of locations that will enable to reduce the uncertainty in climate forcing’s in Africa and globally as well as an overall estimated cost for such an endeavour of about 550 M€ over the next 30 years. We further highlight the importance of the development of an e-infrastructure, the necessity for capacity development and the inclusion of all stakeholders to ensure African ownership.
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76.
  • Micah, Angela E., et al. (författare)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Forskningsöversikt (refereegranskat)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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77.
  • Michel, M., et al. (författare)
  • Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
  • 2022
  • Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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78.
  • Minelli, Caterina, et al. (författare)
  • Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
  • 2022
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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79.
  • Moenaert, Antoine, et al. (författare)
  • Evaluation of Laminaria Digitata Hydrolysate for the Production of Bioethanol and Butanol by Fermentation
  • 2023
  • Ingår i: Fermentation. - : MDPI AG. - 2311-5637. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Seaweeds (macroalgae) are gaining attention as potential sustainable feedstock for the production of fuels and chemicals. This comparative study focuses on the characterization of the microbial production of alcohols from fermentable carbohydrates in the hydrolysate of the macroalgae Laminaria digitata as raw material. The potential of a hydrolysate as a carbon source for the production of selected alcohols was tested, using three physiologically different fermentative microbes, in two main types of processes. For the production of ethanol, Saccharomyces cerevisiae was used as a benchmark microorganism and compared with the strictly anaerobic thermophile Thermoanaerobacterium strain AK17. For mixed production of acetone/isopropanol, butanol, and ethanol (A/IBE), three strictly anaerobic Clostridium strains were compared. All strains grew well on the hydrolysate, and toxicity constraints were not observed, but fermentation performance and product profiles were shown to be both condition- and strain-specific. S. cerevisiae utilized only glucose for ethanol formation, while strain AK17 utilized glucose, mannitol, and parts of the glucan oligosaccharides. The clostridia strains tested showed different nutrient requirements, and were able to utilize glucan, mannitol, and organic acids in the hydrolysate. The novelty of this study embodies the application of different inoculates for fermenting a common brown seaweed found in the northern Atlantic Ocean. It provides important information on the fermentation properties of different microorganisms and pinpoints the value of carbon source utilization when selecting microbes for efficient bioconversion into biofuel and chemical products of interest.
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80.
  • Nickless, Alecia, et al. (författare)
  • Greenhouse gas observation network design for Africa
  • 2020
  • Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 72:1, s. 1-30
  • Tidskriftsartikel (refereegranskat)abstract
    • An optimal network design was carried out to prioritise the installation or refurbishment of greenhouse gas (GHG) monitoring stations around Africa. The network was optimised to reduce the uncertainty in emissions across three of the most important GHGs: CO2, CH4, and N2O. Optimal networks were derived using incremental optimisation of the percentage uncertainty reduction achieved by a Gaussian Bayesian atmospheric inversion. The solution for CO2 was driven by seasonality in net primary productivity. The solution for N2O was driven by activity in a small number of soil flux hotspots. The optimal solution for CH4 was consistent over different seasons. All solutions for CO2 and N2O placed sites in central Africa at places such as Kisangani, Kinshasa and Bunia (Democratic Republic of Congo), Dundo and Lubango (Angola), Zoétélé (Cameroon), Am Timan (Chad), and En Nahud (Sudan). Many of these sites appeared in the CH4 solutions, but with a few sites in southern Africa as well, such as Amersfoort (South Africa). The multi-species optimal network design solutions tended to have sites more evenly spread-out, but concentrated the placement of new tall-tower stations in Africa between 10ºN and 25ºS. The uncertainty reduction achieved by the multi-species network of twelve stations reached 47.8% for CO2, 34.3% for CH4, and 32.5% for N2O. The gains in uncertainty reduction diminished as stations were added to the solution, with an expected maximum of less than 60%. A reduction in the absolute uncertainty in African GHG emissions requires these additional measurement stations, as well as additional constraint from an integrated GHG observatory and a reduction in uncertainty in the prior biogenic fluxes in tropical Africa.
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81.
  • Opgenoorth, Lars, et al. (författare)
  • The GenTree Platform : growth traits and tree-level environmental data in 12 European forest tree species
  • 2021
  • Ingår i: GigaScience. - : Oxford University Press. - 2047-217X. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information.Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species' geographic ranges and reflecting local environmental gradients.Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available.
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82.
  • Pérez-García, M. A., et al. (författare)
  • Hubble constant and nuclear equation of state from kilonova spectro-photometric light curves
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • The merger of two compact objects of which at least one is a neutron star is signalled by transient electromagnetic emission in a kilonova (KN). This event is accompanied by gravitational waves and possibly other radiation messengers such as neutrinos or cosmic rays. The electromagnetic emission arises from the radioactive decay of heavy r-process elements synthesized in the material ejected during and after the merger. In this paper we show that the analysis of KNe light curves can provide cosmological distance measurements and constrain the properties of the ejecta. In this respect, MAAT, the new Integral Field Unit in the OSIRIS spectrograph on the 10.4 m Gran Telescopio CANARIAS (GTC), is well suited for the study of KNe by performing absolute spectro-photometry over the entire 3600 − 10 000 Å spectral range. Here, we study the most representative cases regarding the scientific interest of KNe from binary neutron stars, and we evaluate the observational prospects and performance of MAAT on the GTC to do the following: (a) study the impact of the equation of state on the KN light curve, and determine to what extent bounds on neutron star (NS) radii or compactness deriving from KN peak magnitudes can be identified and (b) measure the Hubble constant, H0, with precision improved by up to 40%, when both gravitational wave data and photometric-light curves are used. In this context we discuss how the equation of state, the viewing angle, and the distance affect the precision and estimated value of H0.
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83.
  • Peripato, Vinicius, et al. (författare)
  • More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia
  • 2023
  • Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6666, s. 103-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
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84.
  • Pie, Marcio R., et al. (författare)
  • Phylogenetic diversity and the structure of host-epiphyte interactions across the Neotropics
  • 2023
  • Ingår i: PeerJ. - 2167-8359. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the mechanisms driving community assembly has been a major focus of ecological research for nearly a century, yet little is known about these mechanisms in commensal communities, particularly with respect to their historical/evolutionary components. Here, we use a large-scale dataset of 4,440 vascular plant species to explore the relationship between the evolutionary distinctiveness (ED) (as measured by the’species evolutionary history’ (SEH)) of host species and the phylogenetic diversity (PD) of their associated epiphyte species. Although there was considerable variation across hosts and their associated epiphyte species, they were largely unrelated to host SEH. Our results mostly support the idea that the determinants of epiphyte colonization success might involve host characteristics that are unrelated to host SEH (e.g., architectural differences between hosts). While determinants of PD of epiphyte assemblages are poorly known, they do not appear to be related to the evolutionary history of host species. Instead, they might be better explained by neutral processes of colonization and extinction. However, the high level of phylogenetic signal in epiphyte PD (independent of SEH) suggests it might still be influenced by yet unrecognized evolutionary determinants. This study highlights how little is still known about the phylogenetic determinants of epiphyte communities.
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85.
  • Pinto, Ana Margarida, et al. (författare)
  • Emotion regulation and the salience network : a hypothetical integrative model of fibromyalgia
  • 2023
  • Ingår i: Nature Reviews Rheumatology. - : Springer Nature. - 1759-4790 .- 1759-4804. ; 19:1, s. 44-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.
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86.
  •  
87.
  • Piqueras Lorente, Ana, 1989, et al. (författare)
  • Analysis of the spinal 3D motion of postmortem human surrogates in nearside oblique impacts
  • 2023
  • Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-957X .- 1538-9588. ; 24:1, s. 69-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective : The objective of this study is to analyze the 6 degrees of freedom (DOF) motion of the spine using the finite helical axis (FHA) in three postmortem human surrogates (PMHS) sled tests. Methods : The sled test configurations corresponded to a 30° nearside oblique impact at 35 km/h. Two different restraint system versions (RSv) were used. RSv1 was used for PMHS A and B while RSv2 was used for PMHS C. The 6 DOF motion of the head and three selected vertebrae have been analyzed using the FHA which describes the 3 D motion of a rigid body between two instants of time as a rotation about and a translation along a unit vector. A minimal amount of rotation is necessary to the FHA calculation, thus the FHA components have been calculated based on a pre-defined interval of 8° of rotation. Results : The analysis of the FHA components demonstrated right lateral bending until around 100 ms, when the rebound phase was reached and the head and the lower spine undergoes left lateral bending. The three PMHS exhibited, in general, flexion movement of the whole body and torsion to the right side of the occupant. This general motion can be associated to the effect of the seatbelt acting as a fulcrum of the rotational movement of the bony landmarks. The interaction of the PMHS with the retention system can be noted by analyzing the time in which the head and the upper spine initiated the rotation and the sudden changes of rotational direction of the three PMHS’s head. Conclusions : The rotational analyses have shown to be more sensitive to experimental events than the trajectory analyses for the studied physical tests. Additionally, the results presented in the present study contributes to the analysis of the body kinematics during an oblique impact and adds new experimental data for Human Body Models (HBM) and Anthropometric Test Devices (ATD) benchmarking.
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88.
  • Ramage, Justine, 1988-, et al. (författare)
  • The Net GHG Balance and Budget of the Permafrost Region (2000–2020) From Ecosystem Flux Upscaling
  • 2024
  • Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 38:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The northern permafrost region has been projected to shift from a net sink to a net source of carbon under global warming. However, estimates of the contemporary net greenhouse gas (GHG) balance and budgets of the permafrost region remain highly uncertain. Here, we construct the first comprehensive bottom-up budgets of CO2, CH4, and N2O across the terrestrial permafrost region using databases of more than 1000 in situ flux measurements and a land cover-based ecosystem flux upscaling approach for the period 2000–2020. Estimates indicate that the permafrost region emitted a mean annual flux of 12 (−606, 661) Tg CO2–C yr−1, 38 (22, 53) Tg CH4–C yr−1, and 0.67 (0.07, 1.3) Tg N2O–N yr−1 to the atmosphere throughout the period. Thus, the region was a net source of CH4 and N2O, while the CO2 balance was near neutral within its large uncertainties. Undisturbed terrestrial ecosystems had a CO2 sink of −340 (−836, 156) Tg CO2–C yr−1. Vertical emissions from fire disturbances and inland waters largely offset the sink in vegetated ecosystems. When including lateral fluxes for a complete GHG budget, the permafrost region was a net source of C and N, releasing 144 (−506, 826) Tg C yr−1 and 3 (2, 5) Tg N yr−1. Large uncertainty ranges in these estimates point to a need for further expansion of monitoring networks, continued data synthesis efforts, and better integration of field observations, remote sensing data, and ecosystem models to constrain the contemporary net GHG budgets of the permafrost region and track their future trajectory.
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89.
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90.
  • Rodriguez-Lopez, Merida, et al. (författare)
  • Multilevel analysis of birthplace effect on the proportion of C-Section in Colombia"
  • 2022
  • Ingår i: Colombia medica. - : Universidad del Valle. - 0120-8322 .- 1657-9534. ; 52:3, s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine the general contextual effect of the department in the variation of Cesarean section in Colombia in 2016, and their individual and contextual related factors.Methods: Cross-sectional study based on a birth cohort. We used the birth certificate database from January 1 to December 31, 2016. Three multilevel logistic models were constructed. Pregnant women were set at the first level and department at the second level. We fitted a null multilevel model followed by two multiple models, including individual and individual and department variables, respectively.Results: The overall prevalence of C-section was 45.5% (95% CI: 45.4-45.6), ranged from 5 to 76%. The variance partition coefficient was 15%. Individual factors did not explain the general contextual effect. However, the region to which these departments belong explained 71% of the variance. The Caribbean region was positively associated with C-section compared to the Andean region (OR:3.88, 95% CI: 2.65-5.67).Conclusions: Multilevel analysis of individual heterogeneity and discriminatory accuracy showed that the department plays an important role in the variation of C-sections in Colombia. Our results suggest that the proportional universalism approach should be applied to reduce the proportion of C-Section, focusing on departments with the highest risk and on the Caribbean and Insular region.
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91.
  • Rudovica, Vita, et al. (författare)
  • Valorization of Marine Waste : Use of Industrial By-Products and Beach Wrack Towards the Production of High Added-Value Products
  • 2021
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 8
  • Forskningsöversikt (refereegranskat)abstract
    • Biomass is defined as organic matter from living organisms represented in all kingdoms. It is recognized to be an excellent source of proteins, polysaccharides and lipids and, as such, embodies a tailored feedstock for new products and processes to apply in green industries. The industrial processes focused on the valorization of terrestrial biomass are well established, but marine sources still represent an untapped resource. Oceans and seas occupy over 70% of the Earth's surface and are used intensively in worldwide economies through the fishery industry, as logistical routes, for mining ores and exploitation of fossil fuels, among others. All these activities produce waste. The other source of unused biomass derives from the beach wrack or washed-ashore organic material, especially in highly eutrophicated marine ecosystems. The development of high-added-value products from these side streams has been given priority in recent years due to the detection of a broad range of biopolymers, multiple nutrients and functional compounds that could find applications for human consumption or use in livestock/pet food, pharmaceutical and other industries. This review comprises a broad thematic approach in marine waste valorization, addressing the main achievements in marine biotechnology for advancing the circular economy, ranging from bioremediation applications for pollution treatment to energy and valorization for biomedical applications. It also includes a broad overview of the valorization of side streams in three selected case study areas: Norway, Scotland, and the Baltic Sea.
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92.
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93.
  • Sack, Ulrich, et al. (författare)
  • Quality and best practice in medical laboratories : specific requests for autoimmunity testing
  • 2020
  • Ingår i: Autoimmun Highlights. - : Springer. - 2038-0305 .- 2038-3274. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines. This process has been organized by the European Autoimmunity Standardisation Initiative (EASI). By identifying the critical items and looking for a consensus, our objective was to define a framework for, in particular, EN/ISO accreditation purposes. Here, we present a review of current publications and guidelines in this field to unify national guidelines and deliver in this way a European handout on quality control and accreditation for laboratories involved in autoantibody testing. We focus on quality items that can be checked during accreditation visits. Despite various local varieties, we encountered an overwhelming dedication to quality assurance in all contributing countries.
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94.
  • Savarese, Marco, et al. (författare)
  • Genotype-phenotype correlations in recessive titinopathies.
  • 2020
  • Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 22:12, s. 2029-2040
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort.METHODS: We analyzed clinical and genetic data in a cohort of patients with biallelic pathogenic or likely pathogenic TTN variants. The cohort included both previously reported cases (100 patients from 81 unrelated families) and unreported cases (23 patients from 20 unrelated families).RESULTS: Overall, 132 causative variants were identified in cohort members. More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene. The remaining patients had a distal or proximal phenotype and a childhood or later (noncongenital) onset. All noncongenital cases had at least one pathogenic variant in one of the final three TTN exons (362-364).CONCLUSION: Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.
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95.
  • Schijven, Dick, et al. (författare)
  • Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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96.
  • Solmi, Marco, et al. (författare)
  • Physical and mental health impact of COVID-19 on children, adolescents, and their families :
  • 2022
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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97.
  • Solmi, Marco, et al. (författare)
  • The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
  • 2022
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
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98.
  • Solmi, Marco, et al. (författare)
  • Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
  • 2023
  • Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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99.
  • Soto-Leon, Vanesa, et al. (författare)
  • Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans
  • 2022
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.
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100.
  • Tarazona, Jose V., et al. (författare)
  • Improving the Risk Assessment of Pesticides through the Integration of Human Biomonitoring and Food Monitoring Data : A Case Study for Chlorpyrifos
  • 2022
  • Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food con-sumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers’ exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer’s internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.
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