| 1. |
- Laurie, Steven, et al.
(författare)
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The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases
- 2022
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733
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Tidskriftsartikel (refereegranskat)abstract
- Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
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| 2. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 3. |
- Catalan, Nuria, et al.
(författare)
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The relevance of environment vs. composition on dissolved organic matter degradation in freshwaters
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:2, s. 306-320
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved organic matter (DOM) composition exerts a direct control on its degradation and subsequent persistence in aquatic ecosystems. Yet, under certain conditions, the degradation patterns of DOM cannot be solely explained by its composition, highlighting the relevance of environmental conditions for DOM degradation. Here, we experimentally assessed the relative influence of composition vs. environment on DOM degradation by performing degradation bioassays using three contrasting DOM sources inoculated with a standardized bacterial inoculum under five distinct environments. The DOM degradation kinetics modeled using reactivity continuum models showed that composition was more important than environment in determining the bulk DOM decay patterns. Changes in DOM composition resulted from the interaction between DOM source and environment. The role of environment was stronger on shaping the bacterial community composition, but the intrinsic nature of the DOM source exerted stronger control on the DOM degradation function.
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| 4. |
- Fumoto, Takayuki, et al.
(författare)
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Measurement of Moisture Content and Volume Change Distribution Inside Cement Paste Specimens Using X-Ray CT Imaging
- 2020
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Ingår i: 15th International Conference on Durability of Building Materials and Components, DBMC 2020 : DBMC 2020 - DBMC 2020. - : CIMNE. - 9788412110180 ; , s. 1511-1518
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Konferensbidrag (refereegranskat)abstract
- The purpose of this study was to clarify the internal change of concrete structures during drying. Therefore, we used X-ray CT to investigate water content and volume changes inside cement paste specimens during drying. Changes in the CT image intensities and measurements on the images indicated water content and volume changes, including local changes detected with digital volume correlation. Next steps will be to understand the link between volume changes and the local water content.
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| 5. |
- González-Jiménez, José M., et al.
(författare)
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Precious metals in magmatic Fe-Ni-Cu sulfides from the Potosí chromitite deposit, eastern Cuba
- 2020
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Ingår i: Ore Geology Reviews. - : Elsevier. - 0169-1368 .- 1872-7360. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- The Moa-Baracoa ophiolite in eastern Cuba is one of the few known ophiolites that display sulfide mineralization attributable to a magmatic origin in association with podiform-chromite ores hosted in the mantle-crust transition. These sulfide ores chiefly consist of Fe-Ni-Cu sulfides, namely pyrrhotite, pentlandite, chalcopyrite and cubanite partly altered to valleriite. The sulfide mineralization is located along the contact between the podiform-like chromite ores and intruding pegmatitic gabroic dykes. The detailed mineralogical study of the sulfide mineralization coupled with the first ever laser ablation ICP-MS analysis reveals that this sulfide mineralization show contents of the precious metals (Os, Ir, Ru, Pt, Re, Au, Ag) and other (semi)-metals (Co, Ni, Cu, Se, Te, Bi, Pb, As Sb) comparable to those sulfides from the magmatic sulfide deposits associated with mafic complexes hosted in the continental crust. The results obtained from this study confirm that Fe-Ni-Cu sulfides at Potosí are magmatic in origin, and very likely derived from the solidification of droplets of sulfide melt segregated by immiscibility from the intruding mafic melts once they interacted with the pre-existing chromitite at the mantle-crust transition zone of the ophiolite. The immiscibility of sulfide melt was achieved as a result of a progressive increase of fS2, very likely triggered by a set of circumstances, including the progressive fractionation of the intruding mafic melt leading to increase of aSiO2 and accumulation of volatiles as well as the crystallization of oxides. Two main generations of pentlandite were observed. One generation is primary in origin and it was locally exsolved along with pyrrhotite from monosulfide solid solution (MSS) during low-temperature cooling. The second type of pentlandite resulted from the reaction of MSS with coexisting droplets of Cu-and Ni-rich sulfide melt. LA-ICP-MS analysis reveals that most precious metals (Ru, Os, Ir, Re, Au, Ag) were concentrated along with the base-metal sulfides (BMS), although their distribution among the different BMS (pyrrhotite, pentlandite, chalcopyrite and cubanite) does not strictly follow the expected distribution according to the known melt-solid and solid-solid partition coefficients. Unlike the other analyzed PGEs, Pt was not preferentially concentrated in BMS but as discrete micrometer-sized sperrylite grains. The crystallization of sperrylite took place before and contemporaneous to sulfide segregation, and Pt-As nanoparticles probably played an important role in the Pt uptake as nucleation seeds for the formation of micron-sized sperrylite grains. These observations highlight the open-system nature of the ore forming system as well as the important role of arsenic in concentrating PGE in high-temperature silicate and sulfide melts.
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| 6. |
- Iglesias, Maria Jesus, et al.
(författare)
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Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
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| 7. |
- Loizides, Michael, et al.
(författare)
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Has taxonomic vandalism gone too far? A case study, the rise of the pay-to-publish model and the pitfalls of Morchella systematics
- 2022
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Ingår i: Mycological progress. - : Springer Science and Business Media LLC. - 1617-416X .- 1861-8952. ; 21:1, s. 7-38
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Tidskriftsartikel (refereegranskat)abstract
- The genus Morchella has gone through turbulent taxonomic treatments. Although significant progress in Morchella systematics has been achieved in the past decade, several problems remain unresolved and taxonomy in the genus is still in flux. In late 2019, a paper published in the open-access journal Scientific Reports raised serious concerns about the taxonomic stability of the genus, but also about the future of academic publishing. The paper, entitled “High diversity of Morchella and a novel lineage of the esculenta clade from the north Qinling Mountains revealed by GCPSR-based study” by Phanpadith and colleagues, suffered from gross methodological errors, included false results and artifactual phylogenies, had misapplied citations throughout, and proposed a new species name invalidly. Although the paper was eventually retracted by Scientific Reports in 2021, the fact that such an overtly flawed and scientifically unsound paper was published in a high-ranked Q1 journal raises alarming questions about quality controls and safekeeping procedures in scholarly publishing. Using this paper as a case study, we provide a critical review on the pitfalls of Morchella systematics followed by a series of recommendations for the delimitation of species, description of taxa, and ultimately for a sustainable taxonomy in Morchella. Problems and loopholes in the academic publishing system are also identified and discussed, and additional quality controls in the pre- and post-publication stages are proposed.
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| 8. |
- Schwartz, David A., et al.
(författare)
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Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury
- 2022
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Ingår i: Archives of Pathology & Laboratory Medicine. - : COLL AMER PATHOLOGISTS. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
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Tidskriftsartikel (refereegranskat)abstract
- Context.-Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.-To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.-Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.-Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.-The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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| 9. |
- Schwartz, David A., et al.
(författare)
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Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury : A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries
- 2022
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Ingår i: Archives of Pathology & Laboratory Medicine. - : Archives of Pathology and Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
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Tidskriftsartikel (refereegranskat)abstract
- Context: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.Objective: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Design: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.Results: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.Conclusions: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
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| 10. |
- Suttie, Ed, et al.
(författare)
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Performance Based Specification of Wood - Project CLICKdesign
- 2020
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Ingår i: Proceedings of the 15th International Conference on Durability of Building Materials and Components, DBMC 2020. - : CIMNE. - 9788412110180 ; , s. 457-464
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Konferensbidrag (refereegranskat)abstract
- This paper introduces the ForestValue research project CLICKdesign - delivering fingertip knowledge to enable service life performance specification of wood. The consortium is working on a primary innovation to move from the complex, fragmented and general to the easy-to-use, consolidated and specific by provision of a digital tool for specifiers. Other materials tackle this and provide designers and architects with software. The specification of performance of wood products is complex and fraught with inconsistency and requires use of multiple platforms for data, experience, standards and national recommendations. CLICKdesign will provide a tool that has within it the decades of research, the complexity of the standards specification systems and the variation of approach due to tradition, materials and culture across Europe and beyond. A simple tool for nonexpert public users will be available as well as a tool accessible to professional users that will be refined with industry to ensure relevancy and accelerate uptake and use.
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