1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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4. |
- Algaba, Juan-Carlos, et al.
(author)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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5. |
- Adams, C. B., et al.
(author)
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Observation of the Gamma-Ray Binary HESS J0632+057 with the HESS, MAGIC, and VERITAS Telescopes
- 2021
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:2
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Journal article (peer-reviewed)abstract
- The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H alpha emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 +/- 4.4 days is reported, consistent with the period of 317.3 +/- 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H alpha parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.
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6. |
- Crous, P. W., et al.
(author)
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Fusarium : more than a node or a foot-shaped basal cell
- 2021
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In: Studies in mycology. - : CENTRAALBUREAU SCHIMMELCULTURE. - 0166-0616 .- 1872-9797. ; :98
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Journal article (peer-reviewed)abstract
- Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).
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8. |
- Bar, N., et al.
(author)
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A reference map of potential determinants for the human serum metabolome
- 2020
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In: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Journal article (peer-reviewed)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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9. |
- De Leoz, M. L. A., et al.
(author)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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In: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Journal article (peer-reviewed)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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10. |
- Langlois, M., et al.
(author)
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The SPHERE infrared survey for exoplanets (SHINE) : II. Observations, data reduction and analysis, detection performances, and initial results
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Journal article (peer-reviewed)abstract
- Context. In recent decades, direct imaging has confirmed the existence of substellar companions (exoplanets or brown dwarfs) on wide orbits (>10 au) around their host stars. In striving to understand their formation and evolution mechanisms, in 2015 we initiated the SPHERE infrared survey for exoplanets (SHINE), a systematic direct imaging survey of young, nearby stars that is targeted at exploring their demographics.Aims. We aim to detect and characterize the population of giant planets and brown dwarfs beyond the snow line around young, nearby stars. Combined with the survey completeness, our observations offer the opportunity to constrain the statistical properties (occurrence, mass and orbital distributions, dependency on the stellar mass) of these young giant planets.Methods. In this study, we present the observing and data analysis strategy, the ranking process of the detected candidates, and the survey performances for a subsample of 150 stars that are representative of the full SHINE sample. Observations were conducted in a homogeneous way between February 2015 and February 2017 with the dedicated ground-based VLT/SPHERE instrument equipped with the IFS integral field spectrograph and the IRDIS dual-band imager, covering a spectral range between 0.9 and 2.3 μm. We used coronographic, angular, and spectral differential imaging techniques to achieve the best detection performances for this study, down to the planetary mass regime.Results. We processed, in a uniform manner, more than 300 SHINE observations and datasets to assess the survey typical sensitivity as a function of the host star and of the observing conditions. The median detection performance reached 5σ-contrasts of 13 mag at 200 mas and 14.2 mag at 800 mas with the IFS (YJ and YJH bands), and of 11.8 mag at 200 mas, 13.1 mag at 800 mas, and 15.8 mag at 3 as with IRDIS in H band, delivering one of the deepest sensitivity surveys thus far for young, nearby stars. A total of sixteen substellar companions were imaged in this first part of SHINE: seven brown dwarf companions and ten planetary-mass companions.These include two new discoveries, HIP 65426 b and HIP 64892 B, but not the planets around PDS70 that had not been originally selected for the SHINE core sample. A total of 1483 candidates were detected, mainly in the large field of view that characterizes IRDIS. The color-magnitude diagrams, low-resolution spectrum (when available with IFS), and follow-up observations enabled us to identify the nature (background contaminant or comoving companion) of about 86% of our subsample. The remaining cases are often connected to crowded-field follow-up observations that were missing. Finally, even though SHINE was not initially designed for disk searches, we imaged twelve circumstellar disks, including three new detections around the HIP 73145, HIP 86598, and HD 106906 systems.Conclusions. Nowadays, direct imaging provides a unique opportunity to probe the outer part of exoplanetary systems beyond 10 au to explore planetary architectures, as highlighted by the discoveries of: one new exoplanet, one new brown dwarf companion, and three new debris disks during this early phase of SHINE. It also offers the opportunity to explore and revisit the physical and orbital properties of these young, giant planets and brown dwarf companions (relative position, photometry, and low-resolution spectrum in near-infrared, predicted masses, and contrast in order to search for additional companions). Finally, these results highlight the importance of finalizing the SHINE systematic observation of about 500 young, nearby stars for a full exploration of their outer part to explore the demographics of young giant planets beyond 10 au and to identify the most interesting systems for the next generation of high-contrast imagers on very large and extremely large telescopes.
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11. |
- Gao, YX, et al.
(author)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Journal article (peer-reviewed)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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12. |
- Vigan, A., et al.
(author)
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The SPHERE infrared survey for exoplanets (SHINE) : III. The demographics of young giant exoplanets below 300 au with SPHERE
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
-
Journal article (peer-reviewed)abstract
- The SpHere INfrared Exoplanet (SHINE) project is a 500-star survey performed with SPHERE on the Very Large Telescope for the purpose of directly detecting new substellar companions and understanding their formation and early evolution. Here we present an initial statistical analysis for a subsample of 150 stars spanning spectral types from B to M that are representative of the full SHINE sample. Our goal is to constrain the frequency of substellar companions with masses between 1 and 75 MJup and semimajor axes between 5 and 300 au. For this purpose, we adopt detection limits as a function of angular separation from the survey data for all stars converted into mass and projected orbital separation using the BEX-COND-hot evolutionary tracks and known distance to each system. Based on the results obtained for each star and on the 13 detections in the sample, we use a Markov chain Monte Carlo tool to compare our observations to two different types of models. The first is a parametric model based on observational constraints, and the second type are numerical models that combine advanced core accretion and gravitational instability planet population synthesis. Using the parametric model, we show that the frequencies of systems with at least one substellar companion are 23.0−9.7+13.5, 5.8−2.8+4.7, and 12.6−7.1+12.9% for BA, FGK, and M stars, respectively. We also demonstrate that a planet-like formation pathway probably dominates the mass range from 1–75 MJup for companions around BA stars, while for M dwarfs, brown dwarf binaries dominate detections. In contrast, a combination of binary star-like and planet-like formation is required to best fit the observations for FGK stars. Using our population model and restricting our sample to FGK stars, we derive a frequency of 5.7−2.8+3.8%, consistent with predictions from the parametric model. More generally, the frequency values that we derive are in excellent agreement with values obtained in previous studies.
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13. |
- Polme, S., et al.
(author)
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FungalTraits: a user-friendly traits database of fungi and fungus-like stramenopiles
- 2020
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 105:1, s. 1-16
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Journal article (peer-reviewed)abstract
- The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold.
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18. |
- Addazi, A., et al.
(author)
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New high-sensitivity searches for neutrons converting into antineutrons and/or sterile neutrons at the HIBEAM/NNBAR experiment at the European Spallation Source
- 2021
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In: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 48:7
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Journal article (peer-reviewed)abstract
- The violation of baryon number, , is an essential ingredient for the preferential creation of matter over antimatter needed to account for the observed baryon asymmetry in the Universe. However, such a process has yet to be experimentally observed. The HIBEAM/NNBAR program is a proposed two-stage experiment at the European Spallation Source to search for baryon number violation. The program will include high-sensitivity searches for processes that violate baryon number by one or two units: free neutron–antineutron oscillation () via mixing, neutron–antineutron oscillation via regeneration from a sterile neutron state (), and neutron disappearance (n → n'); the effective process of neutron regeneration () is also possible. The program can be used to discover and characterize mixing in the neutron, antineutron and sterile neutron sectors. The experiment addresses topical open questions such as the origins of baryogenesis and the nature of dark matter, and is sensitive to scales of new physics substantially in excess of those available at colliders. A goal of the program is to open a discovery window to neutron conversion probabilities (sensitivities) by up to three orders of magnitude compared with previous searches. The opportunity to make such a leap in sensitivity tests should not be squandered. The experiment pulls together a diverse international team of physicists from the particle (collider and low energy) and nuclear physics communities, while also including specialists in neutronics and magnetics.
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20. |
- Tedersoo, L., et al.
(author)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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In: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Journal article (peer-reviewed)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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21. |
- Boretzky, K., et al.
(author)
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NeuLAND: The high-resolution neutron time-of-flight spectrometer for R 3 B at FAIR
- 2021
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 1014
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Journal article (peer-reviewed)abstract
- NeuLAND (New Large-Area Neutron Detector) is the next-generation neutron detector for the R3B (Reactions with Relativistic Radioactive Beams) experiment at FAIR (Facility for Antiproton and Ion Research). NeuLAND detects neutrons with energies from 100 to 1000 MeV, featuring a high detection efficiency, a high spatial and time resolution, and a large multi-neutron reconstruction efficiency. This is achieved by a highly granular design of organic scintillators: 3000 individual submodules with a size of 5 × 5 × 250 cm3 are arranged in 30 double planes with 100 submodules each, providing an active area of 250 × 250 cm2 and a total depth of 3 m. The spatial resolution due to the granularity together with a time resolution of σt≤ 150 ps ensures high-resolution capabilities. In conjunction with calorimetric properties, a multi-neutron reconstruction efficiency of 50% to 70% for four-neutron events will be achieved, depending on both the emission scenario and the boundary conditions allowed for the reconstruction method. We present in this paper the final design of the detector as well as results from test measurements and simulations on which this design is based.
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22. |
- Coccolini, F., et al.
(author)
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Aortic balloon occlusion (REBOA) in pelvic ring injuries: preliminary results of the ABO Trauma Registry
- 2020
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In: Updates in Surgery. - : Springer Science and Business Media LLC. - 2038-131X .- 2038-3312. ; 2020:72, s. 527-536
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Journal article (peer-reviewed)abstract
- EndoVascular and Hybrid Trauma Management (EVTM) has been recently introduced in the treatment of severe pelvic ring injuries. This multimodal method of hemorrhage management counts on several strategies such as the REBOA (resuscitative endovascular balloon occlusion of the aorta). Few data exist on the use of REBOA in patients with a severely injured pelvic ring. The ABO (aortic balloon occlusion) Trauma Registry is designed to capture data for all trauma patients in hemorrhagic shock where management includes REBOA placement. Among all patients included in the ABO registry, 72 patients presented with severe pelvic injuries and were the population under exam. 66.7% were male. Mean and median ISS were respectively 43 and 41 (SD ± 13). Isolated pelvic injuries were observed in 12 patients (16.7%). Blunt trauma occurred in 68 patients (94.4%), penetrating in 2 (2.8%) and combined in 2 (2.8%). Type of injury: fall from height in 15 patients (23.1%), traffic accident in 49 patients (75.4%), and unspecified impact in 1 patient (1.5%). Femoral access was gained pre-hospital in 1 patient, in emergency room in 43, in operating room in 12 and in angio-suite in 16. REBOA was positioned in zone 1 in 59 patients (81,9%), in zone 2 in 1 (1,4%) and in zone 3 in 12 (16,7%). Aortic occlusion was partial/periodical in 35 patients (48,6%) and total occlusion in 37 patients (51,4%). REBOA associated morbidity rate: 11.1%. Overall mortality rate was 54.2% and early mortality rate (≤ 24h) was 44.4%. In the univariate analysis, factors related to early mortality (≤ 24h) are lower pH values (p = 0.03), higher base deficit (p = 0.021), longer INR (p = 0.012), minor increase in systolic blood pressure after the REBOA inflation (p = 0.03) and total aortic occlusion (p = 0.008). None of these values resulted significant in the multivariate analysis. In severe hemodynamically unstable pelvic trauma management, REBOA is a viable option when utilized in experienced centers as a bridge to other treatments; its use might be, however, accompanied with severe-to-lethal complications. © 2020, Italian Society of Surgery (SIC).
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23. |
- Revel, A., et al.
(author)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Journal article (peer-reviewed)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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24. |
- Kawahara, R., et al.
(author)
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Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis
- 2021
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In: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 18, s. 1304-1316
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Journal article (peer-reviewed)abstract
- Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics. This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.
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25. |
- Sellgren, C. M., et al.
(author)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Journal article (peer-reviewed)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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26. |
- Syndikus, I., et al.
(author)
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Probing the Z = 6 spin-orbit shell gap with (p,2p) quasi-free scattering reactions
- 2020
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 809
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Journal article (peer-reviewed)abstract
- The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the Z=6 spin-orbit shell gap towards the neutron dripline. To do so, we employed NA(p,2p)CA−1 quasi-free scattering reactions to measure the proton component of the 21+ state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton 1p1/2−1p3/2 spin-orbit splitting, at variance to recent claims for a prevalent Z=6 magic number towards the neutron dripline.
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27. |
- Hilbert-Carius, Peter, et al.
(author)
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Pre-hospital CPR and early REBOA in trauma patients-results from the ABOTrauma Registry
- 2020
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In: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:1
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Journal article (peer-reviewed)abstract
- © 2020 The Author(s). Background: Severely injured trauma patients suffering from traumatic cardiac arrest (TCA) and requiring cardiopulmonary resuscitation (CPR) rarely survive. The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) performed early after hospital admission in patients with TCA is not well-defined. As the use of REBOA increases, there is great interest in knowing if there is a survival benefit related to the early use of REBOA after TCA. Using data from the ABOTrauma Registry, we aimed to study the role of REBOA used early after hospital admission in trauma patients who required pre-hospital CPR. Methods: Retrospective and prospective data on the use of REBOA were collected from the ABOTrauma Registry from 11 centers in seven countries globally between 2014 and 2019. In all patients with pre-hospital TCA, the predicted probability of survival, calculated with the Revised Injury Severity Classification II (RISC II), was compared with the observed survival rate. Results: Of 213 patients in the ABOTrauma Registry, 26 patients (12.2%) who had received pre-hospital CPR were identified. The median (range) Injury Severity Score (ISS) was 45.5 (25-75). Fourteen patients (54%) had been admitted to the hospital with ongoing CPR. Nine patients (35%) died within the first 24 h, while seventeen patients (65%) survived post 24 h. The survival rate to hospital discharge was 27% (n = 7). The predicted mortality using the RISC II was 0.977 (25 out of 26). The observed mortality (19 out of 26) was significantly lower than the predicted mortality (p = 0.049). Patients not responding to REBOA were more likely to die. Only one (10%) out of 10 non-responders survived. The survival rate in the 16 patients responding to REBOA was 37.5% (n = 6). REBOA with a median (range) duration of 45 (8-70) minutes significantly increases blood pressure from the median (range) 56.5 (0-147) to 90 (0-200) mmHg. Conclusions: Mortality in patients suffering from TCA and receiving REBOA early after hospital admission is significantly lower than predicted by the RISC II. REBOA may improve survival after TCA. The use of REBOA in these patients should be further investigated.
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- Lucking, R., et al.
(author)
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Fungal taxonomy and sequence-based nomenclature
- 2021
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:5, s. 540-548
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Journal article (peer-reviewed)abstract
- The identification and proper naming of microfungi, in particular plant, animal and human pathogens, remains challenging. Molecular identification is becoming the default approach for many fungal groups, and environmental metabarcoding is contributing an increasing amount of sequence data documenting fungal diversity on a global scale. This includes lineages represented only by sequence data. At present, these taxa cannot be formally described under the current nomenclature rules. By considering approaches used in bacterial taxonomy, we propose solutions for the nomenclature of taxa known only from sequences to facilitate consistent reporting and communication in the literature and public sequence repositories. This Perspective discusses fungal taxonomy and provides guidance for the naming of fungal taxa known only from sequences.
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30. |
- Gray, E., et al.
(author)
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A multi-center study of neurofilament assay reliability and inter-laboratory variability
- 2020
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In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 21:5-6, s. 452-458
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Journal article (peer-reviewed)abstract
- Objectives: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S.Methods: Serum, plasma and CSF samples from a group of five ALS and five neurological control patients were distributed across 10 international specialist neurochemical laboratories for analysis by a range of commercial and in-house neurofilament assays. The performance of all assays was evaluated for their ability to differentiate between the groups. The inter-assay coefficient of variation was calculated where appropriate from sample measurements performed across multiple laboratories using the same assay.Results:All assays could differentiate ALS patients from controls in CSF. Inter-assay coefficient of variation of analytical platforms performed across multiple laboratories varied between 6.5% and 41.9%.Conclusions:This study is encouraging for the growing momentum toward integration of neurofilament measurement into the specialized ALS clinic. It demonstrates the importance of 'round robin' studies necessary to ensure the analytical quality required for translation to the routine clinical setting. A standardized neurofilament probe is needed which can be used as international benchmark for analytical performance in ALS.
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31. |
- Storck, Sonja, et al.
(author)
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Lifetime measurement of the 26 0 g.s. At SAMURAI
- 2020
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643:1
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Conference paper (peer-reviewed)abstract
- The ground state of the neutron unbound nucleus O is speculated to have a lifetime in the pico-second regime. In order to determine the decay lifetime of the O ground state with high sensitivity and precision, a new method has been applied. The experiment was performed in December 2016 at the Superconducting Analyzer for MUlti-particle from Radio Isotope Beams (SAMURAI) at the Radioactive Isotope Beam Factory (RIBF) at RIKEN. A F beam was produced in the fragment separator BigRIPS and impinged on a W/Pt target stack where O was produced. According to the lifetime, the decay of O happens either in or outside the target. Thus, the velocity difference between the decay neutrons and the fragment O delivers a characteristic spectrum from which the lifetime can be extracted.
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33. |
- Bock, O., et al.
(author)
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Use of GNSS Tropospheric Products for Climate Monitoring (Working Group 3)
- 2020
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In: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 267-402
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Book chapter (other academic/artistic)abstract
- There has been growing interest in recent years in the use of homogeneously reprocessed ground-based GNSS, VLBI, and DORIS measurements for climate applications. Existing datasets are reviewed and the sensitivity of tropospheric estimates to the processing details is discussed. The uncertainty in the derived IWV estimates and linear trends is around 1 kg m^2 RMS and ± 0.3 kg m^2 per decade, respectively. Standardized methods for ZTD outlier detection and IWV conversion are proposed. The homogeneity of final time series is limited however by changes in the stations equipment and environment. Various homogenization algorithms have been evaluated based on a synthetic benchmark dataset. The uncertainty of trends estimated from the homogenized times series is estimated to ±0.5 kg m^2 per decade. Reprocessed GNSS IWV data are analysed along with satellites data, reanalyses and global and regional climate model simulations. A selection of global and regional reprocessed GNSS datasets and ERA-interim reanalysis are made available through the GOP-TropDB tropospheric database and online service. A new tropo SINEX format, providing new features and simplifications, was developed and it is going to be adopted by all the IAG services.
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- Muro-Arena, G. A., et al.
(author)
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Spirals inside the millimeter cavity of transition disk SR 21
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Journal article (peer-reviewed)abstract
- Context. Hydrodynamical simulations of planet-disk interactions suggest that planets may be responsible for a number of the substructures frequently observed in disks in both scattered light and dust thermal emission. Despite the ubiquity of these features, direct evidence of planets embedded in disks and of the specific interaction features like spiral arms within planetary gaps are still rare.Aims. In this study we discuss recent observational results in the context of hydrodynamical simulations in order to infer the properties of a putative embedded planet in the cavity of a transition disk.Methods. We imaged the transition disk SR 21 in H-band in scattered light with SPHERE/IRDIS and in thermal dust emission with ALMA band 3 (3 mm) observations at a spatial resolution of 0.1 ''. We combine these datasets with existing Band 9 (430 mu m) and Band 7 (870 mu m) ALMA continuum data.Results. The Band 3 continuum data reveals a large cavity and a bright ring peaking at 53 au strongly suggestive of dust trapping. The ring shows a pronounced azimuthal asymmetry, with a bright region in the northwest that we interpret as a dust overdensity. A similarly asymmetric ring is revealed at the same location in polarized scattered light, in addition to a set of bright spirals inside the millimeter cavity and a fainter spiral bridging the gap to the outer ring. These features are consistent with a number of previous hydrodynamical models of planet-disk interactions, and suggest the presence of a similar to 1 M-Jup planet at 44 au and PA = 11 deg. This makes SR21 the first disk showing spiral arms inside the millimeter cavity, and the first disk for which the location of a putative planet can be precisely inferred.Conclusions. The main features of SR 21 in both scattered light and thermal emission are consistent with hydrodynamical predictions of planet-disk interactions. With the location of a possible planet being well constrained by observations, it is an ideal candidate for follow-up observations to search for direct evidence of a planetary companion still embedded in its disk.
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- Hilbert-Carius, Peter, et al.
(author)
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Successfully REBOA performance: does medical specialty matter? International data from the ABOTrauma Registry
- 2020
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In: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:1
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Journal article (peer-reviewed)abstract
- © 2020, The Author(s). Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive procedure being increasingly utilized to prevent patients with non-compressible torso hemorrhage from exsanguination. The increased use of REBOA is giving rise to discussion about “Who is and who should be performing it?” Methods: Data from the international ABO (aortic balloon occlusion) Trauma Registry from between November 2014 and April 2020 were analyzed concerning the question: By who, how, and where is REBOA being performed? The registry collects retrospective and prospective data concerning use of REBOA in trauma patients. Results: During the study period, 259 patients had been recorded in the registry, 72.5% (n = 188) were males with a median (range) age of 46 (10-96) years. REBOA was performed in the ER in 50.5%, in the OR in 41.5%, and in the angiography suite in 8% of patients. In 54% of the patients REBOA was performed by surgeons (trauma surgeons 28%, vascular surgeons 22%, general surgeons 4%) and in 46% of the patients by non-surgeons (emergency physicians 31%, radiologists 9.5%, anesthetists 5.5%). Common femoral artery (CFA) access was achieved by use of external anatomic landmarks and palpation alone in 119 patients (51%), by cutdown in 57 patients (24%), using ultrasound in 49 patients (21%), and by fluoroscopy in 9 patients (4%). Significant differences between surgeons and non-surgeons were found regarding patient’s age, injury severity, access methods, place where REBOA was performed, location patients were taken to from the emergency room, and mortality. Conclusion: A substantial number of both surgical and non-surgical medical disciplines are successfully performing REBOA to an almost equal extent. Surgical cutdown is used less frequently as access to the CFA compared with reports in older literature and puncture by use of external anatomic landmarks and palpation alone is used with a high rate of success. Instead of discussing “Who should be performing REBOA?” future research should focus on “Which patient benefits most from REBOA?”
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- Biederstädt, A., et al.
(author)
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SUMO pathway inhibition targets an aggressive pancreatic cancer subtype
- 2020
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69, s. 1472-1482
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Journal article (peer-reviewed)abstract
- Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies. Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC. Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition. Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype. © 2020 American Medical Association. All rights reserved.
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44. |
- Culina, Antica, et al.
(author)
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Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
- 2021
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In: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
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Journal article (peer-reviewed)abstract
- The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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45. |
- Fransson, P., et al.
(author)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, 3 trial
- 2021
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In: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 22:2, s. 235-245
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Journal article (peer-reviewed)abstract
- Background The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial. Methods HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score >= 7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78.0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the perprotocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0.0001], rush to toilet [p=0.0013], flatulence [p=0.0013], bowel cramp [p<0.0001], mucus [p=0.0014], blood in stool [p<0.0001], and limitation in daily activity [p=0.0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year followup there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5.1% [95% CI -4.4 to 14.6]; p=0.38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5.7% [-3.8 to 15.2]; p=0.33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9.1% [-1.4 to 19.6]; p=0.15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5.0% [-5.0 to 15.0]; p=0.41). Interpretation Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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46. |
- Gobel, K., et al.
(author)
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Coulomb dissociation of 16O into 4He and 12C
- 2020
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1668:1
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Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(a,?)16O fusion reaction and to reach lower center-ofmass energies than measured so far. The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-To-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
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47. |
- Hammarsjö, A., et al.
(author)
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High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses
- 2021
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In: Journal of Human Genetics. - : Springer Nature. - 1434-5161 .- 1435-232X. ; 66:10, s. 995-1008
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Journal article (peer-reviewed)abstract
- Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
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48. |
- Jain, Ruchi, et al.
(author)
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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
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49. |
- Knyazev, A., et al.
(author)
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Tl concentration and its variation in a CsI(Tl) crystal for the CALIFA detector
- 2020
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 975
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Journal article (peer-reviewed)abstract
- One of the factors that can contribute to the resolution of long, doped inorganic scintillators used for nuclear spectroscopy is the variation of the dopant concentration over the length the detector crystal. In this work an investigation of such potential variations in one of the CsI(Tl) scintillators used in the calorimeter, CALIFA, of the R3B experiment at FAIR, has been performed using particle induced X-ray emission. No statistically significant gradient in doping level was found along the long axis of the investigated sample crystal and the mean value of the Tl concentration was measured to be 0.0839(38)% by weight. This corresponds to a light output of 97.3−1.7 +1.3% relative to the maximum attainable light output according to previously published work. By taking the ±1σ bounds, the 3% statistical spread in the relative light output provides a good reference value of the minimum light-output non-uniformity observed for the CALIFA crystals. If the relative light output is estimated pointwise from a set of Tl concentration measurements a light-output non-uniformity of 4.6(2.4)% results. For a γ-ray energy of 662 keV the deduced variation in Tl concentration contributes with 0.48(6)% to the typical resolution of 7.74(6)% measured with a collimated source along the crystal main axis. The result is of interest for the characterization of the detector system performance and for realistic simulations of the light collection process in detector systems that are used for nuclear spectroscopy and calorimetry.
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