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2.	Bousquet, Jean, et al. (author) Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology 2019 In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879 Journal article (peer-reviewed)abstract Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
3.	Kattge, Jens, et al. (author) TRY plant trait database - enhanced coverage and open access 2020 In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Journal article (peer-reviewed)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
4.	Kehoe, Laura, et al. (author) Make EU trade with Brazil sustainable 2019 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Journal article (other academic/artistic)
5.	Luque, R., et al. (author) A planetary system with two transiting mini-Neptunes near the radius valley transition around the bright M dwarf TOI-776 2021 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645 Journal article (peer-reviewed)abstract We report the discovery and characterization of two transiting planets around the bright M1 V star LP 961-53 (TOI-776, J = 8.5 mag, M = 0.54 ± 0.03 M⊙) detected during Sector 10 observations of the Transiting Exoplanet Survey Satellite (TESS). Combining the TESS photometry with HARPS radial velocities, as well as ground-based follow-up transit observations from the MEarth and LCOGT telescopes, for the inner planet, TOI-776 b, we measured a period of Pb = 8.25 d, a radius of Rb = 1.85 ± 0.13 R⊙, and a mass of Mb = 4.0 ± 0.9 M⊙; and for the outer planet, TOI-776 c, a period of Pc = 15.66 d, a radius of Rc = 2.02 ± 0.14 R⊙, and a mass of Mc = 5.3 ± 1.8 M⊙. The Doppler data shows one additional signal, with a period of ~34 d, associated with the rotational period of the star. The analysis of fifteen years of ground-based photometric monitoring data and the inspection of different spectral line indicators confirm this assumption. The bulk densities of TOI-776 b and c allow for a wide range of possible interior and atmospheric compositions. However, both planets have retained a significant atmosphere, with slightly different envelope mass fractions. Thanks to their location near the radius gap for M dwarfs, we can start to explore the mechanism(s) responsible for the radius valley emergence around low-mass stars as compared to solar-like stars. While a larger sample of well-characterized planets in this parameter space is still needed to draw firm conclusions, we tentatively estimate that the stellar mass below which thermally-driven mass loss is no longer the main formation pathway for sculpting the radius valley is between 0.63 and 0.54 M⊙. Due to the brightness of the star, the TOI-776 system is also an excellent target for the James Webb Space Telescope, providing a remarkable laboratory in which to break the degeneracy in planetary interior models and to test formation and evolution theories of small planets around low-mass stars.
6.	Agirre, Jon, et al. (author) The CCP4 suite: integrative software for macromolecular crystallography 2023 In: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461 Journal article (peer-reviewed)abstract The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
7.	Björkman, Anne, 1981, et al. (author) Tundra Trait Team: A database of plant traits spanning the tundra biome 2018 In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411 Journal article (peer-reviewed)abstract © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
8.	Deeg, H., et al. (author) TOI-1416: A system with a super-Earth planet with a 1.07 d period 2023 In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 677 Journal article (peer-reviewed)abstract TOI-1416 (BD+42 2504, HIP 70705) is a V =10 late G- or early K-type dwarf star. TESS detected transits in its Sectors 16, 23, and 50 with a depth of about 455 ppm and a period of 1.07 days. Radial velocities (RVs) confirm the presence of the transiting planet TOI-1416 b, which has a mass of 3.48 ± 0.47 M• and a radius of 1.62 ± 0.08 R•, implying a slightly sub-Earth density of 4.500.83+0.99 g cm3. The RV data also further indicate a tentative planet, c, with a period of 27.4 or 29.5 days, whose nature cannot be verified due to strong suspicions of contamination by a signal related to the Moon s synodic period of 29.53 days. The nearly ultra-short-period planet TOI-1416 b is a typical representative of a short-period and hot (Teq ≈ 1570 K) super-Earth-like planet. A planet model of an interior of molten magma containing a significant fraction of dissolved water provides a plausible explanation for its composition, and its atmosphere could be suitable for transmission spectroscopy with JWST. The position of TOI-1416 b within the radius-period distribution corroborates the idea that planets with periods of less than one day do not form any special group. It instead implies that ultra-short-period planets belong to a continuous distribution of super-Earth-like planets with periods ranging from the shortest known ones up to ≈ 30 days; their period-radius distribution is delimited against larger radii by the Neptune Desert and by the period-radius valley that separates super-Earths from sub-Neptune planets. In the abundance of small, short-periodic planets, a notable plateau has emerged between periods of 0.6- 1.4 days, which is compatible with the low-eccentricity formation channel. For the Neptune Desert, its lower limits required a revision due to the increasing population of short-period planets; for periods shorter then 2 days, we establish a radius of 1.6 R• and a mass of 0.028 Mjup (corresponding to 8.9 M•) as the desert s lower limits. We also provide corresponding limits to the Neptune Desert against the planets insolation and effective temperatures.
9.	Lam, K. W.F., et al. (author) GJ 367b: A dense, ultrashort-period sub-Earth planet transiting a nearby red dwarf star 2021 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6572, s. 1271-1275 Journal article (peer-reviewed)abstract Ultrashort-period (USP) exoplanets have orbital periods shorter than 1 day. Precise masses and radii of USP exoplanets could provide constraints on their unknown formation and evolution processes. We report the detection and characterization of the USP planet GJ 367b using high-precision photometry and radial velocity observations. GJ 367b orbits a bright (V-band magnitude of 10.2), nearby, and red (M-type) dwarf star every 7.7 hours. GJ 367b has a radius of 0.718 ± 0.054 Earth-radii and a mass of 0.546 ± 0.078 Earth-masses, making it a sub-Earth planet. The corresponding bulk density is 8.106 ± 2.165 grams per cubic centimeter—close to that of iron. An interior structure model predicts that the planet has an iron core radius fraction of 86 ± 5%, similar to that of Mercury’s interior.
10.	Van Eylen, Vincent, et al. (author) Masses and compositions of three small planets orbiting the nearby M dwarf L231-32 (TOI-270) and the M dwarf radius valley 2021 In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:2, s. 2154-2173 Journal article (peer-reviewed)abstract We report on precise Doppler measurements of L231-32 (TOI-270), a nearby M dwarf (d = 22 pc, M = 0.39 M, R = 0.38 R), which hosts three transiting planets that were recently discovered using data from the Transiting Exoplanet Survey Satellite (TESS). The three planets are 1.2, 2.4, and 2.1 times the size of Earth and have orbital periods of 3.4, 5.7, and 11.4 d. We obtained 29 high-resolution optical spectra with the newly commissioned Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations (ESPRESSO) and 58 spectra using the High Accuracy Radial velocity Planet Searcher (HARPS). From these observations, we find the masses of the planets to be 1.58 ± 0.26, 6.15 ± 0.37, and 4.78 ± 0.43 M, respectively. The combination of radius and mass measurements suggests that the innermost planet has a rocky composition similar to that of Earth, while the outer two planets have lower densities. Thus, the inner planet and the outer planets are on opposite sides of the 'radius valley'-a region in the radius-period diagram with relatively few members-which has been interpreted as a consequence of atmospheric photoevaporation. We place these findings into the context of other small close-in planets orbiting M dwarf stars, and use support vector machines to determine the location and slope of the M dwarf (Teff < 4000 K) radius valley as a function of orbital period. We compare the location of the M dwarf radius valley to the radius valley observed for FGK stars, and find that its location is a good match to photoevaporation and core-powered mass-loss models. Finally, we show that planets below the M dwarf radius valley have compositions consistent with stripped rocky cores, whereas most planets above have a lower density consistent with the presence of a H-He atmosphere.
11.	Picetti, Edoardo, et al. (author) Early management of adult traumatic spinal cord injury in patients with polytrauma : a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS) 2024 In: World Journal of Emergency Surgery. - : BioMed Central (BMC). - 1749-7922. ; 19 Journal article (peer-reviewed)abstract Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak).Conclusions: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.
12.	Block, Keith I., et al. (author) Designing a broad-spectrum integrative approach for cancer prevention and treatment 2015 In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304 Research review (peer-reviewed)abstract Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
13.	Moretti, Rocco, et al. (author) Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions 2013 In: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987 Journal article (peer-reviewed)abstract Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
14.	Poldrack, RA, et al. (author) The Past, Present, and Future of the Brain Imaging Data Structure (BIDS) 2024 In: ArXiv. - 2331-8422. Journal article (other academic/artistic)
15.	Šubjak, J., et al. (author) TOI-1268b: The youngest hot Saturn-mass transiting exoplanet 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 662 Journal article (peer-reviewed)abstract We report the discovery of TOI-1268b, a transiting Saturn-mass planet from the TESS space mission. With an age of less than 1 Gyr, derived from various age indicators, TOI-1268b is the youngest Saturn-mass planet known to date; it contributes to the small sample of well-characterised young planets. It has an orbital period of P = 8.1577080 ± 0.0000044 days, and transits an early K-dwarf star with a mass of M∗ = 0.96 ± 0.04 M+, a radius of R∗ = 0.92 ± 0.06 R+, an effective temperature of Teff = 5300 ± 100 K, and a metallicity of 0.36 ± 0.06 dex. By combining TESS photometry with high-resolution spectra acquired with the Tull spectrograph at the McDonald Observatory, and the high-resolution spectrographs at the Tautenburg and OndR ejov Observatories, we measured a planetary mass of Mp = 96.4 ± 8.3 Mp and a radius of Rp = 9.1 ± 0.6 Rp. TOI-1268 is an ideal system for studying the role of star-planet tidal interactions for non-inflated Saturn-mass planets. We used system parameters derived in this paper to constrain the planeta's tidal quality factor to the range of 104.5-5.3. When compared with the sample of other non-inflated Saturn-mass planets, TOI-1268b is one of the best candidates for transmission spectroscopy studies.
16.	Zheng, Hou-Feng, et al. (author) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112- Journal article (peer-reviewed)abstract The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
17.	Baud, Maxime O, et al. (author) European trends in epilepsy surgery. 2018 In: Neurology. - 1526-632X. ; 91:2 Journal article (peer-reviewed)abstract Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart.Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor.Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7).Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.
18.	Fridlund, Malcolm, 1952, et al. (author) The TOI-763 system: Sub-Neptunes orbiting a Sun-like star 2020 In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:3, s. 4503-4517 Journal article (peer-reviewed)abstract We report the discovery of a planetary system orbiting TOI-763(aka CD-39 7945), a V = 10.2, high proper motion G-type dwarf star that was photometrically monitored by the TESS space mission in Sector 10. We obtain and model the stellar spectrum and find an object slightly smaller than the Sun, and somewhat older, but with a similar metallicity. Two planet candidates were found in the light curve to be transiting the star. Combining TESS transit photometry with HARPS high-precision radial velocity (RV) follow-up measurements confirm the planetary nature of these transit signals. We determine masses, radii, and bulk densities of these two planets. A third planet candidate was discovered serendipitously in the RV data. The inner transiting planet, TOI-763 b, has an orbital period of Pb = 5.6 d, a mass of Mb = 9.8 ± 0.8 M⊕, and a radius of Rb = 2.37 ± 0.10 R⊕. The second transiting planet, TOI-763 c, has an orbital period of Pc = 12.3 d, a mass of Mc = 9.3 ± 1.0 M⊕, and a radius of Rc = 2.87 ± 0.11 R⊕. We find the outermost planet candidate to orbit the star with a period of ∼48 d. If confirmed as a planet, it would have a minimum mass of Md = 9.5 ± 1.6 M⊕. We investigated the TESS light curve in order to search for a mono transit by planet d without success. We discuss the importance and implications of this planetary system in terms of the geometrical arrangements of planets orbiting G-type stars.
19.	Kirby, Andrew, et al. (author) Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:3, s. 299-303 Journal article (peer-reviewed)abstract Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.
20.	Lindner, Thomas, et al. (author) Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging. 2023 In: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 89:5, s. 2024-2047 Journal article (peer-reviewed)abstract This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.
21.	Meron, E, et al. (author) Meeting Report: Aging Research and Drug Discovery 2022 In: AGING-US. - 1945-4589. ; 14:2, s. 530-543 Journal article (other academic/artistic)
22.	Wijns, William, et al. (author) Guidelines on myocardial revascularization : The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) 2010 In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 31:20, s. 2501-2555 Journal article (peer-reviewed)
23.	Wulf Hanson, Sarah, et al. (author) Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021 2022 In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 328:16, s. 1604-1615 Journal article (peer-reviewed)abstract IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.DESIGN, SETTING, AND PARTICIPANTS: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.EXPOSURES: Symptomatic SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
24.	Albert, Damien, et al. (author) A Decade with VAMDC : Results and Ambitions 2020 In: Atoms. - : MDPI. - 2218-2004. ; 8:4 Journal article (peer-reviewed)abstract This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC.
25.	Connolly, Stuart J., et al. (author) The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study 2013 In: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243 Journal article (peer-reviewed)abstract Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
26.	Danchin, Nicolas, et al. (author) Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries 2016 In: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:3, s. 152-167 Journal article (peer-reviewed)abstract Aims Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. Methods and results Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registrieswere heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% inhospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-Threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). Conclusions Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-Treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.
27.	Granger, Christopher B., et al. (author) Apixaban versus Warfarin in Patients with Atrial Fibrillation 2011 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:11, s. 981-992 Journal article (peer-reviewed)abstract Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
28.	Jung, Christian, et al. (author) A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention 2019 In: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148 Journal article (peer-reviewed)abstract Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
29.	Lettino, Maddalena, et al. (author) Diabetic patients with acute coronary syndromes in contemporary European registries : Characteristics and outcomes 2017 In: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 3:4, s. 198-213 Journal article (peer-reviewed)abstract Aims Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505). In the DM population, the proportion of patients with ST-Segment Elevation Myocardial Infarction (STEMI) ranged from 22.1% to 64.6% (other patients had non-ST-Segment Elevation Myocardial Infarction (NSTEMI-ACS) or unstable angina). All-cause mortality in the registries ranged from 1.4% to 9.4% in-hospital; 2.8% to 7.9% at 30 days post-discharge; 5.1% to 10.7% at 180 days post-discharge; and 3.3% to 10.5% at 1 year post-discharge. Major bleeding events were reported in up to 3.8% of patients while in hospital (8 registries); up to 1.3% at 30 days (data from two registries only), and 2.0% at 1 year (one registry only). Registries differed substantially in terms of study setting, site, patient selection, definition and schedule of endpoints, and use of various P2Y12 inhibitors. In most, but not all, registries, event rates in DM patients were higher than in patients without DM. Pooled risk ratios comparing cohorts with DM vs. no DM were in-hospital significantly higher in DM for all-cause death (1.66; 95% CI 1.42-1.94), for cardiovascular death (2.33; 1.78 - 3.03), and for major bleeding (1.35; 1.21-1.52). Conclusion These registry data from real-life clinical practice confirm a high risk for recurrent events among DM patients with ACS, with great variation across the different registries.
30.	Lloyd, Michael S., et al. (author) Design and rationale of the MODULAR ATP global clinical trial : A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator 2023 In: HEART RHYTHM O2. - : Elsevier. - 2666-5018. ; 4:7, s. 448-456 Journal article (peer-reviewed)abstract BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support.OBJECTIVE: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented.METHODS: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER (TM) Modular Pacing System and EMBLEM (TM) Subcutaneous ICD to Communicate Antitachycardia Pacing) is amulticenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly.85% at 2 years.RESULTS: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described.CONCLUSION: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.
31.	Mancia, Giuseppe, et al. (author) 2007 Guidelines for the management of arterial hypertension : The task gorce for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) 2007 In: European Heart Journal. - Philadelphia : W.B. Saunders. - 0195-668X .- 1522-9645. ; 25:6, s. 1105-87 Journal article (peer-reviewed)
32.	Marto, João Pedro, et al. (author) Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry. 2023 In: Neurology. - 1526-632X. ; 100:7 Journal article (peer-reviewed)abstract COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
33.	McCarthy, Shane, et al. (author) A reference panel of 64,976 haplotypes for genotype imputation 2016 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283 Journal article (peer-reviewed)abstract We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
34.	Murgas, F., et al. (author) HD 20329b: An ultra-short-period planet around a solar-type star found by TESS 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668 Journal article (peer-reviewed)abstract Context. Ultra-short-period (USP) planets are defined as planets with orbital periods shorter than one day. This type of planets is rare, highly irradiated, and interesting because their formation history is unknown. Aims. We aim to obtain precise mass and radius measurements to confirm the planetary nature of a USP candidate found by the Transiting Exoplanet Survey Satellite (TESS). These parameters can provide insights into the bulk composition of the planet candidate and help to place constraints on its formation history. Methods. We used TESS light curves and HARPS-N spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate found around the star HD 20329 (TOI-4524). We performed a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate. Results. We confirm and characterize HD 20329b, a USP planet transiting a solar-type star. The host star (HD 20329, V = 8.74 mag, J = 7.5 mag) is characterized by its G5 spectral type with M∗ = 0.90 ± 0.05 M⊙, R∗ = 1.13 ± 0.02 R⊙, and Teff = 5596 ± 50 K; it is located at a distance d = 63.68 ± 0.29 pc. By jointly fitting the available TESS transit light curves and follow-up radial velocity measurements, we find an orbital period of 0.9261 ± (0.5 ×10-4) days, a planetary radius of 1.72 ± 0.07 R∗, and a mass of 7.42 ± 1.09 M∗, implying a mean density of ρp = 8.06 ± 1.53 g cm-3. HD 20329b joins the ~30 currently known USP planets with radius and Doppler mass measurements.
35.	Nesme, Joseph, et al. (author) Back to the Future of Soil Metagenomics 2016 In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7 Journal article (peer-reviewed)
36.	Orell-Miquel, J., et al. (author) HD 191939 revisited: New and refined planet mass determinations, and a new planet in the habitable zone 2023 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 669 Journal article (peer-reviewed)abstract HD 191939 (TOI-1339) is a nearby (d = 54 pc), bright (V = 9 mag), and inactive Sun-like star (G9 V) known to host a multi-planet transiting system. Ground-based spectroscopic observations confirmed the planetary nature of the three transiting sub-Neptunes (HD 191939 b, c, and d) originally detected by TESS and were used to measure the masses for planets b and c with 3Ï precision. These previous observations also reported the discovery of an additional Saturn-mass planet (HD 191939 e) and evidence for a further, very long-period companion (HD 191939 f). Here, we report the discovery of a new non-transiting planet in the system and a refined mass determination of HD 191939 d. The new planet, HD 191939 g, has a minimum mass of 13.5±2.0 M- and a period of about 280 days. This period places the planet within the conservative habitable zone of the host star, and near a 1:3 resonance with HD 191939 e. The compilation of 362 radial velocity measurements with a baseline of 677 days from four different high-resolution spectrographs also allowed us to refine the properties of the previously known planets, including a 4.6Ï mass determination for planet d, for which only a 2Ï upper limit had been set until now. We confirm the previously suspected low density of HD 191939 d, which makes it an attractive target for attempting atmospheric characterisation. Overall, the planetary system consists of three sub-Neptunes interior to a Saturn-mass and a Uranus-mass planet plus a high-mass long-period companion. This particular configuration has no counterpart in the literature and makes HD 191939 an exceptional multi-planet transiting system with an unusual planet demographic worthy of future observation.
37.	Patterson, Nick, et al. (author) Large-scale migration into Britain during the Middle to Late Bronze Age 2022 In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594 Journal article (peer-reviewed)abstract Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
38.	Peiris, Heshan, et al. (author) A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes 2016 In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5 Journal article (peer-reviewed)abstract Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.
39.	Rich, Rebecca L., et al. (author) A global benchmark study using affinity-based biosensors 2009 In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216 Journal article (peer-reviewed)abstract To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
40.	Santruckova, Hana, et al. (author) Significance of dark CO2 fixation in arctic soils 2018 In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 119, s. 11-21 Journal article (peer-reviewed)abstract The occurrence of dark fixation of CO2 by heterotrophic microorganisms in soil is generally accepted, but its importance for microbial metabolism and soil organic carbon (C) sequestration is unknown, especially under C limiting conditions. To fill this knowledge gap, we measured dark (CO2)-C-13 incorporation into soil organic matter and conducted a C-13-labelling experiment to follow the C-13 incorporation into phospholipid fatty acids as microbial biomass markers across soil profiles of four tundra ecosystems in the northern circumpolar region, where net primary productivity and thus soil C inputs are low. We further determined the abundance of various carboxylase genes and identified their microbial origin with metagenomics. The microbial capacity for heterotrophic CO2 fixation was determined by measuring the abundance of carboxylase genes and the incorporation of C-13 into soil C following the augmentation of bioavailable C sources. We demonstrate that dark CO2 fixation occurred ubiquitously in arctic tundra soils, with increasing importance in deeper soil horizons, presumably due to increasing C limitation with soil depth. Dark CO2 fixation accounted on average for 0.4, 1.0, 1.1, and 16% of net respiration in the organic, cryoturbated organic, mineral and permafrost horizons, respectively. Genes encoding anaplerotic enzymes of heterotrophic microorganisms comprised the majority of identified carboxylase genes. The genetic potential for dark CO2 fixation was spread over a broad taxonomic range. The results suggest important regulatory function of CO2 fixation in C limited conditions. The measurements were corroborated by modeling the long-term impact of dark CO2 fixation on soil organic matter. Our results suggest that increasing relative CO2 fixation rates in deeper soil horizons play an important role for soil internal C cycling and can, at least in part, explain the isotopic enrichment with soil depth.
41.	Smith, Alexis M. S., et al. (author) K2-99 revisited: A non-inflated warm Jupiter, and a temperate giant planet on a 522-d orbit around a subgiant 2022 In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 510:4, s. 5035-5049 Journal article (peer-reviewed)abstract We report new photometric and spectroscopic observations of the K2-99 planetary system. Asteroseismic analysis of the short-cadence light curve from K2's Campaign 17 allows us to refine the stellar properties. We find K2-99 to be significantly smaller than previously thought, with R = 2.55 ± 0.02 R. The new light curve also contains four transits of K2-99 b, which we use to improve our knowledge of the planetary properties. We find the planet to be a non-inflated warm Jupiter, with Rb = 1.06 ± 0.01 RJup. 60 new radial velocity measurements from HARPS, HARPS-N, and HIRES enable the determination of the orbital parameters of K2-99 c, which were previously poorly constrained. We find that this outer planet has a minimum mass Mcsin ic = 8.4 ± 0.2 MJup, and an eccentric orbit (ec = 0.210 ± 0.009) with a period of 522.2 ± 1.4 d. Upcoming TESS observations in 2022 have a good chance of detecting the transit of this planet, if the mutual inclination between the two planetary orbits is small.
42.	Steg, Gabriel, et al. (author) Guía de práctica clínica de la ESC para el manejo del infarto agudo de miocardio en pacientes con elevación del segmento ST : Grupo de Trabajo para el manejo del infarto agudo de miocardio con elevación del segmento ST de la Sociedad Europea de Cardiología (ESC) 2013 In: Revista Española de Cardiología. - : Elsevier BV. - 0300-8932 .- 1579-2242. ; 66:1, s. 53.e1-53.e46 Journal article (peer-reviewed)
43.	Subjak, Jan, et al. (author) TOI-503: The First Known Brown-dwarf Am-star Binary from the TESS Mission 2020 In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:4 Journal article (peer-reviewed)abstract We report the discovery of an intermediate-mass transiting brown dwarf (BD), TOI-503b, from the TESS mission. TOI-503b is the first BD discovered by TESS, and it has circular orbit around a metallic-line A-type star with a period of P.=.3.6772.+/-.0.0001 days. The light curve from TESS indicates that TOI-503b transits its host star in a grazing manner, which limits the precision with which we measure the BD's radius ( = R 1.34+ R b 0.150.26 J). We obtained highresolution spectroscopic observations with the FIES, Ondr.ejov, PARAS, Tautenburg, and TRES spectrographs, and measured the mass of TOI-503b to be Mb.=.53.7.+/-.1.2 MJ. The host star has a mass of Ma.=.1.80.+/-.0.06Me, a radius of Ra.=.1.70.+/-.0.05Re, an effective temperature of Teff.=.7650.+/-.160 K, and a relatively high metallicity of 0.61.+/-.0.07 dex. We used stellar isochrones to derive the age of the system to be 180 Myr, which places its age between that of RIK 72b (a 10 Myr old BD in the Upper Scorpius stellar association) and AD 3116b (a 600 Myr old BD in the Praesepe cluster). Given the difficulty in measuring the tidal interactions between BDs and their host stars, we cannot precisely say whether this BD formed in situ or has had its orbit circularized by its host star over the relatively short age of the system. Instead, we offer an examination of plausible values for the tidal quality factor for the star and BD. TOI-503b joins a growing number of known short-period, intermediate-mass BDs orbiting mainsequence stars, and is the second such BD known to transit an A star, after HATS-70b. With the growth in the population in this regime, the driest region in the BD desert (35-55MJ sin i) is reforesting.
44.	Tricoci, Pierluigi, et al. (author) Thrombin-receptor antagonist vorapaxar in acute coronary syndromes 2012 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 366:1, s. 20-33 Journal article (peer-reviewed)abstract BACKGROUND:Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.METHODS:In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.RESULTS:Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.CONCLUSIONS:In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
45.	Wulf Hanson, Sarah, et al. (author) A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021 2022 Other publication (other academic/artistic)abstract Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
46.	Young, Peter R., et al. (author) Solar Ultraviolet Bursts 2018 In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 214:8 Research review (peer-reviewed)abstract The term ultraviolet (UV) burst is introduced to describe small, intense, transient brightenings in ultraviolet images of solar active regions. We inventorize their properties and provide a definition based on image sequences in transition-region lines. Coronal signatures are rare, and most bursts are associated with small-scale, canceling opposite-polarity fields in the photosphere that occur in emerging flux regions, moving magnetic features in sunspot moats, and sunspot light bridges. We also compare UV bursts with similar transition-region phenomena found previously in solar ultraviolet spectrometry and with similar phenomena at optical wavelengths, in particular Ellerman bombs. Akin to the latter, UV bursts are probably small-scale magnetic reconnection events occurring in the low atmosphere, at photospheric and/or chromospheric heights. Their intense emission in lines with optically thin formation gives unique diagnostic opportunities for studying the physics of magnetic reconnection in the low solar atmosphere. This paper is a review report from an International Space Science Institute team that met in 2016-2017.
47.	Zamora, Juan Carlos, et al. (author) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 In: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Journal article (peer-reviewed)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
48.	Zeymer, Uwe, et al. (author) P2Y12 receptor inhibitors in patients with non-STelevation acute coronary syndrome in the real world : Use, patient selection, and outcomes from contemporary European registries 2016 In: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:4, s. 229-243 Journal article (peer-reviewed)abstract Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total of 10 registries (documenting 84 054 NSTE-ACS patients) provided data in a systematic manner on patient characteristics and outcomes for NSTE-ACS in general, and 6 of these (with 52 173 NSTE-ACS patients) also provided more specific data according to P2Y12 receptor inhibitor used. Unadjusted analyses were performed at the study level, and no formal meta-Analysis was performed due to large heterogeneity between studies in the settings, patient characteristics, and outcome definitions. All-cause death rates across registries ranged from 0.76 to 4.79% in-hospital, from 1.61 to 6.65% at 30 days, from 3.66 to 7.16% at 180 days, and from 3.14 to 9.73% at 1 year. Major bleeding events were reported in up to 2.77% of patients while in hospital (in seven registries), up to 1.08% at 30 days (data from one registry only), and 2.06% at 1 year (one registry). Conclusions There were substantial differences in the use of and patient selection for clopidogrel, prasugrel, and ticagrelor, which were associated with differences in short-And long-Term ischaemic and bleeding events. In future registries, data collection should be performed in a more standardized way with respect to endpoints, definitions, and time points.
49.	Adewumi, Oluseun, et al. (author) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative 2007 In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816 Journal article (peer-reviewed)abstract The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
50.	Airaksinen, Anu J., et al. (author) Massive Online Open Course „Essential Radiochemistry for Society“ 2023 In: Chemicke Listy. - 1213-7103 .- 0009-2770. ; 117:11, s. 708-713 Journal article (peer-reviewed)abstract The massive open online course "Essential radio-chemistry for society" represents a modern form of education. Due to its attractive design, varied content and inter-active nature, it has the potential to appeal to various inter-est groups. Thematically, the course is divided into five weeks: Radiochemistry for the environment, health, indus-try, nuclear energy and society. In addition to radiochem-istry and nuclear chemistry, which are the basis of the course, direct connections can be found to biology, phys-ics, ecology, art and culture. The course is comprehensive; a participant can study only selected chapters or the entire course independently. Recommendations and tips for ef-fectively using the course in classes have been compiled for teachers and lecturers.

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