| 1. |
- Ihne-Schubert, Sandra Michaela, et al.
(author)
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Cardio-Hepatic Interaction in Cardiac Amyloidosis
- 2024
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In: Journal of Clinical Medicine. - 2077-0383. ; 13:5
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Journal article (peer-reviewed)abstract
- Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.
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| 2. |
- Dima, Danai, et al.
(author)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Journal article (peer-reviewed)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 3. |
- Frangou, Sophia, et al.
(author)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Journal article (peer-reviewed)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 4. |
- Wierenga, Lara M., et al.
(author)
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Greater male than female variability in regional brain structure across the lifespan
- 2022
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In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
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Journal article (peer-reviewed)abstract
- For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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| 5. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 7. |
- Arnaudon, Alexis, et al.
(author)
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Diffusion Bridges for Stochastic Hamiltonian Systems and Shape Evolutions
- 2022
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In: SIAM Journal on Imaging Sciences. - 1936-4954. ; 15:1, s. 293-323
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Journal article (peer-reviewed)abstract
- Stochastically evolving geometric systems are studied in shape analysis and computational anatomy for modeling random evolutions of human organ shapes. The notion of geodesic paths between shapes is central to shape analysis and has a natural generalization as diffusion bridges in a sto-chastic setting. Simulation of such bridges is key to solving inference and registration problems in shape analysis. We demonstrate how to apply state-of-the-art diffusion bridge simulation methods to recently introduced stochastic shape deformation models, thereby substantially expanding the appli-cability of such models. We exemplify these methods by estimating template shapes from observed shape configurations while simultaneously learning model parameters.
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| 8. |
- Eliasson, Björn, et al.
(author)
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Nationwide cardiovascular risk categorization : applying the European Society of Cardiology (ESC) guidelines to the Swedish National Diabetes Register
- 2022
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In: European Journal of Preventive Cardiology. - : Oxford University Press. - 2047-4873 .- 2047-4881. ; 824
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Journal article (peer-reviewed)abstract
- AIMS: The 2021 European Society of Cardiology (ESC) guidelines recommend that patients with type 2 diabetes (T2D) with a very high cardiovascular disease (CVD) risk receive cardiovascular (CV)-protective glucose-lowering medication (glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter-2 inhibitors). This analysis compared previous prescribing practices with the ESC recommendations.METHODS AND RESULTS: Patients in the Swedish National Diabetes Register (NDR) with T2D, aged 18-90 years, not receiving CV-protective glucose-lowering medication in 2017 were identified, and the ESC criteria for very high CVD risk was applied. The composite outcome of major adverse CV events (MACE; defined as CV death, non-fatal stroke or non-fatal myocardial infarction) during 2017 was calculated and the number of MACE avoided with semaglutide, an example of a CV-protective glucose-lowering medication, was estimated for patients within a certain CV risk score.Of the 320,028 patients in the NDR with T2D who were not receiving CV-protective glucose-lowering medication, 129,512 patients had a very high CVD risk. Patients with a very high CVD risk had a high incidence of MACE (75.4 events/1000 person-years), which was higher in those with atherosclerotic CVD (ASCVD) with and without elevated glycated haemoglobin (>9%; 136.5 and 90.8 events/1000 person-years, respectively). If patients with a very high CVD risk, according to the ESC, and ASCVD received semaglutide, 803 MACE may have been avoided in 2017.CONCLUSIONS: This analysis highlights differences between previous prescribing practices in Sweden and the 2021 ESC guidelines, and offers strategies to prioritize CV-protective glucose-lowering medication for patients who would benefit most.
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| 9. |
- Falk, Sven, et al.
(author)
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Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion
- 2008
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In: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 2:5, s. 472-483
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Journal article (peer-reviewed)abstract
- Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the presence of FGF and requires Wnt signaling. Moreover, TGF-beta signal activation counteracts Wnt-incluced proliferation of midbrain neuroepithelial cells. Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells.
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| 10. |
- Georgiadis, Marios, et al.
(author)
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Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.
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| 11. |
- Glock, Nicolaas, et al.
(author)
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Metabolic preference of nitrate over oxygen as an electron acceptor in foraminifera from the Peruvian oxygen minimum zone
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:8, s. 2860-2865
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Journal article (peer-reviewed)abstract
- Benthic foraminifera populate a diverse range of marine habitats. Their ability to use alternative electron acceptors—nitrate (NO3 − ) or oxygen (O2 )—makes them important mediators of benthic nitrogen cycling. Nevertheless, the metabolic scaling of the two alternative respiration pathways and the environmental determinants of foraminiferal denitrification rates are yet unknown. We measured denitrification and O2 respiration rates for 10 benthic foraminifer species sampled in the Peruvian oxygen minimum zone (OMZ). Denitrification and O2 respiration rates significantly scale sublinearly with the cell volume. The scaling is lower for O2 respiration than for denitrification, indicating that NO3− metabolism during denitrification is more efficient than O 2 metabolism during aerobic respiration in foraminifera from the Peruvian OMZ. The negative correlation of the O2 respiration rate with the surface/volume ratio is steeper than for the denitrification rate. This is likely explained by the presence of an intracellular NO3− storage in denitrifying foraminifera. Furthermore, we observe an increasing mean cell volume of the Peruvian foraminifera, under higher NO3− availability. This suggests that the cell size of denitrifying foraminifera is not limited by O2 but rather by NO3 − availability. Based on our findings, we develop a mathematical formulation of foraminiferal cell volume as a predictor of respiration and denitrification rates, which can further constrain foraminiferal biogeochemical cycling in biogeochemical models. Our findings show that NO3− is the preferred electron acceptor in foraminifera from the OMZ, where the foraminiferal contribution to denitrification is governed by the ratio between NO3− and O2.
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| 12. |
- Hall, Per, 1954, et al.
(author)
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Influence of Natural Oxygenation of Baltic Proper Deep Water on Benthic Recycling and Removal of Phosphorus, Nitrogen, Silicon and Carbon
- 2017
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 4
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Journal article (peer-reviewed)abstract
- At the end of 2014, a major Baltic inflow (MBI) brought oxygenated, salty water into the Baltic proper and reached the long-term anoxic Eastern Gotland Basin (EGB) by March 2015. In July 2015, we measured benthic fluxes of phosphorus (P), nitrogen (N) and silicon (Si) nutrients and dissolved inorganic carbon (DIC) in situ using an autonomous benthic lander at deep sites (170-210 m) in the EGB, where the bottom water oxygen concentration was 30-45 µM. The same in situ methodology was used to measure benthic fluxes at the same sites in 2008-2010, but then under anoxic conditions. The high efflux of phosphate under anoxic conditions became lower upon oxygenation, and turned into an influx in about 50 % of the flux measurements. The C:P and N:P ratios of the benthic solute flux changed from clearly below the Redfield ratio (on average about 70 and 3-4, respectively) under anoxia to approaching or being well above the Redfield ratio upon oxygenation. These observations demonstrate retention of P in newly oxygenated sediments. We found no significant effect of oxygenation on the benthic ammonium, silicate and DIC flux. We also measured benthic denitrification, anammox and dissimilatory nitrate reduction to ammonium (DNRA) rates at the same sites using isotope-pairing techniques. The bottom water of the long-term anoxic EGB contained less than 0.5 µM nitrate in 2008-2010, but the oxygenation event created bottom water nitrate concentrations of about 10 µM in July 2015 and the benthic flux of nitrate was consistently directed into the sediment. Nitrate reduction to both dinitrogen gas (denitrification) and ammonium (DNRA) was initiated in the newly oxygenated sediments, while anammox activity was negligible. We estimated the influence of this oxygenation event on the magnitudes of the integrated benthic P flux (the internal P load) and the fixed N removal through benthic and pelagic denitrification by comparing with a hypothetical scenario without the MBI. Our calculations suggest that the oxygenation triggered by the MBI in July 2015, extrapolated to the basin-wide scale of the Baltic proper, decreased the internal P load by 23% and increased the total (benthic plus pelagic) denitrification by 18%.
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| 13. |
- Ittner, Lars M, et al.
(author)
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Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells
- 2005
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In: Journal of Biology. - : Springer Science and Business Media LLC. - 1475-4924. ; 4:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular structures are poorly understood. RESULTS: Here we reveal distinct NC contributions to both anterior and posterior mesenchymal eye structures and show that TGFbeta signaling in these cells is crucial for normal eye development. In the anterior eye, TGFbeta2 released from the lens is required for the expression of transcription factors Pitx2 and Foxc1 in the NC-derived cornea and in the chamber-angle structures of the eye that control intraocular pressure. TGFbeta enhances Foxc1 and induces Pitx2 expression in cell cultures. As in patients carrying mutations in PITX2 and FOXC1, TGFbeta signal inactivation in NC cells leads to ocular defects characteristic of the human disorder Axenfeld-Rieger's anomaly. In the posterior eye, NC cell-specific inactivation of TGFbeta signaling results in a condition reminiscent of the human disorder persistent hyperplastic primary vitreous. As a secondary effect, retinal patterning is also disturbed in mutant mice. CONCLUSION: In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.
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| 14. |
- Kaufman, Darrell, et al.
(author)
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A global database of Holocene paleotemperature records
- 2020
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
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Journal article (peer-reviewed)abstract
- A comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in data-sparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. The multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database. This database can be used to reconstruct the spatiotemporal evolution of Holocene temperature at global to regional scales, and is publicly available in Linked Paleo Data (LiPD) format.
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| 15. |
- Kotecha, Dipak, et al.
(author)
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Integrating new approaches to atrial fibrillation management : the 6th AFNET/EHRA Consensus Conference.
- 2018
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In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:3, s. 395-407
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Journal article (peer-reviewed)abstract
- There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF.
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| 16. |
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| 17. |
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| 18. |
- Schäbitz, Wolf-Rüdiger, et al.
(author)
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Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis.
- 2007
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In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 38:7, s. 2165-72
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis. METHODS: The current study analyzed the effects of BDNF on induction of neuronal progenitor cell migration and sensorimotor recovery after cortical photothrombotic stroke. RESULTS: Daily intravenous bolus applications of BDNF during the first 5 days after stroke resulted in significantly improved sensorimotor scores up to 6 weeks. At the structural level, BDNF significantly increased neurogenesis in the dentate gyrus and enhanced migration of subventricular zone progenitor cells to the nearby striatum of the ischemic hemisphere. BDNF treatment could not, however, further stimulate progenitor cell recruitment to the cortex. CONCLUSIONS: These findings consolidate the role of BDNF as a modulator of neurogenesis in the brain and as an enhancer of long-term functional neurological outcome after cerebral ischemia.
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| 19. |
- Solmi, Marco, et al.
(author)
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Physical and mental health impact of COVID-19 on children, adolescents, and their families :
- 2022
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
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Journal article (peer-reviewed)abstract
- Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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| 20. |
- Solmi, Marco, et al.
(author)
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The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
- 2022
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407
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Journal article (peer-reviewed)abstract
- Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
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| 21. |
- Solmi, Marco, et al.
(author)
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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
- 2023
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In: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
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Journal article (peer-reviewed)abstract
- Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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| 22. |
- Sommer, Martha E., et al.
(author)
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The European Research Network on Signal Transduction (ERNEST) : Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling
- 2020
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In: ACS Pharmacology & Translational Science. - : American Chemical Society (ACS). - 2575-9108. ; 3:2, s. 361-370
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Journal article (peer-reviewed)abstract
- G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.
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| 23. |
- Sommer, Stefan, et al.
(author)
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Major Bottom Water Ventilation Events Do Not Significantly Reduce Basin-Wide Benthic N and P Release in the Eastern Gotland Basin (Baltic Sea)
- 2017
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 4:18
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Journal article (peer-reviewed)abstract
- Redox-sensitive mobilization of nutrients from sediments strongly affects the eutrophic state of the central Baltic Sea; a region associated with the spread of hypoxia and almost permanently anoxic and sulfidic conditions in the deeper basins. Ventilation of these basins depends on renewal by inflow of water enriched in oxygen (O2) from the North Sea, occurring roughly once per decade. Benthic fluxes and water column distributions of dissolved inorganic nitrogen species, phosphate (PO43-), dissolved inorganic carbon (DIC), sulfide (HS-) and total oxygen uptake (TOU) were measured along a depth gradient in the Eastern Gotland Basin (EGB). Campaigns were conducted during euxinic conditions of the deep basin in Aug./Sept. 2013 and after two inflow events in July/Aug. 2015 and March 2016 when O2 concentrations in deep waters reached 60 µM. The intrusion of O2-rich North Sea water into the EGB led to an approximate 33 % and 10 % reduction of the seabed PO43- and ammonium (NH4+) release from deep basin sediments. Post-inflow, the deep basin sediment was rapidly colonized by HS- oxidizing bacteria tentatively assigned to the family Beggiatoaceae, and HS- release was completely suppressed. The presence of a hypoxic transition zone (HTZ) between 80 and 120 m water depth was confirmed not only for euxinic deep-water conditions during 2013 but also for post-inflow conditions. Because deep-water renewal did not ventilate the HTZ, where PO43- and NH4+ fluxes were highest, high seabed nutrient release there was relatively unchanged. Extrapolation of the in situ nutrient fluxes indicated that, overall, the reduction in PO43- and NH4+ release in response to deep-water renewal can be considered as minor, reducing the internal nutrient load by 2 and 12 % only, respectively. Infrequent inflow events thus have a limited capacity to sustainably reduce internal nutrient loading in the EGB and mitigate eutrophication.
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| 24. |
- Wurdak, H, et al.
(author)
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Inactivation of TGF beta signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome
- 2005
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In: Genes & Development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 19:5, s. 530-535
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Journal article (peer-reviewed)abstract
- Specific inactivation of TGFbeta signaling in neural crest stem cells (NCSCs) results in cardiovascular defects and thymic, parathyroid, and craniofacial anomalies. All these malformations characterize DiGeorge syndrome, the most common microdeletion syndrome in humans. Consistent with a role of TGFbeta in promoting non-neural lineages in NCSCs, mutant neural crest cells migrate into the pharyngeal apparatus but are unable to acquire non-neural cell fates. Moreover, in neural crest cells, TGFbeta signaling is both sufficient and required for phosphorylation of CrkL, a signal adaptor protein implicated in the development of DiGeorge syndrome. Thus, TGFbeta signal modulation in neural crest differentiation might play a crucial role in the etiology of DiGeorge syndrome.
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| 25. |
- Xie, Long, et al.
(author)
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Deep Label Fusion : A 3D End-To-End Hybrid Multi-atlas Segmentation and Deep Learning Pipeline
- 2021
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In: Information Processing in Medical Imaging - 27th International Conference, IPMI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030781903 ; 12729 LNCS, s. 428-439
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Conference paper (peer-reviewed)abstract
- Deep learning (DL) is the state-of-the-art methodology in various medical image segmentation tasks. However, it requires relatively large amounts of manually labeled training data, which may be infeasible to generate in some applications. In addition, DL methods have relatively poor generalizability to out-of-sample data. Multi-atlas segmentation (MAS), on the other hand, has promising performance using limited amounts of training data and good generalizability. A hybrid method that integrates the high accuracy of DL and good generalizability of MAS is highly desired and could play an important role in segmentation problems where manually labeled data is hard to generate. Most of the prior work focuses on improving single components of MAS using DL rather than directly optimizing the final segmentation accuracy via an end-to-end pipeline. Only one study explored this idea in binary segmentation of 2D images, but it remains unknown whether it generalizes well to multi-class 3D segmentation problems. In this study, we propose a 3D end-to-end hybrid pipeline, named deep label fusion (DLF), that takes advantage of the strengths of MAS and DL. Experimental results demonstrate that DLF yields significant improvements over conventional label fusion methods and U-Net, a direct DL approach, in the context of segmenting medial temporal lobe subregions using 3T T1-weighted and T2-weighted MRI. Further, when applied to an unseen similar dataset acquired in 7T, DLF maintains its superior performance, which demonstrates its good generalizability.
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