| 1. |
- Abdelsayed, Mena, et al.
(författare)
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Repurposing drugs to treat cardiovascular disease in the era of precision medicine
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 19:11, s. 751-764
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Forskningsöversikt (refereegranskat)abstract
- Drug repurposing is the use of a given therapeutic agent for indications other than that for which it was originally designed or intended. The concept is appealing because of potentially lower development costs and shorter timelines than are needed to produce a new drug. To date, drug repurposing for cardiovascular indications has been opportunistic and driven by knowledge of disease mechanisms or serendipitous observation rather than by systematic endeavours to match an existing drug to a new indication. Innovations in two areas of personalized medicine — computational approaches to associate drug effects with disease signatures and predictive model systems to screen drugs for disease-modifying activities — support efforts that together create an efficient pipeline to systematically repurpose drugs to treat cardiovascular disease. Furthermore, new experimental strategies that guide the medicinal chemistry re-engineering of drugs could improve repurposing efforts by tailoring a medicine to its new indication. In this Review, we summarize the historical approach to repurposing and discuss the technological advances that have created a new landscape of opportunities.
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| 2. |
- Adamsson, Mathias
(författare)
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Non-image-forming effects of light : Implications for the design of living and working environments
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Seasonal variation in mood and subjective well-being are common at geographical locations further away from the equator. The 24-h light-dark cycle is the main time cue for synchronizing the human circadian clock to the external day and night.Nowadays, people spend more of their waking day indoors, with less exposure to the natural daylight cycle, relying on artificial lighting which differs to daylight in a number of aspects, including intensity, spectral composition and light exposure pattern.In parallel with the technology development that has been mainly driven by energy-saving reasons, it is important to investigate the non-image-forming effects of different properties of the daily and seasonal light exposure.The overall aim of the thesis was to identify characteristics of the daily light exposure that are important to support physiological and psychological needs of humans. To achieve this objective a number of research questions were posed concerning daily and seasonal light exposure, seasonal variation in physiological processes and psychological parameters, and evaluation of light exposure with respect to non-image-forming effects. The research questions were investigated in a longitudinal research design with measurements conducted each month during the year at a high latitude with large seasonal variation in day lengths.Self-report diaries and instruments for ambulatory- and static measurements were used to examine daily and seasonal light exposure in the working and living environments and for investigating the relationship between different parameters that can be used for evaluating light exposure according to non-image-forming effects of light. Seasonal variation in daily light exposure and regarding the pattern of light exposure was observed. Also, the results indicate a seasonal variation concerning the quality (i.e. spectral composition of the visible radiation) of the exposing light.Two biological markers, melatonin and cortisol, were used for investigating seasonal variation in physiological processes relating to the circadian clock. The results showed higher morning melatonin concentrations and peak level of melatonin during the winter although no seasonal change was observed concerning the phase position of the melatonin rhythm.Seasonal differences in mood and sleep-activity were studied by means of selfreport diaries and questionnaires. Seasonal variations were observed for both parameters. The results showed higher ratings of mood in the summer, particularly 6 in the evening, and a relationship between bedtime and evening light exposure and photoperiod length. Furthermore, longer sleep times was observed in the winter.Appraisal of lighting conditions in the offices during the year was rated by the use of a questionnaire. The results showed some seasonal differences concerning the perceived qualities of the light and some associations between characteristics of the lit environments and positive affect were found.Two methods, static- and ambulatory measurements, were used for recording lighting conditions in the working environments. Taken together, the results showed weak associations between the two methods.Research have demonstrated an increased need for taking non-image-forming effects into consideration when designing working and living environments, especially at geographical locations with large variations in day length where people are exposed to much of the daily light exposure at the workplace. Laboratory research has provided a good understanding of the basic concepts. However, more field research is needed. Also, current research has demonstrated that new methods of measuring and evaluating lighting conditions are needed.
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| 3. |
- Bischoff M. M. J., Fang C. M. , De Groot R. A. , Heijnen G. M. M. , Katsnelson M. I. , Kolesnychenko O. Yu. , De Kort R. , Lichtenstein A. I. , Quinn A. J. , de Parma A. L. V. , Yamada T. K. , and Van Kempen H.
(författare)
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Scanning tunneling spectroscopy study of surface states of 3d metals: Chemical identification, magnetic contrast and orbital Kondo resonance states
- 2003
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Ingår i: Acta Physica Polonica A. ; , s. 231-
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Konferensbidrag (refereegranskat)
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| 4. |
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| 5. |
- Busca, A, et al.
(författare)
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Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry
- 2023
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 14, s. 1125030-
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Tidskriftsartikel (refereegranskat)abstract
- The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT.MethodsThis multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022.ResultsThe median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53).ConclusionsMortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.
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| 6. |
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| 7. |
- de Bakker, Christel, et al.
(författare)
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Occupancy-based lighting control in open-plan office spaces : A state-of-the-art review
- 2017
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Ingår i: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 112, s. 308-321
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Tidskriftsartikel (refereegranskat)abstract
- Lighting accounts for a significant amount of electrical energy consumption in office buildings, up to 45% of the total consumed. This energy consumption can be reduced by as much as 60% through an occupant-dependent lighting control strategy. With particular focus on open-plan offices, where the application of this strategy is more challenging to apply due to differences in individual occupancy patterns, this paper covers (1) to which extent individual occupancy-based lighting control has been tested, (2) developed, and (3) evaluated. Search terms were defined with use of three categories, namely ‘occupancy patterns’, ‘lighting control strategy’, and ‘office’. Relevant articles were selected by a structured search through key online scientific databases and journals. The 24 studies identified as eligible were evaluated on six criteria: (1) study characteristics, (2) office characteristics, (3) lighting system characteristics, (4) lighting control design, (5) post-occupancy evaluation, and (6) conclusions, and this was used to answer the research questions. It was concluded that the strategy has not been tested yet with field studies in open-plan offices, but that it needs further development before it can be applied in these type of offices. Although lighting currently tends to be controlled at workspace level, many aspects of the strategy can be further developed; there is potential to further increase energy savings on lighting within open-plan office spaces. Individual occupancy-based lighting control requires further validation, focussing on the factors influencing its energy savings, on its cost effectiveness, and on its acceptability for users.
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| 8. |
- De Frenne, Pieter, et al.
(författare)
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Latitudinal gradients as natural laboratories to infer species' responses to temperature
- 2013
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 101:3, s. 784-795
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Forskningsöversikt (refereegranskat)abstract
- Macroclimatic variation along latitudinal gradients provides an excellent natural laboratory to investigate the role of temperature and the potential impacts of climate warming on terrestrial organisms. Here, we review the use of latitudinal gradients for ecological climate change research, in comparison with altitudinal gradients and experimental warming, and illustrate their use and caveats with a meta-analysis of latitudinal intraspecific variation in important life-history traits of vascular plants. We first provide an overview of latitudinal patterns in temperature and other abiotic and biotic environmental variables in terrestrial ecosystems. We then assess the latitudinal intraspecific variation present in five key life-history traits [plant height, specific leaf area (SLA), foliar nitrogen:phosphorus (N:P) stoichiometry, seed mass and root:shoot (R:S) ratio] in natural populations or common garden experiments across a total of 98 plant species. Intraspecific leaf N:P ratio and seed mass significantly decreased with latitude in natural populations. Conversely, the plant height decreased and SLA increased significantly with latitude of population origin in common garden experiments. However, less than a third of the investigated latitudinal transect studies also formally disentangled the effects of temperature from other environmental drivers which potentially hampers the translation from latitudinal effects into a temperature signal. Synthesis. Latitudinal gradients provide a methodological set-up to overcome the drawbacks of other observational and experimental warming methods. Our synthesis indicates that many life-history traits of plants vary with latitude but the translation of latitudinal clines into responses to temperature is a crucial step. Therefore, especially adaptive differentiation of populations and confounding environmental factors other than temperature need to be considered. More generally, integrated approaches of observational studies along temperature gradients, experimental methods and common garden experiments increasingly emerge as the way forward to further our understanding of species and community responses to climate warming.
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| 9. |
- De Kort, A. M., et al.
(författare)
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Decreased Cerebrospinal Fluid Amyloid beta 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
- 2023
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 93:6, s. 1173-86
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vascular amyloid beta (A beta) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides A beta 38, A beta 40, A beta 42, and A beta 43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).Methods: A beta peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).Results: We found decreased levels of all A beta peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for A beta 42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82-0.99; for validation: 0.94, 95% CI = 0.89-0.99) and A beta 43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88-1.00; for validation: 0.91, 95% CI = 0.83-1.0). All A beta peptides except A beta 43 were also decreased in sCAA compared to AD (CSF A beta 38: AUC = 0.82, 95% CI = 0.71-0.93; CSF A beta 40: AUC = 0.88, 95% CI = 0.80-0.96; CSF A beta 42: AUC = 0.79, 95% CI = 0.66-0.92).Interpretation: A combined biomarker panel of CSF A beta 38, A beta 40, A beta 42, and A beta 43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023
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| 10. |
- De Kort, Daan W., et al.
(författare)
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Heterogeneity of Network Structures and Water Dynamics in κ-Carrageenan Gels Probed by Nanoparticle Diffusometry
- 2018
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 34:37, s. 11110-11120
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Tidskriftsartikel (refereegranskat)abstract
- A set of functionalized nanoparticles (PEGylated dendrimers, d = 2.8-11 nm) was used to probe the structural heterogeneity in Na+/K+ induced κ-carrageenan gels. The self-diffusion behavior of these nanoparticles as observed by 1H pulsed-field gradient NMR, fluorescence recovery after photobleaching, and raster image correlation spectroscopy revealed a fast and a slow component, pointing toward microstructural heterogeneity in the gel network. The self-diffusion behavior of the faster nanoparticles could be modeled with obstruction by a coarse network (average mesh size <100 nm), while the slower-diffusing nanoparticles are trapped in a dense network (lower mesh size limit of 4.6 nm). Overhauser dynamic nuclear polarization-enhanced NMR relaxometry revealed a reduced local solvent water diffusivity near 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)-labeled nanoparticles trapped in the dense network, showing that heterogeneity in the physical network is also reflected in heterogeneous self-diffusivity of water. The observed heterogeneity in mesh sizes and in water self-diffusivity is of interest for understanding and modeling of transport through and release of solutes from heterogeneous biopolymer gels.
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