| 6861. |
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| 6862. |
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| 6863. |
- Strand, Joanna, et al.
(författare)
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Influence of Macrocyclic Chelators on the Targeting Properties of Ga-68-Labeled Synthetic Affibody Molecules : Comparison with In-111-Labeled Counterparts
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e70028-
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are a class of small (7 kDa) non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET) would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide Ga-68 (T-1/2 = 67.6 min). Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) and 1-(1,3-carboxypropyl)-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA) were conjugated to the N-terminus of the synthetic Affibody molecule Z(HER2:S1) targeting HER2. Affibody molecules were labeled with Ga-68, and their binding specificity and cellular processing were evaluated. The biodistribution of Ga-68-DOTA-Z(HER2:S1), Ga-68-NOTA-Z(HER2:S1) and Ga-68-NODAGA-Z(HER2:S1), as well as that of their In-111-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for Ga-68-DOTA-Z(HER2:S1) (17.9 +/- 0.7%IA/g) was significantly higher than for both Ga-68-NODAGA-Z(HER2:S1) (16.13 +/- 0.67%IA/g) and Ga-68-NOTA-Z(HER2:S1) (13 +/- 3%IA/g) at 2 h after injection. Ga-68-NODAGA-Z(HER2:S1) had the highest tumor-to-blood ratio (60 +/- 10) in comparison with both Ga-68-DOTA-Z(HER2:S1) (28 +/- 4) and Ga-68-NOTA-Z(HER2:S1) (42 +/- 11). The tumor-to-liver ratio was also higher for Ga-68-NODAGA-Z(HER2:S1) (7 +/- 2) than the DOTA and NOTA conjugates (5.5 +/- 0.6 vs. 3.3 +/- 0.6). The influence of chelator on the biodistribution and targeting properties was less pronounced for Ga-68 than for In-111. The results of this study demonstrate that macrocyclic chelators conjugated to the N-terminus have a substantial influence on the biodistribution of HER2-targeting Affibody molecules labeled with Ga-68. This can be utilized to enhance the imaging contrast of PET imaging using Affibody molecules and improve the sensitivity of molecular imaging. The study demonstrated an appreciable difference of chelator influence for Ga-68 and In-111.
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| 6864. |
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| 6865. |
- Strand, Robin, 1978-, et al.
(författare)
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A concept for holistic whole body MRI data analysis, Imiomics
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present and evaluate a whole-body image analysis concept, Imiomics (imaging omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data.Methods: The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis.Results: The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept.Conclusions: The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis.
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| 6866. |
- Strandberg, Louise, 1981, et al.
(författare)
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Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
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| 6867. |
- Strandberg, Sara, et al.
(författare)
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Optimization of PET reconstruction algorithm, SUV thresholding algorithm and PET acquisition time in clinical 11C-acetate PET/CT
- 2018
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Ingår i: PLOS ONE. - : Public Library Science (PLOS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction 11C-acetate (ACE)-PET/CT is used for staging of high-risk prostate cancer. PET data is reconstructed with iterative algorithms, such as VUEPointHD ViP (VPHD) and VUEPoint HD Sharp IR (SharpIR), the latter with additional resolution recovery. It is expected that the resolution recovery algorithm should render more accurate maximum and mean standardized uptake values (SUVmax and SUVmean) and functional tumor volumes (FTV) than the ordinary OSEM. Performing quantitative analysis, choice of volume-of-interest delineation algorithm (SUV threshold) may influence FTV. Optimizing PET acquisition time is justified if image quality and quantitation do not deteriorate. The aim of this study is to identify the optimal reconstruction algorithm, SUV threshold and acquisition time for ACE-PET/CT. Methods ACE-PET/CT data acquired with a General Electric Discovery 690 PET/CT from 16 consecutive high-risk prostate cancer patients was reconstructed with VPHD and SharpIR. Forty pelvic lymph nodes (LNs) and 14 prostate glands were delineated with 42% and estimated threshold. SUVmax, SUVmean, FTV and total lesion uptake were measured. Default acquisition time was four minutes per bed position. In a subset of lesions, acquisition times of one, two and four minutes were evaluated. Structural tumor volumes (STV) of the LNs were measured with CT for correlation with functional volumetric parameters. To validate SUV quantification under different conditions with SharpIR 42%, recovery coefficients (RCs) of SUVmean and FTV were calculated from a phantom with 18F-fluoro-deoxy-glucose (FDG)-filled volumes 0.1–9.2cm3 and signal-to-background (S/B) ratios 4.3–15.9. Results With SharpIR, SUVmax and SUVmean were higher and FTV lower compared with VPHD, regardless of threshold method, in both prostates and LNs. Total lesion uptake determined with both threshold methods was lower with SharpIR compared with VPHD with both threshold methods, except in subgroup analysis of prostate targets where estimated threshold returned higher values. Longer acquisition times returned higher FTV for both threshold methods, regardless of reconstruction algorithm. The FTV difference was most pronounced with one minute’s acquisition per bed position, which also produced visually the highest noise. SUV parameters were unaffected by varying acquisition times. FTV with SharpIR 42% showed the best correspondence with STV. SharpIR 42% gave higher RCs of SUVmean and FTV with increasing phantom size and S/B-ratio, as expected. Conclusions Delineation with SharpIR 42% seems to provide the most accurate combined information from SUVmax, SUVmean, FTV and total lesion uptake. Acquisition time may be shortened to two minutes per bed position with preserved image quality.
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| 6868. |
- Strandberg, Thomas, et al.
(författare)
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Depolarizing American voters : Democrats and Republicans are equally susceptible to false attitude feedback
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- American politics is becoming increasingly polarized, which biases decision-making and reduces open-minded debate. In two experiments, we demonstrate that despite this polarization, a simple manipulation can make people express and endorse less polarized views about competing political candidates. In Study 1, we approached 136 participants at the first 2016 presidential debate and on the streets of New York City. Participants completed a survey evaluating Hillary Clinton and Donald Trump on various personality traits; 72% gave responses favoring a single candidate. We then covertly manipulated their surveys so that the majority of their responses became moderate instead. Participants only noticed and corrected a few of these manipulations. When asked to explain their responses, 94% accepted the manipulated responses as their own and rationalized this neutral position accordingly, even though they reported more polarized views moments earlier. In Study 2, we replicated the experiment online with a more politically diverse sample of 498 participants. Both Clinton and Trump supporters showed nearly identical rates of acceptance and rationalization of their manipulated-to-neutral positions. These studies demonstrate how false feedback can powerfully shape the expression of political views. More generally, our findings reveal the potential for open-minded discussion even in a fundamentally divided political climate.
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| 6869. |
- Strandkvist, Viktor, et al.
(författare)
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Postural control among individuals with and without chronic obstructive pulmonary disease: A cross-sectional study of motor and sensory systems
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic obstructive pulmonary disease (COPD) is considered a heterogenic syndrome with systemic effects, including muscle dysfunction. There is evidence of postural control impairments among individuals with COPD, partly related to muscle weakness. However, research is scarce regarding the other underlying systems of postural control, such as the visual, somatosensory and vestibular system. The aim was to compare postural control, as well as the motor and sensory systems, between individuals with and without COPD.MethodsTwenty-two participants with COPD (mean age 74.0 ±6.2 years) and 34 non-obstructive references (mean age 74.9 ±4.9 years) participated in this cross-sectional study. Postural control was assessed with center of pressure trajectory of postural sway in quiet as well as a limits of stability test, calculating mediolateral and anteroposterior amplitudes for each test. Assessment of function in the motor system included maximum hand grip strength, as well as maximum strength in muscles around the hip, knee and ankle joints. Visual acuity, pressure sensibility, proprioception, vestibular screening, and reaction time were also included. Data was compared between groups, and significant differences in postural control were further analyzed with an orthogonal projection of latent structures regression model.ResultsThere was a significantly increased sway amplitude in the mediolateral direction in quiet stance on soft surface with eyes open (p = 0.014) as well as a smaller anteroposterior amplitude in the limits of stability test (p = 0.019) in the COPD group. Regression models revealed that the mediolateral amplitude was related to visual acuity and the burden of tobacco smoking assessed as pack-years. Further, muscle strength associated with anteroposterior amplitude in limits of stability test in the COPD group, and with age and ankle dorsal flexion strength among the referents. Besides for lower ankle plantar flexion strength in the COPD group, there were however no significant differences in muscle strength.ConclusionsIndividuals with COPD had a decreased postural control and several factors were associated with the impairments. The findings imply that the burden of tobacco smoking and reduced visual acuity relate to increased postural sway in quiet stance, and that muscle weakness is related to decreased limits of stability, among individuals with COPD.
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| 6870. |
- Strandvik, Birgitta, et al.
(författare)
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Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in free-ranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alpha-linolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism.
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