| 1. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 2. |
|
|
| 3. |
- El Fakiri, Mohamed, et al.
(författare)
-
Development and Preclinical Evaluation of [211At]PSAt-3-Ga: An Inhibitor for Targeted a-Therapy of Prostate Cancer
- 2024
-
Ingår i: JOURNAL OF NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667. ; 65:4, s. 593-599
-
Tidskriftsartikel (refereegranskat)abstract
- The application of prostate -specific membrane antigen (PSMA)- targeted a -therapy is a promising alternative to b 2 -particle-based treatments. 211 At is among the potential a -emitters that are favorable for this concept. Herein, 211 At-based PSMA radiopharmaceuticals were designed, developed, and evaluated. Methods: To identify a 211 At-labeled lead, a surrogate strategy was applied. Because astatine does not exist as a stable nuclide, it is commonly replaced with iodine to mimic the pharmacokinetic behavior of the corresponding 211 At-labeled compounds. To facilitate the process of structural design, iodine -based candidates were radiolabeled with the PET radionuclide 68 Ga to study their preliminary in vitro and in vivo properties before the desired 211 At-labeled lead compound was formed. The most promising candidate from this evaluation was chosen to be 211 At-labeled and tested in biodistribution studies. Results: All 68 Ga-labeled surrogates displayed affinities in the nanomolar range and specific internalization in PSMA-positive LNCaP cells. PET imaging of these compounds identified [ 68 Ga]PSGa- 3 as the lead compound. Subsequently, [ 211 At]PSAt- 3 -Ga was synthesized in a radiochemical yield of 35% and showed tumor uptake of 19 +/- 8 percentage injected dose per gram of tissue (%ID/g) at 1 h after injection and 7.6 +/- 2.9 %ID/g after 24 h. Uptake in off -target tissues such as the thyroid (2.0 +/- 1.1 %ID/g), spleen (3.0 +/- 0.6 %ID/g), or stomach (2.0 +/- 0.4 %ID/g) was low, indicating low in vivo deastatination of [ 211 At]PSAt- 3 -Ga. Conclusion: The reported findings support the use of iodine -based and 68 Ga-labeled variants as a convenient strategy for developing astatinated compounds and confirm [ 211 At]PSAt- 3 as a promising radiopharmaceutical for targeted a -therapy.
|
|
| 4. |
- Abdallah, J, et al.
(författare)
-
Rapidity-alignment and p(T) compensation of particle pairs in hadronic Z(0) decays
- 2002
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 533:3-4, s. 243-252
-
Tidskriftsartikel (refereegranskat)abstract
- Observation is made of rapidity-alignment of K+K- and (p) over barp pairs which results from their asymmetric orientation in rapidity, with respect to the direction from primary quark to antiquark. The K+K- and (p) over barp data are consistent with predictions from the fragmentation string model. However, the (p) over barp data strongly disagree with the conventional implementation of the cluster model. The non-perturbative process of 'gluon splitting to diquarks' has to be incorporated into the cluster model for it to agree with the data. Local conservation of PT between particles nearby in rapidity (i.e., p(T) compensation) is analysed with respect to the thrust direction for pi(+)pi(-), K+K-, and (p) over barp pairs. In this case, the string model provides fair agreement with the data. The cluster model is incompatible with the data for all three particle pairs. The model with its central premiss of isotropically-decaying clusters predicts a p(T) correlation not seen in the data. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 5. |
- Abdallah, J, et al.
(författare)
-
Search for charged Higgs bosons in e(+)e(-) collisions root s=189-202 GeV
- 2002
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 525:1-2, s. 17-28
-
Tidskriftsartikel (refereegranskat)abstract
- A search for pair-produced charged Higgs bosons was performed in the high energy data collected by the DELPHI detector at LEP II at centre-of-mass energies from 189 GeV to 202 GeV. The three different final states, taunutaunu, c (s) over bar(c) over bars and c (s) over bar taunu were considered. New methods were applied to reject wrong hadronic jet pairings and for the tau identification, where a discriminator based on tau polarisation and polar angles was used. No excess of data compared to the expected Standard Model processes was observed and the existence of a charged Higgs boson with mass lower than 71.5 GeV/c(2) is excluded at the 95% confidence level. (C) 2002 Published by Elsevier Science B.V.
|
|
| 6. |
- Abdallah, J, et al.
(författare)
-
Searches for neutral Higgs bosons in e(+)e(-), collisions from root s=191.6 to 201.7 GeV
- 2002
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 23:3, s. 409-435
-
Tidskriftsartikel (refereegranskat)abstract
- Neutral Higgs bosons of the Standard Model (SM) and the Minimal Supersymmetric Standard Model (MSSM) were searched for in the data collected in 1999 by the DELPHI experiment at centre-of-mass energies between 191.6 and 201.7 GeV with a total integrated luminosity of 228 pb(-1). These analyses, in combination with our results at lower energies, set 95% confidence level lower mass bounds on the Standard Model Higgs boson (107.3 GeV/c(2)) and on the lightest neutral scalar (85.9 GeV/c(2)) and neutral pseudoscalar (86.5 GeV/c(2)) Higgs bosons in representative scans of the MSSM parameter space. An extended scan of the MSSM parameter space was also performed to test the robustness of these limits.
|
|
| 7. |
- Abreu, P, et al.
(författare)
-
b-tagging in DELPHI at LEP
- 2004
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 32:2, s. 185-208
-
Tidskriftsartikel (refereegranskat)abstract
- The standard method used for tagging b-hadrons in the DELPHI experiment at the CERN LEP Collider is discussed in detail. The main ingredient of b-tagging is the impact parameters of tracks, which relies mostly on the vertex detector. Additional information, such as the mass of particles associated to a secondary vertex, significantly improves the selection efficiency and the background suppression. The paper describes various discriminating variables used for the tagging and the procedure of their combination. In addition, applications of b-tagging to some physics analyses, which depend crucially on the performance and reliability of b-tagging, are described briefly.
|
|
| 8. |
- Adams, Yvonne, et al.
(författare)
-
3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
- 2023
-
Ingår i: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 26:1
-
Tidskriftsartikel (refereegranskat)abstract
- Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
|
|
| 9. |
- Aidas, Kestutis, et al.
(författare)
-
Solvent effects on NMR isotropic shielding constants. A comparison between explicit polarizable discrete and continuum approaches
- 2007
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 111:20, s. 4199-4210
-
Tidskriftsartikel (refereegranskat)abstract
- The gas-to-aqueous solution shifts of the O-17 and C-13 NMR isotropic shielding constants for the carbonyl chromophore in formaldehyde and acetone are investigated. For the condensed-phase problem, we use the hybrid density functional theory/molecular mechanics approach in combination with a statistical averaging over an appropriate number of solute-solvent configurations extracted from classical molecular dynamics simulations. The PBE0 exchange-correlation functional and the 6-311++G(2d,2p) basis set are used for the calculation of the shielding constants. London atomic orbitals are employed to ensure gauge-origin independent results. The effects of the bulk solvent molecules are found to be crucial in order to calculate accurate solvation shifts of the shielding constants. Very good agreement between the computed and experimental solvation shifts is obtained for the shielding constants of acetone when a polarizable water potential is used. Supermolecular results based on geometry-optimized molecular structures are presented. We also compare the results obtained with the polarizable continuum model to the results obtained using explicit MM molecules to model the bulk solvent effect.
|
|
| 10. |
- Ambrosini, Valentina, et al.
(författare)
-
Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
-
Ingår i: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
-
Tidskriftsartikel (refereegranskat)abstract
- Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
|
|
| 11. |
- Baker, Jillian M., et al.
(författare)
-
Postnatal intervention for the treatment of FNAIT : a systematic review
- 2019
-
Ingår i: Journal of Perinatology. - : Springer Science and Business Media LLC. - 0743-8346 .- 1476-5543. ; 39:10, s. 1329-1339
-
Forskningsöversikt (refereegranskat)abstract
- Objective: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human platelet antigen (HPA) selected or unselected platelets, and/or IVIg on platelet increments, hemorrhage and mortality. Study design: MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018. Result: Of 754 neonates, 382 received platelet transfusions (51%). HPA-selected platelets resulted in higher platelet increments and longer response times than HPA-unselected platelets. However, unselected platelets generally led to sufficient platelet increments to 30 × 10 9 /L, a level above which intracranial hemorrhage or other life-threatening bleeding rarely occurred. Platelet increments were not improved with the addition of IVIg to platelet transfusion. Conclusion: Overall, HPA-selected platelet transfusions were more effective than HPA-unselected platelets but unselected platelets were often effective enough to achieve clinical goals. Available studies do not clearly demonstrate a benefit for addition of IVIg to platelet transfusion.
|
|
| 12. |
- Biasin, Elisa, et al.
(författare)
-
Femtosecond X-Ray Scattering Study of Ultrafast Photoinduced Structural Dynamics in Solvated[Co(terpy)2]2$
- 2016
-
Ingår i: Physical Review Letters. - : American Physical Society (APS). - 1079-7114 .- 0031-9007. ; 117:1
-
Tidskriftsartikel (refereegranskat)abstract
- We study the structural dynamics of photoexcited [Co(terpy)2]2+ in an aqueous solution with ultrafast x-ray diffuse scattering experiments conducted at the Linac Coherent Light Source. Through direct comparisons with density functional theory calculations, our analysis shows that the photoexcitation event leads to elongation of the Co-N bonds, followed by coherent Co-N bond length oscillations arising from the impulsive excitation of a vibrational mode dominated by the symmetrical stretch of all six Co-N bonds. This mode has a period of 0.33 ps and decays on a subpicosecond time scale. We find that the equilibrium bond-elongated structure of the high spin state is established on a single-picosecond time scale and that this state has a lifetime of ∼7 ps.
|
|
| 13. |
- Bozkurt, Murat Fani, et al.
(författare)
-
Guideline for PET/CT imaging of neuroendocrine neoplasms with Ga-68-DOTA-conjugated somatostatin receptor targeting peptides and F-18-DOPA
- 2017
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 44:9, s. 1588-1601
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose & Methods Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using Ga-68-DOTA-conjugated peptides, as well as F-18-DOPA imaging for various neuroendocrine neoplasms. Results & Conclusion The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with Ga-68-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.
|
|
| 14. |
- Canton, Sophie, et al.
(författare)
-
Toward Highlighting the Ultrafast Electron Transfer Dynamics at the Optically Dark Sites of Photocatalysts
- 2013
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:11, s. 1972-1976
-
Tidskriftsartikel (refereegranskat)abstract
- Building a detailed understanding of the structure function relationship is a crucial step in the optimization of molecular photocatalysts employed in water splitting schemes. The optically dark nature of their active sites usually prevents a complete mapping of the photoinduced dynamics. In this work, transient X-ray absorption spectroscopy highlights the electronic and geometric changes that affect such a center in a bimetallic model complex. Upon selective excitation of the ruthenium chromophore, the cobalt moiety is reduced through intramolecular electron transfer and undergoes a spin flip accompanied by an average bond elongation of 0.20 +/- 0.03 angstrom. The analysis is supported by simulations based on density functional theory structures (B3LYP*/TZVP) and FEFF 9.0 multiple scattering calculations. More generally, these results exemplify the large potential of the technique for tracking elusive intermediates that impart unique functionalities in photochemical devices.
|
|
| 15. |
- Canton, Sophie, et al.
(författare)
-
Visualizing the non-equilibrium dynamics of photoinduced intramolecular electron transfer with femtosecond X-ray pulses.
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Ultrafast photoinduced electron transfer preceding energy equilibration still poses many experimental and conceptual challenges to the optimization of photoconversion since an atomic-scale description has so far been beyond reach. Here we combine femtosecond transient optical absorption spectroscopy with ultrafast X-ray emission spectroscopy and diffuse X-ray scattering at the SACLA facility to track the non-equilibrated electronic and structural dynamics within a bimetallic donor-acceptor complex that contains an optically dark centre. Exploiting the 100-fold increase in temporal resolution as compared with storage ring facilities, these measurements constitute the first X-ray-based visualization of a non-equilibrated intramolecular electron transfer process over large interatomic distances. Experimental and theoretical results establish that mediation through electronically excited molecular states is a key mechanistic feature. The present study demonstrates the extensive potential of femtosecond X-ray techniques as diagnostics of non-adiabatic electron transfer processes in synthetic and biological systems, and some directions for future studies, are outlined.
|
|
| 16. |
- Dam, Gitte, et al.
(författare)
-
Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.
- 2023
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:5, s. 431-437
-
Tidskriftsartikel (refereegranskat)abstract
- Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.
|
|
| 17. |
|
|
| 18. |
- Gutte, Henrik, et al.
(författare)
-
Automated interpretation of PET/CT images in patients with lung cancer.
- 2007
-
Ingår i: Nuclear Medicine Communications. - 1473-5628. ; 28:2, s. 79-84
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop a completely automated method based on image processing techniques and artificial neural networks for the interpretation of combined [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) images for the diagnosis and staging of lung cancer. Methods: A total of 87 patients who underwent PET/CT examinations due to suspected lung cancer comprised the training group. The test group consisted of PET/CT images from 49 patients suspected with lung cancer. The consensus interpretations by two experienced physicians were used as the 'gold standard' image interpretation. The training group was used in the development of the automated method. The image processing techniques included algorithms for segmentation of the lungs based on the CT images and detection of lesions in the PET images. Lung boundaries from the CT images were used for localization of lesions in the PET images in the feature extraction process. Eight features from each examination were used as inputs to artificial neural networks trained to classify the images. Thereafter, the performance of the network was evaluated in the test set. Results: The performance of the automated method measured as the area under the receiver operating characteristic curve, was 0.97 in the test group, with an accuracy of 92%. The sensitivity was 86% at a specificity of 100%. Conclusions: A completely automated method using artificial neural networks can be used to detect lung cancer with such a high accuracy that the application as a clinical decision support tool appears to have significant potential.
|
|
| 19. |
- Gylling, Anne Theil, et al.
(författare)
-
The influence of prolonged strength training upon muscle and fat in healthy and chronically diseased older adults
- 2020
-
Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 136
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals.Methods: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, approximate to 80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed.Findings: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training.Interpretation: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good compliance and induces consistent changes in physiological parameters of muscle strength, muscle mass and abdominal fat.
|
|
| 20. |
- Herchenhan, Andreas, et al.
(författare)
-
Early Growth Response Genes Increases Rapidly After Mechanical Overloading and Unloading in Tendon Constructs
- 2020
-
Ingår i: Journal of Orthopaedic Research. - : WILEY. - 0736-0266 .- 1554-527X. ; 38:1, s. 173-181
-
Tidskriftsartikel (refereegranskat)abstract
- Tendon cells exist in a dense extracellular matrix and mechanical loading is important for the strength development of this matrix. We therefore use a three-dimensional (3D) culture system for tendon formation in vitro. The objectives of this study were to elucidate the temporal expression of tendon-related genes during the formation of artificial tendons in vitro and to investigate if early growth response-1 (EGR1), EGR2, FOS, and cyclooxygenase-1 and -2 (PTGS1 and PTGS2) are sensitive to mechanical loading. First, we studied messenger RNA (mRNA) levels of several tendon-related genes during formation of tendon constructs. Second, we studied the mRNA levels of, for example, EGR1 and EGR2 after different degrees of loading; dynamic physiologic-range loading (2.5% strain), dynamic overloading (approximately 10% strain), or tension release. The gene expression for tendon-related genes (i.e., EGR2, MKX, TNMD, COL3A1) increased with time after seeding into this 3D model. EGR1, EGR2, FOS, PTGS1, and PTGS2 did not respond to physiologic-range loading. But overloading (and tension release) lead to elevated levels of EGR1 and EGR2 (p amp;lt;= 0.006). FOS and PTGS2 were increased after overloading (both p amp;lt; 0.007) but not after tension release (p = 0.06 and 0.08). In conclusion, the expression of tendon-related genes increases during the formation of artificial tendons in vitro, including EGR2. Furthermore, the gene expression of EGR1 and EGR2 in human tendon cells appear to be sensitive to overloading and unloading but did not respond to the single episode of physiologic-range loading. These findings could be helpful for the understanding of tendon tensional homeostasis. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
|
|
| 21. |
- Jensen, Kim Steen, et al.
(författare)
-
FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function
- 2011
-
Ingår i: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 30:22, s. 4554-4570
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic tumour tissue in vivo and that FoxO3A shor-thairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia. The EMBO Journal (2011) 30, 4554-4570. doi:10.1038/emboj.2011.323; Published online 13 September 2011
|
|
| 22. |
- Jensen, Torben Haugaard, et al.
(författare)
-
Imaging of Metastatic Lymph Nodes by X-ray Phase-Contrast Micro-Tomography
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37-83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.
|
|
| 23. |
- Kjaer, Christina, et al.
(författare)
-
Luminescence Spectroscopy of Rhodamine Homodimer Dications in Vacuo Reveals Strong Dye-Dye Interactions
- 2019
-
Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 20:4, s. 533-537
-
Tidskriftsartikel (refereegranskat)abstract
- Being alone or together makes a difference for the photophysics of dyes but for ionic dyes it is difficult to quantify the interactions due to solvent screening and nearby counter ions. Gas-phase luminescence experiments are desirable and now possible based on recent developments in mass spectrometry. Here we present results on tailor-made rhodamine homodimers where two dye cations are separated by methylene linkers, (CH2)(n). In solution the fluorescence is almost identical to that from the monomer whereas the emission from bare cation dimers redshifts with decreasing n. In the absence of screening, the electric field from the charge on one dye is strong enough to polarize the other dye, both in the ground state and in the excited state. An electrostatic model based on symmetric dye responses (equal induced-dipole moments in ground state) captures the underlying physics and demonstrates interaction even at large distances. Our results have possible implications for gas-phase Forster Resonance Energy Transfer.
|
|
| 24. |
- Kjær, Mette, et al.
(författare)
-
Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia : a systematic review
- 2019
-
Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007. ; 114:1, s. 79-94
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. Materials and Methods: The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. Results: Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88–95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54–97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. Conclusion: HPA-1a antibody level has the potential to predict the severity of FNAIT.
|
|
| 25. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
-
Fetal/neonatal alloimmune thrombocytopenia : A systematic review of impact of HLA-DRB3∗01:01 on fetal/neonatal outcome
- 2020
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:14, s. 3368-3377
-
Forskningsöversikt (refereegranskat)abstract
- The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3∗01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count < 50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3∗01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3∗01:01+ women. For HLA-DRB3∗01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3∗01:01-.
|
|
