| 1. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 2. |
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| 3. |
- Kontro, M, et al.
(author)
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HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia
- 2017
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:2, s. 301-309
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Journal article (peer-reviewed)abstract
- Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to β2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.Leukemia advance online publication, 2 September 2016; doi:10.1038/leu.2016.222.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Sieberts, SK, et al.
(author)
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Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12460-
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.
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| 8. |
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| 9. |
- Andersson, M., et al.
(author)
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Using optical tweezers for measuring the interaction forces between human bone cells and implant surfaces: System design and force calibration
- 2007
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In: Rev Sci Instrum. - : AIP Publishing. ; 78:7
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Journal article (peer-reviewed)abstract
- Optical tweezers were used to study the interaction and attachment of human bone cells to various types of medical implant materials. Ideally, the implant should facilitate cell attachment and promote migration of the progenitor cells in order to decrease the healing time. It is therefore of interest, in a controlled manner, to be able to monitor the cell adhesion process. Results from such studies would help foresee the clinical outcome of integrating medical implants. The interactions between two primary cell culture models, human gingival fibroblasts and bone forming human osteoblast cells, and three different implant materials, glass, titanium, and hydroxyapatite, were studied. A novel type of optical tweezers, which has a newly designed quadrant detector and a powerful 3 W laser was constructed and force calibrated using two different methods: one method in which the stiffness of the optical trap was obtained by monitoring the phase lag between the trap and the moved object when imposing a forced oscillation on the trapped object and another method in which the maximum trapping force was derived from the critical velocity at which the object escapes the trap. Polystyrene beads as well as cells were utilized for the calibrations. This is the first time that cells have been used directly for these types of force calibrations and, hence, direct measurements of forces exerted on cells can be performed, thus avoiding the difficulties often encountered when translating the results obtained from cell measurements to the calibrations obtained with reference materials. This more straightforward approach represents an advantage in comparison to established methods.
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| 10. |
- Carlén, A, et al.
(author)
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Surface characteristics and in vitro biofilm formation on glass ionomer and composite resin
- 2001
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In: Biomaterials. - 0142-9612 .- 1878-5905. ; 22, s. 481-487
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Journal article (peer-reviewed)abstract
- In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. in this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Mineta, H, et al.
(author)
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Low expression of fragile histidine triad gene correlates with high proliferation in head and neck squamous cell carcinoma
- 2003
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In: Oral Oncology. - 1879-0593. ; 39:1, s. 56-63
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Journal article (peer-reviewed)abstract
- Frequent loss of heterozygosity in head and neck squamous cell carcinoma (HNSCC) has been found in several chromosomal regions such as 3p, 9p, 11q, 13q and 17p. Fragile histidine triad (FHIT) gene is located at 3p14.2 encompassing a common fragile site, and is identified as a tumor suppressor gene. We examined 57 patients with HNSCC using immunohistochemistry, western blot, and reverse transcriptase polymerase chain reaction. The association between FHIT expression and clinicopathologic characteristics including p53 and Ki-67 expressions was analyzed. Immunohistochemical analysis revealed 30 patients (53%) of low FHIT expression and 27 patients (47%) of high FHIT expression. Low FHIT expression significantly correlated with high Ki-67 expression, indicating that tumor cells with low FHIT expression can proliferate aggressively. No correlation was found between FHIT expression and clinical characteristics including age, gender, tumor size, lymph node status, stage grouping, histologic grade, p53 expression, and prognosis. FHIT alteration may play an important role in cancer development of HNSCC, however it did not contribute to the prognosis. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Prananingrum, W, et al.
(author)
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Bone ingrowth of various porous titanium scaffolds produced by a moldless and space holder technique : an in vivo study in rabbits
- 2016
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In: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 11:1
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Journal article (peer-reviewed)abstract
- Porous titanium has long been desired as a bone substitute material because of its ability to reduce the stress shielding in supporting bone. In order to achieve the various pore structures, we have evolved a moldless process combined with a space holder technique to fabricate porous titanium. This study aims to evaluate which pore size is most suitable for bone regeneration using our process. The mixture comprising Ti powder, wax binder and PMMA spacer was prepared manually at 70 °C which depended on the mixing ratio of each group. Group 1 had an average pore size of 60 μm, group 2 had a maximum pore size of 100 μm, group 3 had a maximum pore size of 200 μm and group 4 had a maximum pore size of 600 μm. These specimens were implanted into rabbit calvaria for three and 20 weeks. Thereafter, histomorphometrical evaluation was performed. In the histomorphometrical evaluation after three weeks, the group with a 600 μm pore size showed a tendency to greater bone ingrowth. However, after 20 weeks the group with a pore size of 100 μm showed significantly greater bone ingrowth than the other groups. This study suggested that bone regeneration into porous titanium scaffolds is pore size-dependent, while bone ingrowth was most prominent for the group with 100 μm-sized pores after 20 weeks in vivo.
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| 23. |
- Pulkka, OP, et al.
(author)
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Anagrelide for Gastrointestinal Stromal Tumor
- 2019
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 25:5, s. 1676-1687
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Journal article (peer-reviewed)
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| 24. |
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| 25. |
- White, BS, et al.
(author)
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Bayesian multi-source regression and monocyte-associated gene expression predict BCL-2 inhibitor resistance in acute myeloid leukemia
- 2021
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In: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 5:1, s. 71-
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Journal article (peer-reviewed)abstract
- The FDA recently approved eight targeted therapies for acute myeloid leukemia (AML), including the BCL-2 inhibitor venetoclax. Maximizing efficacy of these treatments requires refining patient selection. To this end, we analyzed two recent AML studies profiling the gene expression and ex vivo drug response of primary patient samples. We find that ex vivo samples often exhibit a general sensitivity to (any) drug exposure, independent of drug target. We observe that this “general response across drugs” (GRD) is associated with FLT3-ITD mutations, clinical response to standard induction chemotherapy, and overall survival. Further, incorporating GRD into expression-based regression models trained on one of the studies improved their performance in predicting ex vivo response in the second study, thus signifying its relevance to precision oncology efforts. We find that venetoclax response is independent of GRD but instead show that it is linked to expression of monocyte-associated genes by developing and applying a multi-source Bayesian regression approach. The method shares information across studies to robustly identify biomarkers of drug response and is broadly applicable in integrative analyses.
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| 26. |
- Ameen, Carly, et al.
(author)
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Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
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Journal article (peer-reviewed)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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| 27. |
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| 28. |
- Arvidsson, A., et al.
(author)
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Chemical and topographical analyses of dentine surfaces after Carisolv™ treatment
- 2002
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In: Journal of Dentistry. - 0300-5712 .- 1879-176X. ; 30:2-3, s. 67-75
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Journal article (peer-reviewed)abstract
- Objectives. The aim of this study was to characterise the surface chemistry of cavities after chemomechanical caries excavation, and also to measure the surface topography after caries removal with Carisolv™ or burs, followed by acid etching. Methods. Fourier transform (FT)-Raman spectroscopy was used to study the relative amounts of organic material and minerals of sound enamel, dentine, and cavities, after caries excavation. Fourier transform infrared spectroscopy (FTIR) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) were used for detection of Carisolv™ substances (i.e. mainly sodium hypochlorite, amino acids, and the gelling agent carboxymethyl cellulose). In total, 19 carious and 11 sound extracted teeth were used for the chemical analyses. Topographic examination of 30 carious extracted teeth was performed with a contact profilometer. Results. The relative amounts of organic material and minerals did not significantly differ between sound dentine and the cavities after caries removal with burs or Carisolv™. The FTIR analyses indicated extremely small amounts of Carisolv™ substances at the cavity surface, but the LA-ICP-MS analyses did not confirm those findings. Furthermore, the topographical parameters did not significantly differ between etched cavities after caries removal using burs or Carisolv™. Conclusions. The chemical and topographical analyses in the present study imply that any differences between the cavities after caries excavation with burs or with Carisolv™ are insignificant. © 2002 Elsevier Science Ltd. All rights reserved.
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| 29. |
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| 30. |
- Cecchinato, Francesca, et al.
(author)
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In vitro evaluation of human fetal osteoblast response to magnesium loaded mesoporous TiO2 coating.
- 2014
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In: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 102:11, s. 3862-3871
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Journal article (peer-reviewed)abstract
- This work aimed to evaluate the in vitro response of Transfected Human Foetal Osteoblast (hFOB) cultured on a magnesium-loaded mesoporous TiO2 coating. The application of mesoporous films on titanium implant surfaces has shown very promising potential to enhance osseointegration. This type of coating has the ability to act as a framework to sustain bioactive agents and different drugs. Magnesium is the element that, after calcium, is the most frequently used to dope titanium implant surfaces, since it is crucial for protein formation, growth factor expression, and aids for bone mineral deposition on implant surfaces. Mesoporous TiO2 films with an average pore-size of 6 nm were produced by the evaporation-induced self-assembly method (EISA) and deposited onto titanium discs. Magnesium loading was performed by soaking the mesoporous TiO2 discs in a magnesium chloride solution. Surface characterization was conducted by SEM, XPS, optical interferometry, and AFM. Magnesium release profile was assessed at different time points using a Magnesium Detection kit. Cell morphology and spreading were observed with SEM. The cytoskeletal organization was stained with TRITC-conjugated Phalloidin and cell viability was evaluated through a mitochondrial colorimetric (MTT) assay. Furthermore, gene expression of bone markers and cell mineralization were analyzed by real time RT-PCR and alizarin-red staining, respectively. The surface chemical analysis by XPS revealed the successful adsorption of magnesium to the mesoporous coating. The AFM measurements revealed the presence of a nanostructured surface roughness. Osteoblasts viability and adhesion as well as the gene expression were unaffected by the addition of magnesium possibly due to its rapid burst release, however, were enhanced by the 3D nanostructure of the TiO2 layer.
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| 31. |
- Fahlstedt, P., et al.
(author)
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Dental implant surface morphology, chemical composition, and topography following double wavelength (2780/940 nm) laser irradiation. An in vitro study
- 2023
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In: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 9:1, s. 25-35
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Journal article (peer-reviewed)abstract
- Objective: The aim of this in vitro study was to evaluate morphology alterations, chemical composition, and topography of moderately rough dental implants following double-wavelength laser irradiation. Material and Methods: Commercial-grade titanium dental implants representing different surface characteristics (Osseospeed [OS], TiUnite [TiU], and Roxolid SLActive [RS]) were used. Laser irradiation was performed using a computer-controlled robotic device with calibrated energy/power settings and deionized water spray. Micro-, nano-morphology surface alterations, chemical composition, and surface topography (Sa, Sds, Sdr) in the test group (laser plus water), control group A (water only), and control group B (no treatment) were analyzed using scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), and white light laser profilometer (Interferometry). Results: SEM-evaluation revealed minor between-group differences in micro- and nano-morphology within each implant system. Significant overall differences in surface element content were observed between the test and control group B for all implant systems (p <.05). For the test compared with control group B, statistically significantly higher oxygen content was detected for OS and RS (p <.05), a corresponding significant difference was detected for carbon for TiU (p <.05). For RS, a significantly lower content of titanium and zirconium was detected within the test group (p <.05). A significant difference in topography between test and control group B was observed for OS (Sa: p =.039 and Sdr: p =.041) with the highest roughness value for control group B. Conclusions: Altered chemical composition and surface topography were observed for all implant surfaces compared with untreated control following double wavelength laser irradiation. A clinical evaluation of the impact of the altered surface composition following double wavelength laser irradiation on the ability to reosseointegrate appears warranted.
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| 32. |
- Galli, Silvia, et al.
(author)
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Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone
- 2017
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In: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 105:7, s. 2118-2125
-
Journal article (peer-reviewed)abstract
- ObjectivesThe release of magnesium ions (Mg2+) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. Methods: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. Results: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. Significance: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.
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| 33. |
- Gotfredsen, Klaus, et al.
(author)
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Implants and/or teeth: consensus statements and recommendations.
- 2008
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In: Journal of oral rehabilitation. - : Wiley. - 1365-2842 .- 0305-182X. ; 35:Suppl 1, s. 2-8
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Research review (peer-reviewed)abstract
- In August 23-25, 2007, the Scandinavian Society for Prosthetic Dentistry in collaboration with the Danish Society of Oral Implantology arranged a consensus conference on the topic 'Implants and/or teeth'. It was preceded by a workshop in which eight focused questions were raised and answered in eight review articles using a systematic approach. Twenty-eight academicians and clinicians discussed the eight review papers with the purpose to reach consensus on questions relevant for the topic. At the conference the consensus statements were presented as well as lectures based on the review articles. In this article the methods used at the consensus workshop are briefly described followed by the statements with comments.
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| 34. |
- Göransson, Anna, 1970, et al.
(author)
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An in vitro comparison of possibly bioactive titanium implant surfaces.
- 2009
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In: Journal of Biomedical Materials Research Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 88:4, s. 1037-1047
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Journal article (peer-reviewed)abstract
- The aim of the study was to compare Ca and P formation (CaP) and subsequent bone cell response of a blasted and four different possibly bioactive commercially pure (cp) titanium surfaces; 1. Fluoride etched (Fluoride), 2. Alkali-heat treated (AH), 3. Magnesium ion incorporated anodized (TiMgO), and 4. Nano HA coated and heat treated (nano HA) in vitro. Furthermore, to evaluate the significance of the SBF formed CaP coat on bone cell response. The surfaces were characterized by Optical Interferometry, Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS). CaP formation was evaluated after 12, 24 and 72 h in simulated body fluid (SBF). Primary human mandibular osteoblast-like cells were cultured on the various surfaces subjected to SBF for 72 h. Cellular attachment, differentiation (osteocalcin) and protein production (TGF-beta(1)) was evaluated after 3 h and 10 days respectively. Despite different morphological appearances, the roughness of the differently modified surfaces was similar. The possibly bioactive surfaces gave rise to an earlier CaP formation than the blasted surface, however, after 72 h the blasted surface demonstrated increased CaP formation compared to the possibly bioactive surfaces. Subsequent bone cell attachment was correlated to neither surface roughness nor the amount of formed CaP after SBF treatment. In contrast, osteocalcin and TGF-beta(1) production were largely correlated to the amount of CaP formed on the surfaces. However, bone response (cell attachment, osteocalcin and TGF-F production) on the blasted controls were similar or increased compared to the SBF treated fluoridated, AH and TiMgO surface. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.
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| 35. |
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| 36. |
- Hayashi, Mariko, et al.
(author)
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In vitro characterization and osteoblast responses to nanostructured photocatalytic TiO2 coated surfaces.
- 2012
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In: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 8:6, s. 2411-6
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Journal article (peer-reviewed)abstract
- The aims of the study were to characterize a nanostructured photoactive titanium dioxide (TiO(2)) coating and to compare the cellular response of human osteoblasts before and after ultraviolet (UV) irradiation of the coating. A specific nanostructured TiO(2) powder (Degussa P-25), which consists of approximately 80% anatase and 20% rutile, was spin-coated onto commercially pure titanium discs, and was heat-treated thereafter. After topographical, chemical and photocatalytic property characterizations, human osteoblasts were cultured on the coated discs before and after UV irradiation. Cell morphology was evaluated by scanning electron microscopy (SEM), and cell viability was analysed by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. From the contact angle analysis, the wettability significantly improved after UV irradiation. The cultured cells were flattened with numerous elongated lammellipodia; however, no morphological differences were indicated between -UV and +UV surfaces. The MTT assay analysis showed that -UV surface presented significantly higher viability compared to the +UV surface except for one cell population group at 3h where there were no differences. The nanostructured photoactive TiO(2) surface improved its hydrophilicity by UV irradiation, however no enhancing effect in cell response was confirmed at the time tested compared to the non-irradiated surface.
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| 37. |
- Hayashi, Mariko, et al.
(author)
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Photocatalytically induced hydrophilicity influences bone remodelling at longer healing periods: a rabbit study
- 2014
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In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 25:6, s. 749-754
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Journal article (peer-reviewed)abstract
- ObjectivesPreviously, we have reported that photocatalytically active hydrophilicity of the anatase titanium dioxide (TiO2) nanoparticles coated onto commercially pure titanium discs presented significantly improved hydrophilicity after ultraviolet irradiation. As hydrophilicity has shown enhancement of osseointegration, the in vivo responses were of great interest. The aim of this study was to evaluate whether or not the photo-activated hydrophilicity generated at the time of implant placement has an effect on the longer healing periods for osseointegration. Materials and methodsPhotocatatytically active nanostructured TiO2 powder (Degussa P-25), which consists of approximately 80% anatase and 20% rutile, was spin-coated onto commercially pure titanium discs and was heat-treated thereafter. These P25-coated discs were irradiated with ultraviolet (UV) light for the test (+UV) group, and non-irradiated discs were prepared for the control (-UV) group. Both groups of discs were placed in the rabbits' tibiae. After 12weeks of healing period, histological analysis and gene expression analysis using real-time RT-PCR were performed. ResultsFrom the histological analyses, there were no specific differences between -UV and +UV groups. However, from the gene expression analysis, ALP, RUNX-2 and IL-10 were significantly upregulated for the +UV group compared with the -UV group. ConclusionsThe biologically enhancing effect to photocatalytically activated surfaces remained even after 12weeks of healing time in terms of genetic responses.
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| 38. |
- Jimbo, Ryo, et al.
(author)
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Genetic Responses to Nanostructured Calcium-phosphate-coated Implants.
- 2011
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In: Journal of dental research. - : SAGE Publications. - 1544-0591 .- 0022-0345. ; 90:12, s. 1422-7
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Journal article (peer-reviewed)abstract
- Nanostructured calcium phosphate (CaP) has been histologically and biomechanically proven to enhance osseointegration of implants; however, conventional techniques were not sufficiently sensitive to capture its biological effects fully. Here, we compared the conventional removal torque (RTQ) evaluation and gene expression in tissues around nanostructured CaP-coated implants, using real-time RT-PCR, with those of uncoated implants, in a rabbit model. At 2 wks, RTQ values were significantly higher, alkaline phosphatase (ALP) expression was significantly higher, and runt-related transcription factor 2 and tumor necrosis factor-α expressions were significantly lower in the coated than in the uncoated implants. This indicates that inflammatory responses were suppressed and osteoprogenitor activity increased around the CaP-coated surface. At 4 wks, although RTQ values did not significantly differ between the 2 groups, ALP and osteocalcin (OCN) were significantly up-regulated in the coated group, indicating progressive mineralization of the bone around the implant. Moreover, an osteoclast marker, adenosine triphosphatase, which indicates acidification of the resorption lacunae, was significantly higher for the coated implants, suggesting gradual resorption of the CaP coating. This study reveals detailed genetic responses to nanostructured CaP-coated implants and provides evidence that the effect of nanotopography is significant during the osseointegration cascade.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Kjellin, P., et al.
(author)
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A nanosized zirconium phosphate coating for PEEK implants and its effect in vivo
- 2020
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In: Materialia. - : Elsevier BV. - 2589-1529. ; 10
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Journal article (peer-reviewed)abstract
- Surface treatments and coatings can be applied to polyether ether ketone (PEEK) implants to improve their ability to osseointegrate. A new coating, consisting of amorphous nanosized zirconium phosphate (ZrP) was applied to PEEK and titanium substrates. The coating was applied by using a microemulsion as a carrier for the nanoparticles. It was found that the coating formed a thin continuous porous layer on top of the substrate, with pore diameters of 10–50 nm. The thickness of the coating was estimated to <100 nm. The resistance to acidic (pH = 4) conditions and exposure to ultrasonication was investigated with XPS, which showed no loss of coating. The adherence of the coating was investigated by insertion of implants in simulated bone material, which showed a minor loss in coating. In vitro (SBF) testing showed that the coating promoted crystallization of calcium phosphates, for uncoated PEEK, no crystallization was detected. The in vivo performance of the ZrP coating was examined by coating screw shaped PEEK implants which were implanted in rabbit tibia for 6 weeks. The anchoring strength of the implants was evaluated with removal torque (RTQ) measurements. The average RTQ for the ZrP coated implants was significantly higher compared to the non-coated implants. The results show that a nanosized ZrP coating on PEEK implants can transform the surface from having a low ability to osseointegrate to a surface which stimulates bone tissue growth. This makes the ZrP coating an interesting alternative for coating PEEK implants, such as spinal fusion cages and tendon fixation screws. © 2020
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| 43. |
- Kohonen, P, et al.
(author)
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A transcriptomics data-driven gene space accurately predicts liver cytopathology and drug-induced liver injury
- 2017
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15932-
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Journal article (peer-reviewed)abstract
- Predicting unanticipated harmful effects of chemicals and drug molecules is a difficult and costly task. Here we utilize a ‘big data compacting and data fusion’—concept to capture diverse adverse outcomes on cellular and organismal levels. The approach generates from transcriptomics data set a ‘predictive toxicogenomics space’ (PTGS) tool composed of 1,331 genes distributed over 14 overlapping cytotoxicity-related gene space components. Involving ∼2.5 × 108 data points and 1,300 compounds to construct and validate the PTGS, the tool serves to: explain dose-dependent cytotoxicity effects, provide a virtual cytotoxicity probability estimate intrinsic to omics data, predict chemically-induced pathological states in liver resulting from repeated dosing of rats, and furthermore, predict human drug-induced liver injury (DILI) from hepatocyte experiments. Analysing 68 DILI-annotated drugs, the PTGS tool outperforms and complements existing tests, leading to a hereto-unseen level of DILI prediction accuracy.
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| 44. |
|
|
| 45. |
|
|
| 46. |
- Mpindi, JP, et al.
(author)
-
Consistency in drug response profiling
- 2016
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 540:7631, s. E5-E6
-
Journal article (peer-reviewed)
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| 47. |
- Nordberg Karlsson, Eva, et al.
(author)
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Differences and similarities in enzymes from the neopullulanase subfamily isolated from thermophilic species
- 2008
-
In: Biologia. - : Springer Science and Business Media LLC. - 0006-3088 .- 1336-9563. ; 63:6, s. 1006-1014
-
Conference paper (peer-reviewed)abstract
- Six glycoside hydrolase (GH) family 13 members, classified under the polyspecific neopullulanase subfamily GH13_20 (also termed cyclomaltodextrinase) were analysed. They originate from thermophilic bacterial strains (Anoxybacillus flavithermus, Laceyella sacchari, and Geobacillus thermoleovorans) or from environmental DNA, collected after in situ enrichments in Icelandic hot springs. The genes were isolated following the CODEHOP consensus primer strategy, utilizing the first two of the four conserved sequence regions in GH13. The typical domain structure of GH13 20, including an N-terminal domain (classified as CBM34), the catalytic module composed of the A- and B- domains, and a C- terminal domain, was found in five of the encoded enzymes (abbreviated Amy1, 89, 92, 98 and 132). These five enzymes degraded cyclomaltodextrins (CDs) and starch, while only three, Amy92 (L. sacchari), Amy98 (A. flavithermus) and Amy132 (environmental DNA), also harboured neopullulanase activity. The L. sacchari enzyme was monomeric, but with CD as the preferred substrate, which is an unusual combination. The sixth enzyme (Amy29 from environmental DNA), was composed of the ABC-domains only. Preferred substrate for Amy29 was pullulan, which was degraded to panose, and the enzyme had no detectable activity on CDs. In addition to its different activity pro. le and domain composition, Amy29 also displayed a different conservation (LPKF) in the fifth conserved region (MPKL) proposed to identify the subfamily. All enzymes had apparent temperature optima in the range 50-65 degrees C, while thermostability varied, and was highest for Amy29 with a half-life of 480 min at 80 degrees C. Calcium dependent activity or stability was monitored in four enzymes, but could not be detected for Amy29 or 98. Tightly bound calcium can, however, not be ruled out, and putative calcium ligands were conserved in Amy98.
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