| 1. |
- Dobbins, Sara E., et al.
(författare)
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Common variation at 10p12.31 near MLLT10 influences meningioma risk
- 2011
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Ingår i: Nature Genetics. - London : Nature America, Inc.. - 1061-4036 .- 1546-1718. ; 43:9, s. 825-827
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.
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| 2. |
- Enciso-Mora, Victor, et al.
(författare)
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Deciphering the 8q24.21 association for glioma
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:11, s. 2293-2302
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.
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| 3. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Ghandour, Salim, et al.
(författare)
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A model for the biomechanical assessment of discoplasty in a laboratory setting
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Percutaneous cement discoplasty is a spinal surgical technique which has been rarely tested outside the clinical setting. This study aimed at developing an ovine model framework to allow testing and optimization of discoplasty in a lab-controlled environment.
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| 5. |
- Ghandour, Salim, et al.
(författare)
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An ex-vivo Biomechanical Assessment of Cement Discoplasty
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Spinal fusion is the golden standard for treating degenerative disc disease. However, elderly patients with underlying chronic conditions cannot undergo spinal fusion due to healing impairment, risks of infection, and/or even morbidity. Percutaneous Cement Discoplasty (PCD) is a relatively new procedure that involves injecting poly(methyl methacrylate) (PMMA) cement into the disc to reduce pain and attempt to maintain spinal curvature and height. Therefore, this minimally invasive method could be an advantageous option for patients for whom open surgery is deemed too risky [1]. While this technique has already been attempted clinically, to the authors knowledge, only one preliminary study on the biomechanics of PCD is currently available [2]. This study aims to develop a more clinically relevant and repeatable method to study PCD in a lab setting. To this end, ovine spine was tested in three different categories: healthy disc; injured disc; treated disc. A papain enzyme solution [3] was used to create the vacuum phenomena in the sheep spine to represent the injury as observed in a clinical setting. Preliminary compression testing showed promising results with a significant increase in stability of the segments after treatment. Further on, this testing method can be used to test different materials, surgical methods and biomechanical behaviour to further advance PCD.
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| 6. |
- Ghandour, Salim, et al.
(författare)
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An ex-vivo model for the biomechanical assessment of cement discoplasty
- 2022
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Percutaneous Cement Discoplasty (PCD) is a surgical technique developed to relieve pain in patients with advanced degenerative disc disease characterized by a vacuum phenomenon. It has been hypothesized that injecting bone cement into the disc improves the overall stability of the spinal segment. However, there is limited knowledge on the biomechanics of the spine postoperatively and a lack of models to assess the effect of PCD ex-vivo. This study aimed to develop a biomechanical model to study PCD in a repeatable and clinically relevant manner. Eleven ovine functional spinal units were dissected and tested under compression in three conditions: healthy, injured and treated. Injury was induced by a papain buffer and the treatment was conducted using PMMA cement. Each sample was scanned with micro-computed tomography (CT) and segmented for the three conditions. Similar cement volumes (in %) were injected in the ovine samples compared to volumes measured on clinical PCD CT images. Anterior and posterior disc heights decreased on average by 22.5% and 23.9% after injury. After treatment, the anterior and posterior disc height was restored on average to 98.5% and 83.6%, respectively, of their original healthy height. Compression testing showed a similar stiffness behavior between samples in the same group. A decrease of 51.5% in segment stiffness was found after injury, as expected. The following PCD treatment was found to result in a restoration of stiffness—showing only a difference of 5% in comparison to the uninjured state. The developed ex-vivo model gave an adequate representation of the clinical vacuum phenomena in terms of volume, and a repeatable mechanical response between samples. Discoplasty treatment was found to give a restoration in stiffness after injury. The data presented confirm the effectiveness of the PCD procedure in terms of restoration of axial stiffness in the spinal segment. The model can be used in the future to test more complex loading scenarios, novel materials, and different surgical techniques.
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| 7. |
- Grzeszczak, Ana, 1995-, et al.
(författare)
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Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with Stereolithography
- 2021
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Ingår i: Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with Stereolithography.
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Konferensbidrag (refereegranskat)abstract
- Mechanical and Structural Evaluation of Synthetic Trabecular Bone Models Printed with StereolithographyA. Grzeszczak1, S. Lewin1, O. Eriksson2, J. Kreuger2, C. Persson11Department of Materials Science and Engineering, Uppsala University, Uppsala, Sweden2Department of Medical Cell Biology, Uppsala University, Uppsala, SwedenINTRODUCTION: Synthetic bone models are needed to train surgeons but also to test and design medical equipment. However, currently available models do not accurately mimic the complex structure of trabecular bone [1]. This study aimed to investigate the suitability of stereolithography (SLA) printing to produce synthetic trabecular bone models.METHODS: The synthetic bone models were printed by SLA using a CAD-model generated from micro-computed tomography (micro-CT) synchrotron images of human trabecular bone [2]. To adjust the printing parameters, the influence of the following variables on the mechanical properties was investigated: printer type, orientation, resolution and UV-curing time. Subsequently, the trabecular CAD-model was printed at the original scale (scale factor 1), and with several enlarging factors. Mechanical properties were evaluated by compression and screw pullout tests, and structure replicability was assessed with micro-CT.RESULTS & DISCUSSION: The elastic modulus of the control group was not statistically different from that of the other batches after the printing parameters configuration, standard parameters were therefore used. The orientation of the samples on the build platform of the printer did not seem to have an influence on the ratio Bone Volume/Total Volume for trabecular samples. For the bone models with scaling factors below 1.8, micro-CT image analysis showed major artefacts due to printing and a low accuracy in trabecular thickness distribution. Analysis of the total printed volume showed a difference to the original model higher than 50% for scale 1.5 and lower than 10% for scales 1.8 and above (Fig. 1). A refined overlap comparison with the original bone model showed that the scale 1.8 exhibited errors higher than 20%, implying printing inaccuracies of the smaller details. The pullout strength obtained for SLA-printed parts was higher than for existing synthetic models (Sawbones™) and cadaveric specimens, but within the same range as FDM-printed parts in poly(lactic acid) [2].CONCLUSIONS: Trabecular bone models with a scale factor of 1.8 or greater could be produced with acceptable accuracy, but models with smaller scale factors were not well printed. Nevertheless, for the same 3D model, a higher resolution was reached by SLA as compared to FDM [2].ACKNOWLEDGEMENTS: The authors are grateful to Adam Engberg at U-PRINT: Uppsala University’s 3D-printing facility at the Disciplinary Domain of Medicine and Pharmacy for support and advice on the printers. This research was funded by Sweden’s Innovation Agency VINNOVA, grant number 2019-00029.REFERENCES: [1] M. Poukalova et al., “Pullout strength of suture anchors: Effect of mechanical properties of trabecular bone,” J. Biomech., vol. 43, no. 6, pp. 1138–1145, Apr. 2010, doi: 10.1016/j.jbiomech.2009.12.007. [2] D. Wu, A. Spanou, A. Diez-Escudero, and C. Persson, “3D-printed PLA/HA composite structures as synthetic trabecular bone: A feasibility study using fused deposition modeling,” J. Mech. Behav. Biomed. Mater., vol. 103, p. 103608, Mar. 2020, doi: 10.1016/j.jmbbm.2019.103608.
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| 8. |
- Grzeszczak, Ana, 1995-, et al.
(författare)
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Stereolithography shows potential in additive manufacturing ofsynthetic trabecular bone structures
- 2021
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Ingår i: Stereolithography shows potential in additive manufacturing ofsynthetic trabecular bone structures.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Title and AuthorsTitle: Stereolithography shows potential in additive manufacturing of synthetic trabecular bone structures.Authors: Ana Grzeszczak, Susanne Lewin, Olle Eriksson, Johan Kreuger, Cecilia Persson IntroductionSynthetic bone models are needed to train surgeons but also to test and design medical devices such as screws for fracture fixation. However, currently available models do not accurately mimic the trabecular bone and its complex structure [1]. This study aimed to investigate if stereolithography (SLA) additive manufacturing could produce synthetic trabecular bone models with high accuracy. Experimental methods The synthetic bone models were printed by SLA (Formlabs Black resin, Form3 printer). The CAD-model had been generated from micro-computed tomography (micro-CT) synchrotron images of human trabecular bone [2]. The model was printed at the original scale (scale factor 1), and with upscaling factors up to 4.3. Structure replicability was assessed with micro-CT, and the mechanical properties were evaluated by compression and screw pullout tests. Dense cylinders of the printed material were also tested in compression for material characterization.Results and discussionThe elastic moduli obtained by compression of dense cylinders were approximately ten times lower than average values for human cortical bone. For the trabecular bone models with scaling factors below 1.8, micro-CT image analysis showed major artefacts due to printing and a low accuracy in trabecular thickness distribution. Analysis of the total printed volume showed a difference to the original model higher than 50% for scale 1.5 (Fig. 1). However, this difference was less than 10% for scales 1.8 and above, although a refined overlap comparison with the original bone model showed that the scale 1.8 exhibited errors higher than 20%, implying printing inaccuracies of the smaller details. The pullout strength of SLA-printed parts was higher than for existing synthetic models (Sawbones™) and cadaveric specimens, but within the same range as FDM-printed parts in poly(lactic acid) [2].ConclusionIn conclusion, trabecular bone models with a scale factor of 1.8 or larger could be printed with acceptable accuracy, but models with smaller scale factors were not well represented. However, for the same 3D model, a higher resolution was achieved by SLA as compared to FDM [2]. AcknowledgementsThe authors are grateful to Adam Engberg at U-PRINT: Uppsala University’s 3D-printing facility at the Disciplinary Domain of Medicine and Pharmacy for support and advice on the printers. This research was funded by Sweden’s Innovation Agency VINNOVA, grant number 2019-00029.References[1] M. Poukalova et al., “Pullout strength of suture anchors: Effect of mechanical properties of trabecular bone,” J. Biomech., vol. 43, no. 6, pp. 1138–1145, Apr. 2010, doi: 10.1016/j.jbiomech.2009.12.007.[2] D. Wu, A. Spanou, A. Diez-Escudero, and C. Persson, “3D-printed PLA/HA composite structures as synthetic trabecular bone: A feasibility study using fused deposition modeling,” J. Mech. Behav. Biomed. Mater., vol. 103, p. 103608, Mar. 2020, doi: 10.1016/j.jmbbm.2019.103608.
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| 9. |
- Grzeszczak, Ana, et al.
(författare)
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The Potential of Stereolithography for 3D Printing of Synthetic Trabecular Bone Structures
- 2021
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Ingår i: Materials. - : MDPI. - 1996-1944. ; 14:13
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic bone models are used to train surgeons as well as to test new medical devices. However, currently available models do not accurately mimic the complex structure of trabecular bone, which can provide erroneous results. This study aimed to investigate the suitability of stereolithography (SLA) to produce synthetic trabecular bone. Samples were printed based on synchrotron micro-computed tomography (micro-CT) images of human bone, with scaling factors from 1 to 4.3. Structure replicability was assessed with micro-CT, and mechanical properties were evaluated by compression and screw pull-out tests. The overall geometry was well-replicated at scale 1.8, with a volume difference to the original model of <10%. However, scaling factors below 1.8 gave major print artefacts, and a low accuracy in trabecular thickness distribution. A comparison of the model-print overlap showed printing inaccuracies of similar to 20% for the 1.8 scale, visible as a loss of smaller details. SLA-printed parts exhibited a higher pull-out strength compared to existing synthetic models (Sawbones (TM)), and a lower strength compared to cadaveric specimens and fused deposition modelling (FDM)-printed parts in poly (lactic acid). In conclusion, for the same 3D model, SLA enabled higher resolution and printing of smaller scales compared to results reported by FDM.
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