| 1. |
- Oussi, Ninos, et al.
(author)
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Video analysis in basic skills training : a way to expand the value and use of BlackBox training?
- 2018
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In: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 32:1, s. 87-95
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Journal article (peer-reviewed)abstract
- BackgroundBasic skills training in laparoscopic high-fidelity simulators (LHFS) improves laparoscopic skills. However, since LHFS are expensive, their availability is limited. The aim of this study was to assess whether automated video analysis of low-cost BlackBox laparoscopic training could provide an alternative to LHFS in basic skills training.MethodsMedical students volunteered to participate during their surgical semester at the Karolinska University Hospital. After written informed consent, they performed two laparoscopic tasks (PEG-transfer and precision-cutting) on a BlackBox trainer. All tasks were videotaped and sent to MPLSC for automated video analysis, generating two parameters (Pl and Prtcl_tot) that assess the total motion activity. The students then carried out final tests on the MIST-VR simulator. This study was a European collaboration among two simulation centers, located in Sweden and Greece, within the framework of ACS-AEI.Results31 students (19 females and 12 males), mean age of 26.2 ± 0.8 years, participated in the study. However, since two of the students completed only one of the three MIST-VR tasks, they were excluded. The three MIST-VR scores showed significant positive correlations to both the Pl variable in the automated video analysis of the PEG-transfer (RSquare 0.48, P < 0.0001; 0.34, P = 0.0009; 0.45, P < 0.0001, respectively) as well as to the Prtcl_tot variable in that same exercise (RSquare 0.42, P = 0.0002; 0.29, P = 0.0024; 0.45, P < 0.0001). However, the correlations were exclusively shown in the group with less PC gaming experience as well as in the female group.ConclusionsAutomated video analysis provides accurate results in line with those of the validated MIST-VR. We believe that a more frequent use of automated video analysis could provide an extended value to cost-efficient laparoscopic BlackBox training. However, since there are gender-specific as well as PC gaming experience differences, this should be taken in account regarding the value of automated video analysis.
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| 2. |
- Austrin, Per, et al.
(author)
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Better Balance by Being Biased : A 0.8776-Approximation for Max Bisection
- 2016
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In: ACM Transactions on Algorithms. - : ASSOC COMPUTING MACHINERY. - 1549-6325 .- 1549-6333. ; 13:1
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Journal article (peer-reviewed)abstract
- Recently, Raghavendra and Tan (SODA 2012) gave a 0.85-approximation algorithm for the MAX BISECTION problem. We improve their algorithm to a 0.8776-approximation. As MAX BISECTION is hard to approximate within alpha(GW) + epsilon approximate to 0.8786 under the Unique Games Conjecture (UGC), our algorithm is nearly optimal. We conjecture that MAX BISECTION is approximable within alpha(GW) - epsilon, that is, that the bisection constraint (essentially) does not make MAX CUT harder. We also obtain an optimal algorithm (assuming the UGC) for the analogous variant of MAX 2-SAT. Our approximation ratio for this problem exactly matches the optimal approximation ratio for MAX 2-SAT, that is, alpha(LLZ) + epsilon approximate to 0.9401, showing that the bisection constraint does not make MAX 2-SAT harder. This improves on a 0.93-approximation for this problem from Raghavendra and Tan.
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| 3. |
- Björkman, Andrea, et al.
(author)
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Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells.
- 2015
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 112:7, s. 2157-2162
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Journal article (peer-reviewed)abstract
- Breast cancer type 1 susceptibility protein (BRCA1) has a multitude of functions that contribute to genome integrity and tumor suppression. Its participation in the repair of DNA double-strand breaks (DSBs) during homologous recombination (HR) is well recognized, whereas its involvement in the second major DSB repair pathway, nonhomologous end-joining (NHEJ), remains controversial. Here we have studied the role of BRCA1 in the repair of DSBs in switch (S) regions during immunoglobulin class switch recombination, a physiological, deletion/recombination process that relies on the classical NHEJ machinery. A shift to the use of microhomology-based, alternative end-joining (A-EJ) and increased frequencies of intra-S region deletions as well as insertions of inverted S sequences were observed at the recombination junctions amplified from BRCA1-deficient human B cells. Furthermore, increased use of long microhomologies was found at recombination junctions derived from E3 ubiquitin-protein ligase RNF168-deficient, Fanconi anemia group J protein (FACJ, BRIP1)-deficient, or DNA endonuclease RBBP8 (CtIP)-compromised cells, whereas an increased frequency of S-region inversions was observed in breast cancer type 2 susceptibility protein (BRCA2)-deficient cells. Thus, BRCA1, together with its interaction partners, seems to play an important role in repairing DSBs generated during class switch recombination by promoting the classical NHEJ pathway. This may not only provide a general mechanism underlying BRCA1's function in maintaining genome stability and tumor suppression but may also point to a previously unrecognized role of BRCA1 in B-cell lymphomagenesis.
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| 4. |
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| 5. |
- Georgiou, Konstantinos, et al.
(author)
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Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas
- 2016
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 127:24, s. 3026-3034
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Journal article (peer-reviewed)abstract
- Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of B-cell lymphoma. Deregulation of proto-oncogene expression after a translocation, most notably to the immunoglobulin heavy-chain locus (IGH), is one of the hallmarks of DLBCL. Using whole-genome sequencing analysis, we have identified the PD-L1/PD-L2 locus as a recurrent translocation partner for IGH in DLBCL. PIM1 and TP63 were also identified as novel translocation partners for PD-L1/PD-L2. Fluorescence in situ hybridization was furthermore used to rapidly screen an expanded DLBCL cohort. Collectively, a subset of samples was found to be affected by gains (12%), amplifications (3%), and translocations (4%) of the PD-L1/PD-L2 locus. RNA sequencing data coupled with immunohistochemistry revealed that these cytogenetic alterations correlated with increased expression of PD-L1 but not of PD-L2. Moreover, cytogenetic alterations affecting the PD-L1/PD-L2 locus were more frequently observed in the non-germinal center B cell-like (non-GCB) subtype of DLBCL. These findings demonstrate the genetic basis of PD-L1 overexpression in DLBCL and suggest that treatments targeting the PD-1-PD-L1/PD-L2 axis might benefit DLBCL patients, especially those belonging to the more aggressive non-GCB subtype.
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| 6. |
- Georgiou, Konstantinos
(author)
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Genetics of diffuse large B-cell lymphoma
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Diffuse large B-cell lymphoma (DLBCL) is one the most common forms of non-Hodgkin lymphoma and one of the most aggressive B-cell neoplasms. Although most patients respond to current standard treatments, a significant number of them relapse and become refractory to treatment. Hence, there is a need for new approaches in the management of DLBCL. In recent years, a number of studies using next-generation sequencing (NGS) have contributed to the characterization of the disease and have revealed a set of deregulated cellular mechanisms in DLBCL. However, DLBCL is a very heterogeneous disease and additional work is required in order to achieve a comprehensive understanding of the mechanisms underlying its lymphomagenesis. The work described in this thesis aimed to further characterize the genome of DLBCL and identify novel genomic alterations by employing a number of NGS methods. Furthermore, this thesis sought to functionally describe the effect of some of these alterations and explore how they could be meaningful from a therapeutic perspective. We first embarked on a targeted sequencing approach in order to assess the impact of mutations in a set of key DNA repair genes. DNA repair is critical in B-cell development as it ensures the regulation of antibody diversification processes. The results showed that half of the tumors analyzed carry mutations in DNA repair genes and the most frequently targeted mechanisms are mismatch repair, DNA damage response, homologous recombination and non-homologous end-joining. Moreover, functional analysis enabled the association of a number of those mutations to specific phenotypes. Whole exome sequencing identified a number or previously unreported somatic mutation targets in DLBCL. In addition, it revealed that some genes known to be involved in DLBCL were mutated at a much higher frequency in Chinese patients as compared to patients from Western populations. The impact of mutations in DTX1, a gene encoding for a negative regulator of Notch signaling, was functionally assessed and a number of mutations were found to be deleterious. Finally, whole genome sequencing enabled the identification of structural variations such as translocations in the genome of DLBCL. IGH translocations are a hallmark of DLBCL and the locus is often found juxtaposed to proto-oncogenes which leads to their upregulation. We identified PD-L1, a common culprit of immune suppression in cancer, as a novel IGH translocation partner in DLBCL. Translocations involving the PD-L1 locus were found to impact patient survival and were associated with the more aggressive non-germinal center-like subtype of the disease
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| 7. |
- Österberg, Johanna, et al.
(author)
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Can 3D Vision Improve Laparoscopic Performance in Box Simulation Training when Compared to Conventional 2D Vision?
- 2019
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In: Folia Medica. - : Plovdiv Medical University. - 0204-8043 .- 1314-2143. ; 61:4, s. 491-499
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Three-dimensional (3D) imaging systems have been introduced in laparoscopic surgery to facilitate binocular vision and dexterity to improve surgical performance and safety. Several studies have shown the benefits of 3D imaging in laparoscopy, but until now only a few studies have assessed the outcome by using objective variables. Box trainers are affordable alternatives to virtual laparoscopic surgical training, and the possibility of using real surgical instruments makes them more realistic to use. However, the data and feedback by a virtual simulator have not, until now, been able to assess. Simball Box®, equipped with G-coder sensors®, registers the instrument movements during training and gives the same feedback like a virtual simulator.AIM: The aim of this study was to objectively evaluate the laparoscopic performance in 3D compared to conventional 2D vision by using a box simulation trainer.MATERIALS AND METHODS: Thirty surgeons, residents and consultants, participated in the study. Eighteen had no, or minimal, laparoscopic experience (novices) whereas 12 were experts. They all performed three standard box training exercises (rope race, precision cutting, and basic suturing) in Simball Box. The participants were randomized and started with either 3D HD or traditional 2D HD cameras. The exercises were instructed and supervised. All instrument movements were registered. Variations in time, linear distance, average speed, and motion smoothness were analyzed.RESULTS: The parameters time, distance, speed, and motion smoothness were significantly better when the 3D camera was used.CONCLUSION: All individuals of both subgroups achieved significantly higher speed and better motion smoothness when using 3D.
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