| 1. |
- Bosse, Yohan, et al.
(författare)
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Transcriptome-wide association study reveals candidate causal genes for lung cancer
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:7, s. 1862-1878
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Tidskriftsartikel (refereegranskat)abstract
- We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large‐scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome‐wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never‐ and ever‐smokers). We performed replication analysis using lung data from the Genotype‐Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever‐smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E−99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E−6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3‐adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E−5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk.
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| 2. |
- Dai, Juncheng, et al.
(författare)
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Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:10, s. 2855-2864
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung ncer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant netic polymorphisms in the human genome. INDELs are highly associated with multiple human seases, including lung cancer. However, limited studies with large-scale samples have been available to stematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta- alysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional notations were performed to further explore the potential function of lung cancer risk INDELs. nditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci re identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 x 10(- ; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 x 10(-7); 12p13.31: rs71450133, Deletion, OR = 09, p = 8.83 x 10(-7); and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 x 10(-8)). The eQTL alysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by gulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, e INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be tentially functional genetic variants for lung cancer risk. Further functional experiments are needed to tter understand INDEL mechanisms in carcinogenesis.
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| 3. |
- Huang, Joyce Y., et al.
(författare)
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Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
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| 4. |
- Ji, Xuemei, et al.
(författare)
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Protein-altering germline mutations implicate novel genes related to lung cancer development
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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| 5. |
- Johansson, Roger, et al.
(författare)
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Gaze position regulates memory accessibility during competitive memory retrieval
- 2020
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Ingår i: Cognition. - : Elsevier BV. - 0010-0277. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- While previous research has demonstrated that gaze position can increase the accessibility of previous memories when reconstructing the past (Johansson & Johansson, 2014), the present study tested whether such gaze behavior can assist in selecting target memories in the face of competing memories. An adapted retrieval practice paradigm was used, where participants were engaged in selective retrieval while looking at locations that overlapped with the encoding location of either the target item or the competing item. Replicating previous findings, we show that encoding-retrieval compatibility in gaze positions increases the likelihood of successful remembering. We furthermore provide novel evidence that looking at locations where competing items were encoded during retrieval practice induces forgetting of the competitors during subsequent tests of memory. Corroborating evidence from changes in pupil size suggests that such gaze induced forgetting is modulated by the increased demands to successfully resolve interference from competing memories. This study represents the first demonstration that gaze position can both up- and downregulate memory accessibility during competitive memory retrieval and offers novel insights into the underlying dynamics.
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| 6. |
- Johansson, Roger, et al.
(författare)
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How encoding-retrieval overlap in gaze positions influences episodic memory accessibility in the “real world”
- 2020
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Konferensbidrag (refereegranskat)abstract
- An extensive body of research has shown that episodic remembering involves spontaneous eye movements that largely reproduce the gaze patterns that were present during encoding (e.g. Brandt & Stark, 1997; Johansson, et al., 2006; 2012; Johansson & Johansson, 2014; Richardson & Spivey, 2000). We have further demonstrated that gaze positions showing compatibility between encoding and retrieval increase the likelihood of successful remembering (Johansson & Johansson, 2014, 2020). However, to date, there is virtually no research on how gaze direction influences episodic remembering outside the laboratory. The aim of the present project was, therefore, to systematically investigate this effect in a “real-world” scenario. In a first experiment, participants (N=40, equipped with a mobile eye tracker) entered a room where they were faced with six framed stimuli at six different locations. Each stimulus comprised a letter in the center and an associated item to the left or right side of this letter. Participants were given 60 s to freely inspect and encode how each letter was associated with the items’ three features (shape, color and location). Participants then exited the room and engaged in a two-minute distracter task before they re-entered the room. They were now faced with the six frames again, but this time only the letter cue was present. They were then given 90 s to orally recall the associated items’ features in a free-recall procedure. For each participant, the same encoding-retrieval procedure was repeated over four rounds. During retrieval, the framed letters were either located in the same location as they were encoded in (congruent) or shuffled around to different locations (incongruent). Results overall replicated our previous lab-finding, with superior retrieval performance in the congruent condition. However, the effect was virtually absent for the participants who faced an incongruent condition in their first round of retrieval. In four follow-up experiments, we manipulated the number of congruent and incongruent frames within trials over the four rounds (0, 2, 4 or 6 congruent frames) and also introduced different degrees of interference between associated items. Interference was created by using two exemplars of each shape and each color instead of using unique shapes and unique colors across stimuli frames. In effect, this creates a situation where there are overlapping and competing features between items across frames. Collectively, the results from those follow-up experiments revealed that the congruency benefit is dependent on both contextual expectation and the need to handle interference from competing memories. Specifically, we show that the expectation of how relevant the spatial context is for the retrieval task can be both up- and down-regulated depending on previous rounds and that the congruency effect increases in accordance with the need to handle interference from competing memories. Those findings are further qualified by data from participants’ gaze patterns. In sum, we extend previous work by demonstrating that facilitatory effects of gaze direction on episodic remembering generalize to “real-world” scenarios, and we present novel findings that shed light on the underlying mechanisms.
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| 7. |
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| 8. |
- Roupé, Mattias, 1975, et al.
(författare)
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Virtual collaborative design environment: Supporting seamless integration of multitouch table and immersive VR
- 2020
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Ingår i: Journal of Construction Engineering and Management - ASCE. - 1943-7862 .- 0733-9364. ; 146:12
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Tidskriftsartikel (refereegranskat)abstract
- Throughout the design of a new building it is essential that all involved stakeholders understand, communicate, participate, and collaborate with each other to acquire a high-quality result. To support these shared and creative design processes, this paper presents the design and evaluation of virtual collaborative design environment (ViCoDE) - a new collaborative design system. ViCoDE features seamless integration of several immersive VR systems and a multitouch table that facilitates collaborative and interactive design work with immediate feedback. The evaluation of the system has been done during two real-life collaborative design workshops in a context of designing new healthcare environments. The results show that the VR system and multitouch table complement each other very well by facilitating both collaborative, and individual design spaces - and that it fosters better understanding, participation, communication, knowledge sharing, and collaboration among the different stakeholders. The contribution is two-fold: presentation of a new collaborative design system and the evaluation of its use in a real-life design context, which demonstrate how these new technology-based workshops may facilitate design management.
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| 9. |
- Viklund Tallgren, Mikael, 1983, et al.
(författare)
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BIM-tool development enhancing collaborative scheduling for pre-construction
- 2020
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Ingår i: Journal of Information Technology in Construction. - : International Council for Research and Innovation in Building and Construction. - 1874-4753. ; 25, s. 374-397
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Tidskriftsartikel (refereegranskat)abstract
- Construction projects often suffer from backlashes in relation to poor plans and schedules. Especially pre-construction planning has been challenging due to a high complexity, an extensive amount of information, and a lack of site managers time to make the schedule. To solve these issues for pre-construction planning; new planning processes, methods and tools have been developed over the last decade. However, due to a disregard of the current planning processes these tools have been difficult to adopt in practice. In addition, these developed tools and methods are seldom developed from the user’s point of view. A promising development is the introduction of integrated planning as a concept in construction companies. It involves the use of BIM models in concert with a planning approach where the subcontractors engage in the planning. However, currently available tools are more geared towards experienced users such as expert planners and does not allow for a fully collaborative and integrated planning approach. While many current tools would tick many of the requirements identified, they still fail to address the base requirements from the collaborative work environment literature. This paper contributes with a user-centric design and development of a collaborative planning application showing the integration of the existing collaborative planning process. By adopting a socio-technical approach, the paper focuses on combining technology and processes supporting the users and their way of working in order to enable adoption of the solution. A design science research approach has been used to gather requirements and develop and evaluate the Visual Project Planner (VPP) application. The VPP application applies a collaborative, visual approach supporting interdisciplinary knowledge sharing between all parties involved where the subcontractors actively can contribute to schedule. The VPP application has potential to reduce time for pre-construction planning regardless of the planning approach used.
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| 10. |
- Viklund Tallgren, Mikael, 1983, et al.
(författare)
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Collaborative Scheduling with 4D extended to Virtual Reality
- 2020
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Ingår i: Enabling the Development and Implementation of Digital Twins: Proceedings of the 20th International Conference on Construction Applications of Virtual Reality. ; , s. 73-85
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Konferensbidrag (refereegranskat)abstract
- Construction planning and scheduling processes have been relatively unchanged until the last decades when 4D-planning has been promoted along with the rise of Building Information Modeling (BIM). Some 4D-systems have been developed for visualising schedules rather than to aid in the actual creation of the schedule. In contrast, some scheduling software in more recent years has been enhanced with 4D-modeling capabilities. Furthermore, the use of BIM-viewers during scheduling partly enables both design and schedule review before construction. This paper aims to show how an alternative approach to 4D-modelling could be used to produce schedules. The paper presents a prototype software for planning and scheduling where the production-schedule is created directly from the model in a lean construction Last Planner manner from the building components. Findings from evaluations of the prototype indicate a move of 4D-modelling from a passive visualisation to an active modelling process. This move enables knowledge to be created and exchanged in the social co-creation context of the 4D-schedule by the stakeholders. The co-creation and understanding can be further enhanced with the extension into virtual reality using head-mounted displays where the 4D-schedule can be created and reviewed directly.
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