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Sökning: WFRF:(Johansson Mikael) > (2020)

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1.
  • Folkersen, Lasse, et al. (författare)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • Ingår i: Nature metabolism. - : Springer Nature. - 2522-5812. ; 2:10, s. 1135-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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2.
  • Huang, Joyce Y., et al. (författare)
  • Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
  • 2020
  • Ingår i: ; 146:9, s. 2394-2405
  • 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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3.
  • Roupé, Mattias, 1975, et al. (författare)
  • Virtual collaborative design environment: Supporting seamless integration of multitouch table and immersive VR
  • 2020
  • Ingår i: Journal of Construction Engineering and Management - ASCE. - : American Society of Civil Engineers (ASCE). - 0733-9364. ; 146:12
  • 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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4.
  • Sandstrom, A., et al. (författare)
  • Implantable cardiac devices in adult patients with repaired tetralogy of Fallot
  • 2020
  • Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Implantable cardiac devices are common in patients with tetralogy of Fallot (ToF) (18.3-21.3%) according to previous reports from large centres. We conducted this study to investigate the prevalence and incidence of cardiac devices in a less selected population of patients with ToF and assess factors other than arrhythmia associated with having a device.Design:530 adult (>= 18 years) patients with repaired ToF were identified in the national registry of congenital heart disease (SWEDCON) and matched with data from the Swedish pacemaker registry. Patients with implantable cardiac devices were compared with patients without devices.Results: Seventy-five patients (14.2%) had a device; 51 (9.6%) had a pacemaker and 24 (4.5%) had an implantable cardioverter defibrillator. The incidence in adult age (>= 18 years) was 5.9/1000 patient years. Estimated device free survival was 97.5% at twenty, 87.2% at forty and 63.5% at sixty years of age. Compared with previous studies, the prevalence of devices was lower, especially for ICD. In multivariate logistic regression, cardiovascular medication (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.8), impaired left ventricular function, (OR 2.6, 95%CI 1.3-5.0) and age (OR 1.02, 95%CI 1.002-1.05) were associated with having a device.Conclusion: The prevalence of devices in our population, representing a multicenter register cohort, was lower than previously reported, especially regarding ICD. This can be due to differences in treatment traditions with regard to ICD in this population, but it may also be that previous studies have reported selected patients with more severe disease.
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5.
  • Skoglund, Kristofer, et al. (författare)
  • Effect of medical treatment in patients with systemic right ventricle
  • 2020
  • Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:5, s. 300-305
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Congenitally corrected and surgical atrial redirected transposition of the great arteries (TGA) represents states where the morphological right ventricle serves as a systemic ventricle (S-RV). The S-RV is prone to failure, but data on medical treatment on this problem is limited. The purpose of this study was to evaluate the survival in adults with S-RV, with or without heart failure treatment.Design: The SWEDCON registry was used to collect data. All adults with S-RV and minimum follow-up of 1 year were included retrospectively. Medical treatment was defined as taking beta-blockers and/or ACE inhibitors and/or ARBs for more than 50% of the time.Results: We identified 343 patients with S-RV (median age: 21 years). Surgical atrial redirected TGA was present in 58% and congenitally corrected TGA in 42% of patients. The medically treated group (n = 126) had higher rates of impaired S-RV function, use of diuretics, pacemaker and higher NYHA functional class at baseline compared to controls. The proportion of patients with impaired functional class did not change over time in the medically treated group, but increased in controls (21% vs. 30%, p = .015). In Kaplan–Meier analysis, the mean follow-up was 10.3 years, no difference in survival was seen between the groups.Conclusions: Medical treatment may be beneficial in patients with S-RV and impaired functional class and appears to be safe in the long term. The treatment group had equal survival to controls, despite worse baseline characteristics, which might be a result of slower progression of disease in this group.
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6.
  • Das, O., et al. (författare)
  • Naturally-occurring bromophenol to develop fire retardant gluten biopolymers
  • 2020
  • Ingår i: ; 243
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to impart fire retardancy in wheat gluten polymer through naturally-occurring additives such as lanosol. The fire properties of lanosol were compared with two other conventional brominated fire retardants (Tetrabromobisphenol A and Hexabromocyclododecane). Samples containing fire retardants and gluten were prepared through compression moulding process and then characterised for their fire and mechanical properties. All fire retardants enhanced the reaction-to-fire and thermal properties of gluten while generating V-0 (i.e. vertical position and self-extinguished) ratings in the UL-94 test. The presence of all the fire retardants increased the modulus of the gluten polymer but the fire retardant particles were detrimental for the tensile strength. Nevertheless, lanosol addition delayed ignition and lowered peak heat release rate of gluten by the maximum amount, thereby leading to relatively higher fire performance index (compared to the other fire retardants). Lanosol also allowed the gluten to create a dense char barrier layer during burning that impeded the transfer of heat and flammable volatiles. The fact that only 4 wt% lanosol was able to cause self-extinguishment under direct flame and reduce peak heat release rate by a significant 50% coupled with its inherent occurrence in nature, raises the question if lanosol can be a potential fire retardant in polymeric systems, although it is a bromophenol.
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7.
  • Ji, Xuemei, et al. (författare)
  • Protein-altering germline mutations implicate novel genes related to lung cancer development
  • 2020
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 11:1
  • 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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8.
  • Johansson, Roger, et al. (författare)
  • Gaze position regulates memory accessibility during competitive memory retrieval
  • 2020
  • Ingår i: Cognition. - : Elsevier. - 0010-0277. ; 197
  • 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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9.
  • Johansson, Roger, et al. (författare)
  • How encoding-retrieval overlap in gaze positions influences episodic memory accessibility in the “real world”
  • 2020
  • Ingår i: APS Virtual Poster Showcase,2020-06-01 - 2020-09-01.
  • 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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10.
  • Johansson, V., et al. (författare)
  • Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid
  • 2020
  • Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - 0940-1334 .- 1433-8491. ; 270:7, s. 933-938
  • Tidskriftsartikel (refereegranskat)abstract
    • Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP-1 and tryptophan. No association was detected between MCP-1 and quinolinic acid. Further studies on the mechanism behind the putative relationship between KYNA and MCP-1 are needed. © 2019, The Author(s).
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