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- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)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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| 3. |
- Johansson, Viktoria, et al.
(author)
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Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid
- 2020
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In: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 270:7, s. 933-938
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Journal article (peer-reviewed)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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- Lindner, Philip, et al.
(author)
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Using alcohol consumption diary data from an internet intervention for outcome and predictive modeling : a validation and machine learning study
- 2020
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In: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Alcohol use disorder (AUD) is highly prevalent and presents a large treatment gap. Self-help internet interventions are an attractive approach to lowering thresholds for seeking help and disseminating evidence-based programs at scale. Internet interventions for AUD however suffer from high attrition and since continuous outcome measurements are uncommon, little is known about trajectories and processes. The current study investigates whether data from a non-mandatory alcohol consumption diary, common in internet interventions for AUD, approximates drinks reported at follow-up, and whether data from the first half of the intervention predict treatment success.Methods: N = 607 participants enrolled in a trial of online self-help for AUD, made an entry in the non-mandatory consumption diary (total of 9117 entries), and completed the follow-up assessment. Using multiple regression and a subset of calendar data overlapping with the follow-up, scaling factors were derived to account for missing entries per participant and week. Generalized estimating equations with an inverse time predictor were then used to calculate point-estimates of drinks per week at follow-up, the confidence intervals of which were compared to that from the measurement at follow-up. Next, calendar data form the first half of the intervention were retained and summary functions used to create 18 predictors for random forest machine learning models, the classification accuracies of which were ultimately estimated using nested cross-validation.Results: While the raw calendar data substantially underestimated drinks reported at follow-up, the confidence interval of the trajectory-derived point-estimate from the adjusted data overlapped with the confidence interval of drinks reported at follow-up. Machine learning models achieved prediction accuracies of 64% (predicting non-hazardous drinking) and 48% (predicting AUD severity decrease), in both cases with higher sensitivity than specificity.Conclusions: Data from a non-mandatory alcohol consumption diary, adjusted for missing entries, approximates follow-up data at a group level, suggesting that such data can be used to reveal trajectories and processes during treatment and possibly be used to impute missing follow-up data. At an individual level, however, calendar data from the first half of the intervention did not have high predictive accuracy, presumable due to a high rate of missing data and unclear missing mechanisms.
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- Mårtensson, Johan, et al.
(author)
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White matter microstructure predicts foreign language learning in army interpreters
- 2020
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In: Bilingualism. - : Cambridge University Press. - 1366-7289 .- 1469-1841. ; 23:4, s. 763-771
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Journal article (peer-reviewed)abstract
- Adult foreign language acquisition is challenging, and the degree of success varies among individuals. Anatomical differences in brain structure prior to training can partly explain why some learn more than others. We followed a sample of conscript interpreters undergoing intense language training to study learning-related changes in white-matter microstructure (FA, MD, RD and AD) and associations between differences in brain structure prior to training with acquired language proficiency. No evidence for changes in white matter microstructure relative to a control group was found. Starting values of RD, AD and MD were positively related to final test scores of language proficiency, corroborating earlier findings in the field and highlighting the need for further study of how initial brain structure influences and interacts with learning outcomes.
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| 7. |
- Nyberg, Anna, et al.
(author)
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Status incongruence in human service occupations and implications for mild-to-severe depressive symptoms and register-based sickness absence : A prospective cohort study
- 2020
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In: Scandinavian Journal of Work, Environment and Health. - Helsinki : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 46:2, s. 209-217
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Journal article (peer-reviewed)abstract
- Objective This study aimed to investigate the hypothesis that negative status incongruence may contribute to explain higher risk of mental ill-health and sickness absence in human service occupations (HSO).Methods Participants from the Swedish Longitudinal Occupational Survey of Health who responded to questionnaires in both 2014 and 2016 (N=11 814; 42% men, 58% women) were included. Status incongruence between register-based educational level and subjective social status was assessed. The association between employment in a HSO and status incongruence was estimated in linear regression analyses adjusted for age, income, work hours, sickness absence, childcare, and job qualification match. The prospective associations between status incongruence and mild-to-severe depressive symptoms and register-based sickness absence >= 31 days respectively were estimated with logistic regression analyses in models adjusted for age and outcomes at baseline. All analyses were stratified by gender.Results Employment in a HSO was associated with more negative status incongruence in both genders [standardized coefficient men 0.04, 95% confidence interval (CI) 0.02-0.07; women 0.06, 95% CI 0.04-0.09]. More negative status incongruence was furthermore associated with higher odds of mild-to-severe depressive symptoms (men OR 1.18, 95% CI 1.08-1.29; women OR 1.17, 95% CI 1.09-1.26) and sickness absence >= 31 days (men OR 1.40, 95% CI 1.23-1.59; women OR 1.17, 95% CI 1.07-1.28) two years later.Conclusion Status incongruence is somewhat higher among HSO than other occupations and associated with increased odds of depressive symptoms and sickness absence.
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| 8. |
- Skoglund, Kristofer, 1976, et al.
(author)
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Effect of medical treatment in patients with systemic right ventricle
- 2020
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In: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 54:5, s. 300-305
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Journal article (peer-reviewed)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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- Sundh, Josefin, 1972-, et al.
(author)
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Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial
- 2020
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In: Trials. - : BioMed Central (BMC). - 1745-6215. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.
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