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  • Sundelof, Johan, et al. (författare)
  • Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls
  • 2010
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 22:4, s. 1223-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Cathepsin B is suggested to be involved in amyloid-beta (A beta) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, A beta(1-40) and A beta(1-42), total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (A beta(1-40) and A beta(1-42) and tau), and Cobas C501 analyzer (albumin) in persons with AD (n=101), MCI (n - 84), and healthy control subjects (n - 28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01-4.14, p = 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37-2.30, p = 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.
  • Ahlberg, Erik, et al. (författare)
  • "Vi klimatforskare stödjer Greta och skolungdomarna"
  • Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
  • Azimi, Alireza, et al. (författare)
  • Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors
  • 2018
  • Ingår i: Molecular Systems Biology. - : Blackwell Publishing Ltd. - 1744-4292. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Novel therapies are undergoing clinical trials, for example, the Hsp90 inhibitor, XL888, in combination with BRAF inhibitors for the treatment of therapy-resistant melanomas. Unfortunately, our data show that this combination elicits a heterogeneous response in a panel of melanoma cell lines including PDX-derived models. We sought to understand the mechanisms underlying the differential responses and suggest a patient stratification strategy. Thermal proteome profiling (TPP) identified the protein targets of XL888 in a pair of sensitive and unresponsive cell lines. Unbiased proteomics and phosphoproteomics analyses identified CDK2 as a driver of resistance to both BRAF and Hsp90 inhibitors and its expression is regulated by the transcription factor MITF upon XL888 treatment. The CDK2 inhibitor, dinaciclib, attenuated resistance to both classes of inhibitors and combinations thereof. Notably, we found that MITF expression correlates with CDK2 upregulation in patients; thus, dinaciclib would warrant consideration for treatment of patients unresponsive to BRAF-MEK and/or Hsp90 inhibitors and/or harboring MITF amplification/overexpression.
  • Bergström, Göran, 1964, et al. (författare)
  • The Swedish CArdioPulmonary BioImage Study: objectives and design.
  • 2015
  • Ingår i: Journal of internal medicine. - : Wiley-Blackwell Publishing Ltd. - 1365-2796 .- 0954-6820. ; 278:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
  • Boy, M., et al. (författare)
  • Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
  • 2019
  • Ingår i: Atmospheric Chemistry and Physics. - : COPERNICUS GESELLSCHAFT MBH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
  • Tidskriftsartikel (refereegranskat)abstract
    • The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
  • Eriksson, H., et al. (författare)
  • Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
  • 2013
  • Ingår i: European Journal of Cancer. - Oxford : Elsevier. - 1879-0852 .- 0959-8049. ; 49:12, s. 2705-2716
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. Methods: We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. Results: The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I = 1.6; 95% confidence interval (CI) = 1.5-1.7. OR stage III-IV versus I = 2.3; 95% CI = 1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high = 2.02; 95% CI = 1.80-2.26; p < 0.0001) and intermediate (HR intermediate versus high = 1.35; 95% CI = 1.20-1.51; p < 0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR = 1.13; 95% CI = 1.01-1.27; p = 0.04) but not for intermediate versus high (HR = 1.11; 95% CI = 0.99-1.24; p = 0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. Conclusion: Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies. (C) 2013 Elsevier Ltd. All rights reserved.
  • Klarare, Anna, et al. (författare)
  • Leadership in specialist palliative home care teams : A qualitative study
  • 2019
  • Ingår i: Journal of Nursing Management. - : Wiley-Blackwell. - 0966-0429 .- 1365-2834.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aim of this study was to describe team leaders' experiences of facilitators and barriers of leadership in specialist palliative home care teams. Background: For effective teamwork in specialist palliative care, leadership is crucial; however, defining and agreeing on what leadership comprises may be challenging. In palliative care, teamwork is recognized as imperative for multiprofessional perspectives to meet dying patients' and families' needs. Methods: Qualitative interviews with 13 team leaders in specialist palliative home care were performed, using the Pettigrew and Whipp framework, and analysed with directed content analysis. Results: Team leaders' experiences of conditions influencing the organisation and delivery of specialist palliative home care is multifaceted and leaders seem conflicted in their approach to the multiple levels of leadership, vision and responsibilities. Conclusion: Team leaders in specialist palliative home care described goals of care on differing levels and, for some, fiscal restraints and external pressures influenced their vision and leadership. Team leaders experienced challenges of leadership in relation to organisational issues, feeling burdened by responsibilities, budget restraints and team size. Implications for nursing management: Team leadership is demanding and complex. In specialist palliative home care, affirming values and enabling vision during times of fiscal strain and external pressures, is challenging. For successful leadership that develops both individuals and the health care team, leaders are recommended to adapt the leadership style to the present situation surrounding the team.
  • Molander, Peter, et al. (författare)
  • Internet-Based Acceptance and Commitment Therapy for Psychological Distress Experienced by People With Hearing Problems: Study Protocol for a Randomized Controlled Trial
  • 2015
  • Ingår i: American Journal of Audiology. - : American Speech-Language-Hearing Association. - 1059-0889 .- 1558-9137. ; 24:3, s. 307-310
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2015 American Speech-Language-Hearing Association. Purpose: Psychological distress and psychiatric symptoms are prevalent among people with hearing loss or other audiological conditions, but psychological interventions for these groups are rare. This article describes the study protocol for a randomized controlled trial for evaluating the effect of a psychological treatment delivered over the Internet for individuals with hearing problems and concurrent psychological distress. Method: Participants who are significantly distressed will be randomized to either an 8-week Internet-delivered acceptance-based cognitive behavioral therapy (i.e., acceptance and commitment therapy [ACT]), or wait-list control. We aim to include measures of distress associated with hearing difficulties, anxiety, and depression. In addition, we aim to measure acceptance associated with hearing difficulties as well as quality of life. Conclusion: The results of the trial may further our understanding of how to best treat people who present problems with both psychological distress and hearing in using the Internet.
  • Skillbäck, Tobias, et al. (författare)
  • A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.
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