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| 2. |
- Broström, Anders, et al.
(författare)
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6-month CPAP-treatment in a young male patient with severe obstructive sleep apnoea syndrome - A case study from the couples perspective
- 2008
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Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 7:2, s. 103-112
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obstructive sleep apnoea syndrome (OSAS) is independently associated with an increased risk for hypertension and cardiovascular disease. Continuous positive airway pressure (CPAP) can reduce mortality and morbidity, but low compliance rates are seen. Aim: To explore and describe the experiences of CPAP-treatment in a young male patient with severe OSAS during a 6-month period from the couples perspective. Methods and the case: A single case study with a phenomenographic approach was employed. Diagnostic procedures of OSAS and initiation of treatment with Auto-CPAP, humidifier and a nasal mask were performed during 4 visits. Conceptions were collected at 4 different occasions during the 6-month period (before, and 2 weeks, 3 months, and 6 months after treatment initiation) by means of interviews with a 33-year old male patient and his female partner. Findings: Totally 17 different structural aspects were found to fluctuate during the 6-month period in relation to; influence of stressors, social reactions and adaptation to increase compliance. Conclusion: An increased knowledge about the influence of stressors, the social reactions, and the adaptation can help healthcare personnel to identify and better understand concerns of other patients and spouses during different time phases of the initial 6-month period of CPAP-treatment.
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| 5. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 6. |
- Abrahamsson, Per-Anders, et al.
(författare)
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Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer Receiving Degarelix as Intermittent Androgen Deprivation Therapy
- 2017
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 3:4-5, s. 470-479
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). Objective: To evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. Design, setting, and participants: This multivariable analysis included 191 prostate cancer patients with baseline PSA 4–50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. Results: The full five-factor model showed that baseline PSA (p < 0.0001), age (p = 0.004), prostate cancer stage/previous therapy (p = 0.023), and baseline testosterone (p = 0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p < 0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p < 0.0001) and age (p = 0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. Conclusion: Patients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelix IAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. Patient summary: We describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. Trial registration: Clinicaltrials.gov NCT00801242 Age and prostate-specific antigen levels before and at the end of active treatment seem to predict off-treatment duration for degarelix as intermittent androgen deprivation treatment (ADT). This information could be valuable in proposing an algorithm to predict the off-treatment period, optimise visit schedules, and set the restart sate for ADT.
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| 7. |
- Aczel, Balazs, et al.
(författare)
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Consensus-based guidance for conducting and reporting multi-analyst studies
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.
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| 8. |
- Broström, Anders, et al.
(författare)
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Obstructive sleep apnoea syndrome - Patients' perceptions of their sleep and its effects on their life situation
- 2007
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Ingår i: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 57:3, s. 318-327
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Tidskriftsartikel (refereegranskat)abstract
- Title. Obstructive sleep apnoea syndrome - patients' perceptions of their sleep and its effects on their life situation Aim. This paper reports a descriptive study of how untreated patients with obstructive sleep apnoea syndrome perceived their sleep situation and how the syndrome affected their life situation. Background. Obstructive sleep apnoea syndrome is a prevalent problem independently associated with an increased risk for hypertension, cardiovascular disease, chronic heart failure and mortality. Increased consumption of healthcare resources can often be seen among patients over a long period of time since many have been undiagnosed and untreated. Methods. A phenomenographic approach was employed. Data were collected by interviews during 2005 with 20 purposively selected participants with untreated obstructive sleep apnoea syndrome. Findings. Participants described loud snoring, frequent awakenings, dyspnoea, frustration over nocturia, fear of dying during sleep and partners' anxiety about the apnoea, as being night-time effects of obstructive sleep apnoea syndrome. They described dry and sore throats, tiredness and daytime sleepiness, shame about falling asleep and snoring, thoughts about complications and depressed mood as daytime effects. Needs, such as increased alertness, improved ability to concentrate, improved relationship, adequate information as well as effective treatment, were described. Participants tried self-care strategies such as information-seeking about sleep disturbances and treatment, adapted sleeping routines, change of bedroom arrangements, adapted daily schedules, hyperactivity and avoidance of difficult situations. Conclusion. The perceived effects and needs, as well as tried self-care actions by the patients with obstructive sleep apnoea syndrome in this study, could be used to identify and evaluate concerns of other patients with obstructive sleep apnoea syndrome waiting for treatment. © 2007 The Authors.
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| 9. |
- Kalra, Hina, et al.
(författare)
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Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
- 2012
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Ingår i: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 10:12, s. e1001450-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
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| 10. |
- Lener, Thomas, et al.
(författare)
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Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.
- 2015
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Ingår i: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
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| 11. |
- Simon, Sylvia, et al.
(författare)
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Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway
- 2015
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Small molecule signaling promotes the communication between bacteria as well as between bacteria and eukaryotes. The opportunistic pathogenic bacterium Legionella pneumophila employs LAI-1 (3-hydroxypentadecane-4-one) for bacterial cell-cell communication. LAI-1 is produced and detected by the Lqs (Legionella quorum sensing) system, which regulates a variety of processes including natural competence for DNA uptake and pathogen-host cell interactions. In this study, we analyze the role of LAI-1 in inter-kingdom signaling. L. pneumophila lacking the autoinducer synthase LqsA no longer impeded the migration of infected cells, and the defect was complemented by plasmid-borne lqsA. Synthetic LAI-1 dose-dependently inhibited cell migration, without affecting bacterial uptake or cytotoxicity. The forward migration index but not the velocity of LAI-1-treated cells was reduced, and the cell cytoskeleton appeared destabilized. LAI-1-dependent inhibition of cell migration involved the scaffold protein IQGAP1, the small GTPase Cdc42 as well as the Cdc42-specific guanine nucleotide exchange factor ARHGEF9, but not other modulators of Cdc42, or RhoA, Rac1 or Ran GTPase. Upon treatment with LAI-1, Cdc42 was inactivated and IQGAP1 redistributed to the cell cortex regardless of whether Cdc42 was present or not. Furthermore, LAI-1 reversed the inhibition of cell migration by L. pneumophila, suggesting that the compound and the bacteria antagonistically target host signaling pathway(s). Collectively, the results indicate that the L. pneumophila quorum sensing compound LAI-1 modulates migration of eukaryotic cells through a signaling pathway involving IQGAP1, Cdc42 and ARHGEF9.
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| 13. |
- Uhlmann, Eric, L., et al.
(författare)
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Subjective Evidence Evaluation Survey For Multi-Analyst Studies
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Multi-analyst studies explore how well an empirical claim withstands plausible alternative analyses of the same data set by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g., effect size) provided by each analysis team. Although informative about the range of plausible effects in a data set, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item Subjective Evidence Evaluation Survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous multi-analyst study.
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| 14. |
- Yáñez-Mó, María, et al.
(författare)
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Biological properties of extracellular vesicles and their physiological functions.
- 2015
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Ingår i: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
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Forskningsöversikt (refereegranskat)abstract
- In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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