| 1. |
- Hoshino, Ayuko, et al.
(författare)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Tidskriftsartikel (refereegranskat)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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| 2. |
- Abdellaoui, G., et al.
(författare)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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| 3. |
- Ahlén Bergman, Emma, et al.
(författare)
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Increased CD4+ T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients
- 2018
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Ingår i: Clinical Epigenetics. - : BMC. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4+ T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-γ, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4+ T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.RESULTS: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4+ lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4+ lymphocytes in lymph nodes and blood (lymph nodes vs tumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p > 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4+ T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4+ T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.CONCLUSION: Increased lineage commitment in CD4+ T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4+ T cell lineages as a useful readout for clinical staging.
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| 4. |
- Babazadeh, Roja, et al.
(författare)
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The Ashbya gossypiiEF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae.
- 2011
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Ingår i: FEBS letters. - : Wiley. - 1873-3468 .- 0014-5793.
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Tidskriftsartikel (refereegranskat)abstract
- Protein overexpression based on introduction of multiple gene copies is well established. To improve purification or quantification, proteins are typically fused to peptide tags. In Saccharomyces cerevisiae, this has been hampered by multicopy toxicity of the TAP and GFP cassettes used in the global strain collections. Here, we show that this effect is due to the EF-1α promoter in the HIS3MX marker cassette rather than the tags per se. This promoter is frequently used in heterologous marker cassettes, including HIS3MX, KanMX, NatMX, PatMX and HphMX. Toxicity could be eliminated by promoter replacement or exclusion of the marker cassette. To our knowledge, this is the first report of toxicity caused by introduction of a heterologous promoter alone.
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| 5. |
- Demeke, T., et al.
(författare)
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Comorbidity and health-related quality of life in Somali women living in Sweden
- 2019
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 37:2, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- - Objective: To explore the relationship between low serum vitamin D levels and comorbidity in Somali women, immigrants to Sweden. Design and setting: Cohort study in a Primary Health Care Center and a University Hospital. Subjects: Somali women skin type V, n = 114, aged 18–56 years, from latitude 0–10 ○ N, living in Sweden, latitude 57 ○ N > 2 years were compared with women from a population sample, skin type II-III, n = 69, aged 38–56 years, the WHO MONICA study, Gothenburg, Sweden. Main outcome measures: Serum (S)-25(OH)D, S-parathyroid hormone (PTH), comorbidity and Health-Related Quality of Life (HRQoL) using the Short Form-36 (SF-36) and part of the EQ-5D questionnaires. All calculations were corrected for age. Results: Vitamin D deficiency (S-25(OH)D < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls (p <.0001). S-PTH was elevated (>6.9 pmol/l) in 26% and 9%, respectively (p <.004). Somali women used less medication, 16% vs. 55%, p <.0001) but more allergy medication, 11% vs. 7% (p =.006), had fewer fractures, 2% vs. 28% (p <.0001) and lower HRQoL in 7 out of 9 scales (p <.05–.001), than native controls. There were no differences in the prevalence of diabetes mellitus, hypothyroidism, positive thyroid peroxidase antibodies, vitamin B12 deficiency, celiac disease or hypertension. Conclusions: Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity was low. Both mental, and especially physical HRQoL scores were lower in the Somali women. The effects of long-lasting deficiency are unknown.Key points The aim was to explore the relationship between vitamin D deficiency (S-25(OH)D < 25 nmol/l) and comorbidity in immigrants. Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity of hypothyroidism, diabetes mellitus, hypertension, fractures and use of medications was low. Both mental, and especially physical, Health-Related Quality of Life were lower in the Somali women than in native Swedish women. The effects of long-lasting deficiency are unknown. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 6. |
- Fors, Carina, et al.
(författare)
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Camera-based sleepiness detection : final report of the project SleepEYE
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Two literature reviews were conducted in order to identify indicators of driver sleepiness and distraction. Three sleepiness indicators – blink duration, blink frequency and Perclos – were implemented in the camera system.The aims of the study were firstly to develop and evaluate a low cost 1-camera unit for detection of driver impairment, and secondly to identify indicators of driver sleepiness and to create a sleepiness classifier for driving simulators.The project included two experiments. The first was a field test where 18 participants conducted one alert and one sleepy driving session on a motorway. 16 of the 18 participants also participated in the second experiment which was a simulator study similar to the field test.The field test data was used for evaluation of the 1-camera system, with respect to the sleepiness indicators. Blink parameters from the 1-camera system was compared to blink parameters obtained from a reference 3-camera system and from the EOG. It was found that the 1-camera system missed many blinks and that the blink duration was not in agreement with the blink duration obtained from the EOG and from the reference 3-camera system. However, the results also indicated that it should be possible to improve the blink detection algorithm since the raw data looked well in many cases where the algorithm failed to identify blinks.The sleepiness classifier was created using data from the simulator experiment. In the first step, the indicators identified in the literature review were implemented and evaluated. The indicators also included driving and context related parameters in addition to the blink related ones. The most promising indicators were then used as inputs to the classifier.
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| 7. |
- Fors, Carina, et al.
(författare)
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Investigation of driver sleepiness in FOT data : final report of the project SleepEYE II, part 2
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Driver sleepiness contributes to a great number of motor vehicle accidents every year. In order to reduce the number of sleepiness related accidents, more knowledge on e.g. prevalence, countermeasures and driver behaviour is needed. Data from field operational tests (FOT) has a potential to provide such knowledge with high ecological validity. The objective of the project was to propose and evaluate methods for identification of driver sleepiness in FOT data. More specifically, the aim was to identify objective indicators of sleepiness – based on driving behaviour, eye blink behaviour and models of circadian rhythm – and to evaluate a subjective video scoring method for estimating driver sleepiness levels. Data from two separate projects were used: 1) the ViP-project SleepEYE, in which a controlled field test was conducted, and 2) euroFOT, which was a large scale FOT. In a first step the data quality of blink-based indicators obtained from a camera system was evaluated. It was concluded that the data quality had to be improved and thus, a new detection algorithm was devised and implemented. The new detection algorithm had an acceptable detection rate (approximately 50 %) when applied to data from the SleepEYE field test, but for euroFOT data the number of identified blinks was very low (< 5 blinks/min) in about half of the trips. There is thus a need for further improvements of the blink detection algorithm. An in-depth study on indicators of driver sleepiness was carried out using data collected in the SleepEYE experiment, with the purpose of employing the best indicators to study driver sleepiness in the euroFOT database. The most promising indicators were found to be mean blink duration and number of line crossings. A sleepiness classifier was suggested based on the distribution of the data (i.e. visual inspection). When applied to SleepEYE data the classifier was found to have good specificity while the sensitivity of the classifier was not so good. From euroFOT no true data on the drivers’ sleepiness levels were available and it was therefore not possible to evaluate the performance of the classifier. However, an explorative analysis showed that only very few data points were classified as sleepy. This may be reasonable since most trips were conducted during daytime, but it is a somewhat disappointing result for the project. A study was carried out on whether it is possible to use video recordings of drivers in order to estimate the drivers’ self-rated level of sleepiness. Forty participants rated 54 one-minute video clips of an equal number of sleepy and alert drivers on a scale with three levels (alert, first signs of sleepiness, very sleepy). The results of the study showed that performing such observer rated sleepiness (ORS) estimations on drivers is extremely difficult. The videos available in FOTs are usually of rather poor quality which, clearly limits the possibility of making reliable observer rated sleepiness estimations. In conclusion, studying driver sleepiness in (existing) FOT data is difficult, for several reasons: 1) eye camera based indicators suffer from detection errors and low detection rate, 2) driving-based indicators are influenced by e.g. road curvature and traffic density, 3) models of sleepiness cannot be used since no information on hours slept and time awake is available, and 4) video scoring is not reliable, at least not given the quality of the available video recordings. In future studies on driver sleepiness in FOTs sleepiness should be addressed in the FOT design. Some information about the drivers' sleep and sleepiness (ratings, sleep diaries, etc.) must be collected during the test; otherwise it will be very difficult to get any useful results.
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| 8. |
- Fridell, Mats, et al.
(författare)
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Prediction of psychiatric comorbidity on premature death in a cohort of patients with substance use disorders : A 42-year follow-up
- 2019
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 19:1, s. 150-150
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Tidskriftsartikel (refereegranskat)abstract
- Background: We need to better understand how the use of different substances and psychiatric comorbidity influence premature death generally and cause-specific death by overdose, intoxication and somatic disorders in people with substance use disorders. Method: A cohort of 1405 patients consecutively admitted to a Swedish detoxification unit for substance use disorders in 1970-1995 was followed-up for 42 years. Substances were identified by toxicological analyses. Mortality figures were obtained from a national registry. Causes of death were diagnosed by forensic autopsy in 594 patients deceased by 2012. Predictions were calculated by competing risks analysis. Results: Forty-two per cent of the cohort died during follow-up; more men than women (46.3% vs 30.4%). The standardised mortality ratio (SMR) was calculated as the ratio of observed deaths in males and females in specific age groups in the cohort versus expected deaths in corresponding groups in the general population. SMR was 5.68 for men (CI 95%; 5.04-6.11) and 4.98 (CI 95%; 4.08-5.88) for women. The crude mortality rate (number of deaths divided by number of person observation years) was 2.28% for men and 1.87% for women. Opiates predicted increased risk of premature death while amphetamine and cannabis predicted lower risk. Comorbid psychiatric disorders were identified in 378 cases and personality disorders in 763 cases. Primary psychoses or mood/depression and anxiety disorders predicted a higher risk of premature mortality. Death by overdose was predicted by male gender, younger age at admission to substance treatment, opiate use, and comorbid depression and anxiety syndromes. Cannabis and amphetamine use predicted a lower risk of overdose. Death by intoxication was predicted by male gender, use of sedatives/hypnotics or alcohol/mixed substances, primary psychoses and depression/anxiety syndromes. Premature death by somatic disorder was predicted by male gender and alcohol/mixed abuse. Conclusion: Psychiatric comorbid disorders were important risk factors for premature drug-related death. Early identification of these factors may be life-saving in the treatment of patients with substance use disorders.
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| 9. |
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| 10. |
- Krantz, Jaana, et al.
(författare)
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Experiences of burnout syndrome and the process of recovery: A qualitative analysis of narratives published in autobiographies
- 2021
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Ingår i: European Journal of Mental Health. - Budapest : Semmelweis University, Institute of Mental Health. - 1788-4934 .- 1788-7119. ; 16:1, s. 20-37
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Tidskriftsartikel (refereegranskat)abstract
- Burnout syndrome limits work capacity and the ability to manage a social and family life. Such limitations may lead to alienation from oneself and can result in frustration and anger. The recovery process may include a search for quick fixes from professionals but responsibility is in the hands of the ill with support from professionals, family, and work. Learning about limitations, the need to rest and accepting illness, are vital in the recovery process, but they are also associated with feelings of shame and blaming oneself for causing one’s own burnout by neglecting bodily signals. Objective: Burnout syndrome affects the individual as a whole because it involves emotional exhaustion, depersonalization, and a low sense of personal accomplishment. Research into burnout syndrome has predominantly focused on treatment outcomes measured using quantitative methods. The existing qualitative research has deepened theoretical insights from a lifeworld perspective, although, methodologically speaking, previous qualitative studies have been restricted to interviews. The qualitative interview method is somewhat limited. Hence, the objective of the present study was to analyze how autobiographers narrate their experiences of burnout syndrome and to describe their recovery process. Design: An inductive qualitative approach with a descriptive design was used to gain insights into the authors’ experience of burnout and recovery process, as expressed in writing. Setting/Subjects: The data comprised six autobiographies written by authors from Sweden. Results: The results are presented in three categories: 1) descriptions of estrangement from one’s own body, 2) descriptions of how the phenomenon is manifested in everyday life, and 3) descriptions of recovery processes. Conclusion: Burnout syndrome intersects both work life and family life and reveals the individual as a whole, integrated being. It is vital for healthcare professionals to adopt a person-centered approach that sees the individual as an integrated whole, consisting of body, mind, and soul.
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