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1.
  • Orsmark-Pietras, Christina, et al. (author)
  • Precision Diagnostics in Myeloid Malignancies : Development and Validation of a National Capture-Based Gene Panel
  • 2024
  • In: Genes Chromosomes and Cancer. - 1045-2257. ; 63:7
  • Journal article (peer-reviewed)abstract
    • Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.
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2.
  • Hagström, Charlotte, et al. (author)
  • Inledning
  • 2018
  • In: Enskilda arkiv. - 9789144122441 ; , s. 7-11
  • Book chapter (other academic/artistic)
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3.
  • Patel, Riyaz S., et al. (author)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • In: Circulation. - 2574-8300. ; 12:4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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4.
  • Andreasson, Anna, et al. (author)
  • The prediction of colorectal cancer using anthropometric measures : A Swedish population-based cohort study with 22 years of follow-up
  • 2019
  • In: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:9, s. 1250-1260
  • Journal article (peer-reviewed)abstract
    • Background: Obesity is a risk factor for colorectal cancer (CRC).Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).Methods: Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
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5.
  • Gustavsson, Simon T., et al. (author)
  • Nicotinamide prevents retinal vascular dropout in a rat model of ocular hypertension and supports ocular blood supply in glaucoma patients
  • 2023
  • In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64
  • Journal article (peer-reviewed)abstract
    • PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.
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6.
  • Haas, Josephine, et al. (author)
  • Guided self-determination-young versus standard care in the treatment of young females with type 1 diabetes : study protocol for a multicentre randomized controlled trial
  • 2017
  • In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Female adolescents with type 1 diabetes mellitus (T1DM) have the most unsatisfactory glycaemic control of all age groups and report higher disease burden, poorer perceived health, and lower quality of life than their male counterparts. Females with T1DM face an excess risk of all-cause mortality compared with men with T1DM. New methods are needed to help and support young females with T1DM to manage their disease. A prerequisite for successful diabetes management is to offer individualized, person-centred care and support the patient's own motivation. Guided self-determination (GSD) is a person-centred reflection and problem-solving method intended to support the patient's own motivation in the daily care of her diabetes and help develop skills to manage difficulties in diabetes self-management. GSD has been shown to improve glycaemic control and decrease psychosocial stress in young women with T1DM. The method has been adapted for adolescents and their parents, termed GSD-young (GSD-Y). The aim of this study was to evaluate whether an intervention with GSD-Y in female adolescents with T1DM leads to improved glycaemic control, self-management, treatment satisfaction, perceived health and quality of life, fewer diabetes-related family conflicts, and improved psychosocial self-efficacy.METHODS/DESIGN: This is a parallel-group randomized controlled superiority trial with an allocation ratio of 1:1. One hundred female adolescents with T1DM, 15-20 years of age, and their parents (if < 18 years of age), will be included. The intervention group will receive seven individual GSD-Y education visits over 3 to 6 months. The control group will receive standard care including regular visits to the diabetes clinic. The primary outcome is level of glycaemic control, measured as glycosylated haemoglobin (HbA1c). Secondary outcomes include diabetes self-management, treatment satisfaction, perceived health and quality of life, diabetes-related family conflicts, and psychosocial self-efficacy. Data will be collected before randomization and at 6 and 12 months.DISCUSSION: Poor glycaemic control is common in female adolescents and young adults with T1DM. Long-standing hyperglycaemia increases the risks for severe complications and may also have an adverse impact on the outcome of future pregnancies. In this study, we want to evaluate if the GSD-Y method can be a useful tool in the treatment of female adolescents with T1DM.TRIAL REGISTRATION: Current controlled trials, ISRCTN57528404 . Registered on 18 February 2015.
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7.
  • Haas, Josephine, et al. (author)
  • Treatment satisfaction correlated with glycaemic control and burden of diabetes in Swedish adolescents with type 1 diabetes
  • 2020
  • In: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 109:3, s. 573-580
  • Journal article (peer-reviewed)abstract
    • Aim: To assess treatment satisfaction and perceived discomfort or pain from the treatment, and potential associations with glycaemic control, type of treatment, perceived burden of diabetes, sex and age, in adolescents with type 1 diabetes.Methods: A cross-sectional study was performed at one paediatric and at one adult diabetes clinic in Sweden, preceded by a translation of 'Diabetes Treatment Satisfaction Questionnaire (DTSQ) Teen'. Adolescents with type 1 diabetes (15-20 years) participated. The questionnaires 'DTSQ Teen' and 'Check your health' were used. Data on glycosylated haemoglobin (HbA1c), type of treatment, sex and age were collected.Results: One hundred and thirty-eight adolescents (70 females, mean age 17.3, mean HbA1c 64.0 mmol/mol) participated. Treatment satisfaction correlated inversely with HbA1c (r = -.352, P < .001) and with all types of burden of diabetes (r = -.342 to -0.467, P < .001), but did not differ with type of treatment, sex and age. Perceived pain correlated inversely with burden on physical health (r = -.265, P = .002), mental health (r = -.237, P = .006) and quality of life (r = -.246, P = .004) but not with HbA1c, age or burden on social relations. Females perceived more discomfort or pain.Conclusion: In Swedish adolescents with type 1 diabetes, treatment satisfaction correlated with both glycaemic control and perceived burden of diabetes.
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8.
  • Huang, Peng, et al. (author)
  • Aquaglyceroporins and orthodox aquaporins in human adipocytes
  • 2022
  • In: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736. ; 1864:1
  • Journal article (peer-reviewed)abstract
    • Aquaporins play a crucial role in water homeostasis in the human body, and recently the physiological importance of aquaporins as glycerol channels have been demonstrated. The aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) represent key glycerol channels, enabling glycerol flux across the membranes of cells. Adipocytes are the major source of glycerol and during lipolysis, glycerol is released to be metabolized by other tissues through a well-orchestrated process. Here we show that both AQP3 and AQP7 bind to the lipid droplet protein perilipin 1 (PLIN1), suggesting that PLIN1 is involved in the coordination of the subcellular translocation of aquaglyceroporins in human adipocytes. Moreover, in addition to aquaglyceroporins, we discovered by transcriptome sequencing that AQP1 is expressed in human primary adipocytes. AQP1 is mainly a water channel and thus is thought to be involved in the response to hyper-osmotic stress by efflux of water during hyperglycemia. Thus, this data suggests a contribution of both orthodox aquaporin and aquaglyceroporin in human adipocytes to maintain the homeostasis of glycerol and water during fasting and feeding.
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9.
  • Patel, Riyaz S., et al. (author)
  • Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
  • 2019
  • In: Circulation. - 2574-8300. ; 12:4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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10.
  • Abbas, Zareen, 1962, et al. (author)
  • Synthesis, characterization and particle size distribution of TiO2 colloidal nanoparticles
  • 2011
  • In: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 0927-7757. ; 384:1-3, s. 254-261
  • Journal article (peer-reviewed)abstract
    • Nanoparticles of controlled size, well defined shape, pure phase and of clean surfaces are ideal model systems to investigate surface/interfacial reactions. In this study we have explored the possibility of synthesizing TiO2 nanoparticles in the size range of 7–20 nm under well controlled experimental conditions. A simple method based on the hydrolysis of TiCl4 was used to obtain particles having surfaces free from organics. Stable dispersions of TiO2 nanoparticles of various sizes were obtained by optimizing the reaction/dialysis time and temperature. The synthesized TiO2 particles were found to be predominantly of anatase phase and narrow particle size distributions were obtained. The TiO2 particles were characterized with respect to their phase, size and shape by X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. Particle size distribution in a colloidal dispersion was obtained by the electrospray scanning mobility particle sizer (ES-SMPS) method and compared with an average particle size determined from dynamic light scattering (DLS). The average particle sizes obtained by the DLS and ES-SMPS methods were in good agreement, while a primary particle size of 4 nm was found in X-ray diffraction irrespective of the particle size in solution. Early stages of the nucleation process were monitored by the ES-SMPS method. These results show that small particles of 4–5 nm are initially formed and it is highly likely that large particles are formed due to aggregation of primary particles.
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11.
  • Andreasson, Anna, et al. (author)
  • Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index : A Population-based Cohort Study
  • 2017
  • In: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:8, s. 1294-1301
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.
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12.
  • Bergmark, Ulrika, 1973-, et al. (author)
  • Att leda med omsorg: fyra handledningsmetaforer i aktionsforskning
  • 2022
  • In: Pedagogisk forskning i Sverige. - Växjö : Linnaeus University Press. - 1401-6788 .- 2001-3345. ; 27:2, s. 28-53
  • Journal article (peer-reviewed)abstract
    • Intresset för praktiknära skolforskning är idag stort. Aktionsforskning är en populär form för samarbete mellan forskare och lärare där handledning är centralt. Syftet med denna studie är att problematisera handledning och handledarroller i aktionsforskningsprojekt. Som teoretisk grund ligger den amerikanska utbildningsfilosofen Nel Noddings omsorgsetik. Deltagarna i studien är en forskare och tre lärare som alla har erfarenheter av att leda aktionsforskningsprojekt genomförda inom kommunal skolverksamhet. Datainsamling har skett genom skriftliga reflektioner och kollegiala samtal om handledning och handledarroller. Analysen har utgått ifrån tematisk analys och domäninteraktionsmodell. I analysen framträder fyra handledningsmetaforer i aktionsforskning: trädgårdsmästaren, herden, läraren och brobyggaren. Alla rollerna kan praktiseras samtidigt och fingertoppskänsla avgör när en handledare går in i och ut ur olika roller. Slutsatsen är att omsorgsetik kan bidra till ökad förståelse för handledning som något situerat och relationellt, där ett symmetriskt förhållningssätt mellan handledare och handledd betonas. I handledning är det viktigt att inte behandla alla likadant, utan att i stället lära känna varandra som individer, ha tilltro till varandra och visa omsorg baserad på specifika behov. Handledarens roll omfattar att skapa förståelse för andras perspektiv samt att inbjuda till kommunikation och reflektion. Utifrån studiens resultat kan konstateras att de fyra metaforerna för handledarroller är användbara för att belysa komplexiteten i handledarroller och för att bidra till underlag för reflektion och omformulerande av stereotypa handledarroller.
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13.
  • Bergmark, Ulrika, et al. (author)
  • Leading with care: four mentor metaphors in collaboration between teachers and researchers in action research (Translated from the Swedish and revised by the authors)
  • 2024
  • In: Educational action research. - : Taylor & Francis. - 0965-0792 .- 1747-5074. ; 32:3, s. 475-492
  • Journal article (peer-reviewed)abstract
    • Mentoring is a central aspect of action research processes and raises ethical issues concerning roles and responsibilities, particularly when teachers and researchers collaborate. The purpose of the study is to explore mentoring and the roles of mentors in action research from an ethical stance. The theoretical basis is the philosophy of care ethics developed by the American educational philosopher, Nel Noddings. Participants in the study included one researcher and three teachers with experience serving as mentors in action research. Data collection included written reflections and collegial conversations on mentoring. Thematic analysis and the domain interactional model were used in the analysis, where four mentor metaphors in action research emerged: the gardener, the shepherd, the teacher and the bridge-builder. All roles can be practiced at the same time; sensitivity determines when a mentor moves in and out of different roles. The study finds that care ethics can contribute to an increased understanding of mentoring as something situated and relational, where a symmetrical approach between mentor and mentee is emphasized. The goal of mentoring should not be to treat everyone equally, but instead to build relationships on the individual level in order to establish mutual trust based on individual needs. The study shows that the four mentor metaphors can serve as a useful tool for critical reflection on the complexity of the mentor role and accordingly, the renegotiation of stereotypical mentor roles in relation to the quality of teaching.
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14.
  • Chapellier, Marion, et al. (author)
  • Arrayed molecular barcoding identifies TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells
  • 2019
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 104:10, s. 2006-2016
  • Journal article (peer-reviewed)abstract
    • Dysregulation of cytokines in the bone marrow microenvironment promotes acute myeloid leukemia cell growth. Due to the complexity and low throughput of in vivo stem-cell based assays, studying the role of cytokines in the bone marrow niche in a screening setting is challenging. Herein, we developed an ex vivo cytokine screen using 11 arrayed molecular barcodes, allowing for a competitive in vivo readout of leukemia-initiating capacity. With this approach, we assessed the effect of 114 murine cytokines on MLL-AF9 acute myeloid leukemia mouse cells and identified the tumor necrosis factor ligand superfamily member 13 (TNFSF13) as a positive regulator of leukemia-initiating cells. By using Tnfsf13-/- recipient mice, we confirmed that TNFSF13 supports leukemia-initiation also under physiological conditions. TNFSF13 was secreted by normal myeloid cells but not by leukemia mouse cells, suggesting that mature myeloid bone marrow cells support leukemia cells by secreting TNFSF13. TNFSF13 supported leukemia cell proliferation in an NF-κB-dependent manner by binding TNFRSF17 and suppressed apoptosis. Moreover, TNFSF13 supported the growth and survival of several human myeloid leukemia cell lines, demonstrating that our findings translate to human disease. Taken together, using arrayed molecular barcoding, we identified a previously unrecognized role of TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells. The arrayed barcoded screening methodology is not limited to cytokines and leukemia, but can be extended to other types of ex vivo screens, where a multiplexed in vivo read-out of stem cell functionality is needed.
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15.
  • De Vrieze, S., et al. (author)
  • The effect of temperature and humidity on electrospinning
  • 2009
  • In: Journal of Materials Science. - : Springer Science and Business Media LLC. - 0022-2461 .- 1573-4803. ; 44:5, s. 1357-1362
  • Journal article (peer-reviewed)abstract
    • Electrospinning is a process that generates nanofibres. Temperature and humidity affect this process. In this article the influence of humidity and temperature on the formation and the properties of nanofibres are studied using cellulose acetate (CA) and poly(vinylpyrrolidone) (PVP) as target materials. The experiments indicate that two major parameters are dependent of temperature and have their influence on the average fibre diameter. A first parameter is the solvent evaporation rate that increases with increasing temperature. The second parameter is the viscosity of the polymer solution that decreases with increasing temperature. The trend in variation of the average nanofibre diameter as a function of humidity is different for CA and PVP, which can be explained by variations in chemical and molecular interaction and its influence on the solvent evaporation rate. As the humidity increases, the average fibre diameter of the CA nanofibres increases, whilst for PVP the average diameter decreases. The average diameter of nanofibres made by electrospinning change significantly through variation of temperature and humidity. © 2008 Springer Science+Business Media, LLC.
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16.
  • Engström, Gunnar, et al. (author)
  • Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
  • 2024
  • In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
  • Journal article (peer-reviewed)abstract
    • Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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  • Ericsson, Maria, 1970- (author)
  • No time to waste : Pre-hospital actions and time delays in patients with ST elevation myocardial infarction – temporal trends and prognostic impact on short- and long-term survival
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Background: In ST-elevation myocardial infarction (STEMI) patients, a rapid diagnosis is imperative to reduce total ischaemic time minimizing risk for heart failure, serious arrhythmias, or death. Prehospital context is complex, and the patient delay constitute major part of the pre-hospital phase. Patient delay has been prone hard to impact but the system delay has had major transformation during the years.  Aim: The overall aim was to explore pre-hospital actions and time delays in STEMI patients, investigating temporal trends and estimate prognostic impact on short- and long-term survival.  Methods: Study I, was a multicentre survey study, exploring decisions, and actions in relation to the choice of first medical contact (FMC). Study II was a sub-study to the multicentre survey, exploring the interaction between tele nurses and callers in authentic calls when the caller with an evolving myocardial infarction (MI) chose to call Swedish health care direct (SHD) as FMC. Study III, was based on the same database as study I, exploring early (< 20 minutes) and late (> 90 minutes) response from symptom onset in STEMI patients. Study IV, was based on SWEDEHEART-registry, investigating temporal trends in pre-specified risk groups for pro-longed pre-hospital delay times (PHDT), estimating cumulative survival in short and long term stratified in six different PHDT groups.  Results: Study I, only half of the patients’ contacted emergency medical services (EMS) as their FMC. Choice of FMC prolonged time to diagnosis in relation of calling EMS. Choosing SHD pro-longed delay to diagnosis with 38 minutes. Study II, four interactions were found between tele-nurses and callers, reasoning, distinct, irrational, and indecisive, and type of interaction could lead or mislead the call moving progressively forward or not. Study III, bystanders calling EMS, men, intensive and alarming symptoms such as dyspnoea and weakness and to interpret symptoms attributed from the heart was associated with a rapid action calling an ambulance within 20 minutes, which was performed by one of five patients. Study IV, trend curves for median PHDT was hump shaped for the 20 years studied. Women, older age, and patients with diabetes had consistent pro-longed PHDT, except for the oldest patients (> 80 years). PHDT was an independent risk for short- and long-term survival. Patients with the shortest PHDT 0-1 hour had the highest mortality up to five days. In five-year follow up this group accompanied with the group within 1-2 hours had highest estimated survival.  Conclusion: Pre-hospital delay is an independent predictor of short- and long-term survival. To interpret symptom correctly and knowledge in how to act, calling an ambulance rapidly, impact time to diagnosis and diminish time delays. Pre-hospital delay merits further attention regarding future interventions.  
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21.
  • Fagerlund, A. J., et al. (author)
  • Experiences from patients in mental healthcare accessing their electronic health records : Results from a cross-national survey in Estonia, Finland, Norway, and Sweden
  • 2024
  • In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 24:1
  • Journal article (peer-reviewed)abstract
    • Background: Patients’ online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users’ overall experiences with national PAEHR services. Methods: The study analysed the MHC-part of the NORDeHEALTH 2022 Patient Survey, a large-scale multi-country survey. The survey consisted of 45 questions, including demographic variables and questions related to users’ experiences with ORA. We focused on the questions concerning positive experiences (benefits), negative experiences (errors, omissions, offence), and breaches of security and privacy. Participants were included in this analysis if they reported receiving mental healthcare within the past two years. Descriptive statistics were used to summarise data, and percentages were calculated on available data. Results: 6,157 respondents were included. In line with previous research, almost half (45%) reported very positive experiences with ORA. A majority in each country also reported improved trust (at least 69%) and communication (at least 71%) with healthcare providers. One-third (29.5%) reported very negative experiences with ORA. In total, half of the respondents (47.9%) found errors and a third (35.5%) found omissions in their medical documentation. One-third (34.8%) of all respondents also reported being offended by the content. When errors or omissions were identified, about half (46.5%) reported that they took no action. There seems to be differences in how patients experience errors, omissions, and missing information between the countries. A small proportion reported instances where family or others demanded access to their records (3.1%), and about one in ten (10.7%) noted that unauthorised individuals had seen their health information. Conclusions: Overall, MHC patients reported more positive experiences than negative, but a large portion of respondents reported problems with the content of the PAEHR. Further research on best practice in implementation of ORA in MHC is therefore needed, to ensure that all patients may reap the benefits while limiting potential negative consequences.
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22.
  • Hagström, Anna, et al. (author)
  • A water activity control system for enzymatic reactions in organic media
  • 2007
  • In: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 97:2, s. 235-241
  • Journal article (peer-reviewed)abstract
    • A water activity control system for enzymatic synthesis in organic media, for litre-scale reactors has been constructed. Water activity, a(w), is a key factor when using enzymes in non-conventional media and the optimum value varies for different enzymes. The control system consists of a water activity sensor in the headspace of a jacketed glass reactor (equipped with narrow steel tubes to introduce air), gas-washing bottles containing blue silica gel (a(w) = 0) and water (a(w) = 1), a PC to monitor water activity and a programmable logic controller (PLC) to control the water activity. The system was evaluted by adjusting water activity in the medium, with a defviation from the set point less than +/- 0.05. Synthesis of cetyl palmitate, under controlled water activity and catalysed by two different lipase preparations, namely, Novozym (R) 435 (immobilised Candida anarctica lipase B) and immobilised Candida rugosa lipase, were also performed. Novozym (R) 435 catalyses reactions very well at extremely low water activity while C. rugosa lipase shows low activity for a(w) < 0.05.
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23.
  • Hagström, Anna, et al. (author)
  • Biocatalytic polyester acrylation-process optimization and enzyme stability.
  • 2009
  • In: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 102, s. 693-699
  • Journal article (peer-reviewed)abstract
    • An OH-functional polyester has been acrylated via transesterification of ethyl acrylate, catalyzed by Candida antarctica lipase B (CalB) in two different preparations: Novozym(R) 435 and immobilized on Accurel(R) MP1000. The batch process resulted in incomplete acrylation as well as severe degradation of the polyester. A high degree of acrylation was achieved by optimization through the application of low pressure (15 kPa), continuous inflow of ethyl acrylate and continuous distillation to evaporate the by-product, ethanol. The enzyme preparations displayed good stability with half-lives of 180 and 324 h for Novozym(R) 435 and CalB/MP1000, respectively. This translates into product yields of 3600 and 6200 times the weight of the catalyst, indicating that the enzyme will have a marginal impact on the total process cost. Biotechnol. Bioeng. 2008. (c) 2008 Wiley Periodicals, Inc.
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24.
  • Hagström, Anna, et al. (author)
  • Chemo-enzymatic epoxidation-process options for improving biocatalytic productivity.
  • 2011
  • In: Biotechnology Progress. - : Wiley. - 1520-6033 .- 8756-7938. ; 27:1, s. 67-76
  • Journal article (peer-reviewed)abstract
    • The reactor choice is crucial when designing a process where inactivation of the biocatalyst is a problem. The main bottleneck for the chemo-enzymatic epoxidation has been found to be enzyme inactivation by the hydrogen peroxide, H(2)O(2), substrate. In the work reported here, the effect of reaction parameters on the reaction performance have been investigated and used to establish suitable operating strategies to minimize the inactivation of the enzyme, using rapeseed methyl ester (RME) as a substrate in a solvent-free system. The use of a controlled fed-batch reactor for maintaining H(2)O(2) concentration at 1.5 M resulted in increased productivity, up to 76 grams of product per gram of biocatalyst with higher retention of enzyme activity. Further investigation included a multistage design that separated the enzymatic reaction and the saturation of the RME substrate with H(2)O(2) into different vessels. This setup showed that the reaction rate as well as enzyme inactivation is strongly dependent on the H(2)O(2) concentration. A 20-fold improvement in enzymatic efficiency is required for reaching an economically feasible process. This will require a combination of enzyme modification and careful process design. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010.
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25.
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26.
  • Hagström, Anna (author)
  • Improving Productivity and Enzyme Stability Through Process Design: Lipase-catalysed Synthesis of Epoxides and Esters
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Interest in sustainable development has increased throughout society during the past decades, and the chemical industry is no exception. The appeal for renewable raw materials has consequently increased and has paved the way for the implementation of industrial biotechnology. Since enzymes are used to convert biomass in nature, they may also be a good choice in the chemical industry. However, to identify if the use of enzymes is the best alternative for a particular application they must be evaluated. Investigations can be carried out on the enzyme itself, the reaction, the reactor design or the complete process. Analyses of the environmental impact and the economics of the process are also important. The focus of the interdisciplinary research programme Greenchem at Lund University is to develop speciality chemicals from renewable raw materials using enzymes as catalysts. The work presented in this thesis was focused on the reactor and the process, rather than the catalyst itself, or a specific reaction, as those have been covered in other projects within Greenchem. Lipases are among the most extensively studied enzymes. Candida antarctica lipase B (CalB), which can be used to catalyse several different reactions, is one example. This enzyme was most frequently used in the work described in this thesis, usually in an immobilised preparation, Novozym® 435 (N435). In the initial study presented in this thesis, four wax esters were produced and tested regarding their applicability as wood coatings. Unfortunately, even the best of these waxes showed too low resistance to grease stains. Towards the end of this work a new study was initiated; acrylation of polymers to be used as the main component in lacquers, with the hope of achieving better resistance than that achieved with the wax esters. These acrylates were produced on litre-scale via lipase-catalysed trans-esterification between ethyl acrylate and polyesters and polyethers, respectively, and were found to be comparable to the commercial alternatives available today. A biolubricant, trimethylolpropane (TMP) oleate, was produced via esterification using the same lipase preparation, as well as epoxidised rapeseed methyl ester (RME) through chemo-enzymatic epoxidation. Several parameters must be considered when setting up a biocatalytic process. Water activity is one of them, and a system for water activity control was developed using wax ester synthesis as a model reaction. The system consisted of a sensor, a control unit and the facility to bubble air through the reactor, either dry or saturated with water, to decrease or increase the humidity in the reactor. The optimum water activity for esterification using N435 was determined and found to be close to zero. For comparison, an immobilised lipase from Candida rugosa was used, and this preparation was found to work best at higher water activities, i.e. above 0.5. By-product removal is another important parameter, and this was accomplished by evaporation through bubbling air through the reactor in wax ester synthesis, or by vacuum in the synthesis of acrylates and TMP oleate. The stability of the enzyme and the performance of the processes were investigated by varying different parameters. In the acrylation reaction half-lives of up to 320 h were achieved for two different CalB preparations, which resulted in reasonable catalyst costs for the process. However, when using N435 for TMP oleate synthesis, the process was not viable due to the combination of the long reaction times required at moderate temperatures and the relatively low stability of the enzyme (~90 h half-life). The stability of the biocatalyst was also found to be too low for an economically feasible production of epoxidised RME, although it could be enhanced by appropriate process design. Productivity and enzyme stability were investigated in different reactor designs, and it was found to be crucial to maintain the hydrogen peroxide concentration at a low, controlled level in order to prolong the life-time of the biocatalyst. The work presented in this thesis shows the direct applicability of biocatalysis to some processes such as the acrylation reaction, which has been proven to be competitive with traditional chemical production methods. In other cases, further development regarding choice of biocatalyst, reaction medium and process design are needed. One of the most important factors in investigations regarding industrial biotechnology is the enzyme stability, as this determines the possibility of implementing the process on an industrial scale.
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27.
  • Hagström, Anna, et al. (author)
  • Wax esters produced by solvent-free energy-efficient enzymatic synthesis and their applicability as wood coatings
  • 2005
  • In: Green Chemistry. - : Royal Society of Chemistry (RSC). - 1463-9270 .- 1463-9262. ; 7:12, s. 837-843
  • Journal article (peer-reviewed)abstract
    • The study aimed at developing a process for making a wood coating wax based on the principles of green chemistry. The research was conducted within the Swedish interdisciplinary research programme Greenchem. Wax esters are attractive since they are non-hazardous, biodegradable and can be produced in an atom-efficient process from building blocks obtained from renewable resources. Four wax esters were prepared in a solvent-free process using an immobilised lipase as catalyst. When the water was removed during the process from what was initially an equimolar mixture of the starting materials carboxylic acid and alcohol by a stream of dry air passed through the reactor, there was a 95-99% conversion to the ester. The enzymatic process consumed 34% less energy and generated less waste than chemical esterification using a strong acid as catalyst. Two of the esters worked well in the industrial wood coating equipment employed and produced surfaces resistant to water and somewhat less to fat stains.
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28.
  • Hagström, Hannes, et al. (author)
  • Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease
  • 2020
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:1, s. 200-214
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. METHODS: We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. RESULTS: A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. CONCLUSIONS: Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.
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29.
  • Hagström, Hannes, et al. (author)
  • Alcohol consumption in late adolescence is associated with an increased risk of severe liver disease later in life
  • 2018
  • In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 68:3, s. 505-510
  • Journal article (peer-reviewed)abstract
    • Background & Aims: High alcohol consumption is associated with an increased risk of severe liver disease. Current recommendations suggest it is safe for men to consume 30 grams of alcohol per day. We investigated the association between alcohol consumption early in life and later development of severe liver disease.Methods: We used data on alcohol consumption at conscription to military service from 43,296 men (18-20 years) in Sweden between 1969 and 1970. Outcomes were defined as incident diagnoses of severe liver disease from systematic national registration of clinical events until the end of 2009. A Cox regression model adjusted for body mass index, smoking, use of narcotics, cognitive ability and cardiovascular capacity was applied.Results: During a mean follow-up of 37.8 years, 383 men developed severe liver disease. Alcohol consumption was associated with an increased risk of development of severe liver disease in a dose-response pattern (adjusted hazard ratio for every one gram/day increase 1.02; 95% CI 1.01-1.02). No evidence of a threshold effect was found. Importantly, a clear trend pointed towards an increased risk of severe liver disease in men who consumed less than 30 grams of alcohol per day.Conclusion: Alcohol consumption in young men is associated with an increased risk of severe liver disease, up to 39 years later in life. The risk was dose-dependent, with no sign of a threshold effect. Current guidelines for safe alcohol intake in men might have to be revised.Lay summary: We investigated more than 43,000 Swedish men in their late teens enlisted for conscription in 1969–1970. After almost 40 years of follow-up, we found that alcohol consumption was a significant risk factor for developing severe liver disease, independent of confounders. This risk was dose-dependent, and was most pronounced in men consuming two drinks per day or more.
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30.
  • Hagström, Hannes, et al. (author)
  • Body composition measurements and risk of hematological malignancies : A population-based cohort study during 20 years of follow-up
  • 2018
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
  • Journal article (peer-reviewed)abstract
    • High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.
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31.
  • Hagström, Hannes, et al. (author)
  • Body mass index in early pregnancy and future risk of severe liver disease : a population-based cohort study
  • 2019
  • In: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 49:6, s. 789-796
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.AIM: To study the association between BMI early in life and development of liver disease later in life in women.METHODS: We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.RESULTS: (95% CI 1.02-1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.CONCLUSION: A high BMI early in life in women is associated with a dose-dependent, increased risk for future severe liver disease.
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32.
  • Hagström, Hannes, et al. (author)
  • Improved prediction of 10-year risk of severe liver disease in the general population using commonly available biomarkers
  • 2023
  • In: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 57:4, s. 418-425
  • Journal article (peer-reviewed)abstract
    • Background: Estimating the risk for cirrhosis in the general population is complex. Existing prediction tools are in general unsatisfactory.Aims: To explore if using commonly available biomarkers can improve the commonly used FIB-4 score in the identification of subgroups at risk of cirrhosis.Methods: We used laboratory and clinical data on 126,925 individuals aged 35–79 years in Stockholm, Sweden, undergoing health examinations from 1985 to 1996. We used Swedish nationwide registries to ascertain 10-year cumulative incidence of severe liver disease, a composite of diagnoses corresponding to cirrhosis and its complications. We considered combinations of biomarkers associated with severe liver disease to identify subgroups with different risk profiles.Results: During an average follow-up of 9.3 years, we ascertained 630 incident cases of severe liver disease (0.5%). Age, the FIB-4 score, diabetes or impaired glucose and gamma-glutamyl transferase (gGT) were the most relevant characteristics for classifying risk profiles. Using these factors, we identified 24 groups with a cumulative incidence of severe liver disease at 10 years ranging from 0.2% (age 35–65, low FIB-4, no diabetes or impaired glucose and normal gGT) to 32.1% (age 35–65, high FIB-4, diabetes or impaired glucose and high gGT).Conclusions: Identification of subjects at increased risk of severe liver disease in the general population using the FIB-4 score can be substantially improved by adding age and specific biomarkers commonly available in the primary care setting. These parameters should be considered for inclusion in the development of future risk prediction models.
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33.
  • Hagström, Henrik, et al. (author)
  • Low carbohydrate high fat-diet in real life assessed by diet history interviews
  • 2023
  • In: Nutrition Journal. - : BioMed Central (BMC). - 1475-2891. ; 22:1
  • Journal article (peer-reviewed)abstract
    • Background: Low carbohydrate high fat (LCHF) diet has been a popular low carbohydrate diet in Sweden for 15 years. Many people choose LCHF to lose weight or control diabetes, but there are concerns about the effect on long-term cardiovascular risks. There is little data on how a LCHF diet is composed in real-life. The aim of this study was to evaluate the dietary intake in a population with self-reported adherence to a LCHF diet.Methods: A cross-sectional study of 100 volunteers that considered themselves eating LCHF was conducted. Diet history interviews (DHIs) and physical activity monitoring for validation of the DHIs were performed.Results: The validation shows acceptable agreement of measured energy expenditure and reported energy intake. Median carbohydrate intake was 8.7 E% and 63% reported carbohydrate intake at potentially ketogenic levels. Median protein intake was 16.9 E%. The main source of energy was dietary fats (72.0 E%). Intake of saturated fat was 32 E% and cholesterol was 700 mg per day, both of which exceeded the recommended upper limits according to nutritional guidelines. Intake of dietary fiber was very low in our population. The use of dietary supplements was high, and it was more common to exceed the recommended upper limits of micronutrients than to have an intake below the lower limits.Conclusions: Our study indicates that in a well-motivated population, a diet with very low carbohydrate intake can be sustained over time and without apparent risk of deficiencies. High intake of saturated fats and cholesterol as well as low intake of dietary fiber remains a concern.
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34.
  • Hagström, Hannes, et al. (author)
  • Overweight in late adolescence predicts development of severe liver disease later in life : A 39 years follow-up study
  • 2016
  • In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 65:2, s. 363-368
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: The increased prevalence of overweight has been suggested to contribute to the worldwide increase in liver diseases. We investigated if body mass index (BMI) in late adolescence predicts development of severe liver disease later in life.METHODS: We performed a cohort study using data from 44,248 men (18-20years) conscribed to military service in Sweden between 1969 and 1970. Outcome data were collected from national registers to identify any diagnosis of severe liver disease (i.e., diagnosis of decompensated liver disease, cirrhosis or death in liver disease) until the end of 2009. A Cox regression model was applied using BMI as independent variable. The model was adjusted for use of alcohol, use of narcotics, smoking, high blood pressure and cognitive ability at time of conscription.RESULTS: During a follow-up period of a mean of 37.8years, 393 men were diagnosed with severe liver disease (mean time to diagnosis 24.7years). BMI (Hazard ratio [HR]=1.05 for each unit increase in BMI, 95% confidence interval [CI]: 1.01-1.09, p=0.008) and overweight (HR=1.64 for BMI 25-30 compared to BMI 18.5-22.5, 95% CI: 1.16-2.32, p=0.006) were associated with an increased risk of development of severe liver disease.CONCLUSIONS: Being overweight in late adolescence is a significant predictor of severe liver disease later in life in men.LAY SUMMARY: We investigated close to 45,000 Swedish men in their late teens enlisted for conscription in 1969-1970. After almost 40years of follow-up, we found that being overweight was a risk factor for developing severe liver disease, independent of established risk factors such as alcohol consumption.
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35.
  • Hagström, Hannes, et al. (author)
  • Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease
  • 2020
  • In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 73:5, s. 1023-1029
  • Journal article (peer-reviewed)abstract
    • Background & Aims: It is unclear whether the identification of individuals at risk of cirrhosis using non-invasive tests can be improved by repeated measurements. Herein, we tested whether repeated measurements of fibrosis-4 index (FIB-4) could improve the identification of individuals at risk of severe liver disease.Methods: Data were derived from the population-based Swedish AMORIS cohort with baseline examinations from 1985-1996. FIB4 was calculated at 2 time points within 5 years. Thereafter, we associated changes in FIB-4 with outcomes. Incident severe liver disease data was ascertained through linkage to Swedish national registers until 2011. Hazard ratios (HRs) and CIs for outcomes were calculated using Cox regression.Results: Of 126,942 individuals with available FIB-4 data, 40,729 (32.1%) underwent a second test within 5 years (mean interval 2.4 years). During 613,376 person-years of follow-up, 581 severe liver disease events were documented (0.95/1,000 person-years). An increase of 1 unit in FIB-4 was associated with an elevated risk of severe liver disease (adjusted hazard ratio [aHR] 1.81; 95% CI 1.67-1.96). Transitioning from a low-or intermediate-to a high-risk group was associated with an increased risk of severe liver disease compared with those consistently in the low-risk group (aHR 7.99 and 8.64, respectively). A particularly increased risk of severe liver disease was found in individuals defined as high risk at both tests (aHR 17.04; 95% CI 11.67-24.88). However, almost half of all events occurred in those consistently in the low-risk group.Conclusions: Repeated testing of FIB-4 within 5 years improves the identification of individuals at an increased risk of severe liver disease in the general population. However, the sensitivity is comparatively low and improved tests are needed for screening in a general population or primary care setting.Lay summary: The fibrosis-4 scoring system is often used to estimate the risk of advanced fibrosis in liver diseases. Herein, we found that changes in this score over time are associated with the risk of future severe liver disease in a population-based cohort. However, even if the prediction is improved by repeated testing, the overall ability of the score to predict future events is relatively low.
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36.
  •  
37.
  • Hagström, Hannes, et al. (author)
  • Risk Behaviors Associated with Alcohol Consumption Predict Future Severe Liver Disease
  • 2019
  • In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 64:7, s. 2014-2023
  • Journal article (peer-reviewed)abstract
    • BackgroundExcess consumption of alcohol can lead to cirrhosis, but it is unclear whether the type of alcohol and pattern of consumption affects this risk.AimsWe aimed to investigate whether type and pattern of alcohol consumption early in life could predict development of severe liver disease.MethodsWe examined 43,242 adolescent men conscribed to military service in Sweden in 1970. Self-reported data on total amount and type of alcohol (wine, beer, and spirits) and risk behaviors associated with heavy drinking were registered. Population-based registers were used to ascertain incident cases of severe liver disease (defined as cirrhosis, decompensated liver disease, liver failure, hepatocellular carcinoma, or liver-related mortality). Cox regression models were used to estimate hazard ratios for development of severe liver disease.ResultsDuring follow-up, 392 men developed severe liver disease. In multivariable analysis, after adjustment for BMI, smoking, use of narcotics, cardiovascular fitness, cognitive ability, and total amount of alcohol, an increased risk for severe liver disease was found in men who reported drinking alcohol to alleviate a hangover (“eye-opener”; aHR 1.47, 95% CI 1.02–2.11) and men who reported having been apprehended for being drunk (aHR 2.17, 95% CI 1.63–2.90), but not for any other risk behaviors. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.ConclusionsCertain risk behaviors can identify young men with a high risk of developing severe liver disease. Wine consumption was not associated with a reduced risk for severe liver disease compared to beer and spirits.
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38.
  • Hagström, Hannes, et al. (author)
  • Risk of infections and their role on subsequent mortality in biopsy-proven alcohol-related liver disease
  • 2022
  • In: United European Gastroenterology journal. - : John Wiley & Sons. - 2050-6406 .- 2050-6414. ; 10:2, s. 198-211
  • Journal article (peer-reviewed)abstract
    • Background and Aims: The risk for infection in alcohol-related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital-based infections in a nationwide cohort of biopsy-proven ALD, and the subsequent risk of death.Methods: Population-based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals.Results: Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person-years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85-3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36-3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89-4.78) were linked to subsequent death.Conclusions: Individuals with biopsy-proven ALD have a three-fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.
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39.
  • Hagström, Josefin, et al. (author)
  • Adolescents Identifying Errors and Omissions in Their Electronic Health Records : A National Survey
  • 2023
  • In: Caring is Sharing. - : IOS Press. - 9781643683881 - 9781643683898 ; 302, s. 242-246
  • Conference paper (peer-reviewed)abstract
    • Patient accessible electronic health records (PAEHRs) have been proposed as a means to improve patient safety and documentation quality, as patients become an additional source to detect mistakes in the records. In pediatric care, healthcare professionals (HCP) have noted a benefit of parent proxy users correcting errors in their child's records. However, the potential of adolescents has so far been overlooked, despite reports of reading records to ensure accuracy. The present study examines errors and omissions identified by adolescents, and whether patients reported following up with HCPs. Survey data was collected during three weeks in January and February 2022 via the Swedish national PAEHR. Of 218 adolescent respondents, 60 reported having found an error (27.5%) and 44 (20.2%) had found missing information. Most adolescents did not take any action upon identifying an error or an omission (64.0%). Omissions were more often perceived as serious than errors. These findings call for development of policy and PAEHR design that facilitates reports of errors and omissions for adolescents, which could both improve trust and support the individual's transition into an involved and engaged adult patient.
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40.
  • Hagström, Lina, et al. (author)
  • Miljöparametern i CAD-verktyg
  • 2003
  • Reports (other academic/artistic)abstract
    • För att få miljöaspekter att bli en beslutsparameter under tidiga stadier i produktutvecklingn krävs effektiva och snabba hjälpmedel som kan användas av konstruktörer och produktutvecklare. Idag finns inget konkret hjälpmedel för att bedöma miljöaspekter direkt i produktutvecklingen vilket var anledningen till att projektet Miljöparametern i CAD-verktyg startade.
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41.
  • Heby, Margareta, et al. (author)
  • Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas
  • 2020
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.
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42.
  • Huang, Peng, et al. (author)
  • Molecular basis for human aquaporin inhibition
  • 2024
  • In: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:7
  • Journal article (peer-reviewed)abstract
    • Cancer invasion and metastasis are known to be potentiated by the expression of aquaporins (AQPs). Likewise, the expression levels of AQPs have been shown to be prognostic for survival in patients and have a role in tumor growth, edema, angiogenesis, and tumor cell migration. Thus, AQPs are key players in cancer biology and potential targets for drug development. Here, we present the single-particle cryo-EM structure of human AQP7 at 3.2-Å resolution in complex with the specific inhibitor compound Z433927330. The structure in combination with MD simulations shows that the inhibitor binds to the endofacial side of AQP7. In addition, cancer cells treated with Z433927330 show reduced proliferation. The data presented here serve as a framework for the development of AQP inhibitors.
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43.
  • Hyrenius-Wittsten, Axel, et al. (author)
  • De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia
  • 2018
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD, FLT3 N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells. We identify acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 in KMT2A-MLLT3 leukemia cells that favored clonal expansion. During clonal evolution, we observe serial genetic changes at the Kras G12D locus, consistent with a strong selective advantage of additional Kras G12D . KMT2A-MLLT3 leukemias with signaling mutations enforce Myc and Myb transcriptional modules. Our results provide new insight into the biology of KMT2A-R leukemia with subclonal signaling mutations and highlight the importance of activated signaling as a contributing driver.
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44.
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45.
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46.
  • Hägglund, Maria, Lektor, 1975-, et al. (author)
  • A Nordic Perspective on Patient Online Record Access and the European Health Data Space
  • 2024
  • In: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 26:1
  • Journal article (peer-reviewed)abstract
    • The Nordic countries are, together with the United States, forerunners in online record access (ORA), which has now become widespread. The importance of accessible and structured health data has also been highlighted by policy makers internationally. To ensure the full realization of ORA’s potential in the short and long term, there is a pressing need to study ORA from a cross-disciplinary, clinical, humanistic, and social sciences perspective that looks beyond strictly technical aspects. In this viewpoint paper, we explore the policy changes in the European Health Data Space (EHDS) proposal to advance ORA across the European Union, informed by our research in a Nordic-led project that carries out the first of its kind, large-scale international investigation of patients’ ORA—NORDeHEALTH (Nordic eHealth for Patients: Benchmarking and Developing for the Future). We argue that the EHDS proposal will pave the way for patients to access and control third-party access to their electronic health records. In our analysis of the proposal, we have identified five key principles for ORA: (1) the right to access, (2) proxy access, (3) patient input of their own data, (4) error and omission rectification, and (5) access control. ORA implementation today is fragmented throughout Europe, and the EHDS proposal aims to ensure all European citizens have equal online access to their health data. However, we argue that in order to implement the EHDS, we need more research evidence on the key ORA principles we have identified in our analysis. Results from the NORDeHEALTH project provide some of that evidence, but we have also identified important knowledge gaps that still need further exploration.
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47.
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48.
  • Hägglund, Maria, et al. (author)
  • NORDeHEALTH – Learning from the Nordic Experiences of Patient Online Record Access
  • 2023
  • In: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871.
  • Journal article (other academic/artistic)abstract
    • The Nordic countries are forerunners in online record access (ORA) which has now become widespread. The importance of accessible and structured health data has also been highlighted by policymakers internationally. To ensure the full realization of ORA’spotential in the short and long term, there is a pressing need to study ORA from a cross-disciplinary, technical, clinical, humanistic, and social sciences perspective that looks beyond strictly technical aspects. In this viewpoint paper, we explore the policy changes in the European Health Data Space (EHDS) proposal to advance ORA across the European Union, and introduce a Nordic-led research project that carries out the first of its kind, large-scale international investigation of patients’ ORA; NORDeHEALTH. We argue that the EHDS proposal will pave the way for patients to access and control third-party access to their electronic health records (EHRs). This will have implications within Europe and globally as it will further extend the boundaries for accessing and using EHRs for primary and secondary data use. Research such as that led by the NORDeHEALTH project is essential in guiding the design and implementation of solutions to meet the requirements of the EHDS proposal. Further international collaboration and research are needed to ensure that socio-technical and contextual factors are considered to ensure successful and secure implementation.
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49.
  • Hägglund, Maria, Lektor, 1975-, et al. (author)
  • The NORDeHEALTH 2022 Patient Survey : Cross-Sectional Study of National Patient Portal Users in Norway, Sweden, Finland, and Estonia
  • 2023
  • In: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 25
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Although many surveys have been conducted on patients accessing their own health records in recent years, there is a limited amount of nationwide cross-country data available on patients' views and preferences. To address this gap, an international survey of patient users was conducted in the Nordic eHealth project, NORDeHEALTH. OBJECTIVE: We aimed to investigate the sociodemographic characteristics and experiences of patients who accessed their electronic health records (EHRs) through national patient portals in Norway, Sweden, Finland, and Estonia. METHODS: A cross-sectional web-based survey was distributed using the national online health portals. The target participants were patients who accessed the national patient portals at the start of 2022 and who were aged ≥15 years. The survey included a mixture of close-ended and free-text questions about participant sociodemographics, usability experience, experiences with health care and the EHR, reasons for reading health records online, experience with errors, omissions and offense, opinions about security and privacy, and the usefulness of portal functions. In this paper, we summarized the data on participant demographics, past experience with health care, and the patient portal through descriptive statistics. RESULTS: In total, 29,334 users completed the survey, of which 9503 (32.40%) were from Norway, 13,008 (44.35%) from Sweden, 4713 (16.07%) from Finland, and 2104 (7.17%) from Estonia. National samples were comparable according to reported gender, with about two-thirds identifying as women (19,904/29,302, 67.93%). Age distributions were similar across the countries, but Finland had older users while Estonia had younger users. The highest attained education and presence of health care education varied among the national samples. In all 4 countries, patients most commonly rated their health as "fair" (11,279/29,302, 38.48%). In Estonia, participants were more often inclined to rate their health positively, whereas Norway and Sweden had the highest proportion of negative health ratings. Across the whole sample, most patients received some care in the last 2 years (25,318/29,254, 86.55%). Mental health care was more common (6214/29,254, 21.24%) than oncological care (3664/29,254, 12.52%). Overall, most patients had accessed their health record "2 to 9 times" (11,546/29,306, 39.4%), with the most frequent users residing in Sweden, where about one-third of patients accessed it "more than 20 times" (4571/13,008, 35.14%). CONCLUSIONS: This is the first large-scale international survey to compare patient users' sociodemographics and experiences with accessing their EHRs. Although the countries are in close geographic proximity and demonstrate similar advancements in giving their residents online records access, patient users in this survey differed. We will continue to investigate patients' experiences and opinions about national patient-accessible EHRs through focused analyses of the national and combined data sets from the NORDeHEALTH 2022 Patient Survey. 
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50.
  • Ishchuk, Olena P., et al. (author)
  • Novel centromeric loci of the wine and beer yeast dekkera bruxellensis CEN1 and CEN2
  • 2016
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
  • Journal article (peer-reviewed)abstract
    • The wine and beer yeast Dekkera bruxellensis thrives in environments that are harsh and limiting, especially in concentrations with low oxygen and high ethanol. Its different strains' chromosomes greatly vary in number (karyotype). This study isolates two novel centromeric loci (CEN1 and CEN2), which support both the yeast's autonomous replication and the stable maintenance of plasmids. In the sequenced genome of the D. bruxellensis strain CBS 2499, CEN1 and CEN2 are each present in one copy. They differ from the known "point" CEN elements, and their biological activity is retained within ~900-1300 bp DNA segments. CEN1 and CEN2 have features of both "point" and "regional" centromeres: They contain conserved DNA elements, ARSs, short repeats, one tRNA gene, and transposon-like elements within less than 1 kb. Our discovery of a miniature inverted-repeat transposable element (MITE) next to CEN2 is the first report of such transposons in yeast. The transformants carrying circular plasmids with cloned CEN1 and CEN2 undergo a phenotypic switch: They form fluffy colonies and produce three times more biofilm. The introduction of extra copies of CEN1 and CEN2 promotes both genome rearrangements and ploidy shifts, with these effects mediated by homologous recombination (between circular plasmid and genome centromere copy) or by chromosome breakage when integrated. Also, the proximity of the MITE-like transposon to CEN2 could translocate CEN2 within the genome or cause chromosomal breaks, so promoting genome dynamics. With extra copies of CEN1 and CEN2, the yeast's enhanced capacities to rearrange its genome and to change its gene expression could increase its abilities for exploiting new and demanding niches.
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