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1.
  • Almstedt, Elin, 1988-, et al. (author)
  • Integrative discovery of treatments for high-risk neuroblastoma
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.
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  • Castell, Alina, et al. (author)
  • MYCMI-7 : A Small MYC-Binding Compound that Inhibits MYC: MAX Interaction and Tumor Growth in a MYC-Dependent Manner
  • 2022
  • In: Cancer Research Communications. - : American Association For Cancer Research (AACR). - 2767-9764. ; 2:3, s. 182-201
  • Journal article (peer-reviewed)abstract
    • Deregulated expression of MYC family oncogenes occurs frequently in human cancer and is often associated with aggressive disease and poor prognosis. While MYC is a highly warranted target, it has been considered "undruggable," and no specific anti-MYC drugs are available in the clinic. We recently identified molecules named MYCMIs that inhibit the interaction between MYC and its essential partner MAX. Here we show that one of these molecules, MYCMI-7, efficiently and selectively inhibits MYC:MAX and MYCN:MAX interactions in cells, binds directly to recombinant MYC, and reduces MYC-driven transcription. In addition, MYCMI-7 induces degradation of MYC and MYCN proteins. MYCMI-7 potently induces growth arrest/apoptosis in tumor cells in a MYC/MYCN-dependent manner and downregulates the MYC pathway on a global level as determined by RNA sequencing. Sensitivity to MYCMI-7 correlates with MYC expression in a panel of 60 tumor cell lines and MYCMI-7 shows high efficacy toward a collection of patient-derived primary glioblastoma and acute myeloid leukemia (AML) ex vivo cultures. Importantly, a variety of normal cells be- come G1 arrested without signs of apoptosis upon MYCMI-7 treatment. Finally, in mouse tumor models of MYC-driven AML, breast cancer, and MYCN-amplified neuroblastoma, treatment with MYCMI-7 downregu- lates MYC/MYCN, inhibits tumor growth, and prolongs survival through apoptosis with few side effects. In conclusion, MYCMI-7 is a potent and selective MYC inhibitor that is highly relevant for the development into clinically useful drugs for the treatment of MYC-driven cancer.Significance: Our findings demonstrate that the small-molecule MYCMI-7 binds MYC and inhibits interaction between MYC and MAX, thereby ham- pering MYC-driven tumor cell growth in culture and in vivo while sparing normal cells.
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  • Nysæter, Toril Merete, et al. (author)
  • Preferences for home care to enable home death among adult patients with cancer in late palliative phase - a grounded theory study
  • 2022
  • In: BMC Palliative Care. - : BioMed Central (BMC). - 1472-684X. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Background: The wish to be cared for and to die at home is common among people with end-stage cancer in the western world. However, home deaths are declining in many countries. The aim of this study was to explore the pref‑ erences for home care over time to enable home death among adult patients with cancer in the late palliative phase.Methods: A qualitative method was applied according to grounded theory (Corbin & Strauss, 2008). Data was collected using individual interviews (n=15) with nine adult patients. One to two follow up interviews were conducted with four patients. Sampling, data collection and constant comparative analysis were undertaken simultaneously.Results: The findings are presented as a conceptual model of patients’ preferences for care to enable home death. The core category “Hope and trust to get the care I need to die at home” showed that the preference to die at home seemed stable over time and did not change with deterioration in health status and progression in illness. Five cat‑ egories were related to the core category. The categories “being in the present”, “be safe and in charge” and “be seen and acknowledged” describe the patients’ preferences to live a meaningful life until death and be the same person as always. These preferences depended on the categories describing characteristics of healthcare personnel and the organisation of care: “reliable, compassionate and competent healthcare personnel” and “timely, predictive, continuous and adaptive organisation”.Conclusion: An important preference over time was to be here and now and to live as meaningful a life as possible until death. Moreover, the patients preferred to retain control over their lives, to be autonomous and to be seen as the person they had always been. To achieve this, person-centred care provided by healthcare personnel with competence, skills and enough/ample time were required. In addition, home care needed to be organised in a way that ensured continuity and predictability. Systematic implementation of a person-centred care model and the use of advanced home care plans with continued re-evaluation for patients’ preferences of home care were proposed measures to enable home death.
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  • Olsson, Cecilia, 1971-, et al. (author)
  • Adaption of the Quality From the Patient’s Perspective Instrument for Use in Assessing Gynecological Cancer Care and Patients’ Perceptions of Quality Care Received
  • 2022
  • In: Cancer Care Research Online. - : Wolters Kluwer. - 2691-3623. ; 2:1
  • Journal article (peer-reviewed)abstract
    • Background: Research focusing on patients’ perceptions of the quality of gynecological cancer care is needed.Objective: To adapt the Quality from the Patient’s Perspective instrument for use in gynecological cancer care (QPP-GynCa) and describe patients’ perceptions of their quality of care in terms of the care received and the subjective importance of the aspects of care.Methods: A cross-sectional study 6–8 months after diagnosis was conducted, involving 1511 patients (response rate of 50.4%) included in the Swedish quality registry for gynecologic cancer.Results: The exploratory factor analysis (n = 1431) resulted in the QPP-GynCa with a 5-factor structure and an eigenvalue of ≥1, explaining 73.1% of the total scale variance. The final 27-item version of the QPP-GynCa consisted of 18 items with 8 additional single items and 1 global single item. The Cronbach’s alpha was acceptable for most factors (>.80). Subjective importance scores were higher than corresponding quality of care scores for care received (P ≤ .01)in all dimensions, factors, and items.Conclusions: The QPP-GynCa instrument reflects all 4 dimensions of the theoretical model of quality of care and achieved good validity as a reliable instrument in assessing the quality of gynecological cancer care.Implication for Practice: Information related to self-care, aspects of sexuality, and reducing patient waiting times need improvement.What Is Foundational: This study contributes to a better understanding of quality of gynecological cancer treatment and care. The validated QPP-GynCa instrument will be a platform for more research on how this group of patients experience their received care, as well as importance of each aspect of care.
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  • Olsson, Cecilia, 1971-, et al. (author)
  • Healthcare professionals’ perceptions of palliative care quality in a combined acute oncology-palliative care unit: A cross-sectional study
  • 2021
  • In: Nordic journal of nursing research. - : Sage Publications. - 2057-1585 .- 2057-1593. ; 41:3, s. 121-130
  • Journal article (peer-reviewed)abstract
    • It is a challenge to ensure high-quality palliative care. The aim was to investigate the perceptions of health care professionals(HCPs) working in a combined acute oncology-palliative care unit regarding the quality of the palliative care received by thepatients and how important the care was to the patients. A Swedish total-survey cross-sectional study including 41 HCPs (54%response rate) was conducted with the 52 items Quality from the Patient’s Perspective – Palliative Care instrument, answeredin two different ways: as actual care received and subjective importance. The STROBE-checklist was used. The areas forimprovements were related to symptom relief, spiritual and existential needs, information, patient participation, continuity ofcare, care planning, cooperation and coordination of care, as subjective importance scores were higher than correspondingscores for care received (p .025). Providing high-quality palliative care alongside curative treatments for cancer patients isknown to be challenging and could explain the results in this study. Implementation of a person-centred palliative care modelbased on the hospice philosophy could be a solution.
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  • Allmänningen
  • 2024
  • Artistic workabstract
    • Utställningen Allmänningen handlar om våra gemensamma rum. De torg, stråk och gröningar dit allmänheten idag har tillträde. Mellan tätort och landsbygd, längs med åar och vattendrag, via våtmarker och kulturminnesplatser, över höjder och ängsmarker. Det är platser för demokrati, kulturellt utbyte, handel och rekreation.I utställningen Allmänningen möts historiska spår, planerare och några nedgrävda kartor. Genom olika kartläggningspraktiker som rör sig mellan plats och representation visas hur allmänningen som fenomen har transformerats över tid. Den har genomgått ett antal olika förändringar och människor har trots dessa skiften alltid tagit platser i anspråk: gröningar, gator, parker, stråk, torg – på landsbygd, i tätort, längs med åar och vattendrag, via våtmarker och kulturminnesplatser, över höjder och ängsmarker. Det är platser för demokrati, kulturellt utbyte, handel och vila. Här presenteras allmänningen som ett begrepp, som fysisk plats och kulturell enhet. Från kroppens intima skala till värderingen och regleringen av mark. Utställningen är kopplad till forskningsprojektet Allmänningar och stråk för rumslig rättvisa i urban fullåkersbygd finansierat av forskningsrådet FORMAS.
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  • Bazsefidpay, Nikoo, 1984-, et al. (author)
  • Antibiotic prescription in bone augmentation and dental implant procedures : a multi-center study
  • 2023
  • In: BMC Oral Health. - : BioMed Central (BMC). - 1472-6831. ; 23:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Adherence to antibiotic recommendations and safety aspects of restrictive use are important components when combating antibiotic resistance. The primary aim of this study was to assess the impact of national guidelines on antibiotic prescriptions for bone augmentation procedures among dentists working at three specialized clinics. The secondary aim was to assess the occurrence of postoperative infections.METHODS: Medical charts of 400 patients treated with bone augmentation were reviewed: 200 in the years 2010-2011 and 200 in 2014-2015. The Swedish national recommendations for antibiotic prophylaxis were published in 2012.RESULTS: There was a wide variation in antibiotic regiments prescribed throughout the study. The number of patients treated with antibiotic prophylaxis in a single dose of 2 g amoxicillin, and treated as advocated in the national recommendations, was low and decreasing between the two time periods from 25% (n = 50/200) in 2010-2011 to 18.5% (n = 37/200) in 2014-2015. The number of patients not given any antibiotics either as a prophylactic single dose or during the postoperative phase increased (P < 0.001). The administration of a 3-7-days antibiotic prescription increased significantly from 25.5% in 2010-2011 to 35% in 2014-2015. The postoperative infection rates (4.5% and 6.5%) were without difference between the studied periods. Smoking and omitted antibiotic prophylaxis significantly increased the risk of postoperative infection. Logistic regression analyses showed that patient male gender and suffering from a disease were predictive factors for the clinician to adhere to the guidelines.CONCLUSIONS: After introduction of national recommendations for antibiotic prophylaxis before bone augmentation procedures, the patient group receiving a single preoperative dose decreased while the group not given antibiotic prophylaxis increased. There was no difference in occurrence of postoperative infections between the two time periods. The results indicate a need for educational efforts and strategies for implementation of antibiotic prudence and awareness among surgeons performing bone augmentation procedures.
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  • Bergersen, Emily Beatrice, et al. (author)
  • Adolescents' and young people's needs and preferences for support when living with a parent with life-threatening cancer : a grounded theory study
  • 2022
  • In: BMC Palliative Care. - : BMC. - 1472-684X. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Background Living with a parent facing life-threatening illness and losing a mom or dad at a young age can cause both short- and long-term health problems. Without satisfactory support, adolescents' and young people are at risk of developing low self-esteem, behavioural difficulties (e.g., anger and aggression), long-term illness or premature death caused by severe mental illness, substance abuse, self-harm and suicide attempts. The aim of this study was to explore adolescents' and young people's needs and preferences for support as they live with a parent with life-threatening cancer. Methods Qualitative interviews were conducted with 10 respondents (17-24 years) in Norway and Sweden. Data were analysed through grounded theory according to Charmaz. Results Adolescents' and young peoples' needs and preferences for support were described through the main category 'To feel safe and secure and to be prepared' and further broken down into five subcategories 'Relationships in the immediate family-balancing support and protection'; 'The social network-support and normalcy in a carefully selected group'; 'Maintaining everyday life-challenges in school and working life'; 'The right support at the right time-competence, trust and continuity in meeting health care professionals'; and 'Support outside the home-an opportunity for full transparency'. Conclusion Adolescents' and young peoples' preferences for support when living with a parent facing life-threatening illness are individual and unique, but they share a common need to feel safe and secure and to be prepared. Adolescents and young people express that they primarily want support from parents and friends, but they also want support from health care professionals, especially in situations when the ill parent becomes worse. Therefore, it is of the utmost importance for health care professionals to identify the most vulnerable adolescents and young people by mapping their social networks and paying extra attention to their needs for support when there is deterioration in the parent's illness state. This study also highlights the importance for health care professionals to establish a good relationship with adolescents and young people to meet their needs and preferences for support. In addition, information and support are needed in a timely manner and adapted to the life-threatening ill parent's illness state and individual's needs and preferences to optimise preparedness.
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  • Bergersen, Emily Beatrice, et al. (author)
  • Children and adolescents' preferences for support when living with a dying parent : An integrative review
  • 2022
  • In: Nursing Open. - : Wiley. - 2054-1058. ; 9:3, s. 1536-1555
  • Journal article (peer-reviewed)abstract
    • Aim: To identify and synthesize the evidence base regarding children and adolescents' preferences for support when living with a dying parent. Design: Integrative literature review study. Methods: Searches were conducted in PubMed, CINAHL, PsycINFO, the Cochrane Library, Sociological Abstracts and Scopus, between 1 October 2019 and May 2021. Data were analysed and synthesized using integrative thematic analysis according to the analysis stages specified by Whittermore and Knafl. Results: Twenty-two articles were identified. Children and adolescents' preferences for support were described through one overarching theme, Striving to achieve control and balance, together with six subthemes; "Involvement in the sick parent's care and treatment"; "Wanting to be with the sick parent but needing respite"; "Information must be continuous and individually adapted"; "emotional and communicative support from parents and family members"; "professional, compassionate and informative support"; and "support in friendships and opportunities to maintain normality."
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  • Bergersen, Emily Beatrice (author)
  • When a parent is affected by a life-threatening illness : Exploring children’s and parents’ needs for support
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • This thesis explored the needs and preferences for support in families with children when one of the parents is affected by a life-threatening illness. In this thesis a variation of designs were used, from a literature review, to an interview study, a survey, and a long-term follow-up of an intervention. The results show that there are both individual and shared needs and preferences within a family when a parent has a life-threatening illness, and that HCP should adapt their approach to support accordingly. The children preferred practical and emotional involvement in their parent's illness, while at the same time needing respite and a sense of normality. Parents preferred more individualised illness-related information provided by the HCP, as well as more guidance on how to care for and support their children. Both children and parents who lack social support are particularly vulnerable. Therefore, it is important for healthcare personnel to systematically map families' social network. Moreover, continuous support should be offered throughout all stages of the parents' illness trajectory, including the time after death to meet their needs.
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  • Berggren, Johannes (author)
  • An important part of the whole : The role of metaphors in the teaching and learning of mathematics
  • 2022
  • Licentiate thesis (other academic/artistic)abstract
    • This study aims to investigate the role of metaphor in the teaching and learning of mathematics. Two different studies help to fulfil this aim.The first study involves a configurative literature review of empirical mathematics education research where two interpretations of the metaphor concept are applied: conceptual metaphor and extraneous metaphor, with the purpose of distinguishing patterns in metaphor concept use. The analysis found explicit, vague, or absent theoretical definitions of the metaphor concept as well as several metaphor examples, and generated three categories of concept use: 1) Conceptual metaphor, 2) Extraneous metaphor, and 3) Potentially conceptual/extraneous. The review stresses the need for a theoretical and empirical distinction between different types of metaphors, to sharpen the analytical tools available to researchers and, by extension, to more clearly highlight the specific function of metaphor in teachers’ classroom work.The second study examines the presence of three conceptual metaphors as the basis for rational numbers as fractions in Swedish textbooks for years 1–3 and which aspects of fractions are distinguished in the student responses required in these books. The results are related to process-object theory (Sfard, 1991), intending to discern the different degrees of reification of the mathematical objects that hypothetically have the opportunity to develop with the help of these metaphors. The results show, in three of the book series, an abundance of labelling exercises related to the metaphor Arithmetic is object construction, mainly with images of geometric shapes. One book series reversely introduces fractions with The measuring stick metaphor and Arithmetic is motion along a path, with representations of number lines in focus. All in all, there is a significant variation between the textbooks, which could have consequences for instruction.This thesis shows the importance of theoretically distinguishing conceptual metaphor from extraneous metaphor, and of understanding their different roles in a teaching and learning context. The thesis also shows how the conceptual metaphors underlying the mathematical concepts describe different aspects of these concepts and that several conceptual metaphors need to be taken into account, together with a consideration of different degrees of reification of the mathematical objects. In addition, the thesis shows that metaphors, as they are understood in Conceptual metaphor theory, point to similar conceptual and discursive processes that can be found in Sfard’s (1991, 2008) more established theories on mathematical conceptualisation.
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  • Bhattacharya, Pradyot, et al. (author)
  • Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
  • 2020
  • In: eLIFE. - Cambridge, United Kingdom : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
  • Journal article (peer-reviewed)abstract
    • HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complementopsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
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  • Bjuresäter, Kaisa, 1970-, et al. (author)
  • Self-reported Professional Competence Among Swedish Contact Nurses in Cancer Care : A Cross-sectional Study
  • 2022
  • In: Cancer Care Research Online. - : Wolters Kluwer. - 2691-3623. ; 2:3, s. e024-e024
  • Journal article (peer-reviewed)abstract
    • Background: Since 2011, patients in Swedish cancer care have been offered a contact nurse (CN). The CN role is to improve patient participation, care continuity, and provide information and manage patients’ symptoms and needs across the whole continuum of the cancer pathway. A competence profile for the CN role is yet to be developed, and it is important to assess CNs’ self-reported competence to assure that they are well equipped for the role.Objectives: To assess self-reported professional competence among contact nurses working in Swedish cancer care and relate the findings to education level and clinical experience.Methods: The Nurse Professional Competence scale short form (35 items) was used to assess the nurses’ professional competence. Data were collected through a web-based survey in 2017 in 2 regional cancer centers in Sweden.Results: One hundred eight CNs participated in the study and reported highest scores in “value-based nursing care” and lowest scores in “development, leadership, and organization of nursing care.” Higher age, extended clinical work experience, and academic degree were significantly associated with higher competence.Conclusions: CNs with extensive work experience and CNs with an academic degree reported higher scores concerning their generic competence. There is a need in future studies to assess CNs’ specific competence in cancer care.Implications for Practice: There is room for improvement in the competence development of CNs, primarily in the areas of leadership and organization of nursing care.What is Foundational: CNs’ competence regarding leadership and organization should be improved, preferably as part of academic education.
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  • Björkelund, Cecilia, 1948, et al. (author)
  • Effects of adding early cooperation and a work-place dialogue meeting to primary care management for sick-listed patients with stress-related disorders: CO-WORK-CARE-Stress - a pragmatic cluster randomised controlled trial.
  • 2024
  • In: Scandinavian journal of primary health care. - 1502-7724. ; , s. 1-15
  • Journal article (peer-reviewed)abstract
    • To investigate whether intensified cooperation between general practitioner (GP), care manager and rehabilitation coordinator (RC) for patients sick-listed for stress-related mental disorder, combined with a person-centred dialogue meeting with employer, could reduce sick-leave days compared with usual care manager contact.Pragmatic cluster-randomised controlled trial, randomisation at primary care centre (PCC) level.PCCs in Region Västra Götaland, Sweden, with care manager organisation.Of 30 invited PCCs, 28 (93%) accepted the invitation and recruited 258 patients newly sick-listed due to stress-related mental disorder (n=142 intervention, n=116 control PCCs).Cooperation between GP, care manager and rehabilitation coordinator from start of illness notification plus a person-centred dialogue meeting between patient and employer within 3months. Regular contact with care manager was continued at the control PCCs.12-months net and gross number of sick-leave days. Secondary outcomes: Symptoms of stress, depression, anxiety; work ability and health related quality of life (EQ-5D) over 12months.There were no significant differences between intervention and control groups after 12months: days on sick-leave (12-months net sick-leave days, intervention, mean = 110.7days (95% confidence interval (CI) 82.6-138.8); control, mean = 99.1days (95% CI 73.9-124.3)), stress, depression, or anxiety symptoms, work ability or EQ-5D. There were no significant differences between intervention and control groups concerning proportion on sick-leave after 3, 6, 12months. At 3months 64.8% were on sick-leave in intervention group vs 54.3% in control group; 6months 38% vs 32.8%, and12 months 16.9% vs 15.5%.Increased cooperation at the PCC between GP, care manager and RC for stress-related mental disorder coupled with an early workplace contact in the form of a person-centred dialogue meeting does not reduce days of sick-leave or speed up rehabilitation.Trial registration: ClinicalTrials.gov Identifier: NCT03250026 https://clinicaltrials.gov/study/NCT03250026?tab=results#publicationsCO-WORK-CAREFirst Posted: August 15, 2017. Recruitment of PCCs: September 2017. Inclusion of patients from December 2017.
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  • Björkelund, Cecilia, 1948, et al. (author)
  • Rehabilitation cooperation and person-centred dialogue meeting for patients sick-listed for common mental disorders: 12 months follow-up of sick leave days, symptoms of depression, anxiety, stress and work ability - a pragmatic cluster randomised controlled trial from the CO-WORK-CARE project.
  • 2023
  • In: BMJ open. - 2044-6055. ; 13:6
  • Journal article (peer-reviewed)abstract
    • To study whether early and enhanced cooperation within the primary care centres (PCC) combined with workplace cooperation via a person-centred employer dialogue meeting can reduce days on sick leave compared with usual care manager contact for patients on sick leave because of common mental disorders (CMD). Secondary aim: to study lapse of CMD symptoms, perceived Work Ability Index (WAI) and quality of life (QoL) during 12 months.Pragmatic cluster randomised controlled trial, randomisation at PCC level.28 PCCs in Region Västra Götaland, Sweden, with care manager organisation.30 PCCs were invited, 28 (93%) accepted invitation (14 intervention, 14 control) and recruited 341 patients newly sick-listed because of CMD (n=185 at intervention, n=156 at control PCCs).Complex intervention consisting of (1) early cooperation among general practitioner (GP), care manager and a rehabilitation coordinator, plus (2) a person-centred dialogue meeting between patient and employer within 3 months.regular contact with care manager.12 months net and gross number of sick leave days at group level.12 months depression, anxiety, stress symptoms, perceived WAI and QoL (EuroQoL-5 Dimensional, EQ-5D).No significant differences were found between intervention and control groups concerning days of sick leave (intervention net days of sick leave mean 102.48 (SE 13.76) vs control 96.29 (SE 12.38) p=0.73), return to work (HR 0.881, 95%CI 0.688 to 1.128), or CMD symptoms, WAI or EQ-5D after 12 months.It is not possible to speed up CMD patients' return to work or to reduce sick leave time by early and enhanced coordination among GP, care manager and a rehabilitation coordinator, combined with early workplace contact over and above what 'usual' care manager contact during 3 months provides.NCT03250026.
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20.
  • Björnfot, Cecilia, et al. (author)
  • Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
  • 2024
  • In: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
  • Journal article (peer-reviewed)abstract
    • White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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21.
  • Boke Olén, Niklas, et al. (author)
  • Effects of farm type on food production, landscape openness, grassland biodiversity, and greenhouse gas emissions in mixed agricultural-forestry regions
  • 2021
  • In: Agricultural Systems. - : Elsevier BV. - 0308-521X .- 1873-2267. ; 189
  • Journal article (peer-reviewed)abstract
    • Context: The global demand for food is expected to continue increasing for decades, which may drive both agricultural expansion and intensification. The associated environmental impacts are potentially considerable but will depend on how the agricultural sector develops. Currently, there are contrasting regional developments in agriculture; expansion and/or intensification in some regions and abandonment in others, as well as changes in the type of farming. However, the environmental consequences of changes in farm type are not well understood. Objective: We have evaluated the impacts of farm type on food production and three key environmental variables—landscape openness, grassland biodiversity and greenhouse gas (GHG) emissions—in three marginal agricultural regions in Sweden. Methods: We do this by first dividing the population of farms in each region into types, based on their land-use and livestock holdings using an innovative clustering method. Thereafter we analysed changes in production activities for farm types over time and evaluated the environmental and food-production impacts, where landscape openness is quantified using a novel indicator. Results and conclusion: Our results show that there is not one single farm type that would simultaneously maximize food production, grassland biodiversity, and landscape openness, whilst minimizing GHG emissions. However, there exists considerable potential to manage the trade-offs between food production and these environmental variables. For example, by reducing land use for dairying and instead increasing both cropping for food production and extensive livestock grazing to maintain landscape openness and biodiversity-rich semi-natural pastures, it would keep food production at similar levels. Significance: Our farm typology allows us to assess the multifunctionality of farming, by relating contrasting production activities to multiple ecosystem services, grassland biodiversity and GHG emissions for informing policy towards more sustainable agriculture. We have demonstrated this with examples under Swedish conditions, but it should to a large extent also be applicable for other countries.
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  • Brew, Bronwyn K., et al. (author)
  • Maternal mental health disorders and offspring asthma and allergic diseases : The role of child mental health
  • 2024
  • In: Pediatric Allergy and Immunology. - : Munksgaard Forlag. - 0905-6157 .- 1399-3038. ; 35:2
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders.METHOD: The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders.RESULTS: Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma.CONCLUSION: The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.
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23.
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24.
  • Brueffer, Christian, et al. (author)
  • The Mutational Landscape of the SCAN-B Real-World Primary Breast Cancer Transcriptome
  • 2020
  • Other publication (other academic/artistic)abstract
    • Breast cancer is a disease of genomic alterations, of which the complete panorama of somatic mutations and how these relate to molecular subtypes and therapy response is incompletely understood. Within the Sweden Cancerome Analysis Network–Breast project (SCAN-B; ClinicalTrials.govNCT02306096), an ongoing study elucidating the tumor transcriptomic profiles for thousands of breast cancers prospectively, we developed an optimized pipeline for detection of single nucleotide variants and small insertions and deletions from RNA sequencing (RNA-seq) data, and profiled a large real-world population-based cohort of 3,217 breast tumors. We use it to describe the mutational landscape of primary breast cancer viewed through the transcriptome of a large population-based cohort of patients, and relate it to patient overall survival. We demonstrate that RNA-seq can be used to call mutations in important breast cancer genes such asPIK3CA,TP53, andERBB2, as well as the status of key molecular pathways and tumor mutational burden, and identify potentially druggable genes in 86.8% percent of tumors. To make this rich and growing mutational portraiture of breast cancer available for the wider research community, we developed an open source web-based application, the SCAN-B MutationExplorer, accessible athttp://oncogenomics.bmc.lu.se/MutationExplorer. These results add another dimension to the use of RNA-seq as a potential clinical tool, where both gene expression-based and gene mutation-based biomarkers can be interrogated simultaneously and in real-time within one week of tumor sampling.
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25.
  • Brueffer, Christian, et al. (author)
  • The mutational landscape of the SCAN‐B real‐world primary breast cancer transcriptome
  • 2020
  • In: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 12:10
  • Journal article (peer-reviewed)abstract
    • Breast cancer is a disease of genomic alterations, of which the panorama of somatic mutations and how these relate to subtypes and therapy response is incompletely understood. Within SCAN‐B (ClinicalTrials.gov: NCT02306096), a prospective study elucidating the transcriptomic profiles for thousands of breast cancers, we developed a RNA‐seq pipeline for detection of SNVs/indels and profiled a real‐world cohort of 3,217 breast tumors. We describe the mutational landscape of primary breast cancer viewed through the transcriptome of a large population‐based cohort and relate it to patient survival. We demonstrate that RNA‐seq can be used to call mutations in genes such as PIK3CA, TP53, and ERBB2, as well as the status of molecular pathways and mutational burden, and identify potentially druggable mutations in 86.8% of tumors. To make this rich dataset available for the research community, we developed an open source web application, the SCAN‐B MutationExplorer (http://oncogenomics.bmc.lu.se/MutationExplorer). These results add another dimension to the use of RNA‐seq as a clinical tool, where both gene expression‐ and mutation‐based biomarkers can be interrogated in real‐time within 1 week of tumor sampling.
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26.
  • Caffrey Osvald, Emma, et al. (author)
  • Asthma and all-cause mortality in children and young adults : a population-based study
  • 2020
  • In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 75:12, s. 1040-1046
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Studies suggest an increased all-cause mortality among adults with asthma. We aimed to study the relationship between asthma in children and young adults and all-cause mortality, and investigate differences in mortality rate by also having a life-limiting condition (LLC) or by parental socioeconomic status (SES).METHODS: Included in this register-based study are 2 775 430 individuals born in Sweden between January 1986 and December 2012. We identified asthma cases using the National Patient Register (NPR) and the Prescribed Drug Register. Those with LLC were identified using the NPR. Parental SES at birth (income and education) was retrieved from Statistics Sweden. We estimated the association between asthma and all-cause mortality using a Cox proportional hazards regression model. Effect modification by LLC or parental SES was studied using interaction terms in the adjusted model.RESULTS: The adjusted hazard rate (adjHR) for all-cause mortality in asthma cases versus non-asthma cases was 1.46 (95% CI 1.33 to 1.62). The highest increased rate appeared to be for those aged 5-15 years. In persons with asthma and without LLC, the adjHR remained increased at 1.33 (95% CI 1.18 to 1.50), but differed (p=0.002) from those with asthma and LLC, with an adjHR of 1.87 (95% CI 1.57 to 2.22). Parental SES did not alter the association (income, p=0.55; education, p=0.83).CONCLUSION: This study shows that asthma is associated with an increased mortality in children and young adults regardless of LLC or parental SES. Further research is warranted to investigate the possible mechanisms for this association.
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27.
  • Caffrey Osvald, Emma, et al. (author)
  • Parental socioeconomic status and asthma in children : using a population-based cohort and family design
  • 2022
  • In: Clinical and Experimental Allergy. - : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 52:1, s. 94-103
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The observed association between the parental socioeconomic status (SES, measured as education/income) and asthma or wheezing in offspring may be explained by confounding of unmeasured factors (shared genes and family environment). We aimed to study the association between parental SES and asthma/wheeze using cousin-comparison.METHOD: Data was collected on individuals born in Sweden 2001-2013. Parental SES (education and income) was gathered from Statistics Sweden. Asthma/wheeze was identified using national health registers. The association between parental SES at birth and incident asthma/wheeze was estimated using Cox regression also comparing differently exposed cousins. The association between parental SES at five years and current asthma was estimated using logistic regression.RESULTS: Included were 955 371 individuals. Mothers with compulsory school only (lowest education group) compared to those with further education (highest education group) was associated with incident asthma/wheeze below one year of age HRadj=1.45(1.38-1.52) and over one year of age HRadj=1.17(1.13-1.20). The corresponding estimates for the lowest income group were HRadj=1.61(1.54-1.69) and HRadj=0.94(0.92-0.97) respectively. In maternal cousin-comparisons, the associations for asthma/wheeze over one year of age was HRadj=1.21(1.05-1.40) for compulsory school only and HRadj=0.94 (0.84-1.07) for the lowest income group. The ORadj for current asthma at five years was 1.05(1.00-1.11) for mother's compulsory school only and 0.98(0.94-1.02) for mother's lowest income group. Results for estimates were similar for father's SES.CONCLUSION: We confirm an association between low parental SES (measured as education) and asthma/wheeze. Cousin-comparison suggests that this association is not wholly due to confounding of unknown familial factors, therefore supporting a causal relationship. The relationship between parental income and asthma/wheeze is less clear. This study is important for understanding risk factors for asthma/wheeze and for future prevention strategies. Further research is warranted to investigate the possible mechanisms for association between parental education and asthma/wheeze.
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28.
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29.
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30.
  • Dahlgren, Malin, et al. (author)
  • Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer
  • 2021
  • In: JNCI Cancer Spectrum. - : Oxford University Press (OUP). - 2515-5091. ; 5:2
  • Journal article (peer-reviewed)abstract
    • More than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy (ET). Recently, mutations in ESR1 were identified as acquired mechanisms of resistance to ET, found in 12% to 55% of metastatic breast cancers treated previously with ET. We analyzed 3217 population-based invasive primary (nonmetastatic) breast cancers (within the SCAN-B study, ClinicalTrials.gov NCT02306096), sampled from initial diagnosis prior to any treatment, for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by droplet digital polymerase chain reaction on tumor and normal DNA. Patient outcomes were analyzed using Kaplan-Meier estimation and a series of 2-factor Cox regression multivariable analyses. We identified ESR1 resistance mutations in 30 tumors (0.9%), of which 29 were ER positive (1.1%). In ET-treated disease, presence of ESR1 mutation was associated with poor relapse-free survival and overall survival (2-sided log-rank test P < .001 and P = .008, respectively), with hazard ratios of 3.00 (95% confidence interval = 1.56 to 5.88) and 2.51 (95% confidence interval = 1.24 to 5.07), respectively, which remained statistically significant when adjusted for other prognostic factors. These population-based results indicate that ESR1 mutations at diagnosis of primary breast cancer occur in about 1% of women and identify for the first time in the adjuvant setting that such preexisting mutations are associated to eventual resistance to standard hormone therapy. If replicated, tumor ESR1 screening should be considered in ER-positive primary breast cancer, and for patients with mutated disease, ER degraders such as fulvestrant or other therapeutic options may be considered as more appropriate.
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31.
  • Dahlgren, Mathias, et al. (author)
  • Uncertainty managing patients treated with antiresorptive drugs: a cross-sectional study of attitudes and self-reported behavior among dentists in Sweden
  • 2020
  • In: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 78:2, s. 109-117
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate the level of knowledge and attitudes among Swedish general dentists regarding the behavior and management of patients treated with bisphosphonates and denosumab Materials and Methods: A questionnaire was sent to 656 dentists. The web-based survey included questions on demographics, risk perception of osteonecrosis of the jaws (ONJ), the experience of managing patients treated with bisphosphonates and denosumab and requests to acquire new knowledge. Independence and associations were tested using Fisher’s exact test and the chi-square test function. Results: The overall response rate was 57.6%. Most of the dentists, 69.7%, had been in the profession for more than 5years. The criteria for ONJ were not known by 43.2% and 86.9% did not feel comfortable with their current level of knowledge when managing the patients in question. The rest of the respondents felt uncertain and more than 70% were unaware of the different stages of ONJ, when to refer a patient to a specialist and when to prescribe antibiotics. Conclusion: Dentists practicing in Sweden express a strong need for an improved level of knowledge when managing patients treated with bisphosphonates and denosumab. The results demonstrate a need for the necessary advancement of education and clinical training at dental schools in order to prepare dentists to provide safe, modern care within the healthcare sector.
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32.
  • Edlund, Sara, 1983-, et al. (author)
  • Facing negative emotions : Evaluation of a brief training in validating communication for contact nurses in cancer care
  • 2023
  • In: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 66
  • Journal article (peer-reviewed)abstract
    • Background: Contact nurses in cancer care (CNCC) often face challenges when communicating with patients and their families. The overall aim was to evaluate a brief digital validation training for CNCC, to test whether it was associated with increased validation and decreased invalidation. Associations between communication skills in validation and markers of work-related stress were also investigated. Methods: This intervention study investigated associations between the training and validation skills using a within-group design with repeated measures (at pre, post, and eight-week follow-up). Additionally, associations between the training and occupational self-efficacy, self-validation, and exhaustion symptoms were explored. Results: Seventeen CNCCs (all female with relatively long work experience) completed a five-week digital training program. Results indicated a statistically significant increase in validation and a statistically significant decrease in invalidation, showing that the nurses improved their communication skills following the training. No changes were found in markers of work-related stress. Conclusion: The results indicate that digital validation training for CNCCs is potentially beneficial by means of improving communication skills. This study further demonstrates that a brief digital training in validating communication to CNCC is associated with improved person-centered communication regarding strong negative emotions.
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33.
  • Ehrenstein, V., et al. (author)
  • Osteonecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: Results of a regulator-mandated cohort postauthorization safety study in Denmark, Norway, and Sweden
  • 2021
  • In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:21, s. 4050-4058
  • Journal article (peer-reviewed)abstract
    • BACKGROUND Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country. LAY SUMMARY Denosumab and zoledronic acid reduce the risk of bone fractures, pain, and surgery in patients with advanced cancers involving bone. Osteonecrosis of the jaw (ONJ)-death of a jawbone-is a known side effect of treatment with denosumab or zoledronic acid. The authors examined almost 2900 denosumab- or zoledronic acid-treated patients with cancer in Denmark, Norway, and Sweden. Over the course of 5 years, ONJ developed in 5.7% of the patients whose initial treatment was denosumab, in 1.4% of the patients whose initial treatment was zoledronic acid, and in 6.6% of the patients who switched from zoledronic acid to denosumab.
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34.
  • Enocsson, Helena, et al. (author)
  • Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus
  • 2021
  • In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
  • Journal article (peer-reviewed)abstract
    • Objectives: Type I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-alpha levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE disease activity.Methods: Healthy controls and well-characterized Swedish SLE patients from two cross-sectional cohorts (n=181; n=59) were included, and a subgroup (n=21) was longitudinally followed. Chemokine/cytokine responses in immune complex triggered IFN-alpha activity was studied in healthy donor peripheral blood mononuclear cells (PBMC). Levels of chemokines/cytokines and galectin-9 were measured by immunoassays. Gene expression was quantified by qPCR.Results: The IGS was significantly (p<0.01) correlated with galectin-9 (rho=0.54) and CXCL10 (rho=0.37) levels whereas serum IFN-alpha correlated with galectin-9 (rho=0.36), CXCL10 (rho=0.39), CCL19 (rho=0.26) and CCL2 (rho=0.19). The strongest correlation was observed between galectin-9 and TNF (rho=0.56). IFN-alpha and disease activity (SLEDAI-2K) were correlated (rho=0.20) at cross-sectional analysis, but no significant associations were found between SLEDAI-2K and galectin-9 or chemokines. Several inflammatory mediators increased at disease exacerbation although CCL19, CXCL11, CXCL10, IL-10 and IL-1 receptor antagonist were most pronounced. Immune complex-stimulation of PBMC increased the production of CCL2, CXCL8 and TNF.Conclusion: Galectin-9 and CXCL10 were associated with type I IFN in SLE but correlated stronger with TNF. None of the investigated biomarkers showed a convincing association with disease activity, although CXCL10 and CCL19 performed best in this regard.
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35.
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36.
  • Garcia-Ryde, Martin, et al. (author)
  • Expression of Stress-Induced Genes in Bronchoalveolar Lavage Cells and Lung Fibroblasts from Healthy and COPD Subjects
  • 2024
  • In: International Journal of Molecular Sciences. - 1422-0067. ; 25:12, s. 1-16
  • Journal article (peer-reviewed)abstract
    • Chronic obstructive pulmonary disease (COPD) is commonly caused from smoking cigarettes that induce biological stress responses. Previously we found disorganized endoplasmic reticulum (ER) in fibroblasts from COPD with different responses to chemical stressors compared to healthy subjects. Here, we aimed to investigate differences in stress-related gene expressions within lung cells from COPD and healthy subjects. Bronchoalveolar lavage (BAL) cells were collected from seven COPD and 35 healthy subjects. Lung fibroblasts were derived from 19 COPD and 24 healthy subjects and exposed to cigarette smoke extract (CSE). Gene and protein expression and cell proliferation were investigated. Compared to healthy subjects, we found lower gene expression of CHOP in lung fibroblasts from COPD subjects. Exposure to CSE caused inhibition of lung fibroblast proliferation in both groups, though the changes in ER stress-related gene expressions (ATF6, IRE1, PERK, ATF4, CHOP, BCL2L1) and genes relating to proteasomal subunits mostly occurred in healthy lung fibroblasts. No differences were found in BAL cells. In this study, we have found that lung fibroblasts from COPD subjects have an atypical ER stress gene response to CSE, particularly in genes related to apoptosis. This difference in response to CSE may be a contributing factor to COPD progression.
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37.
  • Glodzik, Dominik, et al. (author)
  • Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Homologous recombination deficiency (HRD) is a defining characteristic in BRCA-deficient breast tumors caused by genetic or epigenetic alterations in key pathway genes. We investigated the frequency of BRCA1 promoter hypermethylation in 237 triple-negative breast cancers (TNBCs) from a population-based study using reported whole genome and RNA sequencing data, complemented with analyses of genetic, epigenetic, transcriptomic and immune infiltration phenotypes. We demonstrate that BRCA1 promoter hypermethylation is twice as frequent as BRCA1 pathogenic variants in early-stage TNBC and that hypermethylated and mutated cases have similarly improved prognosis after adjuvant chemotherapy. BRCA1 hypermethylation confers an HRD, immune cell type, genome-wide DNA methylation, and transcriptional phenotype similar to TNBC tumors with BRCA1-inactivating variants, and it can be observed in matched peripheral blood of patients with tumor hypermethylation. Hypermethylation may be an early event in tumor development that progress along a common pathway with BRCA1-mutated disease, representing a promising DNA-based biomarker for early-stage TNBC.
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38.
  • Govender, Melissa, et al. (author)
  • T cell perturbations persist for at least 6 months following hospitalization for COVID-19
  • 2022
  • In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
  • Journal article (peer-reviewed)abstract
    • COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8(+) TEMRA and exhausted CD57(+) CD8(+) T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T cell activation were upregulated at inclusion, and in the case of CD69(+) CD4(+) T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.
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39.
  • Granrud, Marie Dahlen, et al. (author)
  • Health Care Personnel's Perspectives on Quality of Palliative Care During the COVID-19 Pandemic - A Cross-Sectional
  • 2023
  • In: Journal of Multidisciplinary Healthcare. - : Dove Medical Press. - 1178-2390. ; 16, s. 2893-2903
  • Journal article (peer-reviewed)abstract
    • Purpose: The provision of high-quality palliative care is challenging, especially during a pandemic like COVID-19. The latter entailed major consequences for health care systems and health care personnel (HCP) in both specialist and community health care services, in Norway and worldwide. The aim of this study was to explore how the HCP perceived the quality of palliative care in nursing homes, medical care units, and intensive care units during the COVID-19 pandemic. Methods: This study had a cross-sectional design. A total of 290 HCP from Norway participated in the study (RR = 25.8%) between October and December 2021. The questionnaire comprised items concerning respondents' demographics and quality of care, the latter measured by the short form of the Quality from the Patient's Perspective-Palliative Care instrument, adapted for HCP. The STROBE checklist was used. Results: This study shows that the HCP scored subjective importance as higher in all dimensions, items and single items than their perception of the actual care received. This could indicate a need for improvement in all areas. Information about medication, opportunity to participate in decisions about medical and nursing care and continuity regarding receiving help from the same physician and nurse are examples of areas for improvement. Conclusion: Study results indicate that HCP from nursing homes, medical care units, and intensive care units perceived that quality of palliative care provided was not in line with what they perceived to be important for the patient. This indicate that it was challenging to provide high-quality palliative care during the COVID-19 pandemic.
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40.
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41.
  • Granrud, MD, et al. (author)
  • Health Care Personnel's Perspectives on Quality of Palliative Care During the COVID-19 Pandemic : A Cross-Sectional Study
  • 2023
  • In: Journal of Multidisciplinary Healthcare. - : Dove Medical Press. - 1178-2390. ; 16, s. 2893-2903
  • Journal article (peer-reviewed)abstract
    • Purpose: The provision of high-quality palliative care is challenging, especially during a pandemic like COVID-19. The latter entailed major consequences for health care systems and health care personnel (HCP) in both specialist and community health care services, in Norway and worldwide. The aim of this study was to explore how the HCP perceived the quality of palliative care in nursing homes, medical care units, and intensive care units during the COVID-19 pandemic. Methods: This study had a cross-sectional design. A total of 290 HCP from Norway participated in the study (RR = 25.8%) between October and December 2021. The questionnaire comprised items concerning respondents' demographics and quality of care, the latter measured by the short form of the Quality from the Patient's Perspective-Palliative Care instrument, adapted for HCP. The STROBE checklist was used. Results: This study shows that the HCP scored subjective importance as higher in all dimensions, items and single items than their perception of the actual care received. This could indicate a need for improvement in all areas. Information about medication, opportunity to participate in decisions about medical and nursing care and continuity regarding receiving help from the same physician and nurse are examples of areas for improvement. Conclusion: Study results indicate that HCP from nursing homes, medical care units, and intensive care units perceived that quality of palliative care provided was not in line with what they perceived to be important for the patient. This indicate that it was challenging to provide high-quality palliative care during the COVID-19 pandemic.
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42.
  • Guné, Henrik, et al. (author)
  • Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection
  • 2021
  • In: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 32:4, s. 253-258
  • Journal article (peer-reviewed)abstract
    • Excessive bleeding is a serious complication associated with impaired survival after surgery for acute type A aortic dissection (ATAAD). Different ABO blood groups are associated with variable levels of circulating von Willebrand factor and therefore potentially altered risks of surgical haemorrhage. The current study aimed to assess the impact of blood group on bleeding complications after ATAAD surgery. This was a retrospective cohort study including 336 patients surgically treated for ATAAD between January 2004 and January 2019. Patients with blood group O were compared with non-O patients. In total, 152 blood group O patients were compared with 184 non-O patients. There were no differences in rates of massive bleeding (27.0 vs. 25.5%, P = 0.767) or re-exploration for bleeding (16.4 vs. 13.0%, P = 0.379) in blood group O and non-O patients, respectively. Median chest tube output 12 h after surgery was 520 ml (350-815 ml) in blood group O and 490 ml (278-703 ml) in non-O patients (P = 0.229). Blood group O patients received more fibrinogen concentrate (6.1 ± 4.0 vs. 4.9 ± 3.3 g, P = 0.023) but administered units of packed red blood cells [5 (2-8) vs. 4 (2-9) U, P = 0.736], platelets [4 (2-4) vs. 3 (2-5) U, P = 0.521] or plasma [4 (1-7) vs. 4 (0-7) U, P = 0.562] were similar. This study could not demonstrate any association between blood group and bleeding after surgery for ATAAD. It cannot be ruled out that potential differences were levelled out by blood group O patients receiving significantly more fibrinogen concentrate.
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43.
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44.
  • Harrysson, Hanna, 1987, et al. (author)
  • Effect of storage conditions on lipid oxidation, nutrient loss and colour of dried seaweeds, Porphyra umbilicalis and Ulva fenestrata, subjected to different pretreatments
  • 2021
  • In: Algal Research. - : Elsevier BV. - 2211-9264. ; 56
  • Journal article (peer-reviewed)abstract
    • Here we evaluated the levels of lipid oxidation products, fatty acids, ascorbic acid and colour of Porphyra and Ulva after oven-drying at 40 degrees C, and during subsequent storage for >= 370 days under light, semi-light and dark conditions. Part of the seaweed was pre-soaked in freshwater or pre-coated with a whey protein mixture. Controls consisted of freeze-dried seaweeds. Throughout storage there was a moderate development of the lipid oxidation-derived aldehydes, malondialdehyde, 4-hydroxy-trans-2-hexenal and 4-hydroxy-trans-2-nonenal, while there was a great loss of unsaturated fatty acids and ascorbic acid. Light storage and freeze-drying stimulated the fatty acid loss as well as pigment bleaching, seen as increased a*-values. For Ulva, the coating reduced malondialdehyde, 4-hydroxy-trans-2-hexenal and 4-hydroxy-trans-2-nonenal formation during drying and slightly prevented loss of polyunsaturated fatty acids during light storage. Pre-soaking in freshwater had no effect on the seaweed stability, although it reduced the ash content and thereby increased the relative content of ascorbic acid and fatty acids of the biomasses.
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45.
  • Hopkins, Francis, et al. (author)
  • Pentameric C-reactive protein is a better prognostic biomarker and remains elevated for longer than monomeric CRP in hospitalized patients with COVID-19
  • 2023
  • In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
  • Journal article (peer-reviewed)abstract
    • The differing roles of the pentameric (p) and monomeric (m) C-reactive protein (CRP) isoforms in viral diseases are not fully understood, which was apparent during the COVID-19 pandemic regarding the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we investigated the predictive value of the pCRP and mCRP isoforms for COVID-19 severity in hospitalized patients and evaluated how the levels of the protein isoforms changed over time during and after acute illness. This study utilized samples from a well-characterized cohort of Swedish patients with SARS-CoV-2 infection, the majority of whom had known risk factors for severe COVID-19 and required hospitalization. The levels of pCRP were significantly raised in patients with severe COVID-19 and in contrast to mCRP the levels were significantly associated with disease severity. Additionally, the pCRP levels remained elevated for at least six weeks post inclusion, which was longer compared to the two weeks for mCRP. Our data indicates a low level of inflammation lasting for at least six weeks following COVID-19, which might indicate that the disease has an adverse effect on the immune system even after the viral infection is resolved. It is also clear that the current standard method of testing pCRP levels upon hospitalization is a useful marker for predicting disease severity and mCRP testing would not add any clinical relevance for patients with COVID-19.
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46.
  • Hopkins, Francis R., et al. (author)
  • Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
  • 2023
  • In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
  • Journal article (peer-reviewed)abstract
    • Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.
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47.
  • Jain, Karishma, et al. (author)
  • 3D printable composites of modified cellulose fibers and conductive polymers and their use in wearable electronics
  • 2023
  • In: APPLIED MATERIALS TODAY. - : Elsevier BV. - 2352-9407. ; 30
  • Journal article (peer-reviewed)abstract
    • There are many bioelectronic applications where the additive manufacturing of conductive polymers may be of use. This method is cheap, versatile and allows fine control over the design of wearable electronic devices. Nanocellulose has been widely used as a rheology modifier in bio-based inks that are used to print electrical components and devices. However, the preparation of nanocellulose is energy and time consuming. In this work an easy-to-prepare, 3D-printable, conductive bio-ink; based on modified cellulose fibers and poly(3,4-ethylene dioxythiophene) poly(styrene sulfonate) (PEDOT:PSS), is presented. The ink shows excellent printability, the printed samples are wet stable and show excellent electrical and electrochemical performance. The printed structures have a conductivity of 30 S/cm, high tensile strains (>40%), and specific capacitances of 211 F/g; even though the PEDOT:PSS only accounts for 40 wt% of the total ink composition. Scanning electron microscopy (SEM), wide-angle X-ray scattering (WAXS), and Raman spectroscopy data show that the modified cellulose fibers induce conformational changes and phase separation in PEDOT:PSS. It is also demonstrated that wearable supercapacitors and biopotential-monitoring devices can be prepared using this ink.
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48.
  • Johansson, Martin, et al. (author)
  • Different aspects of visual perception are important for 12-year social functioning depending on gestational age
  • 2023
  • In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 112:7, s. 1537-1547
  • Journal article (peer-reviewed)abstract
    • AimPerceptual mechanisms in social functioning might promote interventions. We investigated relations between visual perception and social functioning, in preterm children.MethodsA prospective preterm cohort born in Uppsala County, Sweden, in 2004–2007 and 49 full-term controls were examined at 12 years. Aspects of visual perception, including static shapes, emotions and time to detect biological motion, were related to social functioning and visual acuity.ResultsThe preterm group comprised 25 extremely preterm children, EPT, born below 28 gestational weeks and 53 children born between 28 and 31 weeks. Preterm children had difficulties in perception of static shapes (p = 0.004) and biological motion (p < 0.001), but not in emotion perception, compared to controls. In the EPT children, poorer shape perception and lower scores on emotion perception were associated with more social problems (p = 0.008) and lower visual acuity (p = 0.004). Shape perception explained more variance in social functioning than emotion perception. In controls, fewer social problems were linked to faster biological motion perception (p = 0.04).ConclusionStatic shape and biological motion perception was affected in the preterm groups. Biological motion perception was relevant for social functioning in full-term children. In EPT children, only shape perception was linked to social functioning, suggesting differential visual perception mechanisms for social deficits.
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49.
  • Karimi, Annette, et al. (author)
  • Brain MRI findings and their association with visual impairment in young adolescents born very preterm
  • 2024
  • In: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 66:1, s. 145-154
  • Journal article (peer-reviewed)abstract
    • PurposeVery preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes.MethodsWe included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up.ResultsEvans index (0.27 vs 0.25, p<0.001) and a proposed “posterior ventricle index” (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (β=10.7, 95%CI 0.59–20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78–1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108–3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (β=0.04, 95%CI 0.002–0.07).ConclusionMore white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.
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50.
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