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2. |
- Ahlström, Aisling, 1976, et al.
(författare)
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Conventional morphology performs better than morphokinetics for prediction of live birth after day 2 transfer
- 2016
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Ingår i: Reproductive Biomedicine Online. - : Elsevier BV. - 1472-6483. ; 33:1, s. 61-70
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have reported on the potential value of time-lapse variables for prediction of embryo viability. However, these variables have not been evaluated in combination with conventional morphological grading and patient characteristics. The aim of this study was to assess the ability of patient characteristics and embryo morphology together with morphokinetic variables to predict live birth after day 2 transfer. This retrospective analysis included 207 transferred embryos from 199 couples cultured in a time-lapse system up to day 2 of development. Good prediction of live birth or ranking of embryos with respect to live birth potential was achieved with early cleavage combined with fragmentation grade at 43-45 h. These variables were selected as the strongest predictors of live birth, as assessed by stepwise logistic regression, and additional inclusion of morphokinetic variables did not improve the model significantly. Also, neither logistic regression models nor classification tree models with morphokinetic variables were able to achieve equally good prediction of live birth, as measured by AUC on an external data set not used for model development. In conclusion, for fresh day 2 transfers early cleavage in combination with fragmentation grade at 43-45 h should be considered when selecting between good quality embryos. (C) 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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4. |
- Arkani, Samara, et al.
(författare)
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Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort
- 2018
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Ingår i: Human genome variation. - : Springer Nature. - 2054-345X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Bladder exstrophy is a congenital closure defect of the urinary bladder with a profound effect on morbidity. Although the malformation is usually sporadic, a genetic background is supported by an increased recurrence risk in relatives, higher concordance rates in monozygotic twins and several associated chromosomal aberrations. Recently, the ISL1 gene was presented as a candidate gene for bladder exstrophy and epispadias complex (BEEC) development in two different studies. In our study, we screened for genetic variants in the ISL1 gene in DNA from 125 Swedish patients using Sanger sequencing and array-CGH analysis. In addition, we evaluated ISL1 expression in RNA of human bladder during embryonic and fetal weeks 5–10 relative to that in lung tissue (week 9). In total, 21 single-nucleotide variants were identified, including a potentially novel missense variant, c.137C>G p.(Ala46Gly), substituting a conserved amino acid. This variant was inherited from an unaffected mother. No structural variants were identified. RNA sequencing revealed ISL1 mRNA expression during the critical time frame of human bladder development. In conclusion, we did not detect any known or likely pathogenic variants in the ISL1 gene in 125 Swedish BEEC patients, indicating that variation in the ISL1 gene is not a common genetic mechanism of BEEC development in the Swedish population.
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6. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Fifteen years after a ferry disaster : Clinical interviews and survivors’ self-assessment of their experience
- 2013
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Ingår i: European Journal of Psychotraumatology. - : Informa UK Limited. - 2000-8198 .- 2000-8066. ; 4, s. 20650-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Disasters yield increased rates of psychological disorders decades later. Other consequences, however, have received little attention in the past.Objective:We aimed to examine diagnostic status and survivors’ views on disaster-related consequences and social support.Methods:A mixed-methods approach was used with 22 survivors (of 49 eligible) 15 years after a ferry disaster. Data collection included audiotaped interviews with open-ended questions and diagnostic assessment of Axis-I disorders.Results:The post-disaster incidence was 54% (12/22) for Axis-I disorders, and 45% (10/22) for full or subsyndromal posttraumatic stress disorder. Thematic analysis revealed that survivor perception of the longterm consequences included positive (character change) and negative aspects (being ascribed a survivor identity). Participants’ sought social support for several years, yet many felt hindered by experiential dissimilarity and distress of significant others.Conclusions:Axis-I disorders were prevalent, but not salient to survivors’ perceptions in the long-term. Postdisaster interventions need to attend to common barriers to support.
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7. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Prospective longitudinal long-term studies 14-20 years after three disasters
- 2011
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Ingår i: European Journal of Psychotraumatology. ; , s. 72-72
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Konferensbidrag (refereegranskat)abstract
- Although clinical experience and past research have shown that posttraumatic stress (PTS) can last for decades after a disaster, long-term follow-ups are scarce and little is known about predictors of chronic PTS. In this presentation, long-term consequences of disasters will be described by a summary of the findings from three surveys of man-made/technological disasters with 2-4 assessments during the first 34-4 years and with a long-term assessment of PTSD and general mental health after 14-20 years (Ns = 33-57). Similarities and dissimilarities in the course of PTS between the disasters will be presented. The influence of traumatic bereavement, psychological or pharmacological treatment, and additional negative life events on long-term PTS will be discussed, and experiences form conducting long-term studies will be communicated.
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8. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Social support moderates posttraumatic stress and general distress after disaster
- 2012
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 25:6, s. 721-727
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Tidskriftsartikel (refereegranskat)abstract
- Social support buffers the negative impact of stressful events. Less, however, is known about the characteristics of this association in the context of disaster and findings have been discrepant regarding direct and buffering effects. This study tested whether the protective effects of social support differed across levels of exposure severity (i.e., buffered distress) and assessed whether the buffering effect differed between event-specific and general distress. Participants were 4,600 adult Swedish tourists (44% of invited; 55% women) repatriated within 3 weeks after the 2004 Indian Ocean tsunami. A survey 14 months after the disaster included the Crisis Support Scale, the Impact of Event Scale-Revised (IES-R), and the General Health Questionnaire (GHQ-12). Social support buffered the negative impact of exposure on both outcomes. The support and distress association ranged from very small in participants with low exposure to moderate in those with high exposure (ηp2 = .004 to .053). The buffering effect was not found to differ between the IES-R and GHQ-12, F(2, 4589) = 0.87, p = .42. The findings suggest that social support moderates the stressor-distress relationship after disasters. This study might help explain discrepant findings and point to refinements of postdisaster interventions.
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9. |
- Arnberg, Filip K, et al.
(författare)
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Traumatic bereavement, acute dissociation, and posttraumatic stress : 14 years after the MS Estonia disaster
- 2011
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:2, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- This prospective longitudinal study aimed to examine posttraumatic stress in survivors 14 years after a ferry disaster, and estimate short- and long-term changes in stress associated with traumatic bereavement and acute dissociation. There were 852 people who perished in the disaster, 137 survived. The 51 Swedish survivors were surveyed with the Impact of Event Scale-Revised (IES-R) at 3 months, 1, 3, and 14 years (response rates 82%, 65%, 51%, and 69%). Symptoms decreased from 3 months to 1 year; no change was found thereafter. After 14 years, 27% reported significant symptoms. Traumatic bereavement, but not acute dissociation, was associated with long-term symptom elevation. Chronic posttraumatic stress can persist in a minority of survivors, and traumatic bereavement appears to hinder recovery.
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10. |
- Arnberg, Filip, 1981-
(författare)
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Long-Term Posttraumatic Stress in Survivors from Disasters and Major Accidents
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Disasters and major accidents are a significant cause of distress worldwide. High levels of posttraumatic stress can become chronic after severe and prolonged psychological trauma, raising concerns about the extent of adverse long-term consequences after single events. The present thesis aimed to describe the course and burden of posttraumatic stress in survivors from a ferry disaster in the Baltic Sea, an airliner crash-landing in Gottröra, Sweden, and a bus accident involving Swedish 6th grade schoolchildren in Måbødalen, Norway. The participants were surveyed 1 month to 4 years after the events and again after 14 to 20 years. The follow-up surveys included 33 ferry disaster survivors, 70 airline survivors, and 7 surviving schoolchildren with a comparison group from the same school (n = 33). Short- and long-term changes in posttraumatic stress were estimated separately in generalised regression models refined by linear splines. In-depth interviews were conducted with 22 ferry survivors 15 years after the disaster, including structured clinical interviews and thematic analysis of survivors’ descriptions of consequences of the event and social support. Approximately half of all survivors experienced significant posttraumatic stress at the initial assessments. Significant long-term distress was noted in one fourth of the ferry survivors and one sixth of the airline survivors. The bus crash was not associated with significant long-term posttraumatic stress. A poorer long-term outcome was noted in women and in bereaved survivors. The thematic analysis revealed that long-term consequences not only included negative aspects but also positive ones, including personal growth and existential awareness. There was ample availability of social support, although the need for support extended over a period of several years. Barriers to support from significant others were described in detail by the survivors. The results extend previous research by providing a comprehensive account of long-term consequences of disasters and major accidents in light of early reactions. The interviews provide some new insights into features of social support that warrant further study. Important future challenges include evaluating whether timely attention to survivors at risk for chronic distress and significant others can facilitate recovery.
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11. |
- Bergh, Christina, 1953, et al.
(författare)
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Chromosomal abnormality rate in human pre-embryos derived from in vitro fertilization cycles cultured in the presence of Follicular-Fluid Meiosis Activating Sterol (FF-MAS)
- 2004
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Ingår i: Hum Reprod. ; 19:9, s. 2109-17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of the study was to investigate the effect of Follicular-Fluid Meiosis Activating Sterol (FF-MAS) when added to the culture media on the incidence of chromosomal abnormalities and pre-embryo development in human pre-embryos. METHODS: 243 women undergoing IVF/ICSI treatment donated 353 oocytes in a multicentre, prospective, randomized, double blind, four-arm, controlled trial performed at Danish and Swedish public and private IVF centers. Metaphase II oocytes were randomly assigned to: FF-MAS 5 microM, FF-MAS 20 microM, ethanol 0.2% (vehicle control) or water for injection (inert control). The exposure regimen of FF-MAS to the human oocytes was 4 h prior to fertilization by ICSI and 20 h exposure post ICSI. The primary endpoint was the incidence of numerical chromosomal abnormalities. Secondary endpoints were cleavage rate and pre-embryo quality. RESULT: On the pre-embryo level, no significant differences in chromosomal abnormality rate were observed among the four groups. However, the percentage of uniformly normal pre-embryos was significantly lower in the pooled FF-MAS group (5 microM: 12% and 20 microM: 17%) than in the pooled control group (inert control 32% and vehicle control 42%). A high level of mosaicism (41-60%) was found in all groups. At the blastomere level, the percentage of blastomeres categorized as normal was significantly lower in the FF-MAS 5 microM group (41%) and the FF-MAS 20 microM (29%) group versus the inert (52%) and the vehicle (61%) groups. Significantly reduced cleavage and good quality pre-embryo rates were found in both FF-MAS groups. CONCLUSION: FF-MAS increased the rate of aneuploidy and had detrimental effects on cleavage and pre-embryo development, when exposed both before and after fertilization.
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13. |
- Bergh Johannesson, Kerstin, 1949-, et al.
(författare)
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Impact of Exposure to Trauma on Posttraumatic Stress Disorder Symptomatology in Swedish Tourist Tsunami Survivors
- 2009
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 197:5, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine long-term mental health and posttraumatic stress symptomatology in a Swedish tourist population after exposure to the 2004 Southeast Asian tsunami. Data from 4822 returned questionnaires 14 months after the disaster were analyzed. Respondents were categorized into 3 subgroups: (1) danger-to-life exposure group (having been caught or chased by the waves), (2) nondanger-to-life exposure group (exposed to other disaster-related stressors), and (3) low exposure group. Main outcome measures were General Health Questionnaire-12 and Impact of Event Scale-22-Revised. Danger-to-life exposure was an important factor in causing more severe posttraumatic stress symptoms and in affecting mental health. Female gender, single status, and former trauma experiences were associated with greater distress. Other factors related to more severe symptoms were loss of relatives, physical injuries, viewing many dead bodies, experiencing life threat, and showing signs of cognitive confusion. Disaster exposure has a substantial impact on survivors, which stresses the need for long-lasting support.
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14. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Prolonged Grief Among Traumatically Bereaved Relatives Exposed and Not Exposed to a Tsunami
- 2011
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:4, s. 456-464
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies on the mental health consequences of traumatic exposure to a disaster compare those exposed to those not exposed. Relatively few focus on the effect of the death of a close relative caused by the disaster-suffering a traumatic bereavement. This study compared the impact on 345 participants who lost a close relative in the 2004 Indian Ocean tsunami, but who were themselves not present, to 141 who not only lost a relative, but also were themselves exposed to the tsunami. The focus was on psychological distress assessed during the second year after the sudden bereavement. Findings were that exposure to the tsunami was associated with prolonged grief (B = 3.81) and posttraumatic stress reactions (B 665), and doubled the risk for impaired mental health. Loss of children increased the risk for psychological distress (prolonged grief B = 692; The Impact of Event Scale-Revised: B = 610; General Health Questionnaire-12: OR = 2.34). Women had a higher frequency of prolonged grief For men, loss of children presented a higher risk for prolonged grief in relation to other types of bereavement (B = 636 vs. loss of partner). Further long-term follow-up could deepen the understanding of how recovery after traumatic loss is facilitated.
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15. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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The effect of Traumatic Bereavement on Tsunami-Exposed Survivors
- 2009
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 22:6, s. 497-504
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen months after the 2004 tsunami, mental health outcome was assessed in 187 bereaved relatives, 308 bereaved friends, and in 3,020 nonbereaved Swedish survivors. Of the bereaved relatives, 41% reported posttraumatic stress reactions and 62% reported impaired general mental health. Having been caught or chased by the tsunami in combination with bereavement was associated with increased posttraumatic stress reactions. Complicated grief reactions among relatives were almost as frequent as posttraumatic stress reactions. The highest levels of psychological distress were found among those who had lost children. Traumatic bereavement, in combination with exposure to life danger, is probably a risk factor for mental health sequelae after a natural disaster.
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18. |
- Bergh Johannesson, Kerstin, 1949-
(författare)
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Traumatic Exposure, Bereavement and Recovery among Survivors and Close Relatives after Disasters
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- International studies of disasters indicate the risk for developing posttraumatic stress reactions among survivors is high. Modern life implicates increased traveling. During the last decades a large number of Swedish citizens were confronted with disasters taking place outside of their country. The prevalence of trauma reactions in a population that does not normally experience natural disasters, but are able to return to a community unaffected by the catastrophe, is not well studied. In addition, the effects of bereavement after traumatic circumstances have not been satisfactorily explored. Longitudinal studies on the effects of natural disasters are underrepresented and there are few studies investigating the course of recovery after traumatic exposure. The aim for this thesis was to examine long-term post-traumatic stress reactions, mental health, and complicated grief after disaster exposure and traumatic bereavement. Data from returned questionnaires were analysed from bereaved Italian and Swedish relatives 18 months after the Linate airplane disaster 2001, and at 14 months and three years from Swedish travelers returning from Southeast Asia after the 2004 tsunami disaster, and from home staying bereaved relatives within the second year after the tsunami disaster. The main outcome measures were GHQ-12, IES-R and Inventory of Complicated Grief. The findings indicated many survivors were resilient and had ability to recover, but severe exposure to a disaster had considerable impact on psychological distress. Life threat was associated with higher levels of post-traumatic stress reactions, and increased the risk for affected mental health and suicidal ideation. Loss in combination with severe life threat exposure indicated a further increased risk of posttraumatic stress reactions and for complicated grief; this should be considered a substantial risk factor for general mental health. Loss of close relatives, especially loss of children, was associated with higher levels of posttraumatic stress and created a greater risk for complicated grief. Many survivors recovered over time; however, severe exposure and traumatic loss appeared to slow the recovery process. The findings have implications for government and health agencies, regarding the importance of knowledge and awareness of these risks for health, and for organizational structure, training, and accessibility of support and adequate treatment.
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20. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Tsunami-exposed tourist survivors : Signs of recovery in an 3-year perspective
- 2011
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 199:3, s. 162-169
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Tidskriftsartikel (refereegranskat)abstract
- Long-term follow-up after disaster exposure indicates increased rates of psychological distress. However, trajectories and rates of recovery in large samples of disaster-exposed survivors are largely lacking. A group of 3457 Swedish survivors temporarily on vacation in Southeast Asia during the 2004 tsunami were assessed by postal questionnaire at 14 months and 3 years after the tsunami regarding post-traumatic stress reactions (IES-R) and general mental health (GHQ-12). There was a general pattern of resilience and recovery 3 years postdisaster. Severe exposure and traumatic bereavement were associated with increased post-traumatic stress reactions and heightened risk for impaired mental health. The rate of recovery was lower among respondents exposed to life threat and among bereaved. Severe trauma exposure and bereavement seem to have considerable long-term impact on psychological distress and appear to slow down the recovery process. Readiness among health agencies for identification of symptoms and provision of interventions might facilitate optimal recovery.
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21. |
- Besevic, Jelena, et al.
(författare)
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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
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23. |
- Borgmästars, Emmy, et al.
(författare)
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Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
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25. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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26. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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27. |
- Borgmästars, Emmy, et al.
(författare)
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Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma : a nested case-control study
- 2024
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
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28. |
- Bossér, Ulrika, 1976-
(författare)
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Exploring the complexities of integrating socioscientific issues in science teaching
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Socioscientific issues, SSI, can briefly be described as societal issues in which science plays a role. Dealing with SSI in science education is a means to prepare and empower students for active and responsible participation in a complex, democratic society. The implementation of SSI-based teaching calls for classroom practices in which scientific evidence alongside for example social and ethical perspectives are considered. Discourse-based teaching activities are emphasized as a means to provide opportunities for students to practice negotiations of SSI and explore diverse viewpoints on the issues. Dealing with SSI in science teaching is recognized as a challenging task for science teachers. This thesis aims to provide knowledge to support the implementation of SSI-based science teaching. Three studies involving two upper secondary school science teachers are performed to achieve this aim. The first study makes use of video-stimulated discussions to investigate the two teachers’reflections on their classroom practices while they implement SSI throughout an academic year. The second study utilizes the concept positioning as a tool to identify and describe the ways in which one teacher’s interactions with students during group work make available different parts for the students to play as participants, when dealing with SSI in the classroom. The third study makes use of the concept communicative approach to investigate how the two teachers’ management of classroom discussions sets conditions for the consideration of multiple perspectives relevant to SSI, including the students’ viewpoints. The results provide knowledge useful when making considerations about the design and enactment of teaching activities in relation to specific educational goals. The results suggest that a specific challenge with designing and enacting SSI-based teaching activities is to balance between controlling and directing the teaching activities to promote specific learning goals and providing space for students’ participation and perspectives. The results of employing the analytical tools elucidate how this challenge can play out in classroom practice and contribute with knowledge of the ways in which teachers’ discursive practices play a role in addressing this challenge. Strategies to support teachers’ implementation of SSI-based teaching that take account of teachers’ existing practices are discussed.
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29. |
- Braem, Marieke G. M., et al.
(författare)
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Coffee and tea consumption and the risk of ovarian cancer : a prospective cohort study and updated meta-analysis
- 2012
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Ingår i: American Journal of Clinical Nutrition. - Bethesda : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 95:5, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). Objective: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. Design: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. Results: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% Cl: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. Conclusion: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer. Am J Clin Nutr 2012;95:1172-81.
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30. |
- Braem, Marieke G. M., et al.
(författare)
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Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
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31. |
- Caisander, Gunilla, et al.
(författare)
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Chromosomal integrity maintained in five human embryonic stem cell lines after prolonged in vitro culture
- 2006
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Ingår i: Chromosome Res. ; 14:2, s. 131-7
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Tidskriftsartikel (refereegranskat)abstract
- There have been recent reports of human embryonic stem cell (hESC) lines developing chromosomal aberrations after long-term culture, indicating an unstable genomic status due to the in vitro milieu. This raises concern, since it would limit their use in therapeutics. In this study the chromosomal status of five well-characterized hESC lines, SA002, SA002.5, AS034.1.1, SA121 and SA461, was monitored during long-term in vitro culture. The criteria of defined hESCs were met by all of the five hESC lines (four diploid and one trisomic for chromosome 13). The genomes were screened for chromosomal aberrations and rearrangements using comparative genomic hybridization (CGH), interphase fluorescence in situ hybridization (FISH) and traditional karyotyping on several occasions while in culture. The genomic integrity was shown to be maintained after repeated freeze-thaw procedures and continuous culture in vitro for up to 22 months (148 passages). We discuss the most common de novo chromosomal aberrations reported in hESCs, as well as their possible origin.
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32. |
- Carney Almroth, Bethanie, 1974, et al.
(författare)
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Assessing the effects of textile leachates in fish using multiple testing methods: From gene expression to behavior
- 2021
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 207
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Tidskriftsartikel (refereegranskat)abstract
- The textile industry, while of major importance in the world economy, is a toxic industry utilizing and emitting thousands of chemical substances into the aquatic environment. The aim of this project was to study the potentially harmful effects associated with the leaching of chemical residues from three different types of textiles: sportswear, children’s bath towels, and denim using different fish models (cell lines, fish larvae and juvenile fish). A combination of in vitro and in vivo test systems was used. Numerous biomarkers, ranging from gene expression, cytotoxicity and biochemical analysis to behavior, were measured to detect effects of leached chemicals. Principle findings indicate that leachates from all three types of textiles induced cytotoxicity on fish cell lines (RTgill-W1). Leachates from sportswear and towels induced mortality in zebrafish embryos, and chemical residues from sportswear reduced locomotion responses in developing larval fish. Sportswear leachate increased Cyp1a mRNA expression and EROD activity in liver of exposed brown trout. Leachates from towels induced EROD activity and VTG in rainbow trout, and these effects were mitigated by the temperature of the extraction process. All indicators of toxicity tested showed that exposure to textile leachate can cause adverse reactions in fish. These findings suggested that chemical leaching from textiles from domestic households could pose an ecotoxicological threat to the health of the aquatic environment.
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33. |
- Cust, Anne E., et al.
(författare)
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Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 14:3, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
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34. |
- Dossus, Laure, et al.
(författare)
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Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.
- 2013
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 177:8, s. 787-799
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Tidskriftsartikel (refereegranskat)abstract
- A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.
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35. |
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36. |
- Englund, Mikael C. O., 1971, et al.
(författare)
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The establishment of 20 different human embryonic stem cell lines and subclones; a report on derivation, culture, characterisation and banking.
- 2010
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Ingår i: In vitro cellular & developmental biology. Animal. - : Springer Science and Business Media LLC. - 1543-706X .- 1071-2690. ; 46:3-4, s. 217-30
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Tidskriftsartikel (refereegranskat)abstract
- This report summarises our efforts in deriving, characterising and banking of 20 different human embryonic stem cell lines. We have derived a large number of human embryonic stem cell lines between 2001 and 2005. One of these cell lines was established under totally xeno-free culture conditions. In addition, several subclones have been established, including a karyoptypical normal clone from a trisomic mother line. A master cell banking system has been utilised in concert with an extensive characterisation programme, ensuring a supply of high quality pluripotent stem cells for further research and development. In this report we also present the first data on a proprietary novel antibody, hES-Cellect, that exhibits high specificity for undifferentiated hES cells. In addition to the traditional manual dissection approach of propagating hES cells, we here also report on the successful approaches of feeder-free cultures as well as single cell cultures based on enzymatic digestion. All culture systems used as reported here have maintained the hES cells in a karyotypical normal and pluripotent state. These systems also have the advantage of being the principal springboards for further scale up of cultures for industrial or clinical applications that would require vastly more cells that can be produced by mechanical means.
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37. |
- Franklin, Oskar, et al.
(författare)
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Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma
- 2015
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Ingår i: Cancer Biomarkers. - : IOS Press. - 1574-0153. ; 15:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE: To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort.METHODS: Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls.RESULTS: The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre-nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival.CONCLUSIONS: PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.
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38. |
- Franklin, Oskar, et al.
(författare)
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Plasma micro-RNA alterations appear late in pancreatic cancer
- 2018
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 267:4, s. 775-781
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.
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39. |
- Fritzell, Peter, et al.
(författare)
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Bacteria : back pain, leg pain and Modic sign—a surgical multicentre comparative study
- 2019
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Ingår i: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:12, s. 2981-2989
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence.Methods: Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33–49) and 20 control patients with scoliosis (median age 17, IQR 15–20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes.Results: No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated.Conclusions: Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned.
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40. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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41. |
- Gejervall, Ann-Louise, 1963, et al.
(författare)
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Effect of alfentanil dosage during oocyte retrieval on fertilization and embryo quality.
- 2010
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Ingår i: European journal of obstetrics, gynecology, and reproductive biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 150:1, s. 66-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A possible negative effect of pain-relieving analgesics used during oocyte retrieval on fertilization and embryo development has been discussed. This study examines whether alfentanil dosage adversely affects fertilization and/or embryo quality. STUDY DESIGN: In a retrospective observational study the effect of different doses of alfentanil on two primary endpoints, fertilization rate and good quality embryo (GQE) rate, were compared in 663 women. RESULTS: In group A (0.5mg alfentanil) mean fertilization rate was 0.6+/-0.3 versus 0.6+/-0.2 (P=0.678, adjusted P=0.937, 95% CI for the difference -0.041; 0.044) and mean GQE rate was 0.6+/-0.3 versus 0.5+/-0.3 (P=0.207, adjusted P=0.179, 95% CI for the difference -0.015; 0.078), respectively. A paired comparison of 65 women who underwent repeated IVF cycles found that, compared with 0.5mg alfentanil had no adverse effects on fertilization rate (mean difference 0.05+/-0.3, P=0.231, 95% CI -0.02; 0.12) or GQE rate (mean difference -0.02+/-0.4, P=0.970, 95% CI -0.12; 0.09). CONCLUSION: The amount of alfentanil is not associated with adverse effects on fertilization rate, embryo development, or clinical pregnancy rate, which is reassuring and indicates that women can be offered adequate pain relief.
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42. |
- Grahn, Oskar, et al.
(författare)
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Peritoneal infection after colorectal cancer surgery induces substantial alterations in postoperative protein levels : an exploratory study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis.Methods: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed.Results: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K/Akt) and transforming growth factor beta (TGF-β) signaling.Conclusion: These affected proteins and pathways could provide clues as to why these patients might suffer increased cancer recurrence, mortality and cardiovascular morbidity.
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43. |
- Gram, Inger T, et al.
(författare)
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Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130:9, s. 2204-2210
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Tidskriftsartikel (refereegranskat)abstract
- New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.
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44. |
- Grivans, Christina, 1963, et al.
(författare)
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A Scandinavian survey of drug administration through inhalation, suctioning and recruitment maneuvers in mechanically ventilated patients.
- 2009
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576. ; 53:6, s. 710-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to describe current practices for drug administration through inhalation, endotracheal suctioning and lung recruitment maneuvers in mechanically ventilated patients in Scandinavian intensive care units (ICUs). METHODS: We invited 161 ICUs to participate in a web-based survey regarding (1) their routine standards and (2) current treatment of ventilated patients during the past 24 h. In order to characterize the patients, the lowest PaO(2) with the corresponding highest FiO(2), and the highest PaO(2) with the corresponding lowest FiO(2) during the 24-h study period were recorded. RESULTS: Eighty-seven ICUs answered and reported 186 patients. Positive end-expiratory pressure (PEEP) levels (cmH(2)O) were 5-9 in 65% and >10 in 31% of the patients. Forty percent of the patients had heated humidification and 50% received inhalation of drugs. Endotracheal suctioning was performed >7 times during the study period in 40% of the patients, of which 23% had closed suction systems. Twenty percent of the patients underwent recruitment maneuvers. The most common recruitment maneuver was to increase PEEP and gradually increase the inspiratory pressure. Twenty-six percent of the calculated PaO(2)/FiO(2) ratios varied >13 kPa for the same patient. CONCLUSION: Frequent use of drug administration through inhalation and endotracheal suctioning predispose to derecruitment of the lungs, possibly resulting in the large variations in PaO(2)/FiO(2) ratios observed during the 24-h study period. Recruitment maneuvers were performed only in one-fifth of the patients during the day of the survey.
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45. |
- Grivans, Christina, 1963, et al.
(författare)
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Positive end-expiratory pressure-induced changes in end-expiratory lung volume measured by spirometry and electric impedance tomography.
- 2011
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 55:9, s. 1068-77
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Tidskriftsartikel (refereegranskat)abstract
- A bedside tool for monitoring changes in end-expiratory lung volume (ΔEELV) would be helpful to set optimal positive end-expiratory pressure (PEEP) in acute lung injury/acute respiratory distress syndrome patients. The hypothesis of this study was that the cumulative difference of the inspiratory and expiratory tidal volumes of the first 10 breaths after a PEEP change accurately reflects the change in lung volume following a PEEP alteration.
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46. |
- Gåsvaer, Daniel, et al.
(författare)
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Att utveckla den smarta svetscellen : Lean, svetsteknik och automation
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En svetscell producerar och är produktiv när svetsning pågår och ljubågen brinner. Då skapas värde i en svetscell. För att nå teknisk och ekonomisk framgång, behöver svetscellen fungera "smart" med effektiva flöden, hög tillgänglighet, optimerad svetsteknik och ur flera aspekter goda miljöegenskaper. Skriften fungerar som hjälp när företag vill utveckla sin svetsverkstad och förbättra svetsproduktionen, utifrån lean, svetsteknik och automation.
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47. |
- Hadziabdic, Emina, et al.
(författare)
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Boundaries and conditions of interpretation in multilingual and multicultural elderly healthcare
- 2015
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Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 15, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundElderly migrants who do not speak the official language of their host country have increased due to extensive international migration, and will further increase in the future. This entails major challenges to ensure good communication and avoid communication barriers that can be overcome by the use of adequate interpreter services. To our knowledge, there are no previous investigations on interpreting practices in multilingual elderly healthcare from different healthcare professionals’ perspectives. This study examines issues concerning communication and healthcare through a particular focus on interpretation between health professionals and patients of different ethnic and linguistic backgrounds. The central aim of the project is to explore interpretation practices in multilingual elderly healthcare.MethodsA purposive sample of 33 healthcare professionals with experience of using interpreters in community multilingual elderly healthcare. Data were collected between October 2013 and March 2014 by 18 individual and four focus group interviews and analysed with qualitative content analysis.ResultsThe main results showed that interpreting practice in multilingual elderly healthcare was closely linked to institutional, interpersonal and individual levels. On the organizational level, however, guidelines for arranging the use of interpreters at workplaces were lacking. Professional interpreters were used on predictable occasions planned long in advance, and bilingual healthcare staff and family members acting as interpreters were used at short notice in everyday caring situations on unpredictable occasions. The professional interpreter was perceived as a person who should interpret spoken language word-for-word and who should translate written information. Furthermore, the use of a professional interpreter was not adapted to the context of multilingual elderly healthcare.ConclusionThis study found that interpreter practice in multilingual elderly healthcare is embedded in the organizational environment and closely related to the individual’s language skills, cultural beliefs and socio-economic factors. In order to formulate interpreter practice in the context of multilingual elderly healthcare it is important to consider organizational framework and cultural competence, cultural health knowledge, beliefs and customs.
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48. |
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49. |
- Hanson, Charles, 1958, et al.
(författare)
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Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.
- 2009
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 24:11, s. 2960-4
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Tidskriftsartikel (refereegranskat)abstract
- In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo.
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50. |
- Herr, Patrick, et al.
(författare)
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A genome-wide IR-induced RAD51 foci RNAi screen identifies CDC73 involved in chromatin remodeling for DNA repair
- 2015
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Ingår i: Cell discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- To identify new regulators of homologous recombination repair, we carried out a genome-wide short-interfering RNA screen combined with ionizing irradiation using RAD51 foci formation as readout. All candidates were confirmed by independent short-interfering RNAs and validated in secondary assays like recombination repair activity and RPA foci formation. Network analysis of the top modifiers identified gene clusters involved in recombination repair as well as components of the ribosome, the proteasome and the spliceosome, which are known to be required for effective DNA repair. We identified and characterized the RNA polymerase II-associated protein CDC73/Parafibromin as a new player in recombination repair and show that it is critical for genomic stability. CDC73 interacts with components of the SCF/Cullin and INO80/NuA4 chromatin-remodeling complexes to promote Histone ubiquitination. Our findings indicate that CDC73 is involved in local chromatin decondensation at sites of DNA damage to promote DNA repair. This function of CDC73 is related to but independent of its role in transcriptional elongation.
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