| 1. |
- Frosi, Y, et al.
(författare)
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Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4854-
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Tidskriftsartikel (refereegranskat)abstract
- An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications.
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| 2. |
- Dewitte, Marieke, et al.
(författare)
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A Network Analysis of the Fear Avoidance Model of Genital Pain
- 2024
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Ingår i: Journal of Sex Research. - : Routledge. - 0022-4499 .- 1559-8519.
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Tidskriftsartikel (refereegranskat)abstract
- Using a novel data-driven network approach, this study aimed to examine the interconnection between the key elements of the Fear-Avoidance Model of female genital pain - sexual arousal, fear-avoidant cognitions, and motivational coping - and its associated factors to predict the intensity and frequency of genital pain across women over time. Network modeling allowed for a comprehensive evaluation of the Fear-Avoidance model while capturing the dynamic features of genital pain. We estimated a cross-sectional and a temporal, contemporaneous, and between-persons network model on convenience-based data of 543 female students (mean age = 23.7 years, SD = 3.6) collected at three time points. Results showed that lubrication, pain catastrophizing, pain avoidance, fear-avoidance beliefs, sexual satisfaction, anxiety, and frequency of coital and non-coital sex predicted pain, with lubrication being the most consistent predictor across estimations. The network of women with recurrent genital pain showed a similar pattern as the network of the total sample, except that pain avoidance and fear-avoidance beliefs rather than pain catastrophizing predicted pain directly, and frequency of coital and non-coital sexual activities played a more prominent role. These results suggest that the main problem of genital pain centers around women not being sufficiently aroused during intercourse and inadequate ways of pain coping, which are critical targets of cognitive-behavioral therapy treatment and should be developed further.
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| 3. |
- Ekholm, Elin, 1981-, et al.
(författare)
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Coping with provoked vestibulodynia in a relational context-A cluster analysis of coping patterns and their associations with relational cognitions and goals
- 2024
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Ingår i: European Journal of Pain. - : John Wiley & Sons. - 1090-3801 .- 1532-2149.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProvoked vestibulodynia (PVD) is a common pain condition, negatively impacting the relationships and sexual lives of sufferers. Women's coping behaviour has been associated with psychosexual outcomes, yet coping patterns in clinical PVD samples are unexplored, and it is not known how women's coping relates to their relational context.MethodWomen (N = 128) with PVD answered questionnaires about psychosexual function, pain coping (avoidance and endurance), relational- and pain catastrophizing, sexual goals and perceived partner responses. Cluster analysis was used to explore coping patterns; clusters were validated on measures of pain and psychosexual function and compared on catastrophizing, sexual goals and partner responses using multivariate analyses of variance.ResultsThe analysis yielded four clusters: endurance; combined high avoidance and endurance; avoidance; and combined low. The group with high levels of both avoidance and endurance coping displayed the worst psychosexual outcomes and high levels of pain- and relational catastrophizing, approach and avoidance goals and perceived negative partner responses.ConclusionThere are distinct patterns of coping among women with PVD, and these coping patterns are associated with psychosexual outcomes and relational cognitions and goals, and perceived partner responses. Women who alternate between avoidance and endurance are more distressed and report worse psychosexual functioning. This pattern needs to be identified and addressed in the treatment of PVD.Significance StatementThis study extends previous findings on vulvar pain coping patterns to a clinical population of women with PVD. It is further the first study to address the relationship between relational variables, such as partner responses and relational catastrophizing and different coping patterns. Thus, the contribution of this study is the contextualizing of coping patterns among women with PVD. The results showed that a combined pattern of avoidance and endurance coping is associated with high distress, poor psychosexual outcomes, and indications of insufficient relational coping, highlighting the need for clinical assessment and intervention to target both women's individual coping patterns and their relational context.
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| 4. |
- Engman, Linnea, 1987-, et al.
(författare)
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An initial proof of concept : A replicated single-case study of a CBT group treatment with partner involvement for vulvodynia.
- 2022
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Ingår i: Cognitive Behaviour Therapy. - : Routledge. - 1650-6073 .- 1651-2316. ; 51:6, s. 503-519
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Tidskriftsartikel (refereegranskat)abstract
- Vulvodynia is common and has an immense impact on affected women and their partners. Psychological factors have been found to contribute to pain maintenance and exacerbation, and treatments addressing psychological factors have yielded positive results. This study employed a replicated single-case experimental design to examine a cognitive behavioral therapy (CBT) group treatment with partner involvement in vulvodynia. Repeated measures of pain intensity related to pain-inflicting behaviors were collected weekly throughout baseline and treatment phases. Associated outcomes were measured pre-, post- and at two follow-up assessments. Participants were 18-45-year-old women, in a stable sexual relationship with a man, experiencing vulvodynia. Five women completed the treatment consisting of 10 group sessions and 3 couple sessions. Data were analyzed through visual inspection and supplementary nonparametric calculations. The study showed promising results of the CBT treatment in alleviating pain intensity in connection to specific pain-inflicting behavior since three out of five participants showed improvements. For the participants who improved, sexual function, pain catastrophizing, avoidance, and endurance behavior changed during treatment and were maintained at follow-ups. These results warrant further study of the CBT treatment, in larger, and controlled formats.
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| 5. |
- Flink, Ida K., 1980-, et al.
(författare)
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Expecting the uncertain : The applicability of the intolerance of uncertainty model on fear of childbirth
- 2023
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Ingår i: Journal of Psychosomatic Obstetrics and Gynaecology. - : Taylor & Francis. - 0167-482X .- 1743-8942. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- A considerable number of pregnant women experience fear of childbirth (FOC), characterized by worries and fear of the unpredictable. Despite this, the psychological processes in FOC have received notably little attention. The aim of this study was to advance the understanding by exploring the applicability of the Intolerance of Uncertainty (IU) model on FOC. Anonymous data was collected in a sample of pregnant women (N = 357) with varying levels of FOC. Analyses supported the associations between FOC and all proposed psychological processes: IU, negative problem orientation, positive beliefs about worry and avoidance of inner experiences. The exploration of potential mediators of the relation between IU and FOC revealed that, of the three processes from the model, only positive beliefs about worry were a mediator, and more specifically, a partial mediator between IU and FOC. These findings add to the theoretical understanding of FOC, by indicating that the role of IU may be similar to other conditions inflicted by worry and anxiety, which may inform treatment development. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 6. |
- Jennions, Elizabeth, et al.
(författare)
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A novel homozygous pathogenic missense variant in COX6B1: Further delineation of the phenotype
- 2024
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Ingår i: AMERICAN JOURNAL OF MEDICAL GENETICS PART A. - 1552-4825 .- 1552-4833.
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Tidskriftsartikel (refereegranskat)abstract
- Cytochrome c oxidase (COX) deficiency is a phenotypically diverse group of diseases caused by variants in over 30 genes. Biallelic pathogenic variants in COX6B1 have been described in four patients to date with varying disease manifestations. We describe the clinical features and follow-up of a patient with a novel homozygous pathogenic variant in COX6B1 who presented acutely with severe encephalomyopathy associated with an infection. New findings include ophthalmological evaluation and follow-up of neuroradiological investigations. The novel p.Trp31Arg variant was predicted to be pathogenic in silico, and further functional analyses with biochemical analysis of mitochondrial function showed isolated COX deficiency. Muscle biopsy showed a specific lack of COX6B1 protein together with complex IV deficiency on western blot, enzyme histochemistry, and immuno-histochemistry.
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| 7. |
- Olsson, K., et al.
(författare)
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Cognitive Development in Single-Suture Craniosynostosis : A Systematic Review
- 2023
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Ingår i: Developmental Neuropsychology. - : Taylor & Francis Group. - 8756-5641 .- 1532-6942. ; 48:5, s. 215-247
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Forskningsöversikt (refereegranskat)abstract
- There is conflicting evidence whether single-suture craniosynostosis (SSC), is linked to adversities of cognitive development. To assess the evidence for a link between SSC and cognition, a systematic literature search was conducted and eligible studies assessed for inclusion by two independent readers. Forty-eight studies met inclusion criteria. Small to medium but persistent effects on both general and some specific cognitive functions across age bands were found in higher quality studies for SSC overall. There was limited evidence for effects related to surgical correction. Methodologies varied substantially and there was a lack of longitudinal studies using broad assessment batteries.
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