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| 2. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 3. |
- Weilenmann, S., et al.
(författare)
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Emotion transfer, emotion regulation, and empathy-related processes in physician-patient interactions and their association with physician well-being : A theoretical model
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 9:AUG
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Tidskriftsartikel (refereegranskat)abstract
- Physicians experience many emotionally challenging situations in their professional lives, influencing their emotional state through emotion contagion or social appraisal processes. Successful emotion regulation is crucial to sustain health, enable well-being, foster resilience, and prevent burnout or compassion fatigue. Despite the alarmingly high rate of stress-related disorders in physicians, affecting not only physician well-being, but also outcomes such as physician performance, quality of care, or patient satisfaction, research on how to deal with emotionally challenging situations in physicians is lacking. Based on extant literature, the present article proposes a theoretical model depicting emotions, emotion regulation, and empathy-related processes and their relation to well-being in provider-client interactions. This model serves as a basis for future research and interventions aiming at improving physician well-being and professional functioning. As a first step, interviews with 21 psychiatrists were conducted. Results of qualitative and initial quantitative analyses provided detailed descriptions of the model’s components confirming its usefulness for detecting mechanisms linking emotion regulation and well-being in psychiatrist-patient interactions. Additionally, results lend preliminary support for the validity of the model, suggesting that successful regulation of emotions (i.e., achieving a desired emotional state) elicited by cyclical transfer processes in provider-client interactions is associated with both short- and long-term well-being and resilience. Furthermore, empathy-related emotions and their regulation seem to be linked to well-being. Based on the results of the present study, a prospective longitudinal study is under preparation, which is intended to inform effective interventions targeting emotion transfer, empathy-related processes, and emotion regulation in physicians’ professional lives. The model and results are also potentially applicable to other health care and social services providers. © 2018 Weilenmann, Schnyder, Parkinson, Corda, von KÀnel and Pfaltz.
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| 4. |
- Weilenmann, S., et al.
(författare)
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Self-worth and bonding emotions are related to well-being in health-care providers : a cross-sectional study
- 2021
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Ingår i: BMC Medical Education. - : BioMed Central Ltd. - 1472-6920. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interacting with patients can elicit a myriad of emotions in health-care providers. This may result in satisfaction or put providers at risk for stress-related conditions such as burnout. The present study attempted to identify emotions that promote provider well-being. Following eudaimonic models of well-being, we tested whether certain types of emotions that reflect fulfilment of basic needs (self-worth, bonding with patients) rather than positive emotions in general (as suggested by hedonic models) are linked to well-being. Specifically, we hypothesized that well-being is associated with positive emotions directed at the self, which reflect self-worth, and positive as well as negative emotions (e.g., worry) directed at the patient, which reflect bonding. However, we expected positive emotions directed at an object/situation (e.g., curiosity for a treatment) to be unrelated to well-being, because they do not reflect fulfilment of basic needs. Methods: Fifty eight physicians, nurses, and psychotherapists participated in the study. First, in qualitative interviews, they reported their emotions directed at the self, the patient, or an object/situation during distressing interactions with patients. These emotions were categorised into positive emotions directed towards the self, the patient, and an object/situation, and negative emotions directed towards the patient that reflect bonding. Second, providers completed questionnaires to assess their hedonic and eudaimonic well-being. The well-being scores of providers who did and did not experience these emotions were compared. Results: Providers who experienced positive emotions directed towards the self or the patient had higher well-being than those who did not. Moreover, for the first time, we found evidence for higher well-being in providers reporting negative patient-directed emotions during distressing interactions. There was no difference between providers who did and did not experience positive object/situation-directed emotions. Conclusions: These findings may point towards the importance of “eudaimonic†emotions rather than just positive emotions in interactions with patients. Emotions such as contentment with oneself, joy for the patient’s improvement, and, notably, grief or worry for the patient may build a sense of self-worth and strengthen bonding with the patient. This may explain their association with provider well-being. © 2021, The Author(s).
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| 5. |
- Andersson, Mattias K, 1979, et al.
(författare)
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ATR is a MYB regulated gene and potential therapeutic target in adenoid cystic carcinoma
- 2020
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Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Adenoid cystic carcinoma (ACC) is a rare cancer that preferentially occurs in the head and neck, breast, as well as in other sites. It is an aggressive cancer with high rates of recurrence and distant metastasis. Patients with advanced disease are generally incurable due to the lack of effective systemic therapies. Activation of the master transcriptional regulator MYB is the genomic hallmark of ACC. MYB activation occurs through chromosomal translocation, copy number gain or enhancer hijacking, and is the key driving event in the pathogenesis of ACC. However, the functional consequences of alternative mechanisms of MYB activation are still uncertain. Here, we show that overexpression of MYB or MYB-NFIB fusions leads to transformation of human glandular epithelial cells in vitro and results in analogous cellular and molecular consequences. MYB and MYB-NFIB expression led to increased cell proliferation and upregulation of genes involved in cell cycle control, DNA replication, and DNA repair. Notably, we identified the DNA-damage sensor kinase ATR, as a MYB downstream therapeutic target that is overexpressed in primary ACCs and ACC patient-derived xenografts (PDXs). Treatment with the clinical ATR kinase inhibitor VX-970 induced apoptosis in MYB-positive ACC cells and growth inhibition in ACC PDXs. To our knowledge, ATR is the first example of an actionable target downstream of MYB that could be further exploited for therapeutic opportunities in ACC patients. Our findings may also have implications for other types of neoplasms with activation of the MYB oncogene.
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| 6. |
- Bishop, D. Timothy, et al.
(författare)
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Genome-wide association study identifies three loci associated with melanoma risk
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:8, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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| 7. |
- Leonard, Hampton L., et al.
(författare)
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The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data
- 2023
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Ingår i: npj Parkinson's Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.
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| 8. |
- Lüscher, Bernhard, et al.
(författare)
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ADP-ribosyltransferases, an update on function and nomenclature
- 2022
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:23, s. 7399-7410
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Tidskriftsartikel (refereegranskat)abstract
- ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD+ onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases. Importantly, inhibitors of ARTs are approved or are being developed for clinical use. Moreover, ADP-ribosylhydrolases are being assessed as therapeutic targets, foremost as antiviral drugs and for oncological indications. Due to the development of novel reagents and major technological advances that allow the study of ADP-ribosylation in unprecedented detail, an increasing number of cellular processes and pathways are being identified that are regulated by ADP-ribosylation. In addition, characterization of biochemical and structural aspects of the ARTs and their catalytic activities have expanded our understanding of this protein family. This increased knowledge requires that a common nomenclature be used to describe the relevant enzymes. Therefore, in this viewpoint, we propose an updated and broadly supported nomenclature for mammalian ARTs that will facilitate future discussions when addressing the biochemistry and biology of ADP-ribosylation. This is combined with a brief description of the main functions of mammalian ARTs to illustrate the increasing diversity of mono- and poly-ADP-ribose mediated cellular processes.
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