| 21. |
- Schröder Håkansson, Anna, 1964, et al.
(författare)
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Balancing values and obligations when obtaining informed consent: Healthcare professionals' experiences in Swedish paediatric oncology
- 2020
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 109:5, s. 1040-1048
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Tidskriftsartikel (refereegranskat)abstract
- Aim To explore Swedish healthcare professionals' (HCPs) clinical experiences of the informed consent process (ICP) and to compare experiences between the professions. Methods In this nationwide study six paediatric oncologists (POs) and eight research nurses (ReNs) from all Swedish paediatric oncology centres were interviewed. The material was analysed using Grounded theory, a qualitative constant comparative method. Results The participants' main concern was how to fulfil research obligations without putting too much strain on a family in acute crisis, which led to the core category of balancing values and obligations of both healthcare and research. To handle the challenges the participants' struggled to safeguard the families from psychological harm, tried to adjust to the families, and gradually introduced research while building trust. The conceptual model developed in the study highlights potential consequences of this balancing act with a risk of diminishing the family's autonomy through HCPs acting authoritatively (in particular POs) or with overprotection (in particular ReNs). Conclusion Paediatric oncology is a research integrated healthcare environment. The HCPs need personal, professional and institutional support regarding ICP-related ethical issues, decisions and implications in this intertwined context. Furthermore, HCPs need to be aware of the potential long-term risk of developing professional moral distress.
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| 22. |
- Weiland, F., et al.
(författare)
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Ovarian Blood Sampling Identifies Junction Plakoglobin as a Novel Biomarker of Early Ovarian Cancer
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the most lethal gynecologic malignancy. Early detection would improve survival, but an effective diagnostic test does not exist. Novel biomarkers for early ovarian cancer diagnosis are therefore warranted. We performed intraoperative blood sampling from ovarian veins of stage I epithelial ovarian carcinomas and analyzed the serum proteome. Junction plakoglobin (JUP) was found to be elevated in venous blood from ovaries with malignancies when compared to those with benign disease. Peripheral plasma JUP levels were validated by ELISA in a multicenter international patient cohort. JUP was significantly increased in FIGO serous stage IA+B (1.97-fold increase; p < 0.001; n = 20), serous stage I (2.09-fold increase; p < 0.0001; n = 40), serous stage II (1.81-fold increase, p < 0.001, n = 23) and serous stage III ovarian carcinomas (1.98-fold increase; p < 0.0001; n = 34) vs. normal controls (n = 109). JUP plasma levels were not increased in early stage breast cancer (p = 0.122; n = 12). In serous ovarian cancer patients, JUP had a sensitivity of 85% in stage IA+B and 60% in stage IA-C, with specificities of 76 and 94%, respectively. A logistic regression model of JUP and Cancer Antigen 125 (CA125) revealed a sensitivity of 70% for stage IA+B and 75% for stage IA-C serous carcinomas at 100% specificity. Our novel ovarian blood sampling – proteomics approach identified JUP as a promising new biomarker for epithelial ovarian cancer, which in combination with CA125 might fulfill the test criteria for ovarian cancer screening. © Copyright © 2020 Weiland, Lokman, Klingler-Hoffmann, Jobling, Stephens, Sundfeldt, Hoffmann and Oehler.
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| 23. |
- Pozzoli, Susanna, et al.
(författare)
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Domain expertise–agnostic feature selection for the analysis of breast cancer data*
- 2020
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Ingår i: Artificial Intelligence in Medicine. - : Elsevier B.V.. - 0933-3657 .- 1873-2860. ; 108
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Tidskriftsartikel (refereegranskat)abstract
- Progress in proteomics has enabled biologists to accurately measure the amount of protein in a tumor. This work is based on a breast cancer data set, result of the proteomics analysis of a cohort of tumors carried out at Karolinska Institutet. While evidence suggests that an anomaly in the protein content is related to the cancerous nature of tumors, the proteins that could be markers of cancer types and subtypes and the underlying interactions are not completely known. This work sheds light on the potential of the application of unsupervised learning in the analysis of the aforementioned data sets, namely in the detection of distinctive proteins for the identification of the cancer subtypes, in the absence of domain expertise. In the analyzed data set, the number of samples, or tumors, is significantly lower than the number of features, or proteins; consequently, the input data can be thought of as high-dimensional data. The use of high-dimensional data has already become widespread, and a great deal of effort has been put into high-dimensional data analysis by means of feature selection, but it is still largely based on prior specialist knowledge, which in this case is not complete. There is a growing need for unsupervised feature selection, which raises the issue of how to generate promising subsets of features among all the possible combinations, as well as how to evaluate the quality of these subsets in the absence of specialist knowledge. We hereby propose a new wrapper method for the generation and evaluation of subsets of features via spectral clustering and modularity, respectively. We conduct experiments to test the effectiveness of the new method in the analysis of the breast cancer data, in a domain expertise–agnostic context. Furthermore, we show that we can successfully augment our method by incorporating an external source of data on known protein complexes. Our approach reveals a large number of subsets of features that are better at clustering the samples than the state-of-the-art classification in terms of modularity and shows a potential to be useful for future proteomics research.
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| 24. |
- Rydén, Isabelle, et al.
(författare)
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Return to work following diagnosis of low-grade glioma: A nationwide matched cohort study.
- 2020
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 95:7, s. e856-e866
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Tidskriftsartikel (refereegranskat)abstract
- Return-to-work (RTW) following diagnosis of infiltrative low-grade gliomas (LGG) is unknown.Swedish patients with histopathological verified WHO grade II diffuse glioma diagnosed between 2005-2015 were included. Data were acquired from several Swedish registries. A total of 381 patients aged 18-60 were eligible. A matched control population (n=1900) was acquired. Individual data on sick leave, compensations, comorbidity and treatments assigned were assessed. Predictors were explored using multivariable logistic regression.One year before surgery/index date, 88 % of cases were working compared to 91 % of controls. The proportion of controls working remained constant, while patients had a rapid increase in sick leave approximately six months prior to surgery. After one and two years respectively, 52 % and 63 % of the patients were working. Predictors for no-RTW after one year were previous sick leave (OR 0.92, 95 % CI 0.88-0.96, p <0.001), older age (OR 0.96, 95 % CI 0.94-0.99, p=0.005) and lower functional level (OR 0.64 95% CI, 0.45-0.91 p=0.01). Patients receiving adjuvant treatment were less likely to RTW within the first year. At two years, biopsy (as opposed to resection), female sex and comorbidity were also unfavorable, while age and adjuvant treatment were no longer significant.Approximately half of the patients RTW within the first year. Lower functional status, previous sick leave, older age and adjuvant treatment were risk factors for no-RTW at one year after surgery. Female sex, comorbidity and biopsy only were also unfavorable for RTW at two years.
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| 25. |
- Järvholm, Stina, et al.
(författare)
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INFLUENCE OF FERTILITY ON FAMILY PLANNING DECISIONS AMONG MIDDLEAGED SURVIVORS OF CHILDHOOD CANCER: A QUALITATIVE STUDY
- 2020
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Ingår i: Journal of Cancer Rehabilitation (EDISCIENCES). - 2704-6494. ; 3, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- Background As the number of childhood cancer survivors increases, there is a need to affront associated issues in adulthood such as anxiety, depression, and infertility. The aim of this qualitative study was to examine how childhood cancer survivors at the end of their fertile period were informed about fertility earlier in life and to investigate how this information influenced family planning decisions during adulthood. Methods The study included childhood cancer survivors in western Sweden ages 37–45 years identified from the Childhood Cancer Registry. Ten women and eight men ultimately participated in the study. Participants had been treated for cancer at a median age of 14 years (range, 2.5–17.5 years) and the median time since diagnosis was 26.0 years (range, 21.0–44.5 years). The study design consisted of a semi-structured interview and thematic analysis. Results A master theme that emerged from interviews was A long and uncertain road, which was divided into three underlying subthemes: Pictures of fertility e.g., from healthcare providers or parents; Experience of fertility e.g., searching as an adult, feeling like everyone else, not for me; and Emotions and fertility e.g., better not to think about it, cancer will affect my child. Women scored consistently lower than men on questionnaires regarding quality of life. Conclusion Most participants felt that they received insufficient information about fertility after cancer. The present study also highlighted a lack of support for cancer survivors into adulthood, which affected their psychological well-being and their inclination to become parents themselves.
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| 26. |
- Björn, Niclas, 1990-, et al.
(författare)
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Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients
- 2020
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Ingår i: npj Systems Biology and Applications. - : Nature Publishing Group. - 2056-7189. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p ≤ 1 × 10−3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3–4) and low (CTCAE 0–1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.
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| 27. |
- Tomic, Tajana Tesan, et al.
(författare)
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MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression
- 2020
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors. © 2020 Tomic et al.
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| 28. |
- Li, Xiangyu, et al.
(författare)
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Classification of clear cell renal cell carcinoma based on PKM alternative splicing
- 2020
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
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| 29. |
- Limeta, Angelo, 1996, et al.
(författare)
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Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma.
- 2020
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Ingår i: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDIdentifying factors conferring responses to therapy in cancer is critical to select the best treatment for patients. For immune checkpoint inhibition (ICI) therapy, mounting evidence suggests that the gut microbiome can determine patient treatment outcomes. However, the extent to which gut microbial features are applicable across different patient cohorts has not been extensively explored.METHODSWe performed a meta-analysis of 4 published shotgun metagenomic studies (Ntot = 130 patients) investigating differential microbiome composition and imputed metabolic function between responders and nonresponders to ICI.RESULTSOur analysis identified both known microbial features enriched in responders, such as Faecalibacterium as the prevailing taxa, as well as additional features, including overrepresentation of Barnesiella intestinihominis and the components of vitamin B metabolism. A classifier designed to predict responders based on these features identified responders in an independent cohort of 27 patients with the area under the receiver operating characteristic curve of 0.625 (95% CI: 0.348-0.899) and was predictive of prognosis (HR = 0.35, P = 0.081).CONCLUSIONThese results suggest the existence of a fecal microbiome signature inherent across responders that may be exploited for diagnostic or therapeutic purposes.FUNDINGThis work was funded by the Knut and Alice Wallenberg Foundation, BioGaia AB, and Cancerfonden.
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| 30. |
- Moll, Jonas, 1982-, et al.
(författare)
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Oncology health-care professionals' perceived effects of patient accessible electronic health records 6 years after launch : A survey study at a major university hospital in Sweden
- 2020
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Ingår i: Health Informatics Journal. - : Sheffield Academic Press. - 1460-4582 .- 1741-2811. ; 26:2, s. 1392-1403
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Tidskriftsartikel (refereegranskat)abstract
- Patient accessible electronic health records have been launched in many countries, and generally, health-care professionals have had strong initial concerns related to the areas patient contact, documentation practices and quality of care. Especially, oncology care was discussed in media when launching patient accessible electronic health records in Sweden. However, few studies have investigated clinician-perceived effects several years after the launch. A survey covering these areas, as well as supposed effects for patients, was distributed to oncology health-care professionals 6 years after the launch of patient accessible electronic health records and answered by N = 176. Results show that patient accessible electronic health records have had small effects within the covered areas, and that the area most affected was documentation practices. Very few significant differences could be found between physicians and nurses. A comparison with results from interviews and surveys conducted shortly after the launch of patient accessible electronic health records clearly indicates that the experienced negative effects are not as big as originally feared.
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