| 1. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 2. |
- Danielsson, Johanna, et al.
(författare)
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Medical students’ experiences in learning to perform pelvic examinations : a mixed-methods study
- 2021
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Ingår i: International Journal of Medical Education. - Nottingham : Medical Education Unit University of Nottingham. - 2042-6372. ; 12, s. 233-242
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We aimed to explore learning experiences among medical students learning to perform pelvic examinations and to identify factors that facilitate their training.Methods: A mixed-methods study including a web-based survey and focus group discussions (FGDs) was conducted among medical students who had completed their obstetrics and gynaecology (ObGyn) clerkship. The FGDs were recorded, transcribed and analysed using qualitative content analysis with systematic text condensation. Survey factors were compared using the χ2 test or Fisher's exact test.Results: 160 students (97 female, 61 male, two other) at six universities in Sweden responded to the survey. Two mixed FGDs were conducted. The majority (87%) of the students experienced confidence in performing pelvic examinations, stating that sufficient, repeated training opportunities and support from a clinical tutor were crucial components of the learning experience. Prior to the ObGyn clerkship, negative expectations were more common among male students. The male participants experienced having a disadvantage because of their gender, while female students considered their gender an advantage (p<0.001, N=121, Fisher's Exact Test). The clinical tutor and the use of professional patients (PPs) had a fundamental role in providing learning opportunities by including the student in patient care activities.Conclusions: The importance of the clinical tutor, as well as the use of PPs, are important factors when planning education in pelvic examinations, and this knowledge could be used when educating other intimate examinations during medical school. In addition, similar investigations on students' experience in training other intimate examinations could be considered.
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| 3. |
- Garvanska, Dimitriya H., et al.
(författare)
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The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions
- 2024
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Ingår i: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
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Tidskriftsartikel (refereegranskat)abstract
- Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.
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| 4. |
- Green, Caroline, et al.
(författare)
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Combined treatment with radiotherapy, chemotherapy and avelumab results in regression of metastatic Merkel cell carcinoma and improvement of associated Lambert‑Eaton myasthenic syndrome : a case report
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:5
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Tidskriftsartikel (refereegranskat)abstract
- Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mecha‑ noreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert‑Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenom‑ enon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67‑year‑old man presenting with progressive proximal muscle weakness, auto‑ nomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage‑gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radio‑ therapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduc‑ tion. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.
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| 5. |
- Israelsson, Pernilla, et al.
(författare)
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Immunoreactivity of LMO7 and other molecular markers as potential prognostic factors in oropharyngeal squamous cell carcinoma
- 2024
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Ingår i: BMC Oral Health. - : BioMed Central (BMC). - 1472-6831. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043).Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.
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| 6. |
- Kacperczyk-Bartnik, Joanna, et al.
(författare)
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Clinician attitude towards sexual counseling in women with gynecologic malignancies : European Network of Young Gynaecological Oncologists (ENYGO) survey
- 2022
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 32:10, s. 1309-1315
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Both the location of primary disease and treatment side effects may have an impact on sexual function in oncogynecological patients. The aim of this study was to examine the prevalence, strategies, difficulties, and ideas for improvement in sexual counseling among specialists managing patients with gynecologic malignancies.METHODS: This was a cross-sectional survey study performed among healthcare professionals treating patients with gynecologic malignancies. A self-prepared questionnaire included 61 questions concerning general demographic information and different aspects of sexual counseling in the gynecologic oncology practice. Analysis included attitudes, behaviors, management strategies, difficulties, and ideas for possible systemic improvements. Statistical analysis involved descriptive statistics, two-sided chi-square test, and Fisher's exact test.RESULTS: A total of 150 respondents from 46 countries answered the survey. The majority of survey participants stated that sexual counseling of oncological patients is very important (n=73, 49%) or important (n=46, 31%). One hundred and two (68%) respondents agreed that sexual counseling of gynecologic oncology patients should be routinely provided by the specialist managing the primary disease. However, collecting information concerning sexual function is performed often or always by only 21% of respondents and 19% discuss the topic rarely or never. The most frequently indicated barriers leading to difficulties in sexual counseling include lack of time (74%), lack of specialist knowledge (55%), and patient embarrassment (48%). One hundred and seven (71%) respondents expressed interest in participating in sexual counseling workshops organized by the European Society of Gynaecological Oncology (ESGO)/European Network of Young Gynaecological Oncologists (ENYGO), 74 (49%) would like to access webinars on the topic, and 120 (80%) would be interested in materials in the ESGO online educational resources.CONCLUSION: One of the proposed solutions to insufficient access to sexual care for women with gynecologic malignancies is providing access to specialist educational programs for both patients and healthcare specialists.
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| 7. |
- La Russa, Mariaclelia, et al.
(författare)
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Assessment of palliative care training in gynaecological oncology : a survey among European Network of Young Gynae-Oncologists (ENYGO) members
- 2020
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Ingår i: BMJ Supportive & Palliative Care. - : BMJ Publishing Group Ltd. - 2045-435X .- 2045-4368.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Palliative care is an important aspect of gynaecological oncology practice. In order to successfully integrate end-of-life (EOL) care in the disease trajectory, it is crucial to incorporate systematic training in subspecialty programmes in gynaecological oncology. We aimed to evaluate the quality of training in palliative care across gynaecological oncology fellows in Europe and to provide a framework to facilitate learning opportunities.METHODS: A web-based questionnaire was sent to members of the European Network of Young Gynae-Oncologists (ENYGO). The survey consisted of 36 items covering six domains: respondents' characteristics, quality and quantity of teaching, curriculum achievements, observation and feedback, EOL clinical practice and attitudes about palliative care.RESULTS: Of the 703 clinicians enrolled in the study, 142 responded (20.2%). Although the majority worked in university hospitals, only half of them (47%) were in a formal subspecialty programme. The majority of respondents (60%) were trained without a mandatory rotation in palliative care units and considered the quality of EOL care teaching as 'very poor' or 'poor' (57.7%). The majority of respondents (71.6%) did not receive any supervision or feedback at the time of their first consultation on changing the goals of care.CONCLUSION: Our study underlines lack of structured teaching and supervision in palliative care contents among European fellows in gynaecological oncology. Broad education of healthcare providers is a key factor to achieve the integration of palliative care in gynaecological oncology practice. Stakeholders like European Society of Gynaecological Oncology/ENYGO play an important role to facilitate educational activities and training programmes targeting to EOL care.
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| 8. |
- Lindemann, K., et al.
(författare)
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Elderly gynaecological cancer patients at risk for poor end of life care : a population-based study from the Swedish Register of Palliative Care
- 2020
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 59:6, s. 636-643
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Poorer end-of-life (EOL) care for elderly cancer patients has been reported. We assessed the impact of age on 13 indicators for the quality of EOL care as well as adherence to 6 national quality indicators in gynaecological cancer patients.Methods: Age-dependent differences in 13 palliative care quality indicators were studied in gynaecological cancer patients registered in the population-based Swedish Register of Palliative Care. Association between the patient's age and each quality indicator was analyzed by logistic regression, adjusted for place of death where appropriate. Adherence to six national quality indicators determined by the Swedish National Board of Health and Welfare was estimated in all patients.Results: We included 3940 patients with the following age distribution: 1.6% were 18-39 years of age, 12.3% 40-59 years, 37.2% 60-74 years, 28.9% 75-84 years and 20% were ≥85 years. Age-dependent differences in implementation rate were present for some of the 13 quality indicators. Compared to elderly cancer patients, younger patients were more likely to be cared for by a specialized palliative care service, more often informed about imminent death as well as assessed for pain. For most national quality indicators, the goal level was not met. Only for the 'on demand prescription for pain', the goal level was reached.Conclusions: EOL care did not meet national quality indicators in this population-based data from Sweden, in particular in the elderly population. Elderly gynaecological cancer patients are at high risk of poorer EOL care without the involvement of specialized palliative care services. Palliative care services need to be implemented across all institutions of EOL care to ensure good and equal care.
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| 9. |
- Lorenzzi Löfgren de Melo, Alexandra, et al.
(författare)
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Single-molecule array assay reveals the prognostic impact of plasma LRIG1 in ovarian carcinoma
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:11, s. 1425-1433
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously.Materials and methods: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses.Results: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma.Conclusion: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.
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| 10. |
- Malapelle, Umberto, et al.
(författare)
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Reference standards for gene fusion molecular assays on cytological samples : an international validation study
- 2023
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 76:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- Aims Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. Methods Cell lines harbouring EML4(13)–ALK(20) and SLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. Results Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. Conclusions Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.
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