Oncogenic Merkel Cell Polyomavirus T Antigen Truncating Mutations are Mediated by APOBEC3 Activity in Merkel Cell Carcinoma

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Election promises on children’s wellbeing and health 2015 to 2021 – a study of Finnish voting advice applications database

Background: According to the UN Convention on the Rights of the Child, children’s views should be heard in policymaking. But it remains unclear to what extent children’s wellbeing is considered in election promises Methods: We investigated the extent to which Finnish political candidates consider children and their wellbeing in their election promises. We used YLE, the national broadcaster’s voting advice application database, and analysed some 35,000 politicians’ election promises made in the 2015 and 2019 parliamentary and the 2017 and 2021 municipal elections. We calculated the proportion of candidates who mentioned children and examined the content of the election promises in which children were mentioned. Logistic regression models were used to examine the role of the background of the characteristics of candidates. Results: In the 2015 and 2019 elections, some 12% and 19% of candidates, respectively, mentioned children in their election promises. The figures for the 2017 and 2021 municipal elections were higher at 19% and 24%, respectively. In the 2021 election, the candidates considering children in their election promises were younger and had higher education qualifications. Inspection of a random set of 350 promises indicated that common issues mentioned in respect of children were education and hobby activities. Concrete proposals to improve the wellbeing of children were rarely put forward. Conclusions: Political candidates are increasingly considering children in their election promises but concrete proposals to improve the wellbeing and health of children are rare. Effective policy solutions to improve the health of children should be discussed in election debates.©2022 SAGE Publications. The article is protected by copyright and reuse is restricted to non-commercial and no derivative uses. Users may also download and save a local copy of an article accessed in an institutional repository for the user's personal reference.fi=vertaisarvioitu|en=peerReviewed

Is there a need for neoadjuvant short-course radiotherapy in T3 rectal cancer with positive lymph node involvement? A single-center retrospective cohort study

Background Neoadjuvant short-course radiotherapy is used to reduce local recurrences in stage III rectal cancer. Radiotherapy is not harmless, and meticulous total mesorectal excision surgery alone has been reported to result in low local recurrence rate in favorable stage III tumors. The aim was to evaluate the effect of short-course (5 x 5 Gy) radiotherapy on the local recurrence risk in patients with pT3N1-2 rectal cancer. Materials and methods This was a retrospective study with 151 consecutive pT3N1-2M0 rectal cancer patients operated on at Helsinki University Hospital, Helsinki, Finland, during January 2005 to June 2014. Short-course radiotherapy was given to 94 patients, and 57 patients were operated on without neoadjuvant radiotherapy. The main outcome measurement was the effect of radiotherapy on local recurrence. Also, the risk factors for local recurrence were analyzed. Results Local recurrence occurred in a total 17 of 151 (11.3%) patients, 8 of 57 (14.0%) in surgery only group compared with 9 of 94 (9.6%) in radiotherapy plus surgery group (p = 0.44). In univariate Cox regression analysis, the risk factors for local recurrence were tumor location under 6 cm from the anal verge (p = 0.01), involved lateral margin (p <0.001), tumor perforation (p <0.001), and mucinous histology (p = 0.006). In multivariate analysis, risk factors were tumor location under 6 cm from anal verge (p = 0.03) and involved lateral margin (p = 0.002). Conclusion Neoadjuvant short-course radiotherapy did not affect the local recurrence risk of pT3N1-2M0 rectal cancer. Further studies with larger patient number are needed to evaluate the role of short-course radiotherapy in different T3 subgroups (3a-c) as well as in N1 and N2 cancers in separate.Peer reviewe

Incidence of surgically treated post-traumatic hydrocephalus 6 months following head injury in patients undergoing acute head computed tomography

Background Post-traumatic hydrocephalus (PTH) is a well-known complication of head injury. The percentage of patients experiencing PTH in trauma cohorts (0.7-51.4%) varies greatly in the prior literature depending on the study population and applied diagnostic criteria. The objective was to determine the incidence of surgically treated PTH in a consecutive series of patients undergoing acute head computed tomography (CT) following injury. Methods All patients (N=2908) with head injuries who underwent head CT and were treated at the Tampere University Hospital's Emergency Department (August 2010-July 2012) were retrospectively evaluated from patient medical records. This study focused on adults (18 years or older) who were residents of the Pirkanmaa region at the time of injury and were clinically evaluated and scanned with head CT at the Tampere University Hospital's emergency department within 48 h after injury (n = 1941). A thorough review of records for neurological signs and symptoms of hydrocephalus was conducted for all patients having a radiological suspicion of hydrocephalus. The diagnosis of PTH was based on clinical and radiological signs of the condition within 6 months following injury. The main outcome was surgical treatment for PTH. Clinical evidence of shunt responsiveness was required to confirm the diagnosis of PTH. Results The incidence of surgically treated PTH was 0.15% (n = 3). Incidence was 0.08% among patients with mild traumatic brain injury (TBI) and 1.1% among those with moderate to severe TBI. All the patients who developed PTH underwent neurosurgery during the initial hospitalization due to the head injury. The incidence of PTH among patients who underwent neurosurgery for acute traumatic intracranial lesions was 2.7%. Conclusion The overall incidence of surgically treated PTH was extremely low (0.15%) in our cohort. Analyses of risk factors and the evaluation of temporal profiles could not be undertaken due to the extremely small number of cases.Peer reviewe

Oncogenic Merkel Cell Polyomavirus T Antigen Truncating Mutations are Mediated by APOBEC3 Activity in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive skin cancer, which is frequently caused by Merkel cell polyomavirus (MCPyV). Mutations of MCPyV tumor (T) antigens are major pathologic events of virus-positive (MCPyV+) MCCs, but their source is unclear. Activation-induced cytidine deaminase (AID)/APOBEC family cytidine deaminases contribute to antiviral immunity by mutating viral genomes and are potential carcinogenic mutators. We studied the contribution of AID/APOBEC cytidine deaminases to MCPyV large T (LT) truncation events. The MCPyV LT area in MCCs was enriched with cytosine-targeting mutations, and a strong APOBEC3 mutation signature was observed in MCC sequences. AICDA and APOBEC3 expression were detected in the Finnish MCC sample cohort, and LT expression correlated with APOBEC3H and APOBEC3G. Marginal but statistically significant somatic hypermutation targeting activity was detected in the MCPyV regulatory region. Our results suggest that APOBEC3 cytidine deaminases are a plausible cause of the LT truncating mutations in MCPyV+ MCC, while the role of AID in MCC carcinogenesis is unlikely.</p

Towards Circular Economy Business Models : Consumer Acceptance of Novel Services

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Body composition in children with chronic inflammatory diseases: A systematic review

Background & aimsAberrations in body composition are expected in children suffering from chronic inflammatory conditions. The objective is to examine whether children with inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis), coeliac disease, asthma and juvenile idiopathic arthritis (JIA) have an altered body composition as compared to healthy children.MethodsA systematic review, registered in Prospero (registration number: CRD42018107645), was conducted according to PRISMA guidelines. We conducted a search of three databases, Pubmed, Cochrane and Scopus. An assessment of the quality of the study was performed.ResultsData from 50 studies, 32 with IBD, 8 with coeliac disease, 2 with asthma and 8 with JIA, involving 2399 children were selected for review after applying the eligibility criteria. In all but 4 studies, children with Crohn's disease exhibited decreased amounts of fat mass and fat free mass. Reductions in fat mass were also evident in studies in children with coeliac disease. It is uncertain whether body composition is altered in children with asthma or JIA.ConclusionsChildren with Crohn's disease manifest with lowered adiposity and lean mass and therefore are likely to be at risk for suffering malnutrition-related clinical complications. Apart from Crohn's disease, data examining body composition in children with chronic inflammatory conditions are scarce and there is a paucity of reports examining the relationship between inflammation and body composition. Interpretation of the current study results is hampered by the low quality of the studies and due to the fact that the analyses have been habitually secondary outcomes.</p

The effect of music performance on the transcriptome of professional musicians

Music performance by professional musicians involves a wide-spectrum of cognitive and multi-sensory motor skills, whose biological basis is unknown. Several neuroscientific studies have demonstrated that the brains of professional musicians and non-musicians differ structurally and functionally and that musical training enhances cognition. However, the molecules and molecular mechanisms involved in music performance remain largely unexplored. Here, we investigated the effect of music performance on the genome-wide peripheral blood transcriptome of professional musicians by analyzing the transcriptional responses after a 2-hr concert performance and after a 'music-free' control session. The up-regulated genes were found to affect dopaminergic neurotransmission, motor behavior, neuronal plasticity, and neurocognitive functions including learning and memory. Particularly, candidate genes such as SNCA, FOS and DUSP1 that are involved in song perception and production in songbirds, were identified, suggesting an evolutionary conservation in biological processes related to sound perception/production. Additionally, modulation of genes related to calcium ion homeostasis, iron ion homeostasis, glutathione metabolism, and several neuropsychiatric and neurodegenerative diseases implied that music performance may affect the biological pathways that are otherwise essential for the proper maintenance of neuronal function and survival. For the first time, this study provides evidence for the candidate genes and molecular mechanisms underlying music performance.Peer reviewe

Multi-inflammatory syndrome and Kawasaki disease in children during the COVID-19 pandemic : A nationwide register-based study and time series analysis

Aim We investigated whether the ongoing COVID-19 pandemic was associated with the occurrence of Kawasaki disease or with multi-inflammatory syndrome in children (MIS-C). Methods This national Finnish register-based study was based on laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, MIS-C and Kawasaki disease cases. We performed a time series analysis on the occurrence of Kawasaki disease in 2016-2020. Results In 2020, there were 5170 laboratory-confirmed COVID-19 cases in children under 18 years of age and five fulfilled the MIS-C case definition. The occurrence of MIS-C was 0.97 per 1000 (95% confidence interval: 0.31-2.26) laboratory-confirmed SARS-CoV-2 infections in children. Our time series analysis showed that Kawasaki disease cases decreased during the COVID-19 pandemic. The seasonally adjusted incidence rate ratio was 0.49 (95% confidence interval: 0.32-0.74) when it was compared to pre-pandemic levels. This coincided with a reduced occurrence of respiratory infections, due to social distancing in the population. Conclusion This nationwide register-based study found that MIS-C was a rare complication of the SARS-CoV-2 infection. The occurrence of Kawasaki disease and respiratory infections decreased during the pandemic. This suggests that transmissible microbes may play an important role in Kawasaki disease and social distancing may have a protective effect.Peer reviewe