Kohti mahdollistavaa tiedediplomatiaa: Suomalaisen tiedediplomatian tila ja kehittämistarpeet

Globaalit ilmiöt, kuten ilmastomuutos tai koronapandemia, ja ylikansalliset keskinäisriippuvuudet ovat korostaneet tiedediplomatian merkitystä. Kansallisten ja kansainvälisten tavoitteiden saavuttaminen tiedediplomatian keinoin edellyttää paitsi ilmiön tunnettavuuden edistämistä, myös sen strategista haltuunottoa.Tässä hankkeessa on selvitetty suomalaisen tiedediplomatian tilaa ja kehittämistarpeita. Selvitys lähtee liikkeelle tiedediplomatian kolmijaosta: science in diplomacy (tieteellisen tiedon hyödyntäminen päätöksenteossa), diplomacy for science (diplomatian merkitys tieteellisen yhteistyön tukemisessa) ja science for diplomacy (tieteellisen yhteistyön merkitys kansainvälisten suhteiden kehittämisessä). Tämän lisäksi huomioidaan niin kansallinen intressipohjaisuus, kuin kansainväliset verkostot. Selvityksessä tehdään laaja läpileikkaus tiedediplomatian kansainväliseen tilaan, jossa käsitellään Suomelle merkityksellisiä areenoita ja toimijoita. Tiedediplomatiaverkostojen merkitystä tarkastellaan Kansainvälisen ilmastopaneelin (IPCC) ja Kansainvälisen biodiversiteettipaneelin (IPBES) toiminnassa.Suomalaisen tiedediplomatian nykytilan arvioimiseksi hankkeessa on hyödynnetty hallinnon ja tiedeyhteisön edustajille suunnattua kyselyä, asiantuntijahaastatteluita ja työpajoja. Arvioinnissa tunnistetaan Suomen tiedediplomatian haasteita, sekä pohditaan ennakoivan tiedediplomatiastrategian mahdollisuuksia. Lopuksi raportissa esitetään kymmenen kehittämissuositusta suomalaisen tiedediplomatian vahvistamiseksi.</p

Kohti mahdollistavaa tiedediplomatiaa : Suomalaisen tiedediplomatian tila ja kehittämistarpeet

Globaalit ilmiöt, kuten ilmastomuutos tai koronapandemia, ja ylikansalliset keskinäisriippuvuudet ovat korostaneet tiedediplomatian merkitystä. Kansallisten ja kansainvälisten tavoitteiden saavuttaminen tiedediplomatian keinoin edellyttää paitsi ilmiön tunnettavuuden edistämistä, myös sen strategista haltuunottoa. Tässä hankkeessa on selvitetty suomalaisen tiedediplomatian tilaa ja kehittämistarpeita. Selvitys lähtee liikkeelle tiedediplomatian kolmijaosta: science in diplomacy (tieteellisen tiedon hyödyntäminen päätöksenteossa), diplomacy for science (diplomatian merkitys tieteellisen yhteistyön tukemisessa) ja science for diplomacy (tieteellisen yhteistyön merkitys kansainvälisten suhteiden kehittämisessä). Tämän lisäksi huomioidaan niin kansallinen intressipohjaisuus, kuin kansainväliset verkostot. Selvityksessä tehdään laaja läpileikkaus tiedediplomatian kansainväliseen tilaan, jossa käsitellään Suomelle merkityksellisiä areenoita ja toimijoita. Tiedediplomatiaverkostojen merkitystä tarkastellaan Kansainvälisen ilmastopaneelin (IPCC) ja Kansainvälisen biodiversiteettipaneelin (IPBES) toiminnassa. Suomalaisen tiedediplomatian nykytilan arvioimiseksi hankkeessa on hyödynnetty hallinnon ja tiedeyhteisön edustajille suunnattua kyselyä, asiantuntijahaastatteluita ja työpajoja. Arvioinnissa tunnistetaan Suomen tiedediplomatian haasteita, sekä pohditaan ennakoivan tiedediplomatiastrategian mahdollisuuksia. Lopuksi raportissa esitetään kymmenen kehittämissuositusta suomalaisen tiedediplomatian vahvistamiseksi.Tämä julkaisu on toteutettu osana valtioneuvoston selvitys- ja tutkimussuunnitelman toimeenpanoa. (tietokayttoon.fi) Julkaisun sisällöstä vastaavat tiedon tuottajat, eikä tekstisisältö välttämättä edusta valtioneuvoston näkemystä

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease–Associated Colorectal Cancer

doi: 10.1053/j.gastro.2021.04.042Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. Results Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. Conclusions Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. METHODS: Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC. RESULTS: Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNTinduced epithelial-mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4 alpha binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 50 untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs. CONCLUSIONS: Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.Peer reviewe

Determinants of self-rated health and self-rated physical fitness in middle and old age

Self-rated health (SRH) correlates with psychological factors, mortality and functional capacity. Self-rated physical fitness (SRF) has been examined less, and the relationship between SRH and SRF has remained unclear. The aim of this study was to explore the determinants, differences and similarities of these concepts in middle and old age. In total, 2 000 persons at the mean age of 50.6 years were examined at baseline in, and 1449 were re-examined when they were aged between 65 and 79 years. On both occasions, the participants underwent a comprehensive clinical examination and health status/habit assessment. We found a strong correlation between SRH and SRF. In midlife, low income, hopelessness, active use of health care services, physical inactivity, history of angina pectoris, arthropathy, and elevated blood pressure were associated with both poor SRH and SRF. In old age, high income, alcohol abstinence, physical inactivity, hopelessness, difficulties in activities of daily living, history of angina pectoris, asthma, rheumatoid arthritis and musculoskeletal disease of the back, and (in men) urinary tract infection were associated with poor SRH and SRF. Income, hopelessness, physical activity and angina pectoris correlated with both instruments in both age groups. In general, a wider range of variables was associated with SRH than with SRF. The determinants of SRH and SRF were relatively similar in the younger and older age groups. However, SRH appeared to be more multi-dimensional instrument than SRF. SRH and SRF are considered reliable indicators of mental and physical health status, and should be accorded more importance when evaluating health among middle aged and older people. Key words: cross-sectional study, self-rated health, self-rated fitness, self-perceptio

The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells. We also briefly summarize the consequences of constitutive Nrf2 activation in cancer cells and how this can be exploited in cancer gene therapy