| 1. |
- Bekkhus, Tove, et al.
(författare)
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Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Tumor draining lymph nodes (TDLNs) are the most common metastatic sites in human cancer but are also essential sites for induction of tumor immunity. How different types of primary tumors affect the anti-tumor immune response in the LNs is not fully understood. By analyzing biobank tissue from breast cancer patients, we demonstrate that invasive breast cancer induce dramatic pre-metastatic LN changes affecting the structure and function of the specialized LN vasculature and associated stromal cells, required for recruitment of T-lymphocytes into the LNs. These changes could not be seen in patients with non-invasive breast cancer and provide new insights of how invasive tumors can disrupt essential functions within the immune system. The data also shows promise of LN stromal and vascular changes as possible future biomarkers for prediction of disease progression in human cancer. The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
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| 2. |
- Brandao, Luiz Eduardo M., et al.
(författare)
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Acute sleep loss alters circulating fibroblast growth factor 21 levels in humans: A randomised crossover trial
- 2022
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 31:2
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Tidskriftsartikel (refereegranskat)abstract
- The hormone fibroblast growth factor 21 (FGF21) modulates tissue metabolism and circulates at higher levels in metabolic conditions associated with chronic sleep-wake disruption, such as type 2 diabetes and obesity. In the present study, we investigated whether acute sleep loss impacts circulating levels of FGF21 and tissue-specific production, and response pathways linked to FGF21. A total of 15 healthy normal-weight young men participated in a randomised crossover study with two conditions, sleep loss versus an 8.5-hr sleep window. The evening before each intervention, fasting blood was collected. Fasting, post-intervention morning skeletal muscle and adipose tissue samples underwent quantitative polymerase chain reaction and DNA methylation analyses, and serum FGF21 levels were measured before and after an oral glucose tolerance test. Serum levels of FGF21 were higher after sleep loss compared with sleep, both under fasting conditions and following glucose intake (similar to 27%-30%, p = 0.023). Fasting circulating levels of fibroblast activation protein, a protein which can degrade circulating FGF21, were not altered by sleep loss, whereas DNA methylation in the FGF21 promoter region increased only in adipose tissue. However, even though specifically the muscle exhibited transcriptional changes indicating adverse alterations to redox and metabolic homeostasis, no tissue-based changes were observed in expression of FGF21, its receptors, or selected signalling targets, in response to sleep loss. In summary, we found that acute sleep loss resulted in increased circulating levels of FGF21 in healthy young men, which may occur independent of a tissue-based stress response in metabolic peripheral tissues. Further studies may decipher whether changes in FGF21 signalling after sleep loss modulate metabolic outcomes associated with sleep or circadian disruption.
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| 3. |
- Brandao, Luiz Eduardo M., et al.
(författare)
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Social Jetlag Changes During the COVID-19 Pandemic as a Predictor of Insomnia - A Multi-National Survey Study
- 2021
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Ingår i: Nature and Science of Sleep. - : Dove Medical Press. - 1179-1608. ; 13, s. 1711-1722
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) - ie, the difference between sleep timing on working vs free days - and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23-54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms - even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.
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| 4. |
- Havukainen, Martti, et al.
(författare)
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A Case Study on Co-designing Digital Games with Older Adults and Children : Game Elements, Assets, and Challenges
- 2020
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Ingår i: The Computer Games Journal. - : Springer. - 2052-773X. ; 9:2, s. 163-188
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Tidskriftsartikel (refereegranskat)abstract
- Digital games have traditionally been targeted at younger generations, although the proportion of older adult players is increasing. However, the design processes of digital games often do not consider the special needs of older adults. Co-design is a potential method to address this, but there is little research on co-designing games with older adults. In our study, we proposed a co-design process model that considers the intergenerational perspective. Using this model, eight older adults (two males and six females aged 47–80) and 22 sixth graders (11 males and 11 females aged 12–13) co-designed a digital game. The content of the game was based on old concepts used by the designers during their childhood. Similarly, game content involving new words and concepts were produced by the sixth graders. We collected data using semi-structured interviews and observations during the co-design process over a period of 24 months and then processed the data using grounded theory. The results indicated that the older adults identified seven game elements as essential to make games fun—appearance and aesthetics, competition, manageability of gameplay, social impact, familiarity, unpredictability, and intergenerational gameplay. Furthermore, we identified six assets that older adults have as game co-designers and five challenges that co-designing games with older adults may entail.
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| 5. |
- Lepistö, Teemu, et al.
(författare)
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Particle lung deposited surface area (LDSAal) size distributions in different urban environments and geographical regions : Towards understanding of the PM2.5 dose–response
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that monitoring only fine particulate matter (PM2.5) may not be enough to understand and tackle the health risk caused by particulate pollution. Health effects per unit PM2.5 seem to increase in countries with low PM2.5, but also near local pollution sources (e.g., traffic) within cities. The aim of this study is to understand the differences in the characteristics of lung-depositing particles in different geographical regions and urban environments. Particle lung deposited surface area (LDSAal) concentrations and size distributions, along with PM2.5, were compared with ambient measurement data from Finland, Germany, Czechia, Chile, and India, covering traffic sites, residential areas, airports, shipping, and industrial sites. In Finland (low PM2.5), LDSAal size distributions depended significantly on the urban environment and were mainly attributable to ultrafine particles (<100 nm). In Central Europe (moderate PM2.5), LDSAal was also dependent on the urban environment, but furthermore heavily influenced by the regional aerosol. In Chile and India (high PM2.5), LDSAal was mostly contributed by the regional aerosol despite that the measurements were done at busy traffic sites. The results indicate that the characteristics of lung-depositing particles vary significantly both within cities and between geographical regions. In addition, ratio between LDSAal and PM2.5 depended notably on the environment and the country, suggesting that LDSAal exposure per unit PM2.5 may be multiple times higher in areas having low PM2.5 compared to areas with continuously high PM2.5. These findings may partly explain why PM2.5 seems more toxic near local pollution sources and in areas with low PM2.5. Furthermore, performance of a typical sensor based LDSAal measurement is discussed and a new LDSAal2.5 notation indicating deposition region and particle size range is introduced. Overall, the study emphasizes the need for country-specific emission mitigation strategies, and the potential of LDSAal concentration as a health-relevant pollution metric.
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| 6. |
- Martikainen, Teemu, et al.
(författare)
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Effects of curtailed sleep on cardiac stress biomarkers following high-intensity exercise.
- 2022
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Ingår i: Molecular metabolism. - : Elsevier. - 2212-8778. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Physical exercise - especially at high intensity - is known to impose cardiac stress, as mirrored by, e.g., increased blood levels of cardiac stress biomarkers, such as cardiac Troponin T (cTnT) and NT-proBNP. Here, we examined in healthy young participants whether a few nights of short sleep duration alters the effects of acute exercise on these blood biomarkers.METHODS: Sixteen men participated in a randomized order in a crossover design, comprising three consecutive nights of a) normal sleep duration (NS, 8.5 hours of sleep/night) and b) sleep restriction (SR, 4.25 hours of sleep/night). Blood was repeatedly sampled for determination of NT-proBNP and cTnT serum levels before and after a high-intensity exercise protocol (i.e., 75% VO2maxReserve cycling on an ergometer).RESULTS: Under pre-exercise sedentary conditions, blood levels of cTnT and NT-proBNP did not significantly differ between the sleep conditions (P>0.10). However, in response to exercise, the surge of circulating cTnT was significantly greater following SR than NS (+37-38% at 120-240 min post-exercise, P≤0.05). While blood levels of NT-proBNP rose significantly in response to exercise, they did not differ between the sleep conditions.CONCLUSION: Recurrent sleep restriction may increase the cardiac stress response to acute high-intensity exercise in healthy young individuals. However, our findings must be confirmed in for example older subjects or in patients with a history of heart disease.
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| 7. |
- Roslin, Tomas, et al.
(författare)
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A molecular-based identification resource for the arthropods of Finland
- 2022
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:2, s. 803-822
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Tidskriftsartikel (refereegranskat)abstract
- To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.
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| 8. |
- Voigt, Carolina, et al.
(författare)
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Increased nitrous oxide emissions from Arctic peatlands after permafrost thaw
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:24, s. 6238-6243
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost in the Arctic is thawing, exposing large carbon and nitrogen stocks for decomposition. Gaseous carbon release from Arctic soils due to permafrost thawing is known to be substantial, but growing evidence suggests that Arctic soils may also be relevant sources of nitrous oxide (N2O). Here we show that N2O emissions from subarctic peatlands increase as the permafrost thaws. In our study, the highest postthaw emissions occurred from bare peat surfaces, a typical landform in permafrost peatlands, where permafrost thaw caused a fivefold increase in emissions (0.56 +/- 0.11 vs. 2.81 +/- 0.6 mg N2O m(-2) d(-1)). These emission rates match those from tropical forest soils, the world's largest natural terrestrial N2O source. The presence of vegetation, known to limit N2O emissions in tundra, did decrease (by similar to 90%) but did not prevent thaw-induced N2O release, whereas waterlogged conditions suppressed the emissions. We show that regions with high probability for N2O emissions cover one-fourth of the Arctic. Our results imply that the Arctic N2O budget will depend strongly on moisture changes, and that a gradual deepening of the active layer will create a strong noncarbon climate change feedback.
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| 9. |
- Voigt, Carolina, et al.
(författare)
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Increased nitrous oxide emissions from Arctic peatlands after permafrost thaw
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 114:24, s. 6238-6243
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost in the Arctic is thawing, exposing large carbon and nitrogen stocks for decomposition. Gaseous carbon release from Arctic soils due to permafrost thawing is known to be substantial, but growing evidence suggests that Arctic soils may also be relevant sources of nitrous oxide (N2O). Here we show that N2O emissions from subarctic peatlands increase as the permafrost thaws. In our study, the highest postthaw emissions occurred from bare peat surfaces, a typical landform in permafrost peatlands, where permafrost thaw caused a fivefold increase in emissions (0.56 ± 0.11 vs. 2.81 ± 0.6 mg N2O m-2 d-1). These emission rates match those from tropical forest soils, the world's largest natural terrestrial N2O source. The presence of vegetation, known to limit N2O emissions in tundra, did decrease (by ∼90%) but did not prevent thaw-induced N2O release, whereas waterlogged conditions suppressed the emissions. We show that regions with high probability for N2O emissions cover one-fourth of the Arctic. Our results imply that the Arctic N2O budget will depend strongly on moisture changes, and that a gradual deepening of the active layer will create a strong noncarbon climate change feedback.
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