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  • Salonen, Ari Heimo Kalevi; Salmi, Pauliina; Keskitalo, Jorma (2021)
  • Viitanen, Arto Ilmari; Gullmets, Josef; Morikka, Jack George Anthony; Katajisto, Pekka; Mattila, Jaakko; Hietakangas, Ville (2021)
    The intestine is divided into functionally distinct regions along the anteroposterior (A/P) axis. How the regional identity influences the function of intestinal stem cells (ISCs) and their offspring remain largely unresolved. We introduce an imaging-based method, “Linear Analysis of Midgut” (LAM), which allows quantitative, regionally defined cellular phenotyping of the whole Drosophila midgut. LAM transforms image-derived cellular data from three-dimensional midguts into a linearized representation, binning it into segments along the A/P axis. Through automated multivariate determination of regional borders, LAM allows mapping and comparison of cellular features and frequencies with subregional resolution. Through the use of LAM, we quantify the distributions of ISCs, enteroblasts, and enteroendocrine cells in a steady-state midgut, and reveal unprecedented regional heterogeneity in the ISC response to a Drosophila model of colitis. Altogether, LAM is a powerful tool for organ-wide quantitative analysis of the regional heterogeneity of midgut cells.
  • Candolin, Ulrika; Goncalves, Sara; Pant, Pankaj (2021)
    Recruitment is usually negatively density-dependent with fewer offspring surviving when more are produced. Parental care could alter the pattern as behaviours that maximize individual fitness are not necessarily adaptive at the population level. We manipulated the number of eggs spawned into the nests of male threespine stickleback, and found egg survival to be positively density-dependent. This reversed negative density-dependent survival observed in the absence of parental care. The reversal was caused my males investing more in parental care when receiving more eggs, while favouring future reproductive opportunities when receiving few eggs. Density-dependent parental care thus amplified changes in offspring production in relation to number of eggs spawned. Such amplification may occur in disturbed environments where human activities have altered female fecundity and males may receive more or less eggs than expected. The optimal balancing between present and future parental investment can then be distorted, resulting in maladaptive parental behaviour that reduces offspring survival. These results suggest that behaviours that have evolved to maximize individual fitness under pristine conditions can become mal-adaptive under disturbed conditions and influence the recruitment of offspring into a population. Considering that human activities are rapidly transforming environments, such mal-adaptive behavioural responses could be common and magnify negative effects of human activities on population dynamics.
  • Peake, Sandra L.; Delaney, Anthony; Bailey, Michael; Bellomo, Rinaldo; Cameron, Peter A.; Cooper, D. James; Higgins, Alisa M.; Holdgate, Anna; Howe, Belinda D.; Webb, Steven A. R.; Williams, Patricia; ARISE Investigators; ANZICS Clinical Trials Grp; Pettilä, Ville (2014)
    BACKGROUND Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain. METHODS In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization. RESULTS Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (+/- SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964 +/- 1415 ml vs. 1713 +/- 1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE number, NCT00975793.)
  • Zosa, Elaine; Shekhar, Ravi; Karan, Mladen; Purver, Matthew (ACL Anthology, 2021)
    Moderation of reader comments is a significant problem for online news platforms. Here, we experiment with models for automatic moderation, using a dataset of comments from a popular Croatian newspaper. Our analysis shows that while comments that violate the moderation rules mostly share common linguistic and thematic features, their content varies across the different sections of the newspaper. We therefore make our models topic-aware, incorporating semantic features from a topic model into the classification decision. Our results show that topic information improves the performance of the model, increases its confidence in correct outputs, and helps us understand the model's outputs.
  • Ozgumus, Turkuler; Sulaieva, Oksana; Jessen, Leon Eyrich; Jain, Ruchi; Falhammar, Henrik; Nystrom, Thomas; Catrina, Sergiu-Bogdan; Jorneskog, Gun; Groop, Leif; Eliasson, Mats; Eliasson, Bjorn; Brismar, Kerstin; Stokowy, Tomasz; Nilsson, Peter M.; Lyssenko, Valeriya (2021)
    Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.
  • Lee, Lik-Hang; Braud, Tristan; Zhou, Pengyuan; Wang, Lin; Xu, Dianlei; Lin, Zijun; Kumar, Abhishek; Bermejo, Carlos; Hui, Pan (2021)
  • Loukiala, Antti; Joutsenlahti, Juha-Pekka; Raatikainen, Mikko; Mikkonen, Tommi; Lehtonen, Timo (Springer, 2022)
    Lecture Notes in Computer Science (LNCS)
  • Lindström, Irmeli; Lantto, Jussi; Karvala, Kirsi; Soini, Satu; Ylinen, Katriina; Suojalehto, Hille; Suuronen, Katri (2021)
    Background Exposures leading to irritant-induced asthma (IIA) are poorly documented. Methods We retrospectively screened the medical records of patients with IIA diagnosed in an occupational medicine clinic during 2000-2018. We classified the cases into acute (onset after single exposure) and subacute (onset after multiple exposures) IIA. We analysed in detail, occupations, causative agents and their air levels in the workplace, exposure events and the root causes of high exposure. Results Altogether 69 patients were diagnosed with IIA, 30 with acute and 39 with subacute IIA. The most common occupational groups were industrial operators (n=23, 33%), metal and machinery workers (n=16, 11%) and construction workers (n=12, 8%). Among industrial operators significantly more cases had subacute IIA than acute IIA (p=0.002). Forty cases (57%) were attributable to some type of corrosive acidic or alkaline chemical. Acute IIA followed accidents at work in different types of occupation, while subacute IIA was typical among industrial operators performing their normal work tasks under poor work hygiene conditions. The most common root cause was lack of information or false guidance in acute IIA (n=11, 36%) and neglect of workplace hygiene measures in subacute IIA (n=29, 74%). Conclusions Accidents are the main causes of acute IIA, whereas subacute IIA can develop in normal work in risk trades with poor work hygiene. Airborne strong acids or bases seem to be the most important causative agents of acute and subacute IIA. The different risk profiles of acute and subacute IIA should be considered in the prevention and identification of the cases.
  • Rantala, Heikki; Ikkala, Esko; Koho, Mikko; Tuominen, Jouni; Rohiola, Ville; Hyvönen, Eero (, 2021)
    CEUR Workshop Proceedings
  • Heino, Matti T.; Salmi, Anna-Kaisa; Äikäs, Tiina; Mannermaa, Kristiina; Kirkinen, Tuija; Sablin, Mikhail; Ruokonen, Minna; Nunez, Milton; Okkonen, Jari; Dahlen, Love; Aspi, Jouni (2021)
    Reindeer herding emerged among the indigenous Sámi of Northern Fennoscandia between ca. 800 and 1500 CE. While the details of the reindeer domestication process are still actively debated, it has been hypothesized that the transition to reindeer herding affected Sámi ritual practice, especially animal offerings given at various sacred sites. To explore this hypothesis, we analyzed DNA from reindeer bone samples dating to ca. 1200–1700 CE from Sámi offering sites located in present-day Northern Finland as well as from samples originating from ancient dwelling site in Southern Finland and Kola Peninsula, Russia. The results show that haplotypes related to wild Finnish forest reindeer (Rangifer tarandus fennicus) began to be replaced by haplotypes common in modern domesticated reindeer in the faunal assemblages from offering sites starting between 1400 and 1600 CE. The results suggest that, although the role of reindeer herding in the economy of the Sámi communities varied greatly, the transition to reindeer herding may have affected ritual practices, testifying to a shared way of reciprocating with the land and animals.
  • Hyvönen, Eero; Ikkala, Esko; Koho, Mikko; Tuominen, Jouni; Burrows, Toby; Ransom, Lynn; Wijsman, Hanno (Springer, 2021)
    Lecture Notes in Computer Science
  • GoLEAD Consortium; SUMMIT Consortium; van Zuydam, Natalie R.; Stiby, Alexander; Abdalla, Moustafa; Dahlström, Emma H.; Vlachopoulou, Efthymia; Sandholm, Niina; Forsblom, Carol; Sinisalo, Juha; Perola, Markus; Kallio, Milla; Groop, Per-Henrik; Groop, Leif; Kullo, Iftikhar J. (2021)
    Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. Results: We identified 5 genome-wide significant (P-association
  • Perkiömäki, Mika (2021)
    Artikkeli tarkastelee ekokriittisestä näkökulmasta neuvostoaikaisen kirjailijan Boris Šerginin pomorien kansanperinteeseen perustuvista kertomuksista koostuvan tuotannon pohjoisen kuviteltua maantiedettä sekä sen suhdetta luontoon muun muassa kristinuskon ja neuvostomodernisaation konteksteissa. Se esittää, että Šerginin tuotanto rakentaa pomorien narratiivista identiteettiä, jolle keskeisiä ovat rikas elämä meren ehdoilla luonnonvarojen puolesta köyhällä alueella, kristinusko, vanha kulttuuriperintö sekä yhä uusien pohjoisten alueiden hallinta uusien teknologioiden avulla. Šerginiä Venäjän pohjoisen sakraalin maantieteen ja venäläisen kirjallisuuden pohjoisen tekstin kautta lukeva tutkimus on hahmottanut Venäjän Pohjolan kollektiivista identiteettiä keskittyen sen mytopoeettisiin merkityksiin. Tämä artikkeli tuo Šerginin materiaalisen ympäristön vahvemmin esiin ja tarkastelee Šerginin pohjoisen tekstin tutkimusta osana pomorien narratiivista identiteettiä.
  • Shaheryar, Zaib A.; Khan, Mahtab A.; Adnan, Ch. Sherjeel; Zaidi, Awais Ali; Hänggi, Daniel; Muhammad, Sajjad (2021)
    Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the 'neuroinflammatory triangle': ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.
  • Loisel, J.; Loisel, J.; Amesbury, Matthew J.; Magnan, G.; Anshari, G.; Beilman, D. W.; Benavides, J. C.; Blewett, J.; Camill, P.; Charman, D. J.; Chawchai, S.; Hedgpeth, A.; Kleinen, T.; Korhola, Atte; Large, D.; Mansilla, C. A.; Muller, J.; van Bellen, S.; West, J. B.; Yu, Z.; Bubier, J. L.; Garneau, M.; Moore, T.; Sannel, A. B. K.; Page, S.; Valiranta, Minna; Bechtold, M.; Brovkin, Victor; Cole, L. E. S.; Chanton, J. P.; Christensen, T. R.; Davies, M. A.; De Vleeschouwer, F.; Finkelstein, S. A.; Frolking, S.; Galka, M.; Gandois, L.; Girkin, N.; Harris, L.; Heinemeyer, A.; Hoyt, A. M.; Jones, M. C.; Joos, F.; Juutinen, Sari; Kaiser, K.; Lacourse, T.; Lamentowicz, M.; Larmola, T.; Leifeld, J.; Lohila, Annalea Katriina; Milner, A. M.; Minkkinen, Kari; Moss, P.; Naafs, B. D. A.; Nichols, J.; O'Donnell, J.; Payne, R.; Philben, M.; Piilo, Sanna; Quillet, A.; Ratnayake, A. S.; Roland, T. P.; Sjogersten, S.; Sonnentag, O.; Swindles, G. T.; Swinnen, W.; Talbot, J.; Treat, C.; Valach, A. C.; Wu, J. (2021)
    Peatlands are impacted by climate and land-use changes, with feedback to warming by acting as either sources or sinks of carbon. Expert elicitation combined with literature review reveals key drivers of change that alter peatland carbon dynamics, with implications for improving models. The carbon balance of peatlands is predicted to shift from a sink to a source this century. However, peatland ecosystems are still omitted from the main Earth system models that are used for future climate change projections, and they are not considered in integrated assessment models that are used in impact and mitigation studies. By using evidence synthesized from the literature and an expert elicitation, we define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future. We also identify uncertainties and knowledge gaps in the scientific community and provide insight towards better integration of peatlands into modelling frameworks. Given the importance of the contribution by peatlands to the global carbon cycle, this study shows that peatland science is a critical research area and that we still have a long way to go to fully understand the peatland-carbon-climate nexus.
  • Tayem, Raneem; Niemann, Catherin; Pesch, Monika; Morgner, Jessica; Niessen, Carien M.; Wickström, Sara A.; Aumailley, Monique (2021)
    The skin epidermis is attached to the underlying dermis by a laminin 332 (Lm332)-rich basement membrane. Consequently, loss of Lm332 leads to the severe blistering disorder epidermolysis bullosa junctionalis in humans and animals. Owing to the indispensable role of Lm332 in keratinocyte adhesion in vivo, the severity of the disease has limited research into other functions of the protein. We have conditionally disrupted Lm332 expression in basal keratinocytes of adult mice. Although blisters develop along the interfollicular epidermis, hair follicle basal cells provide sufficient anchorage of the epidermis to the dermis, making inducible deletion of the Lama3 gene compatible with life. Loss of Lm332 promoted the thickening of the epidermis and exaggerated desquamation. Global RNA expression analysis revealed major changes in the expression of keratins, cornified envelope proteins, and cellular stress markers. These modifications of the keratinocyte genetic program are accompanied by changes in cell shape and disorganization of the actin cytoskeleton. These data indicate that loss of Lm332-mediated progenitor cell adhesion alters cell fate and disturbs epidermal homeostasis.
  • Lindström, Ulf; Di Giuseppe, Daniela; Delcoigne, Benedicte; Glintborg, Bente; Moller, Burkhard; Ciurea, Adrian; Pombo-Suarez, Manuel; Sanchez-Piedra, Carlos; Eklund, Kari; Relas, Heikki; Gudbjornsson, Bjorn; Love, Thorvardur Jon; Jones, Gareth T.; Codreanu, Catalin; Ionescu, Ruxandra; Nekvindova, Lucie; Zavada, Jakub; Atas, Nuh; Yolbas, Servet; Fagerli, Karen Minde; Michelsen, Brigitte; Rotar, Ziga; Tomsic, Matija; Iannone, Florenzo; Santos, Maria Jose; Avila-Ribeiro, Pedro; Ornbjerg, Lykke Midtboll; Ostergaard, Mikkel; Jacobsson, Lennart T. H.; Askling, Johan; Nissen, Michael J. (2021)
    Background Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.
  • Li, Tong; Zhang, Mingyang; Li, Yong; Lagerspetz, Eemil; Tarkoma, Sasu; Hui, Pan (2021)
    The outbreak of Covid-19 changed the world as well as human behavior. In this article, we study the impact of Covid-19 on smartphone usage. We gather smartphone usage records from a global data collection platform called Carat, including the usage of mobile users in North America from November 2019 to April 2020. We then conduct the first study on the differences in smartphone usage across the outbreak of Covid-19. We discover that Covid-19 leads to a decrease in users' smartphone engagement and network switches, but an increase in WiFi usage. Also, its outbreak causes new typical diurnal patterns of both memory usage and WiFi usage. Additionally, we investigate the correlations between smartphone usage and daily confirmed cases of Covid-19. The results reveal that memory usage, WiFi usage, and network switches of smartphones have significant correlations, whose absolute values of Pearson coefficients are greater than 0.8. Moreover, smartphone usage behavior has the strongest correlation with the Covid-19 cases occurring after it, which exhibits the potential of inferring outbreak status. By conducting extensive experiments, we demonstrate that for the inference of outbreak stages, both Macro-F1 and Micro-F1 can achieve over 0.8. Our findings explore the values of smartphone usage data for fighting against the epidemic.

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