MDPI-artikkelit: Recent submissions

Now showing items 1-20 of 781
  • Jamshidi, Maral; Fagerholm, Rainer; Muranen, Taru A.; Kaur, Sippy; Potdar, Swapnil; Khan, Sofia; Netti, Eliisa; Mpindi, John-Patrick; Yadav, Bhagwan; Kiiski, Johanna I.; Aittomäki, Kristiina; Heikkilä, Päivi; Saarela, Jani; Bützow, Ralf; Blomqvist, Carl; Nevanlinna, Heli (Multidisciplinary Digital Publishing Institute, 2021)
    Deregulated miRNA expression has been suggested in several stages of breast cancer pathogenesis. We have studied the miR-30 family, in particular miR-30d, in relation to breast cancer patient survival and treatment outcomes. With tumor specimens from 1238 breast cancer patients, we analyzed the association of miR-30d expression with tumor characteristics with the 5-year occurrence of breast cancer-specific death or distant metastasis (BDDM), and with 10-year breast cancer survival (BCS). We conducted a two-stage drug-screen to investigate the impact of miR-30 family members (miR-30a-30e) on sensitivity to doxorubicin and lapatinib in six breast cancer cell lines HCC1937, HCC1954, MDA-MB-361, MCF7, MDA-MB-436 and CAL-120, using drug sensitivity scores (DSS) to compare the miR-30 family mimics to their specific inhibitors. The study was complemented with Ingenuity Pathway Analysis (IPA) with the METABRIC data. We found that while high miR-30d expression is typical for aggressive tumors, it predicts better metastasis-free (<i>p</i><sub>BDDM</sub> = 0.035, HR = 0.63, 95% CI = 0.4–0.9) and breast cancer-specific survival (<i>p</i><sub>BCS </sub>= 0.018, HR = 0.61, 95% CI = 0.4–0.9), especially in HER2-positive (<i>p</i><sub>BDDM</sub> = 0.0009), ER-negative (<i>p</i><sub>BDDM </sub>= 0.003), p53-positive (<i>p</i><sub>BDDM </sub>= 0.011), and highly proliferating (<i>p</i><sub>BDDM </sub>= 0.0004) subgroups, and after adjuvant chemotherapy (<i>p</i><sub>BDDM </sub>= 0.035). MiR-30d predicted survival independently of standard prognostic markers (<i>p</i><sub>BDDM </sub>= 0.0004). In the drug-screening test, the miR-30 family sensitized the HER2-positive HCC1954 cell line to lapatinib (<i>p</i> &lt; 10<sup>–2</sup>) and HCC1937, MDA-MB-361, MDA-MB-436 and CAL120 to doxorubicin (<i>p</i> &lt; 10<sup>–4</sup>) with an opposite impact on MCF7. According to the pathway analysis, the miR-30 family has a suppressive effect on cell motility and metastasis in breast cancer. Our results suggest prognostic and predictive potential for the miR-30 family, which warrants further investigation.
  • Krali, Olga; Palle, Josefine; Bäcklin, Christofer L.; Abrahamsson, Jonas; Norén-Nyström, Ulrika; Hasle, Henrik; Jahnukainen, Kirsi; Jónsson, Ólafur Gísli; Hovland, Randi; Lausen, Birgitte; Larsson, Rolf; Palmqvist, Lars; Staffas, Anna; Zeller, Bernward; Nordlund, Jessica (Multidisciplinary Digital Publishing Institute, 2021)
    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/<i>RUNX1-RUNX1T1</i>, normal karyotype, and <i>MLL/KMT2A</i>-rearranged subgroups (<i>p</i> &lt; 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML.
  • Mitu, Sabrina Jannat; Schneider, Petra; Islam, Md. Shahidul; Alam, Masud; Mozumder, Mohammad Mojibul Hoque; Hossain, Mohammad Mosarof; Shamsuzzaman, Md. Mostafa (Multidisciplinary Digital Publishing Institute, 2021)
    The south-east coast, specifically the Cox’s Bazar region, of Bangladesh has achieved a tremendous impetus for producing a large volume of dried fish by involving thousands of marginalized coastal people. This study aimed to assess the socio-economic profile, livelihood strategies, and resilience of the communities engaged in fish drying on the south-east coast using a mixed-methods approach and an Analytic Hierarchy Process (AHP). The study’s findings revealed that communities involved in drying were socio-economically undeveloped due to their lower literacy, unstable incomes, and labor-intensive occupations. Apart from notable child labor employed in fish drying in Nazirertek, female workers had relatively higher participation than males. Nevertheless, the female workers had less control over their daily wages and reported working at USD 3.54–5.89 per day, which was relatively lower than male workers who received USD 4.15–8.31 per day. Through fish drying activities, very few workers, producers, and traders were found to be self-reliant. In contrast, the livelihoods of the workers were not as secure as the processors and traders. In addition to suffering from various shocks and constraints, dried fish processors and workers, dried fish traders, off-season income, an abundance of fish species, fish drying facilities, trader’s association, and social interrelationship played a significant role in maintaining community resilience. The study recommends appropriate interventions to alternative income diversification options, strong collaboration between communities, local authorities, and government for sustainable livelihoods and better community resilience.
  • Russo, Fabrizio; De Salvatore, Sergio; Ambrosio, Luca; Vadalà, Gianluca; Fontana, Luca; Papalia, Rocco; Rantanen, Jorma; Iavicoli, Sergio; Denaro, Vincenzo (Multidisciplinary Digital Publishing Institute, 2021)
    Low back pain (LBP) is currently the leading cause of disability worldwide and the most common reason for workers’ compensation (WC) claims. Studies have demonstrated that receiving WC is associated with a negative prognosis following treatment for a vast range of health conditions. However, the impact of WC on outcomes after spine surgery is still controversial. The aim of this meta-analysis was to systematically review the literature and analyze the impact of compensation status on outcomes after lumbar spine surgery. A systematic search was performed on Medline, Scopus, CINAHL, EMBASE and CENTRAL databases. The review included studies of patients undergoing lumbar spine surgery in which compensation status was reported. Methodological quality was assessed through ROBINS-I and quality of evidence was estimated using the GRADE rating. A total of 26 studies with a total of 2668 patients were included in the analysis. WC patients had higher post-operative pain and disability, as well as lower satisfaction after surgery when compared to those without WC. Furthermore, WC patients demonstrated to have a delayed return to work. According to our results, compensation status is associated with poor outcomes after lumbar spine surgery. Contextualizing post-operative outcomes in clinical and work-related domains helps understand the multifactorial nature of the phenomenon.
  • Mroczkowska, Agnieszka; Pawłowski, Dominik; Gauthier, Emilie; Mazurkevich, Andrey; Luoto, Tomi P.; Peyron, Odile; Kotrys, Bartosz; Brooks, Stephen J.; Nazarova, Larisa B.; Syrykh, Liudmila; Dolbunova, Ekaterina V.; Thiebaut, Eva; Płóciennik, Mateusz; Antczak-Orlewska, Olga; Kittel, Piotr (Multidisciplinary Digital Publishing Institute, 2021)
    Although extensive archeological research works have been conducted in the Serteya region in recent years, the Holocene climate history in the Western Dvina Lakeland in Western Russia is still poorly understood. The Neolithic human occupation of the Serteyka lake–river system responded to climate oscillations, resulting in the development of a pile-dwelling settlement between 5.9 and 4.2 ka cal BP. In this paper, we present the quantitative paleoclimatic reconstructions of the Northgrippian stage (8.2–4.2 ka cal BP) from the Great Serteya Palaeolake Basin. The reconstructions were created based on a multiproxy (Chironomidae, pollen and Cladocera) approach. The mean July air temperature remained at 17–20 °C, which is similar to the present temperature in the Smolensk Upland. The summer temperature revealed only weak oscillations during 5.9 and 4.2 ka cal BP. A more remarkable feature during those events was an increase in continentality, manifested by a lower winter temperature and lower annual precipitation. During the third, intermediate oscillation in 5.0–4.7 ka cal BP, a rise in summer temperature and stronger shifts in continental air masses were recorded. It is still unclear if the above-described climate fluctuations are linked to the North Atlantic Oscillation and can be interpreted as an indication of Bond events because only a few high-resolution paleoclimatic reconstructions from the region have been presented and these reconstructions do not demonstrate explicit oscillations in the period of 5.9 and 4.2 ka cal BP.
  • Bogacheva, Mariia S.; Bystriakova, Margarita A.; Lou, Yan-Ru (Multidisciplinary Digital Publishing Institute, 2021)
    Human induced pluripotent stem cells (hiPSCs) hold great potential as an unlimited source for obtaining hepatocyte-like cells (HLCs) for drug research. However, current applications of HLCs have been severely limited by the inability to produce mature hepatocytes from hiPSCs in vitro. Thyroid hormones are one of the hormones that surge during the perinatal period when liver maturation takes place. Here we assessed the influence of thyroid hormone on hepatic progenitor differentiation to HLCs. We analyzed gene and protein expression of early and late hepatic markers and demonstrated the selective activity of thyroid hormone on different genes. Particularly, we demonstrated thyroid hormone-dependent inhibition of the fetal hepatic marker AFP. Our study sheds light on the role of thyroid hormone during liver differentiation and maturation.
  • Zięba, Agata; Laitinen, Tuomo; Patel, Jayendra Z.; Poso, Antti; Kaczor, Agnieszka A. (Multidisciplinary Digital Publishing Institute, 2021)
    This work aimed to construct 3D-QSAR CoMFA and CoMSIA models for a series of 31 FAAH inhibitors, containing the 1,3,4-oxadiazol-2-one moiety. The obtained models were characterized by good statistical parameters: CoMFA Q<sup>2</sup> = 0.61, R<sup>2</sup> = 0.98; CoMSIA Q<sup>2</sup> = 0.64, R<sup>2</sup> = 0.93. The CoMFA model field contributions were 54.1% and 45.9% for steric and electrostatic fields, respectively. In the CoMSIA model, electrostatic, steric, hydrogen bond donor, and hydrogen acceptor properties were equal to 34.6%, 23.9%, 23.4%, and 18.0%, respectively. These models were validated by applying the leave-one-out technique, the seven-element test set (CoMFA r<sup>2</sup><sub>test-set</sub> = 0.91; CoMSIA r<sup>2</sup><sub>test-set</sub> = 0.91), a progressive scrambling test, and external validation criteria developed by Golbraikh and Tropsha (CoMFA r<sup>2</sup><sub>0</sub> = 0.98, k = 0.95; CoMSIA r<sup>2</sup><sub>0</sub> = 0.98, k = 0.89). As the statistical significance of the obtained model was confirmed, the results of the CoMFA and CoMSIA field calculation were mapped onto the enzyme binding site. It gave us the opportunity to discuss the structure–activity relationship based on the ligand–enzyme interactions. In particular, examination of the electrostatic properties of the established CoMFA model revealed fields that correspond to the regions where electropositive substituents are not desired, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one moiety. This highlights the importance of heterocycle, a highly electronegative moiety in this area of each ligand. Examination of hydrogen bond donor and acceptor properties contour maps revealed several spots where the implementation of another hydrogen-bond-donating moiety will positively impact molecules’ binding affinity, e.g., in the neighborhood of the 1,3,4-oxadiazol-2-one ring. On the other hand, there is a large isopleth that refers to the favorable H-bond properties close to the terminal phenoxy group of a ligand, which means that, generally speaking, H-bond acceptors are desired in this area.
  • Hiltunen, Mimmu K.; Beyer, Hannes M.; Iwaï, Hideo (Multidisciplinary Digital Publishing Institute, 2021)
    Inteins are prevalent among extremophiles. Mini-inteins with robust splicing properties are of particular interest for biotechnological applications due to their small size. However, biochemical and structural characterization has still been limited to a small number of inteins, and only a few serve as widely used tools in protein engineering. We determined the crystal structure of a naturally occurring Pol-II mini-intein from <i>Pyrococcus horikoshii</i> and compared all three mini-inteins found in the genome of <i>P. horikoshii</i>. Despite their similar sizes, the comparison revealed distinct differences in the insertions and deletions, implying specific evolutionary pathways from distinct ancestral origins. Our studies suggest that sporadically distributed mini-inteins might be more promising for further protein engineering applications than highly conserved mini-inteins. Structural investigations of additional inteins could guide the shortest path to finding novel robust mini-inteins suitable for various protein engineering purposes.
  • Linnakoski, Riikka; Lasarov, Ilmeini; Veteli, Pyry; Tikkanen, Olli-Pekka; Viiri, Heli; Jyske, Tuula; Kasanen, Risto; Duong, Tuan A.; Wingfield, Michael J. (Multidisciplinary Digital Publishing Institute, 2021)
    The European spruce bark beetle (<i>Ips typographus</i>) has become a major forest pest in Finland in recent years. The beetle is a well-known vector of mainly ophiostomatoid fungi causing blue-stain of timber and pathogens that have the ability to amplify the insect damage. It also vectors other associated organisms, such as phoretic mites. The ecology of these mites remains poorly understood, including their associations with fungi. In this study, we considered filamentous fungi and yeasts associated with mites phoretic on <i>I. typographus</i>. Fungal identifications were based on DNA sequences and phylogenetic analyses of the ITS and/or partial β-tubulin gene regions. Fifteen fungal species were detected, including eight yeasts and seven filamentous fungi. Eleven percent of the beetles carried mites and of these 74% carried at least one fungal species. An average of two fungal species were carried per mite. The most commonly found filamentous fungi were <i>Grosmannia penicillata</i> (25%), <i>Ophiostoma bicolor</i> (19%), <i>O. ainoae</i> (12%) and <i>O. brunneolum</i> (12%). Of the yeast species, the most commonly found was <i>Wickerhamomyces bisporus</i> (47%). This study is the first to report yeasts associated with <i>I. typographus</i> and its phoretic mites in Finland. Majority of the filamentous fungal species found are those previously reported in association with <i>I. typographus</i>. The results also confirmed that many of the fungal species commonly found on <i>I. typographus</i> are also associated with its phoretic mites. However, the nature of the symbiosis between the mites, beetles and fungal associates remains to be understood.
  • Sjöblom, Anni; Stenman, Ulf-Håkan; Hagström, Jaana; Jouhi, Lauri; Haglund, Caj; Syrjänen, Stina; Mattila, Petri; Mäkitie, Antti; Carpén, Timo (Multidisciplinary Digital Publishing Institute, 2021)
    Background: We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. Materials and methods: The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012–2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). Results: A significant correlation was found between S-TATI positivity and poor OS (<i>p</i> &lt; 0.001) and DSS (<i>p</i> = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (<i>p</i> = 0.01) and DSS (<i>p</i> = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (<i>p</i> = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (<i>p</i> &lt; 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. Conclusion: Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.
  • Kokociński, Mikołaj; Dziga, Dariusz; Antosiak, Adam; Soininen, Janne (Multidisciplinary Digital Publishing Institute, 2021)
    Bacterioplankton community composition has become the center of research attention in recent years. Bacteria associated with toxic cyanobacteria blooms have attracted considerable interest. However, little is known about the environmental factors driving the bacteria community, including the impact of invasive cyanobacteria. Therefore, our aim has been to determine the relationships between heterotrophic bacteria and phytoplankton community composition across 24 Polish lakes with different contributions of cyanobacteria including the invasive species <i>Raphidiopsis raciborskii.</i> This analysis revealed that cyanobacteria were present in 16 lakes, while <i>R. raciborskii</i> occurred in 14 lakes. Our results show that bacteria communities differed between lakes dominated by cyanobacteria and lakes with minor contributions of cyanobacteria but did not differ between lakes with <i>R. raciborskii</i> and other lakes. Physical factors, including water and Secchi depth, were the major drivers of bacteria and phytoplankton community composition. However, in lakes dominated by cyanobacteria, bacterial community composition was also influenced by biotic factors such as the amount of <i>R. raciborskii</i>, chlorophyll-a and total phytoplankton biomass. Thus, our study provides novel evidence on the influence of environmental factors and <i>R. raciborskii</i> on lake bacteria communities.
  • Zsebeházi, Gabriella; Mahó, Sándor István (Multidisciplinary Digital Publishing Institute, 2021)
    Land surface models with detailed urban parameterization schemes provide adequate tools to estimate the impact of climate change in cities, because they rely on the results of the regional climate model, while operating on km scale at low cost. In this paper, the SURFEX land surface model driven by the evaluation and control runs of ALADIN-Climate regional climate model is validated over Budapest from the aspect of urban impact on temperature. First, surface temperature of SURFEX with forcings from ERA-Interim driven ALADIN-Climate was compared against the MODIS land surface temperature for a 3-year period. Second, the impact of the ARPEGE global climate model driven ALADIN-Climate was assessed on the 2 m temperature of SURFEX and was validated against measurements of a suburban station for 30 years. The spatial extent of surface urban heat island (SUHI) is exaggerated in SURFEX from spring to autumn, because the urbanized gridcells are generally warmer than their rural vicinity, while the observed SUHI extent is more variable. The model reasonably simulates the seasonal means and diurnal cycle of the 2 m temperature in the suburban gridpoint, except summer when strong positive bias occurs. However, comparing the two experiments from the aspect of nocturnal UHI, only minor differences arose. The thorough validation underpins the applicability of SURFEX driven by ALADIN-Climate for future urban climate projections.
  • Haatainen, Outi; Turkka, Jaakko; Aksela, Maija (Multidisciplinary Digital Publishing Institute, 2021)
    To understand how integrated science education (ISE) can be transferred into successful classroom practices, it is important to understand teachers’ perceptions and self-efficacy. The focus of this study is twofold: (1) to understand how teachers perceive ISE and (2) to assess if science teachers’ perceptions of and experiences with integrated education correlate with their views on self-efficacy in relation to ISE. Ninety-five Finnish science teachers participated in an online survey study. A mixed method approach via exploratory factor analysis and data-driven content analysis was used. Self-efficacy emerged as a key factor explaining teachers’ perceptions of and their lack of confidence in implementing ISE as well as their need for support. In addition, teachers regarded ISE as a relevant teaching method, but challenging to implement, and teachers primarily applied integrated approaches irregularly and seldom. Furthermore, teachers’ experiences with integrated activities and collaboration correlated with their views on integrated education and self-efficacy. These findings indicate teachers need support to better understand and implement ISE.
  • Viertiö, Tyko; Kivelä, Viivi; Putkonen, Matti; Kihlman, Johanna; Simell, Pekka (Multidisciplinary Digital Publishing Institute, 2021)
    Steel filter discs were catalytically activated by ALD, using a coating of supporting Al<sub>2</sub>O<sub>3</sub> layer and an active NiO layer for gas cleaning. Prepared discs were tested for model biomass gasification and gas catalytic filtration to reduce or eliminate the need for a separate reforming unit for gasification gas tars and lighter hydrocarbons. Two different coating methods were tested. The method utilizing the stop-flow setting was shown to be the most suitable for the preparation of active and durable catalytic filters, which significantly decreases the amount of tar compounds in gasification gas. A pressure of 5 bar and temperatures of over 850 °C are required for efficient tar reforming. In optimal conditions, applying catalytic coating to the filter resulted in a seven-fold naphthalene conversion increase from 7% to 49%.
  • Pyöriä, Lari; Valtonen, Maarit; Luoto, Raakel; Grönroos, Wilma; Waris, Matti; Heinonen, Olli J.; Ruuskanen, Olli; Perdomo, Maria F. (Multidisciplinary Digital Publishing Institute, 2021)
    Exercise-induced immune perturbations have been proposed to increase susceptibility to viral infections. We investigated the replication of persisting viruses as indicators of immune function in elite cross-country skiers after ten months of sustained high-performance exercise. The viruses evaluated, nine human herpesviruses (HHVs) and torque teno virus (TTV), are typically restrained in health but replicate actively in immunosuppressed individuals. We collected sera from 27 Finnish elite cross-country skiers at the end of the competition’s season and 27 matched controls who perform moderate exercise. We quantified all the HHVs and—TTV via highly sensitive qPCRs. To verify equal past exposures between the groups, we assessed the IgG antibody prevalences toward HHV-4 (Epstein–Barr virus, EBV) and HHV-5 (human cytomegalovirus, HCMV). We found equal TTV DNA prevalences in athletes (63%) and controls (63%) and loads with respective geometric means of 1.7 × 10<sup>3</sup> and 1.2 × 10<sup>3</sup> copies/mL of serum. Overall, the copy numbers were low and consistent with those of healthy individuals. Neither of the groups presented with herpesvirus viremia despite similar past exposures to HHVs (seroprevalences of EBV 70% vs. 78% and HCMV 52% vs. 44% in athletes and controls, respectively). We found no evidence of increased replication of persistent viruses in elite athletes, arguing against impaired viral immunity due to high-performance exercise.
  • Douglas, Kirk Osmond; Cayol, Claire; Forbes, Kristian Michael; Samuels, Thelma Alafia; Vapalahti, Olli; Sironen, Tarja; Gittens-St. Hilaire, Marquita (Multidisciplinary Digital Publishing Institute, 2021)
    Background: Rodents are reservoirs for several zoonotic pathogens that can cause human infectious diseases, including orthohantaviruses, mammarenaviruses and orthopoxviruses. Evidence exists for these viruses circulating among rodents and causing human infections in the Americas, but much less evidence exists for their presence in wild rodents in the Caribbean. Methods: Here, we conducted serological and molecular investigations of wild rodents in Barbados to determine the prevalence of orthohantavirus, mammarenavirus and orthopoxvirus infections, and the possible role of these rodent species as reservoirs of zoonotic pathogens. Using immunofluorescent assays (IFA), rodent sera were screened for the presence of antibodies to orthohantavirus, mammarenavirus (Lymphocytic choriomeningitis virus—LCMV) and orthopoxvirus (Cowpox virus—CPXV) infections. RT-PCR was then conducted on orthohantavirus and mammarenavirus-seropositive rodent sera and tissues, to detect the presence of viral RNA. Results: We identified antibodies against orthohantavirus, mammarenavirus, and orthopoxvirus among wild mice and rats (3.8%, 2.5% and 7.5% seropositivity rates respectively) in Barbados. No orthohantavirus or mammarenavirus viral RNA was detected from seropositive rodent sera or tissues using RT–PCR. Conclusions: Key findings of this study are the first serological evidence of orthohantavirus infections in <i>Mus musculus</i> and the first serological evidence of mammarenavirus and orthopoxvirus infections in <i>Rattus norvegicus</i> and <i>M. musculus</i> in the English-speaking Caribbean. Rodents may present a potential zoonotic and biosecurity risk for transmission of three human pathogens, namely orthohantaviruses, mammarenaviruses and orthopoxviruses in Barbados.
  • Sivonen, Ville; Sinkkonen, Saku T.; Willberg, Tytti; Lamminmäki, Satu; Jääskelä-Saari, Hilkka; Aarnisalo, Antti A.; Dietz, Aarno (Multidisciplinary Digital Publishing Institute, 2021)
    Bilateral cochlear implantation is increasing worldwide. In adults, bilateral cochlear implants (BICI) are often performed sequentially with a time delay between the first (CI1) and the second (CI2) implant. The benefits of BICI have been reported for well over a decade. This study aimed at investigating these benefits for a consecutive sample of adult patients. Improvements in speech-in-noise recognition after CI2 were followed up longitudinally for 12 months with the internationally comparable Finnish matrix sentence test. The test scores were statistically significantly better for BICI than for either CI alone in all assessments during the 12-month period. At the end of the follow-up period, the bilateral benefit for co-located speech and noise was 1.4 dB over CI1 and 1.7 dB over CI2, and when the noise was moved from the front to 90 degrees on the side, spatial release from masking amounted to an improvement of 2.5 dB in signal-to-noise ratio. To assess subjective improvements in hearing and in quality of life, two questionnaires were used. Both questionnaires revealed statistically significant improvements due to CI2 and BICI. The association between speech recognition in noise and background factors (duration of hearing loss/deafness, time between implants) or subjective improvements was markedly smaller than what has been previously reported on sequential BICI in adults. Despite the relatively heterogeneous sample, BICI improved hearing and quality of life.
  • Ropponen, Annina; Wang, Mo; Narusyte, Jurgita; Silventoinen, Karri; Böckerman, Petri; Svedberg, Pia (Multidisciplinary Digital Publishing Institute, 2021)
    <i>Background</i>: A unified or consensus definition of “sustainable working life” remains lacking, although studies investigating risk factors for labour market exit are numerous. In this study, we aimed (1) to update the information and to explore a definition of “sustainable working life” via a systematic literature review and (2) to describe the working life trajectories via the prevalence of sickness absence (SA), disability pension (DP), and unemployment in a Swedish twin cohort to provide a sample overview in our Sustainable Working Life-project. <i>Methods</i>: A systematic literature review was conducted to explore the studies with the search phrase “sustainable working life” in PubMed, PsycInfo, and the Web of Science Database of Social Sciences in January 2021, resulting in a total of 51 references. A qualitative synthesis was performed for the definitions and the measures of “sustainable working life.” Based on the Swedish Twin project Of Disability pension and Sickness absence (STODS), the current dataset to address sustainable working life includes 108 280 twin individuals born between 1925 and 1990. Comprehensive register data until 2016 for unemployment, SA and DP were linked to all individuals. Using STODS, we analysed the annual prevalence of SA, DP, and unemployment as working life trajectories over time across education and age groups. <i>Results</i>: The reviewed 16 full articles described several distinct definitions for sustainable working life between 2007 and 2020 from various perspectives, i.e., considering workplaces or employees, the individual, organizational or enterprise level, and the society level. The definition of “sustainable working life” appearing most often was the swAge-model including a broad range of factors, e.g., health, physical/mental/psychosocial work environment, work motivation/satisfaction, and the family situation and leisure activities. Our dataset comprised of 81%–94% of individuals who did not meet SA, DP, or unemployment during the follow-up in 1994–2016, being indicative for “sustainable working life.” The annual prevalence across years had a decreasing trend of unemployment over time, whereas the prevalence of SA had more variation, with DP being rather stable. Both unemployment and DP had the highest prevalence among those with a lower level of education, whereas in SA, the differences in prevalence between education levels were minor. Unemployment was highest across the years in the youngest age group (18–27 years), the age group differences for SA were minor, and for DP, the oldest age group (58–65 years) had the highest prevalence. <i>Conclusions</i>: No consensus exists for a “sustainable working life,” hence meriting further studies, and we intend to contribute by utilising the STODS database for the Sustainable Working Life project. In the upcoming studies, the existing knowledge of available definitions and frameworks will be utilised. The dataset containing both register data and self-reports enables detailed follow-up for labour market participation for sustainable working life.
  • Prabhakar, Neeraj; Merisaari, Joni; Le Joncour, Vadim; Peurla, Markus; Karaman, Didem Şen; Casals, Eudald; Laakkonen, Pirjo; Westermarck, Jukka; Rosenholm, Jessica M. (Multidisciplinary Digital Publishing Institute, 2021)
    Glioblastoma (GB) is the most frequent malignant tumor originating from the central nervous system. Despite breakthroughs in treatment modalities for other cancer types, GB remains largely irremediable due to the high degree of intratumoral heterogeneity, infiltrative growth, and intrinsic resistance towards multiple treatments. A sub-population of GB cells, glioblastoma stem cells (GSCs), act as a reservoir of cancer-initiating cells and consequently, constitute a significant challenge for successful therapy. In this study, we discovered that PEI surface-functionalized mesoporous silica nanoparticles (PEI-MSNs), without any anti-cancer drug, very potently kill multiple GSC lines cultured in stem cell conditions. Very importantly, PEI-MSNs did not affect the survival of established GB cells, nor other types of cancer cells cultured in serum-containing medium, even at 25 times higher doses. PEI-MSNs did not induce any signs of apoptosis or autophagy. Instead, as a potential explanation for their lethality under stem cell culture conditions, we demonstrate that the internalized PEI-MSNs accumulated inside lysosomes, subsequently causing a rupture of the lysosomal membranes. We also demonstrate blood–brain-barrier (BBB) permeability of the PEI-MSNs in vitro and in vivo. Taking together the recent indications for the vulnerability of GSCs for lysosomal targeting and the lethality of the PEI-MSNs on GSCs cultured under stem cell culture conditions, the results enforce in vivo testing of the therapeutic impact of PEI-functionalized nanoparticles in faithful preclinical GB models.
  • Yang, Xuan; Yagodzinskyy, Yuriy; Ge, Yanling; Lu, Eryang; Lehtonen, Joonas; Kollo, Lauri; Hannula, Simo-Pekka (Multidisciplinary Digital Publishing Institute, 2021)
    This study investigates the effects of laser powder bed fusion (LPBF) on the hydrogen uptake of the face-centered cubic (FCC) equiatomic CrFeNiMn multicomponent alloy after cathodic hydrogen charging (HC). Hydrogen desorption was evaluated using thermal desorption spectroscopy (TDS), and microstructural changes after the TDS test were examined. Results reveal that the amount of hydrogen absorbed by LPBF CrFeNiMn alloy was significantly higher than that in pulsed electric current sintered (PECS) CrFeNiMn alloy or in conventional 316L austenitic stainless steel. The observations are ascribed to the differences in the amount of hydrogen absorbed by the multicomponent lattice, dislocation densities, width of segregation range at cell walls created by the rapid cooling in LBPF, and vacancies remaining after cooling to room temperature. A hydrogen-charged LBPF transmission electron microscope (TEM) specimen was also characterized. Stacking faults and cracks along the (111)-planes of austenite were observed. Scanning electron microscopy (SEM) of the surface of the TDS-tested samples also indicated hydrogen-induced cracks and hydrogen-induced submicron pits at the grain boundary inclusions.