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  • Lehto, Elviira; Lehto, Reetta; Ray, Carola; Pajulahti, Riikka; Sajaniemi, Nina; Erkkola, Maijaliisa; Roos, Eva (2021)
    Background: Childhood obesity is a major public health concern, especially in low socioeconomic groups. Sedentary time (SED) is an important predictor of obesity. To be able to diminish SED it is important to find modifiable predictors of sedentary behavior. The home environment associated with children's SED may vary by parental socioeconomic status. This study aims to clarify the association between parental educational level (PEL) and the home environment of 3-6-year-old children, and to examine how home environment associates with children's SED, and whether PEL modifies these associations. Methods: A cross-sectional Increased health and wellbeing in preschools (DAGIS) study was conducted in 2015-2016 in Finland. The parents (n = 809) filled in questionnaires assessing PEL, and the home physical and social environment related to children's SED. Children's SED was measured with accelerometers, which the children (n = 745) wore for 1 week. Results: High PEL was associated with a home environment restraining sedentary behaviour compared with low PEL. Stricter descriptive norms about screen time, considering it important to limit the child's screen time, and satisfaction about the child's screen time associated with children's lower SED. The association with parental psychological control and SED was influenced by PEL. In the PEL stratified analyses, however, the associations between psychological control and SED did not reach statistical significance. Conclusions: Future interventions aiming to decrease SED should pay attention to relevant factors in children's sedentary behaviour home environment. It is important to acknowledge the possible PEL differences in these factors.
  • Eronen, Aleksi E. K.; Mannistö, Jere K.; Moslova, Karina; Nieger, Martin; Heliövaara, Eeva; Repo, Timo (2020)
    Herein we report a unique method for preparing diaryl hydroxyl dicarboxylic acids in a diastereospecific manner. The three-component reaction occurs between amino acid, aromatic aldehyde, and primary alcohol in alkaline solutions under microwave-assisted conditions. The dicarboxylic acids are isolated as sodium salts in high yields (up to 77%) by direct precipitation from the reaction solution. The experimental results suggest that the diastereospecificity originates from a [3,3]-sigmatropic rearrangement followed by a sodium-assisted hydride transfer. As further shown, the previously unreported dicarboxylic acids are easily turned into corresponding delta-lactones.
  • Kasurinen, Aaro; Laitinen, Alli; Kokkola, Arto; Stenman, Ulf-Håkan; Böckelman, Camilla; Haglund, Caj (2020)
    Introduction: Tumor-associated trypsin inhibitor (TATI) limits serine proteases, promotes carcinogenesis in several cancers and functions as an acute-phase reactant. Tumor-associated trypsin-2 (TAT-2), a proteolytic target enzyme for TATI, can enhance invasion by promoting extracellular matrix degradation. Here, we aimed to study serum TATI and TAT-2 levels, including the TAT-2/TATI ratio, as prognostic and diagnostic biomarkers in gastric cancer. We compared the results with the plasma level of C-reactive protein (CRP). Material and Methods: We selected 240 individuals operated on for gastric adenocarcinoma at the Helsinki University Hospital, Finland, between 2000 and 2009. We determined the preoperative serum TAT-2, TATI and plasma CRP levels using time-resolved immunofluorometric assays using monoclonal antibodies. Results: The medium serum TAT-2 level was higher among gastric cancer patients [8.68 ng/ml; interquartile range (IQR) 5.93-13.2] than among benign controls (median 5.41 ng/ml; IQR 4.12-11.8; p = .005). Five-year survival among patients with a high serum TAT-2 was 22.9% [95% confidence interval (CI) 11.7-34.1], compared to 52.2% (95% CI 44.6-59.8; p <.001) among those with a low level. The five-year survival among patients with a high serum TATI was 30.6% (95% CI 20.4-40.8), compared to 52.9% (95% CI 44.7-61.1; p <.001) among those with a low level. The serum TATI level remained significant in the multivariable survival analysis (hazard ratio 2.01; 95% CI 1.32-3.07). An elevated plasma CRP level associated with a high serum TATI level (p = .037). Conclusions: This study shows for the first time that a high serum TAT-2 may function as a prognostic biomarker in gastric cancer and that TAT-2 levels may be elevated compared to controls. Additionally, we show that the prognosis is worse among gastric cancer patients with a high serum TATI. These biomarkers serve as prognostic factors particularly among patients with a metastatic or a locally advanced disease.
  • Cai, Runlong; Jiang, Jingkun (2020)
    An adverse electric field is often encountered or utilized when classifying charged nanoparticles or ions according to their electrical mobility. For instance, the classified charged particles usually have to be transported through an adverse electric field against the aerosol sample flow before exiting the outlet of a differential mobility analyzer (DMA). Recently, we reported the transmission of charged nanoparticles through the DMA adverse axial electric field and its improvements. Herein, the simplified analytical model used in that study and a new simplified numerical model to evaluate particle transmission efficiency through the adverse axial electric field are introduced in detail. In addition to the DMA sample outlet, these models are also tested for the electrical mobility filter (EMF) for segregating charged nanoparticles, especially under the unfavorable conditions when the assumptions for these models are violated. The modeled results are compared to a Monte Carlo method based on single-particle tracking and the experimentally determined transmission efficiencies. For the typical geometries and test conditions of a half-mini DMA sample outlet and the EMF, the mean absolute differences between these models and the Monte Carlo method are less than 1%. However, the accuracy of these models is guaranteed only when their assumptions are satisfied, i.e., when the adverse electric field is longer than 4 times the tube radius so that the field lines are axially parallel and the tube length before the adverse electric field is at least half of the entrance length for the air flow. In addition, the simplified analytical model may deviate from the true transmission efficiency when the adverse electric field is longer than 10% of the entire tube. In such cases that the assumptions for both the simplified analytical model and the simplified numerical model are violated, the Monte Carlo method can be used instead.
  • Hailikari, Telle; Sund, Reijo; Haarala-Muhonen, Anne; Lindblom-Ylänne, Sari (2020)
    Despite vast research on transitioning to higher education and student diversity, little longitudinal evidence exists of how individual differences of first-year students predict their graduation times. The present study explored the relation between first-year students' study profiles and graduation times in two different disciplines, by following the same students' (N = 65) study progress for six years using student records data. Profiling students was based on student interviews. Statistical analysis of time to degree completion was conducted using event history analysis. The results revealed that first-study-year study profiles clearly predict graduation times and degree completion. Disciplinary differences existed between graduation times, which may be explained by the different structures of the disciplines. The results imply that individual students need tailored support at different phases of their studies.
  • Risnes, Kari; Bilsteen, Josephine Funck; Brown, Paul; Pulakka, Anna; Andersen, Anne-Marie Nybo; Opdahl, Signe; Kajantie, Eero; Sandin, Sven (2021)
    IMPORTANCE Adverse long-term outcomes in individuals born before full gestation are not confined to individuals born at extreme gestational ages. Little is known regarding mortality patterns among individuals born in the weeks close to ideal gestation, and the exact causes are not well understood; both of these are crucial for public health, with the potential for modification of risk. OBJECTIVE To examine the risk of all-cause and noncommunicable diseases (NCD) deaths among young adults born preterm and early term. DESIGN, SETTING, AND PARTICIPANTS This multinational population-based cohort study used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland for individuals born between 1967 and 2002. Individuals identified at birth who had not died or emigrated were followed up for mortality from age 15 years to 2017. Analyses were performed from June 2019 to May 2020. EXPOSURES Categories of gestational age (ie, moderate preterm birth and earlier [23-33 weeks], late preterm [34-36 weeks], early term [37-38 weeks], full term [39-41 weeks] and post term [42-44 weeks]). MAIN OUTCOMES AND MEASURES All-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD). RESULTS A total of 6 263 286 individuals were followed up for mortality from age 15 years. Overall, 339 403 (5.4%) were born preterm, and 3 049 100 (48.7%) were women. Compared with full-term birth, the adjusted hazard ratios (aHRs) for all-cause mortality were 1.44 (95% CI, 1.34-1.55) for moderate preterm birth and earlier; 1.23 (95% CI, 1.18-1.29) for late preterm birth; and 1.12 (95% CI, 1.09-1.15) for early-term birth. The association between gestational age and all-cause mortality were stronger in women than in men (P for interaction = .03). Preterm birth was associated with 2-fold increased risks of death from CVD (aHR, 1.89; 95% CI, 1.45-2.47), diabetes (aHR, 1.98; 95% CI, 1.44-2.73), and chronic lung disease (aHR, 2.28; 95% CI, 1.36-3.82). The main associations were replicated across countries and could not be explained by familial or individual confounding factors. CONCLUSIONS AND RELEVANCE The findings of this study strengthen the evidence of increased risk of death from NCDs in young adults born preterm. Importantly, the increased death risk was found across gestational ages up to the ideal term date and includes the much larger group with early-term birth. Excess mortality associated with shorter gestational age was most pronounced for CVDs, chronic lung disease, and diabetes.
  • Vaananen, Jouko (2019)
    We show that if (M, is an element of(1), is an element of(2)) satisfies the first-order Zermelo-Fraenkel axioms of set theory when the membership relation is is an element of(1) and also when the membership relation is is an element of(2), and in both cases the formulas are allowed to contain both is an element of(1) and is an element of(2), then (M, is an element of(1)) congruent to (M, is an element of(2)), and the isomorphism is definable in (M, is an element of(1 ),( )is an element of(2)). This extends Zermelo's 1930 theorem in [6].
  • Arredondo-Alonso, Sergio; Top, Janetta; Corander, Jukka; Willems, Rob J. L.; Schurch, Anita C. (2021)
    Background Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations. Methods We performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012-2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination. Results On average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination. Conclusions In related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.
  • Bennaceur, K.; Dobaczewski, J.; Haverinen, T.; Kortelainen, M. (2020)
    We present preliminary results obtained with a finite-range two-body pseudopotential complemented with zero-range spin-orbit and density-dependent terms. After discussing the penalty function used to adjust parameters, we discuss predictions for binding energies of spherical nuclei calculated at the mean-field level, and we compare them with those obtained using the standard Gogny D1S finite-range effective interaction. © Published under licence by IOP Publishing Ltd.
  • Gao, Hui (2019)
    In this note, we study the relation between Fontaine-Laffaille modules and strongly divisible modules, without assuming the main theorem of Fontaine-Laffaille (but we need to assume the main results concerning strongly divisible modules). This in particular gives a new proof for the main theorem of Fontaine-Laffaille (for p > 2).
  • Qi, Shengcai; Zhang, Pengfei; Ma, Ming; Yao, Minghua; Wu, Jinjin; Mäkilä, Ermei; Salonen, Jarno; Ruskoaho, Heikki; Xu, Yuanzhi; Santos, Helder A.; Zhang, Hongbo (2019)
    Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.
  • Zhang, Hongbo; Zhu, Yueqi; Qu, Liangliang; Wu, Huayin; Kong, Haixin; Yang, Zhou; Chen, Dong; Mäkilä, Ermei; Salonen, Jarno; Santos, Helder A.; Hai, Mingtan; Weitz, David A. (2018)
    Porous silicon nanoparticles (PSiNPs) and gold nanorods (AuNRs) can be used as biocompatible nanocarriers for delivery of therapeutics but undesired leakage makes them inefficient. By encapsulating the PSiNPs and AuNRs in a hydrogel shell, we create a biocompatible functional nano carrier that enables sustained release of therapeutics. Here, we report the fabrication of AuNRs-conjugated PSi nanoparticles (AuNRsPSiNPs) through two-step chemical reaction for high capacity loading of hydrophobic and hydrophilic therapeutics with photothermal property. Furthermore, using water-in-oil microemulsion templates, we encapsulate the AuNRsPSiNPs within a calcium alginate hydrogel nanoshell, creating a versatile biocompatible nanocarrier to codeliver therapeutics for biomedical applications. We find that the functionalized nanohydrogel effectively controls the release rate of the therapeutics while maintaining a high loading efficiency and tunable loading ratios. Notably, combinations of therapeutics coloaded in the functionalized nanohydrogels significantly enhance inhibition of multidrug resistance through synergism and promote faster cancer cell death when combined with photothermal therapy. Moreover, the AuNRs can mediate the conversion of near-infrared laser radiation into heat, increasing the release of therapeutics as well as thermally inducing cell damage to promote faster cancer cell death. Our AuNRsPSiNPs functionalized calcium alginate nanohydrogel holds great promise for photothermal combination therapy and other advanced biomedical applications.
  • Figueiredo, Patricia; Lintinen, Kalle; Hirvonen, Jouni T.; Kostiainen, Mauri A.; Santos, Helder A. (2018)
    Biorenewable polymers have emerged as an attractive alternative to conventional metallic and organic materials for a variety of different applications. This is mainly because of their biocompatibility, biodegradability and low cost of production. Lignocellulosic biomass is the most promising renewable carbon-containing source on Earth. Depending on the origin and species of the biomass, lignin consists of 20-35% of the lignocellulosic biomass. After it has been extracted, lignin can be modified through diverse chemical reactions. There are different categories of chemical modifications, such as lignin depolymerization or fragmentation, modification by synthesizing new chemically active sites, chemical modification of the hydroxyl groups, and the production of lignin graft copolymers. Lignin can be used for different industrial and biomedical applications, including biofuels, chemicals and polymers, and the development of nanomaterials for drug delivery but these uses depend on the source, chemical modifications and physicochemical properties. We provide an overview on the composition and properties, extraction methods and chemical modifications of lignin in this review. Furthermore, we describe different preparation methods for lignin-based nanomaterials with antioxidant UV-absorbing and antimicrobial properties that can be used as reinforcing agents in nanocomposites, in drug delivery and gene delivery vehicles for biomedical applications. (C) 2017 Elsevier Ltd. All rights reserved.
  • Ullah, Hanif; Almeida Santos, Helder; Khan, Taous (2016)
    Bacterial cellulose (BC) is a versatile biopolymer with better material properties, such as purity, high degree of porosity, relative high permeability to liquid and gases, high water-uptake capacity, tensile strength and ultrafine network. This review explores the applications of BC and its hydrogels in the fields of food, cosmetics and drug delivery. Applications of BC in foods are ranging from traditional dessert, low cholesterol diet, vegetarian meat, and as food additive and dietary aid to novel applications, such as immobilization of enzymes and cells. Applications in cosmetics include facial mask, facial scrub, personal cleansing formulations and contact lenses. BC for controlled drug delivery, transdermal drug delivery, dental drug delivery, protein delivery, tissue engineering drug delivery, macromolecular prodrug delivery and molecularly imprinted polymer based enantioselective drug delivery are also discussed in this review. The applications of BC in food and cosmetics provide the basis for BC-based functional foods, nutraceuticals, cosmeceuticals and medicated cosmetics. On the basis of current studies, the BC-based drug delivery could be further fine-tuned to get more sophisticated control on stimuli-responsive drug release. Along with the currently available literature, further experiments are required to obtain a blueprint of drug in vivo performance, bioavailability and in vitro–in vivo correlation.
  • Wang, Chang-Fang; Santos, Hélder A. (Springer Science+Business Media, 2018)
    Methods in Pharmacology and Toxicology
    Strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry is the chemical reaction between azide and cyclooctyne groups. This reaction can conjugate biological molecules, such as peptides, in a highly selective way under mild conditions without cross-reaction with the most widely existing reactive groups, such as amine, carboxylic acid, and hydroxide. Thus, the SPAAC reaction is very versatile for biomolecules conjugation. In this book chapter, we provide detailed protocols of conjugation of integrin targeting peptides to either amine or carboxylic acid terminated porous silicon nanovectors by SPAAC, which can be used to enhance the cellular uptake for intracellular cancer drug delivery and for in vivo cancer theranostics.
  • Tuan, Nguyen Huy; Khoa, Vo Anh; Truong, Mai Thanh Nhat; Hung, Tran The; Minh, Mach Nguyet (2019)
    The main goal of this paper is applying the cut-off projection for solving one-dimensional backward heat conduction problem in a two-slab system with a perfect contact. In a constructive manner, we commence by demonstrating the Fourier-based solution that contains the drastic growth due to the high-frequency nature of the Fourier series. Such instability leads to the need of studying the projection method where the cut-off approach is derived consistently. In the theoretical framework, the first two objectives are to construct the regularized problem and prove its stability for each noise level. Our second interest is estimating the error in -norm. Another supplementary objective is computing the eigen-elements. All in all, this paper can be considered as a preliminary attempt to solve the heating/cooling of a two-slab composite system backward in time. Several numerical tests are provided to corroborate the qualitative analysis.
  • Carvalho, Tiago; Guedes, Gabriela; Sousa, Filipa L.; Freire, Carmen S. R.; Santos, Hélder A. (2019)
    Bacterial cellulose (BC) is a nanocellulose form produced by some nonpathogenic bacteria. BC presents unique physical, chemical, and biological properties that make it a very versatile material and has found application in several fields, namely in food industry, cosmetics, and biomedicine. This review overviews the latest state-of-the-art usage of BC on three important areas of the biomedical field, namely delivery systems, wound dressing and healing materials, and tissue engineering for regenerative medicine. BC will be reviewed as a promising biopolymer for the design and development of innovative materials for the mentioned applications. Overall, BC is shown to be an effective and versatile carrier for delivery systems, a safe and multicustomizable patch or graft for wound dressing and healing applications, and a material that can be further tuned to better adjust for each tissue engineering application, by using different methods.
  • Fontana, Flavia; Martins, Joao P.; Torrieri, Giulia; Santos, Helder A. (2019)
    Nanotechnology holds the promise of bringing revolutionary therapeutic strategies into the clinic. However, an enormous fraction of the currently proposed nanotechnology-based therapies suffers from lack of reproducibility, complexity, high costs, and scale-up-related issues. For these reasons, the research community is moving toward the miniaturization of biomaterials and fabrication methods. Customizable microfluidic-based products have gained tremendous relevance in the development of biomedical technologies. This review provides an overview of different materials that can be used for the fabrication of microfluidic devices, as well as the other parameters influencing the production of biomaterials and biosensors. Moreover, several advanced microfluidic-based technologies that are designed to overcome the current challenges of cancer, immunotherapy, and diabetes therapy, among others are described. Then, the pros and cons of microfluidics as alternative to conventional preparation methods, and the challenges of translating this technique to an industrial context are highlighted. Overall, microfluidic technologies and their accessibility to the research community offer a set of exciting opportunities to bridge the development of innovative therapies and their commercialization in the foreseeable future.
  • Zhu, Yueqi; Zhang, Hongbo; Zhang, Yiran; Wu, Huayin; Wei, Liming; Zhou, Gen; Zhang, Yuezhou; Deng, Lianfu; Cheng, Yingsheng; Li, Minghua; Almeida Santos, Helder; Cui, Wenguo (2019)
    Cerebrovascular disease involves various medical disorders that obstruct brain blood vessels or deteriorate cerebral circulation, resulting in ischemic or hemorrhagic stroke. Nowadays, platinum coils with or without biological modification have become routine embolization devices to reduce the risk of cerebral aneurysm bleeding. Additionally, many intracranial stents, flow diverters, and stent retrievers have been invented with uniquely designed structures. To accelerate the translation of these devices into clinical usage, an in‐depth understanding of the mechanical and material performance of these metal‐based devices is critical. However, considering the more distal location and tortuous anatomic characteristics of cerebral arteries, present devices still risk failing to arrive at target lesions. Consequently, more flexible endovascular devices and novel designs are under urgent demand to overcome the deficiencies of existing devices. Herein, the pros and cons of the current structural designs are discussed when these devices are applied to the treatment of diseases ranging broadly from hemorrhages to ischemic strokes, in order to encourage further development of such kind of devices and investigation of their use in the clinic. Moreover, novel biodegradable materials and drug elution techniques, and the design, safety, and efficacy of personalized devices for further clinical applications in cerebral vasculature are discussed.

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