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Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process.

Cytokines are soluble proteins that mediate cell-to-cell communication. Based on the discovery of the potent anti-tumour activities of several pro-inflammatory cytokines in animal models, clinical research led to the approval of recombinant interferon-alpha and interleukin-2 for the treatment of several malignancies, even if efficacy was only modest. These early milestones in immunotherapy have been followed by the recent addition to clinical practice of antibodies that inhibit immune checkpoints, as well as chimeric antigen receptor T cells. A renewed interest in the anti-tumour properties of cytokines has led to an exponential increase in the number of clinical trials that explore the safety and efficacy of cytokine-based drugs, not only as single agents, but also in combination with other immunomodulatory drugs. These second-generation drugs under clinical development include known molecules with novel mechanisms of action, new targets, and fusion proteins that increase half-life and target cytokine activity to the tumour microenvironment or to the desired effector immune cells. In addition, the detrimental activity of immunosuppressive cytokines can be blocked by antagonistic antibodies, small molecules, cytokine traps or siRNAs. In this review, we provide an overview of the novel trends in the cytokine immunotherapy field that are yielding therapeutic agents for clinical trials.

Rationale/background: Though much smaller than the bovine industry, the porcine sector in Argentina involves a large number of farms and represents a significant economic sector. In recent years Argentina has implemented a national registry of swine movements amongst other measures, in an effort to control and eventually eradicate endemic Aujesky’s disease. Such information can prove valuable in assessing the risk of transmission between farms for endemic diseases but also for other diseases at risk of emergence. Methods: Shipment data from 2011 to 2016 were analyzed in an effort to define strategic locations and times at which control and surveillance efforts should be focused to provide cost-effective interventions. Social network analysis (SNA) was used to characterize the network as a whole and at the individual farm and market level to help identify important nodes. Spatio-temporal trends of pig movements were also analyzed. Finally, in an attempt to classify farms and markets in different groups based on their SNA metrics, we used factor analysis for mixed data (FAMD) and hierarchical clustering. Results: The network involved approximate 136,000 shipments for a total of 6 million pigs. Over 350 markets and 17,800 production units participated in shipments with another 83,500 not participating. Temporal data of shipments and network metrics showed peaks in shipments in September and October. Most shipments where within provinces, with Buenos Aires, Cordoba and Santa Fe concentrating 61% of shipments. Network analysis showed that markets are involved in relatively few shipments but hold strategic positions with much higher betweenness compared to farms. Hierarchical clustering yielded four groups based on SNA metrics and node characteristics which can be broadly described as: 1. small and backyard farms; 2. industrial farms; 3. markets; and 4. a single outlying market with extreme centrality values. Conclusion: Characterizing the network structure and spatio-temporal characteristics of Argentine swine shipments provides valuable information that can guide targeted and more cost-effective surveillance and control programs. We located key nodes where efforts should be prioritized. Pig network characteristics and patterns can be used to create dynamic disease transmission models, which can both be used in assessing the impact of emerging diseases and guiding efforts to eradicate endemic ones.

Problematic Internet use (PIU) has begun to be linked to the development of certain eating disorders. This uncontrolled use of the Internet is mainly found in the student population. The purposes of this paper were to determine PIU-related eating disorders in students from a systematic review of the literature and to analyze the incidence of PIU in eating disorders through a meta-analysis of the literature. We used two electronic databases (Web of Science and Scopus) from inception to June 2019. The systematic literature review was based on fixed inclusion and exclusion criteria. A total of 12 studies were identified (systematic review) and 10 studies for meta-analysis, which included 16,520 students. Different eating disorders were associated with PIU: anorexia nervosa, bulimia nervosa, binge-eating disorder, food preoccupation, loss of control eating, and dieting. Furthermore, meta-analysis confirmed that PIU is a predictor of eating disorders in students. The groups of students with PIU presented a higher rate in the presence of eating disorders, these differences being significant. Finally, this study showed empirical evidence on the link between PIU and eating disorders. The need for prevention in childhood and adolescence is highlighted.

The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes β1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility.

Water use efficiency in agriculture (WUEA) has become a priority given increasing limitations on hydric resources. As a result, this area of research has increased in importance, becoming one of the most prolific lines of study. The main aim of this study was to present a review of worldwide WUEA research over the last 30 years. A bibliometric analysis was developed based on the Scopus database. The sample included 6063 articles. The variables analyzed were: articles per year, category, journal, country, institution, author, and keyword. The results indicate that a remarkable growth in the number of articles published per year is occurring. The main category is environmental science and the main journal Agricultural Water Management. The countries with the highest number of articles were China, the United States of America, and India. The institution that published the most articles was the Chinese Academy of Sciences and the authors from China also were the most productive. The most frequently used keywords were irrigation, crop yield, water supply, and crops. The findings of this study can assist researchers in this field by providing an overview of worldwide research.

The 21st-century problem of Internet addiction is increasing globally, but especially among university students. Not surprisingly, then, problematic Internet use is associated with university students' academic procrastination. Because studies are scarce in Mexico and Spain has one of the highest rates of Internet addiction in Europe, this paper (i) analyzed the presence and degree of Internet addiction among university students in Mexico and Spain, (ii) determined potential sociodemographic factors influencing Internet addiction, and (iii) established the type of correlation between Internet addiction and academic procrastination. The cross-sectional study design used an online questionnaire to measure problematic Internet use and academic procrastination through convenience sampling at one university in Mexico and one in Spain. The questionnaire contained three sections: participants' sociodemographic data, the Internet Addiction Test, and the Academic Procrastination Scale. The final sample comprised 758 university students, 387 from Mexico, and 371 from Spain, aged from 18 to 35 (M = 20.08, SD = 3.16). Results revealed similar prevalence rates of problematic and daily Internet use for leisure, potentially influencing Internet addiction in all three models (i.e., Mexico, Spain, and Total). Additionally, significant positive correlation was revealed between problematic Internet use and academic procrastination (p < .001). Finally, findings showed relevant data on Internet addiction's prevalence in Mexican and Spanish university contexts, along with its influential sociodemographic factors.

Artificial intelligence has experienced major developments in recent years and represents an emerging technology that will revolutionize the ways in which human beings live. This technology is already being introduced in the field of higher education, although many teachers are unaware of its scope and, above all, of what it consists of. Therefore, the purpose of this paper was to analyse the scientific production on artificial intelligence in higher education indexed in Web of Science and Scopus databases during 2007–2017. A bespoke methodology of bibliometric studies was used in the most relevant databases in social science. The sample was composed of 132 papers in total. From the results obtained, it was observed that there is a worldwide interest in the topic and that the literature on this subject is just at an incipient stage. We conclude that, although artificial intelligence is a reality, the scientific production about its application in higher education has not been consolidated.

Phenolic compounds present in mango peel byproducts have been reported to have several beneficial health properties. In this study, we carried out an optimization of phenolic compounds using ultrasound-assisted extraction via ultrasonic bath and sonotrode. To optimize the variables of extraction, a Box–Behnken design was used to evaluate the best conditions to obtain high total phenolic compound extraction and high antioxidant activity evaluated by different methods (DPPH, ABTS, and FRAP). The optimal ultrasonic bath conditions were 45% ethanol, 60 min, and 1/450 ratio sample/solvent (w/v) whereas optimal sonotrode conditions were 55% ethanol, 18 min, and 65% amplitude. The extracts obtained at the optimal conditions were characterized by HPLC–ESI-TOF-MS. A total of 35 phenolic compounds were determined and, to our knowledge, several of them were tentatively identified for the first time in mango peel. The samples were composed mainly by phenolic acids derivatives, specifically of galloylglucose and methylgallate, which represented more than 50% of phenolic compounds of mango peel byproducts. In conclusion, sonotrode is a valuable green technology able to produce enriched phenolic compound extracts from mango peel byproducts that could be used for food, nutraceutical, and cosmeceutical applications.

Urogenital schistosomiasis caused by Schistosoma haematobium is highly endemic in the municipality of Cubal in Angola. Currently, diagnosis is based on the observation of S. haematobium eggs in urine samples by microscopy but this method has low sensitivity. Few studies have been performed using molecular techniques in high-prevalence areas for the detection of S. haematobium. The objective of this study is to evaluate the usefulness of real-time PCR as a diagnostic technique for urogenital schistosomiasis among preschool-age children and its correlation with morbidity data. A cross-sectional study was conducted in Cubal, Angola, involving 97 urine samples from preschool-age children analyzed by the dipstick test, microscopic examination of filtered urine, and real-time PCR. The diagnosis of urogenital schistosomiasis was based on microscopy and/or real-time PCR results. Clinical and ultrasonography evaluation was performed to rule out complications of schistosomiasis. We detected a total of 64.95% of samples positive by real-time PCR and 37.11% by microscopy. The sensitivity of parasitological diagnosis of urogenital schistosomiasis by real-time PCR and microscopy was 95.45% and 54.55%, respectively, and the sensitivity of real-time PCR compared with microscopy was 91.67%. A positive real-time PCR result was significantly related to older age (mean = 3.22 years), detection of eggs by microscopy, and abnormal urine dipstick results (18.56% with proteinuria, 31.96% with leukocyturia, and 31.96% with microhematuria) (p-value<0.05). Ultrasound analysis showed that 23.94% of children had urinary tract abnormalities, and it was significantly related to the real-time PCR diagnosis (p-value<0.05). Real-time PCR is a more sensitive technique than microscopy for urinary schistosomiasis diagnosis in preschool-age children in Cubal. This increase in sensitivity would allow earlier diagnosis and treatment, thus reducing the morbidity associated with schistosomiasis in its early stages.