bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective Feelings of Polish Doctors after Receiving the COVID-19 Vaccine
Authors: Zdziarski Krzysztof , Landowski Marek , Zabielska Paulina , Karakiewicz Beata
Published: June 2021

The COVID-19 pandemic has caused enormous confusion around the world in our daily existence. The security measures taken, such as physical distance, wearing a mask, quarantine or closing shopping malls, and even isolating large groups of the population, did not contribute to the complete overcoming of the problem. Information on the positive results of research into the COVID-19 vaccine and, finally, its administration offered hope that the pandemic would be overcome. The undertaken problem of research concerning the subjective analysis of the feelings of doctors in Poland after receiving the COVID-19 vaccine shows an important area of the medical world, which is directly responsible for their own health and the patients entrusted to them. In addition, 149 people participated in the study (8–13 February 2021), including 57% of women and 43% of men. The minimum and maximum age of the respondents are 26 and 69 years old. Furthermore, 85% of respondents took two doses of the vaccine and 15% took one. The authorial questionnaire was completed by the participants in the study online in February 2021. The results obtained indicate that the COVID-19 vaccine generates hope for stopping the pandemic. In addition, 96% of research participants think so. Doctors in middle and mature age are the most optimistic, while the youngest ones are less optimistic. In addition, 57% of respondents do not worry about side effects after taking the vaccine. Fear at the time of vaccination was experienced by over 9% of doctors. The most frequently reported post-vaccination reactions are injection site pain, fatigue and headache. Increased temperature occurred in older female respondents. From a psychosocial perspective, men are more likely to fear being infected personally with the virus, and women are more likely to be infected with their loved ones. The presented subjective assessment presents the physicians’ view captured at the moment in terms of existential and emotional. The presented feelings of the research participants reflect their personal satisfaction, responsibility for their own health, care for their relatives and patients.
Personality Determinants of Success in Men’s Sports in the Light of the Big Five
Authors: Piepiora Paweł , Piepiora Zbigniew
Published: June 2021

The aim of the study is to describe personality profiles and determinants of success in sports in relation to the Big Five Personality Model. In order to achieve this aim, personality profiles of players from various sports disciplines was set against the personality profile of champions—players who are considerably successful in sports competitions. Subsequently, an attempt was made to determine which personality traits significantly determine belonging to the group of champions—and therefore determine success in sport. The participants were men aged between 20 and 29 from the Polish population of sportsmen. A total of 1260 athletes were tested, out of whom 118 were qualified to the champions sample—those athletes had significant sports achievements. The research used the NEO-FFI Personality Questionnaire. Basic descriptive statistics, a series of Student’s t-tests for independent samples using the bootstrapping method, as well as a logistic regression model were performed. In relation to other athletes, champions were characterized by a lower level of neuroticism and a higher level of extraversion, openness to experience, agreeableness, and conscientiousness. An important personality determinant was neuroticism: the lower the level of neuroticism, the greater the probability of an athlete being classified as a champion. There are differences between champions and other athletes in all personality dimensions in terms of the Big Five. Based on the result of the research, it can be stated that personality differences should be seen as a consequence of athletes’ success, rather than as a reason for athletes’ success, based on their age between 20 and 29.
Occupational Heat Stress: Multi-Country Observations and Interventions
Authors: Ioannou Leonidas G. , Mantzios Konstantinos , Tsoutsoubi Lydia , Nintou Eleni , Vliora Maria , Gkiata Paraskevi , Dallas Constantinos N. , Gkikas Giorgos , Agaliotis Gerasimos , Sfakianakis Kostas , Kapnia Areti K. , Testa Davide J. , Amorim Tânia , Dinas Petros C. , Mayor Tiago S. , Gao Chuansi , Nybo Lars , Flouris Andreas D.
Published: June 2021

Background: Occupational heat exposure can provoke health problems that increase the risk of certain diseases and affect workers’ ability to maintain healthy and productive lives. This study investigates the effects of occupational heat stress on workers’ physiological strain and labor productivity, as well as examining multiple interventions to mitigate the problem. Methods: We monitored 518 full work-shifts obtained from 238 experienced and acclimatized individuals who work in key industrial sectors located in Cyprus, Greece, Qatar, and Spain. Continuous core body temperature, mean skin temperature, heart rate, and labor productivity were collected from the beginning to the end of all work-shifts. Results: In workplaces where self-pacing is not feasible or very limited, we found that occupational heat stress is associated with the heat strain experienced by workers. Strategies focusing on hydration, work-rest cycles, and ventilated clothing were able to mitigate the physiological heat strain experienced by workers. Increasing mechanization enhanced labor productivity without increasing workers’ physiological strain. Conclusions: Empowering laborers to self-pace is the basis of heat mitigation, while tailored strategies focusing on hydration, work-rest cycles, ventilated garments, and mechanization can further reduce the physiological heat strain experienced by workers under certain conditions.
Using Intervention Mapping to Develop a Media Literacy-Based Smoking Prevention Program for Female Adolescents
Authors: Kim Sookyung
Published: June 2021

Smoking prevalence among female adolescents in South Korea has increased gradually, despite a decreasing trend seen for male adolescents. Smoking scenes or cigarette advertisements in the media have influenced female adolescents’ initiation into smoking. It is therefore crucial to develop a smoking prevention program to enhance female adolescents’ smoking media literacy by implementing gender-specific approach. The purpose of this study is to describe how intervention mapping protocol (IMP) was used to develop a media literacy-based smoking prevention program (MLSP) for female adolescents. The IMP was used in six steps: needs assessment (literature review and focus groups comprising 24 female adolescents and 12 teachers), program goal setting, selection of intervention methods, production of program components and materials, program implementation planning, and program evaluation by ten experts and three adolescents. Six performance objectives and 14 change objectives were generated. Each module consisted of theory-based methods such as raising consciousness. Half of the modules covered topics regarding smoking media literacy, while half covered topics related to gender-specific intervention. The major advantages of utilizing IMP are that MLSP has been developed to reflect multiple perspectives, including of adolescents, teachers, and professors through a systematic process, and identified to be acceptable and valid.
The Relationship between Nutrition Knowledge and Nutrition Facts Table Use in China: A Structural Equation Model
Authors: Huang Zeying , Huang Beixun , Huang Jiazhang
Published: June 2021

Since 2013, China has implemented a nutrition label regulation that aims to provide essential nutrition information through nutrition facts tables labeled on the back of food packages. Yet, the relationship between people’s nutrition knowledge and their nutrition label use remains less clear. This study adopted the structural equation modeling approach to analyze a nationally representative survey of 1500 Chinese individuals through the cognitive processing model, interrelated nutrition knowledge, attention to nutrition information on the nutrition facts table, comprehension of nutrition information, food choice and dietary intake. It was found that nutrition knowledge positively influenced attention to nutrition information; a better comprehension of nutrition information, which could benefit healthier food choices, did not relate to a higher level of attention to that information; dietary intake was affected significantly by nutrition knowledge, but it had little impact on food choice. The results signify that nutrition knowledge hardly supports nutrition facts table use among the Chinese people, mainly due to incomprehensible labeled information. Therefore, it emphasizes the need to enhance people’s comprehension through front-of-package labels and corresponding smartphone applications.
The Pathways Linking to Sleep Habits among Children and Adolescents: A Complete Survey at Setagaya-ku, Tokyo
Authors: Noi Shingo , Shikano Akiko , Tanaka Ryo , Tanabe Kosuke , Enomoto Natsuko , Kidokoro Tetsuhiro , Yamada Naoko , Yoshinaga Mari
Published: June 2021

It has been noted that Japanese children sleep the least in the world, and this has become a major social issue. This study examined the pathways linked to sleep habits (SH) among children and adolescents. A questionnaire-based survey was conducted in March 2019 on children and their parents at all 63 public elementary and 29 public junior high schools in Setagaya-ku, Tokyo. For the analysis, 22,385 pairs of children–parent responses (valid response rate: 68.8%) with no missing data were used. This survey collected data on SH, physical activity (PA), screen time (ST) for the child, and lifestyle and neighborhood social capital (NSC) for the parents. Moreover, the pathways linking ‘NSC’ → ‘parental lifestyle’ → ‘child’s PA/ST’ →‘child’s SH’ were examined through structural equation modeling. The results indicated that children’s SH were affected by their PA and ST and influenced by the lifestyle of their parents and the NSC that surrounds them. Thus, we concluded that it is necessary to provide direct interventions and take additional measures with regard to parent lifestyle and their NSC to solve persistent sleep problems in children.
Diagnostic Accuracy of a New Antigen Test for SARS-CoV-2 Detection
Authors: Di Domenico Marina , De Rosa Alfredo , Di Gaudio Francesca , Internicola Pietro , Bettini Cinzia , Salzano Nicola , Castrianni Davide , Marotta Andrea , Boccellino Mariarosaria
Published: June 2021

Background and aims: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. Methods: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. Results: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from February 2021 until April 2021. The new cyto-salivary antigen had a sensitivity of 100% and a specificity of 94.2%. The sensitivity and the specificity of the lateral flow test were 55% and 100%, respectively. Conclusions: The new cyto-salivary antigen test detected more positive cases than the RT-PCR in a sample of asymptomatic subjects, demonstrating to be a promising tool for a more sensitive diagnosis of COVID-19. Further studies are warranted to better characterize its diagnostic accuracy.
Get Close to the Robot: The Effect of Risk Perception of COVID-19 Pandemic on Customer–Robot Engagement
Authors: Wu Jifei , Zhang Xiangyun , Zhu Yimin , Yu-Buck Grace Fang
Published: June 2021

The purpose of this study was to examine the effect of the COVID-19 pandemic on customer–robot engagement in the Chinese hospitality industry. Analysis of a sample of 589 customers using service robots demonstrated that the perceived risk of COVID-19 has a positive influence on customer–robot engagement. The positive effect is mediated by social distancing and moderated by attitudes towards risk. Specifically, the mediating effect of social distancing between the perceived risk of COVID-19 and customer–robot engagement is stronger for risk-avoiding (vs. risk-seeking) customers. Our results provide insights for hotels when they employ service robots to cope with the shock of COVID-19 pandemic.
Dog Walking before and during the COVID-19 Pandemic Lockdown: Experiences of UK Dog Owners
Authors: Owczarczak-Garstecka Sara C. , Graham Taryn M. , Archer Debra C. , Westgarth Carri
Published: June 2021

Background: This study investigated the impacts of the first COVID-19 UK lockdown on dog walking and ownership. Methods: An online survey was circulated via social media (May–June 2020). Completed responses (n = 584) were analysed using within- and between-group comparisons, and multivariable linear and logistic regression models were created. Open-ended data were coded into key themes. Results: During lockdown, dogs were walked less frequently, yet for a similar duration per week and closer to home. Dogs whose owners lived alone, or whose owners or household members had heightened vulnerability to COVID-19 were walked less than before, as were high-energy dogs. A minority of owners continued dog walking despite exhibiting symptoms or needing to self-isolate, justifying lack of help, dog behavioural problems, living in less populated areas, and the importance of outdoor exercise for their mental health. Dog ownership had multiple benefits (companionship, purpose and motivation; break from bad; positive to focus on) as well as challenges (changes in dog behaviour, balancing dog needs with public health guidance, accessing pet food/supplies and services, and sharing crowded outdoor spaces with others). Most did not have an emergency care plan for their pet before the pandemic and only a handful developed one. Conclusions: Findings can be used to inform public health and dog welfare strategies for future lockdown situations or other disasters and emergencies likely to impact on daily routines.
The Role of Motor Imagery in Predicting Motor Skills in Young Male Soccer Players
Authors: Zapała Dariusz , Zabielska-Mendyk Emilia , Cudo Andrzej , Jaśkiewicz Marta , Kwiatkowski Marcin , Kwiatkowska Agnieszka
Published: June 2021

The study aimed to find out whether the imagery ability within the two subcomponents of motor imagery (visual and kinesthetic) allows predicting the results in simple response time task and eye–hand coordination task in a group of young male soccer players (9–15 years old). Non-specific simple response time and eye–hand coordination play a key role in predicting specific sports performance level. Participants performed Reaction Time Task, Eye–Hand Coordination Task, and completed Motor Imagery Questionnaire–Revised. Data were submitted to the structural equations analysis based on the maximum likelihood method in order to estimate a structural model of relationship between variables. Results indicate visual rather than kinesthetic motor imagery is associated with non-specific motor skills. Higher scores on the visual motor imagery scale were observed to correlate with faster reaction times and better coordination in the study group. This supports the idea that during learning a new perceptual-motor-task the visual control is required. Results provide the evidence for the specific role of the third-person perspective imagery in young athletes playing soccer.
Yearly and Daily Relationship Assessment between Air Pollution and Early-Stage COVID-19 Incidence: Evidence from 231 Countries and Regions
Authors: Meng Yuan , Wong Man Sing , Xing Hanfa , Kwan Mei-Po , Zhu Rui
Published: June 2021

The novel coronavirus disease 2019 (COVID-19) has caused significantly changes in worldwide environmental and socioeconomics, especially in the early stage. Previous research has found that air pollution is potentially affected by these unprecedented changes and it affects COVID-19 infections. This study aims to explore the non-linear association between yearly and daily global air pollution and the confirmed cases of COVID-19. The concentrations of tropospheric air pollution (CO, NO2, O3, and SO2) and the daily confirmed cases between 23 January 2020 and 31 May 2020 were collected at the global scale. The yearly discrepancies of air pollutions and daily air pollution are associated with total and daily confirmed cases, respectively, based on the generalized additive model. We observed that there are significant spatially and temporally non-stationary variations between air pollution and confirmed cases of COVID-19. For the yearly assessment, the number of confirmed cases is associated with the positive fluctuation of CO, O3, and SO2 discrepancies, while the increasing NO2 discrepancies leads to the significant peak of confirmed cases variation. For the daily assessment, among the selected countries, positive linear or non-linear relationships are found between CO and SO2 concentrations and the daily confirmed cases, whereas NO2 concentrations are negatively correlated with the daily confirmed cases; variations in the ascending/declining associations are identified from the relationship of the O3-confirmed cases. The findings indicate that the non-linear relationships between global air pollution and the confirmed cases of COVID-19 are varied, which implicates the needs as well as the incorporation of our findings in the risk monitoring of public health on local, regional, and global scales.
Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases
Authors: Candelli Marcello , Franza Laura , Pignataro Giulia , Ojetti Veronica , Covino Marcello , Piccioni Andrea , Gasbarrini Antonio , Franceschi Francesco
Published: June 2021

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.
In Vitro Characterization of Guanylyl Cyclase BdPepR2 from Brachypodium distachyon Identified through a Motif-Based Approach
Authors: Duszyn Maria , Świeżawska-Boniecka Brygida , Wong Aloysius , Jaworski Krzysztof , Szmidt-Jaworska Adriana
Published: June 2021

In recent years, cyclic guanosine 3′,5′-cyclic monophosphate (cGMP) and guanylyl cyclases (GCs), which catalyze the formation of cGMP, were implicated in a growing number of plant processes, including plant growth and development and the responses to various stresses. To identify novel GCs in plants, an amino acid sequence of a catalytic motif with a conserved core was designed through bioinformatic analysis. In this report, we describe the performed analyses and consider the changes caused by the introduced modification within the GC catalytic motif, which eventually led to the description of a plasma membrane receptor of peptide signaling molecules—BdPepR2 in Brachypodium distachyon. Both in vitro GC activity studies and structural and docking analyses demonstrated that the protein could act as a GC and contains a highly conserved 14-aa GC catalytic center. However, we observed that in the case of BdPepR2, this catalytic center is altered where a methionine instead of the conserved lysine or arginine residues at position 14 of the motif, conferring higher catalytic activity than arginine and alanine, as confirmed through mutagenesis studies. This leads us to propose the expansion of the GC motif to cater for the identification of GCs in monocots. Additionally, we show that BdPepR2 also has in vitro kinase activity, which is modulated by cGMP.
Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2
Authors: Ogazon del Toro Alejandro , Jimenez Lidia , Serrano Rubi Mauricio , Cereijido Marcelino , Ponce Arturo
Published: June 2021

Ouabain is a cardiac glycoside that has been described as a hormone, with interesting effects on epithelial physiology. We have shown previously that ouabain induces gap junctional intercellular communication (GJIC) in wild, sensitive cells (MDCK-S), but not in cells that have become insensitive (MDCK-I) by modifying their Na+-K+-ATPase. We have also demonstrated that prostaglandin E2 (PGE2) is able to induce increased GJIC by a mechanism other than ouabain, that does not depend on Na+-K+-ATPase. In this work we show, by dye transfer assays, that when MDCK-S and MDCK-I are randomly mixed, to form monolayers, the latter stablish GJIC, because of stimulation by a compound released to the extracellular media, by MDCK-S cells, after treatment with ouabain, as evidenced by the fact that monolayers of only MDCK-I cells, treated with a conditioned medium (CM) that is obtained after incubation of MDCK-S monolayers with ouabain, significantly increase their GJIC. The further finding that either (1) pre-treatment with COX-2 inhibitors or (2) addition to CM of antagonists of EP2 receptor abolish CM’s ability to induce GJIC in MDCK-I monolayers indicate that PGE2 is the GJIC-inducing compound. Therefore, these results indicate that, in addition to direct stimulation, mediated by Na+-K+-ATPase, ouabain enhances GJIC indirectly through the paracrine production of PGE2.
Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape
Authors: Sadeghi Laia , Wright Anthony P.
Published: June 2021

Lymphocyte migration to and sequestration in specific microenvironments plays a crucial role in their differentiation and survival. Lymphocyte trafficking and homing are tightly regulated by signaling pathways and is mediated by cytokines, chemokines, cytokine/chemokine receptors and adhesion molecules. The production of cytokines and chemokines is largely controlled by transcription factors in the context of a specific epigenetic landscape. These regulatory factors are strongly interconnected, and they influence the gene expression pattern in lymphocytes, promoting processes such as cell survival. The epigenetic status of the genome plays a key role in regulating gene expression during many key biological processes, and it is becoming more evident that dysregulation of epigenetic mechanisms contributes to cancer initiation, progression and drug resistance. Here, we review the signaling pathways that regulate lymphoma cell migration and adhesion with a focus on Mantle cell lymphoma and highlight the fundamental role of epigenetic mechanisms in integrating signals at the level of gene expression throughout the genome.
Synthesis of Novel Spiro-Tetrahydroquinoline Derivatives and Evaluation of Their Pharmacological Effects on Wound Healing
Authors: Liou Yan-Cheng , Lin Yan-An , Wang Ke , Yang Juan-Cheng , Jang Yeong-Jiunn , Lin Wenwei , Wu Yang-Chang
Published: June 2021

A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These activities of these derivatives were then tested in human keratocyte cells. The responses of cells to treatment with selected compounds were studied using scratch analysis, and the compounds were tested in a mouse excision wound model. Three of the derivatives demonstrated significant wound-healing activities.
Transdermal Delivery Systems for Ibuprofen and Ibuprofen Modified with Amino Acids Alkyl Esters Based on Bacterial Cellulose
Authors: Ossowicz-Rupniewska Paula , Rakoczy Rafał , Nowak Anna , Konopacki Maciej , Klebeko Joanna , Świątek Ewelina , Janus Ewa , Duchnik Wiktoria , Wenelska Karolina , Kucharski Łukasz , Klimowicz Adam
Published: June 2021

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.
Molecular Biomarkers in Idiopathic Pulmonary Fibrosis: State of the Art and Future Directions
Authors: Stainer Anna , Faverio Paola , Busnelli Sara , Catalano Martina , Della Zoppa Matteo , Marruchella Almerico , Pesci Alberto , Luppi Fabrizio
Published: June 2021

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.
Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes
Authors: Domenis Rossana , Cifù Adriana , Mio Catia , Fabris Martina , Curcio Francesco
Published: June 2021

Exosomes released from tumor cells are instrumental in shaping the local tumor microenvironment to allow cancer progression. Recently, it has been shown that tumor exosomes carry large fragments of dsDNA, which may reflect the mutational status of parental cells. Although it has been described that a stressful microenvironment can influence exosomal cargo, the effects on DNA packing and its transfer into recipient cells have yet to be investigated. Here, we report that exosomes derived from SW480 (human colorectal adenocarcinoma cell line) cells can carry dsDNA fragments containing the entire coding sequence of both TP53 and KRAS genes, harboring the SW480-related TP53 c.818G > A and KRAS c.35G > T typical mutations. We also report the following: that cell stimulation with lipopolysaccharides (LPS) promotes the selective packaging of the TP53 gene, but not the KRAS gene; that exosomes secreted by SW480 cells efficiently transfer the mutated sequences into normal CCD841-CoN colon epithelial and THLE-2 hepatic cells; that this mechanism is more efficient when the cells had been previously incubated with pro-inflammatory cytokines; that the TP53 gene appears actively transcribed in both recipient cells; and that mutated mRNA levels are not influenced by cytokine treatment. Our data strongly suggest that pro-inflammatory stimulation promotes the horizontal transfer of an oncogene by exosomes, although this remains a rare event. Further studies are needed to assess the impact of the oncogenic transfer by exosomes in malignant transformation and its role in tumor progression.
Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy
Authors: Nenkov Miljana , Ma Yunxia , Gaßler Nikolaus , Chen Yuan
Published: June 2021

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.
Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders
Authors: Bakare Ajibola B. , Daniel Julienne , Stabach Joshua , Rojas Anapaula , Bell Austin , Henry Brooke , Iyer Shilpa
Published: June 2021

Mitochondria are dynamic organelles that undergo rounds of fission and fusion and exhibit a wide range of morphologies that contribute to the regulation of different signaling pathways and various cellular functions. It is important to understand the differences between mitochondrial structure in health and disease so that therapies can be developed to maintain the homeostatic balance of mitochondrial dynamics. Mitochondrial disorders are multisystemic and characterized by complex and variable clinical pathologies. The dynamics of mitochondria in mitochondrial disorders is thus worthy of investigation. Therefore, in this study, we performed a comprehensive analysis of mitochondrial dynamics in ten patient-derived fibroblasts containing different mutations and deletions associated with various mitochondrial disorders. Our results suggest that the most predominant morphological signature for mitochondria in the diseased state is fragmentation, with eight out of the ten cell lines exhibiting characteristics consistent with fragmented mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in cell lines with a wide array of developmental and mitochondrial disorders. A more thorough analysis of the correlations between mitochondrial dynamics, mitochondrial genome perturbations, and bioenergetic dysfunction will aid in identifying unique morphological signatures of various mitochondrial disorders in the future.
Structural and Biochemical Characterization of a Dye-Decolorizing Peroxidase from Dictyostelium discoideum
Authors: Rai Amrita , Klare Johann P. , Reinke Patrick Y. A. , Englmaier Felix , Fohrer Jörg , Fedorov Roman , Taft Manuel H. , Chizhov Igor , Curth Ute , Plettenburg Oliver , Manstein Dietmar J.
Published: June 2021

A novel cytoplasmic dye-decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds, and general peroxidase substrates such as ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN− molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H2O2 during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.
Bacterial Cellulose Membrane Containing Epilobium angustifolium L. Extract as a Promising Material for the Topical Delivery of Antioxidants to the Skin
Authors: Nowak Anna , Ossowicz-Rupniewska Paula , Rakoczy Rafał , Konopacki Maciej , Perużyńska Magdalena , Droździk Marek , Makuch Edyta , Duchnik Wiktoria , Kucharski Łukasz , Wenelska Karolina , Klimowicz Adam
Published: June 2021

Bacterial cellulose membranes (BCs) are becoming useful as a drug delivery system to the skin. However, there are very few reports on their application of plant substances to the skin. Komagataeibacter xylinus was used for the production of bacterial cellulose (BC). The BC containing 5% and 10% ethanolic extract of Epilobium angustifolium (FEE) (BC-5%FEE and BC-10%FEE, respectively) were prepared. Their mechanical, structural, and antioxidant properties, as well as phenolic acid content, were evaluated. The bioavailability of BC-FESs using mouse L929 fibroblasts as model cells was tested. Moreover, In Vitro penetration through the pigskin of the selected phenolic acids contained in FEE and their accumulation in the skin after topical application of BC-FEEs was examined. The BC-FEEs were characterized by antioxidant activity. The BC-5% FEE showed relatively low toxicity to healthy mouse fibroblasts. Gallic acid (GA), chlorogenic acid (ChA), 3,4-dihydroxybenzoic acid (3,4-DHB), 4-hydroxybenzoic acid (4-HB), 3-hydroxybenzoic acid (3-HB), and caffeic acid (CA) found in FEE were also identified in the membranes. After topical application of the membranes to the pigskin penetration of some phenolic acid and other antioxidants through the skin as well as their accumulation in the skin was observed. The bacterial cellulose membrane loaded by plant extract may be an interesting solution for topical antioxidant delivery to the skin.
Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34
Authors: Naziris Nikolaos , Pippa Natassa , Sereti Evangelia , Chrysostomou Varvara , Kędzierska Marta , Kajdanek Jakub , Ionov Maksim , Miłowska Katarzyna , Balcerzak Łucja , Garofalo Stefano , Limatola Cristina , Pispas Stergios , Dimas Konstantinos , Bryszewska Maria , Demetzos Costas
Published: June 2021

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.
Endothelial Dysfunction and Neutrophil Degranulation as Central Events in Sepsis Physiopathology
Authors: Martín-Fernández Marta , Tamayo-Velasco Álvaro , Aller Rocío , Gonzalo-Benito Hugo , Martínez-Paz Pedro , Tamayo Eduardo
Published: June 2021

Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The progressive increase of both the incidence and prevalence of sepsis has translated into a significant socioeconomic burden for health systems. Currently, it is the leading cause of noncoronary mortality worldwide and represents one of the most prevalent pathologies both in hospital emergency services and in intensive care units. In this article, we review the role of both endothelial dysfunction and neutrophil dysregulation in the physiopathology of this disease. The lack of a key symptom in sepsis makes it difficult to obtain a quick and accurate diagnosis of this condition. Thus, it is essential to have fast and reliable diagnostic tools. In this sense, the use of biomarkers can be a very important alternative when it comes to achieving these goals. Both new biomarkers and treatments related to endothelial dysfunction and neutrophil dysregulation deserve to be further investigated in order to open new venues for the diagnosis, treatment and prognosis of sepsis.
Targeting the NAD Salvage Synthesis Pathway as a Novel Therapeutic Strategy for Osteosarcomas with Low NAPRT Expression
Authors: Franceschini Natasja , Oosting Jan , Tamsma Maud , Niessen Bertine , Bruijn Inge Briaire-de , van den Akker Brendy , Kruisselbrink Alwine B. , Palubeckaitė Ieva , Bovée Judith V. M. G. , Cleton-Jansen Anne-Marie
Published: June 2021

For osteosarcoma (OS), the most common primary malignant bone tumor, overall survival has hardly improved over the last four decades. Especially for metastatic OS, novel therapeutic targets are urgently needed. A hallmark of cancer is aberrant metabolism, which justifies targeting metabolic pathways as a promising therapeutic strategy. One of these metabolic pathways, the NAD+ synthesis pathway, can be considered as a potential target for OS treatment. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the classical salvage pathway for NAD+ synthesis, and NAMPT is overexpressed in OS. In this study, five OS cell lines were treated with the NAMPT inhibitor FK866, which was shown to decrease nuclei count in a 2D in vitro model without inducing caspase-driven apoptosis. The reduction in cell viability by FK866 was confirmed in a 3D model of OS cell lines (n = 3). Interestingly, only OS cells with low nicotinic acid phosphoribosyltransferase domain containing 1 (NAPRT1) RNA expression were sensitive to NAMPT inhibition. Using a publicly available (Therapeutically Applicable Research to Generate Effective Treatments (TARGET)) and a previously published dataset, it was shown that in OS cell lines and primary tumors, low NAPRT1 RNA expression correlated with NAPRT1 methylation around the transcription start site. These results suggest that targeting NAMPT in osteosarcoma could be considered as a novel therapeutic strategy, where low NAPRT expression can serve as a biomarker for the selection of eligible patients.
Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study
Authors: Fernández María , de Coo Alicia , Quintela Inés , García Eliane , Diniz-Freitas Márcio , Limeres Jacobo , Diz Pedro , Blanco Juan , Carracedo Ángel , Cruz Raquel
Published: June 2021

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10−5, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10−5, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10−5, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10−5, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10−5, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10−2, p = 5.1 × 10−3, p = 1.2 × 10−2, respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.
MNCF: Prediction Method for Reliable Blockchain Services under a BaaS Environment
Authors: Xu Jianlong , Zhuang Zicong , Xia Zhiyu , Li Yuhui
Published: June 2021

Blockchain is an innovative distributed ledger technology that is widely used to build next-generation applications without the support of a trusted third party. With the ceaseless evolution of the service-oriented computing (SOC) paradigm, Blockchain-as-a-Service (BaaS) has emerged, which facilitates development of blockchain-based applications. To develop a high-quality blockchain-based system, users must select highly reliable blockchain services (peers) that offer excellent quality-of-service (QoS). Since the vast number of blockchain services leading to sparse QoS data, selecting the optimal personalized services is challenging. Hence, we improve neural collaborative filtering and propose a QoS-based blockchain service reliability prediction algorithm under BaaS, named modified neural collaborative filtering (MNCF). In this model, we combine a neural network with matrix factorization to perform collaborative filtering for the latent feature vectors of users. Furthermore, multi-task learning for sharing different parameters is introduced to improve the performance of the model. Experiments based on a large-scale real-world dataset validate its superior performance compared to baselines.
Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update
Authors: Stasi Cristina , Tiengo Giacomo , Sadalla Sinan , Zignego Anna Linda
Published: June 2021

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.
From Automation System to Autonomous System: An Architecture Perspective
Authors: Chen Hualong , Wen Yuanqiao , Zhu Man , Huang Yamin , Xiao Changshi , Wei Tao , Hahn Axel
Published: June 2021

Autonomy is the core capability of future systems, and architecture design is one of the critical issues in system development and implementation. To discuss the architecture of autonomous systems in the future, this paper reviews the developing progress of architectures from automation systems to autonomous systems. Firstly, the autonomy and autonomous systems in different fields are summarized. The article classifies and summarizes the architecture of typical automated systems and infer three suggestions for building an autonomous system architecture: extensibility, evolvability, and collaborability. Accordingly, this paper builds an autonomous waterborne transportation system, and the architecture is composed of the object layer, cyberspace layer, cognition layer, and application layer, the proposed suggestions made in the construction of the architecture are reflected in the inter-relationships at all layers. Through the cooperation of four layers, the autonomous waterborne transportation system can autonomously complete the system functions, such as system control and transportation service. In the end, the characteristics of autonomous systems are concluded, from which the future primary research directions and the challenges of autonomous systems are provided.