bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Bacterial and Fungal Richness and Network Exhibit Different Responses to Long-Term Throughfall Reduction in a Warm-Temperate Oak Forest
Authors: Zhang Jinglei , Liu Shirong , Liu Cuiju , Wang Hui , Luan Junwei , Liu Xiaojing , Guo Xinwei , Niu Baoliang
Published: January 2021

Prolonged drought results in serious ecological consequences in forest ecosystems, particularly for soil microbial communities. However, much is unknown about soil microbial communities in their response to long-term consecutive droughts in warm-temperate forests. Here, we conducted a 7-year manipulated throughfall reduction experiment (TFR) to examine the responses of bacterial and fungal communities in terms of richness and networks. Our results show that long-term TFR reduced bacterial, but not fungal, richness, with rare bacterial taxa being more sensitive to TFR than dominant taxa. The bacterial network under the TFR treatment featured a simpler network structure and fewer competitive links compared to the control, implying weakened interactions among bacterial species. Bacterial genes involved in xenobiotic biodegradation and metabolism, and lignin-degrading enzymes were enhanced under TFR treatment, which may be attributed to TFR-induced increases in fine root biomass and turnover. Our results indicate that soil bacterial communities are more responsive than fungi to long-term TFR in a warm-temperate oak forest, leading to potential consequences such as the degradation of recalcitrant organics in soil.
Acknowledgment to Reviewers of Fire in 2020
Authors:   Fire Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Fire maintains its standards for the high quality of its published papers [...]
Transcriptomic Insights into the Insect Immune Response to Nematode Infection
Authors: Eleftherianos Ioannis , Heryanto Christa
Published: January 2021

Insects in nature interact with a wide variety of microbial enemies including nematodes. These include entomopathogenic nematodes that contain mutualistic bacteria and together are able to infect a broad range of insects in order to complete their life cycle and multiply, filarial nematodes which are vectored by mosquitoes, and other parasitic nematodes. Entomopathogenic nematodes are commonly used in biological control practices and they form excellent research tools for understanding the genetic and functional bases of nematode pathogenicity and insect anti-nematode immunity. In addition, clarifying the mechanism of transmission of filarial nematodes by mosquitoes is critical for devising strategies to reduce disease transmission in humans. In all cases and in order to achieve these goals, it is vital to determine the number and type of insect host genes which are differentially regulated during infection and encode factors with anti-nematode properties. In this respect, the use of transcriptomic approaches has proven a key step for the identification of insect molecules with anti-nematode activity. Here, we review the progress in the field of transcriptomics that deals with the insect response to nematode infection. This information is important because it will expose conserved pathways of anti-nematode immunity in humans.
Ethical, Legal and Social Issues (ELSI) Associated with Non-Invasive Prenatal Testing: Reflections on the Evolution of Prenatal Diagnosis and Procreative Choices
Authors: Zaami Simona , Orrico Alfredo , Signore Fabrizio , Cavaliere Anna Franca , Mazzi Marta , Marinelli Enrico
Published: January 2021

New technologies such as non-invasive prenatal testing (NIPT), capable of analyzing cell-free fetal DNA in the maternal bloodstream, have become increasingly widespread and available, which has in turn led to ethical and policy challenges that need addressing. NIPT is not yet a diagnostic tool, but can still provide information about fetal genetic characteristics (including sex) very early in pregnancy, and there is no denying that it offers valuable opportunities for pregnant women, particularly those at high risk of having a child with severe genetic disorders or seeking an alternative to invasive prenatal testing. Nonetheless, the ethical, legal and social implications (ELSI) include multiple aspects of informed decision-making, which can entail risks for the individual right to procreative autonomy, in addition to the potential threats posed by sex-selective termination of pregnancy (in light of the information about fetal sex within the first trimester), and the stigmatization and discrimination of disabled individuals. After taking such daunting challenges into account and addressing NIPT-related medicolegal complexities, the review’s authors highlight the need for an ethically and legally sustainable framework for the implementation of NIPT, which seems poised to become a diagnostic tool, as its scope is likely to broaden in the near future.
Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey
Authors: Bozdogan Sevcan Tug , Mujde Cem , Boga Ibrahim , Sonmezler Ozge , Hanta Abdullah , Rencuzogullari Cagla , Ozcan Dilek , Altintas Derya Ufuk , Bisgin Atil
Published: January 2021

Background: Cystic fibrosis (CF) is the most common worldwide, life-shortening multisystem hereditary disease, with an autosomal recessive inheritance pattern caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The national newborn screening (NBS) program for CF has been initiated in Turkey since 2015. If the immunoreactive trypsinogen (IRT) is elevated (higher than 70 μg/L in the second control) and confirmed by sweat test or clinical findings, genetic testing is performed. The aims of this study are to emphasize the effect of NBS on the status of genetic diagnosis centers with the increasing numbers of molecular testing methods, and to determine the numbers and types of CFTR mutations in Turkey. Methods: The next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) results of 1595 newborns, who were referred to Cukurova University Adana Genetic Diseases Diagnosis and Treatment Center (AGENTEM) for molecular genetic testing, were evaluated with positive CF NBS program results since 2017. Results: According to the results; 560 (35.1%) of the 1595 patients carried at least 1 (one) CF-related variant, while 1035 patients (64.9%) had no mutation. Compound heterozygosity for two mutations was the most common in patients, while two detected variants were homozygote in 14 patients. A total of 161 variants were detected in 561 patients with mutations. Fifteen novel variants that have not been previously reported were found. Moreover, p.L997F was identified as the most frequent pathogenic mutation that might affect the IRT measurements used for the NBS. The distribution of mutation frequencies in our study showed a difference from those previously reported; for example, the well-known p.F508del was the third most common (n = 42 alleles), rather than the first. The most striking finding is that 313 cases had a pathogenic variant together with the V470M variant, which might have a cumulative effect on CF perpetuation. Conclusion: This study is the first to determine the mutational spectrum of CFTR in correlation with the NBS program in the Turkish population. NBS for CF raises issues regarding screening in diverse populations, both medical and non-medical benefits, and carrier identification. Through the lens of NBS, we focused on the integrated diagnostic algorithms and their effect on the results of genetic testing.
Rivers in the Focus of Natural-Anthropogenic Situations at Catchments
Authors: Lisetskii Fedor
Published: January 2021

Although surface water is the most accessible type of water resource for industrial and agricultural use, it is the most vulnerable to depletion in quantity and quality [...]
Socioeconomic Inequalities in COVID-19 in a European Urban Area: Two Waves, Two Patterns
Authors: Marí-Dell’Olmo Marc , Gotsens Mercè , Pasarín M Isabel , Rodríguez-Sanz Maica , Artazcoz Lucía , Garcia de Olalla Patricia , Rius Cristina , Borrell Carme
Published: January 2021

Background: The objective of this paper is to analyze social inequalities in COVID-19 incidence, stratified by age, sex, geographical area, and income in Barcelona during the first two waves of the pandemic. Methods: We collected data on COVID-19 cases confirmed by laboratory tests during the first two waves of the pandemic (1 March to 15 July and 16 July to 30 November, 2020) in Barcelona. For each wave and sex, we calculated smooth cumulative incidence by census tract using a hierarchical Bayesian model. We analyzed income inequalities in the incidence of COVID-19, categorizing the census tracts into quintiles based on the income indicator. Results: During the two waves, women showed higher COVID-19 cumulative incidence under 64 years, while the trend was reversed after that threshold. The incidence of the disease was higher in some poor neighborhoods. The risk ratio (RR) increased in the poorest groups compared to the richest ones, mainly in the second wave, with RR being 1.67 (95% Credible Interval-CI-: 1.41–1.96) in the fifth quintile income group for men and 1.71 (95% CI: 1.44–1.99) for women. Conclusion: Our results indicate the existence of inequalities in the incidence of COVID-19 in an urban area of Southern Europe.
Effectiveness of Online Mindfulness-Based Intervention (iMBI) on Inattention, Hyperactivity–Impulsivity, and Executive Functioning in College Emerging Adults with Attention-Deficit/Hyperactivity Disorder: A Study Protocol
Authors: Pheh Kai-Shuen , Tan Kit-Aun , Ibrahim Normala , Sidik Sherina Mohd
Published: January 2021

Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental disorder, often persists into adulthood. In Malaysia, the prevalence rate of hyperactivity symptoms is highest among Chinese Malaysians. There are limited evidence-based treatment options targeting the core symptoms of ADHD, as well as executive functioning. In addition, conventional psychotherapeutic approaches for adults with ADHD have been found to be highly labor-intensive. The present study will evaluate the effectiveness of an online mindfulness-based intervention to reduce inattention and hyperactivity–impulsivity and improve executive functioning among Chinese Malaysian college emerging adults with ADHD. Informed by established literature, we will design an 8-week online mindfulness-based intervention (i.e., iMBI). We will conduct a two-arm randomized controlled trial comparing an iMBI plus treatment-as-usual group (n = 54) and an enhanced treatment-as-usual control group (n = 54). Outcome measures of inattention, hyperactivity–impulsivity, and executive functioning will be collected at baseline, immediately post-intervention, and 1-month post-intervention. The findings of the present study will not only demonstrate the implementation of iMBI as a new treatment modality but also inform practitioners on the effectiveness of iMBI in reducing the burden of adults living with ADHD.
An Estimation Model of Urban Land Accessibility
Authors: Wang Wei , Chen Jian , Wang Zhiyuan , Chen Jun , Cheng Wen , Zhou Zihao
Published: January 2021

Given that there are no practical quantitative indicators of traffic conditions for facility location selection in the process of urbanization, this article proposes a comprehensive accessibility index of location and its measurement method. Urban land is rasterized using GIS to obtain the grids, and the road network data are used to calculate the external accessibility and internal accessibility of the grids. The external accessibility and the internal accessibility of a grid are combined to obtain the comprehensive accessibility of the location. The comprehensive accessibilities of grids are measured for Zhicheng, an urban area in China. The results show that the pattern of gradual spatial changes in the comprehensive accessibility of the grids in Zhicheng is highly consistent with the urban land’s spatial development trend, which verifies the feasibility and accuracy of the comprehensive accessibility measurement method. On one hand, the comprehensive accessibility of the grid is more portable than the accessibility of a single point and can be calculated in batches. On the other hand, it is more specific than the regional accessibility and better guides the location selection of urban facilities.
Acknowledgment to Reviewers of IJERPH in 2020
Authors:   IJERPH Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that IJERPH maintains its standards for the high quality of its published papers [...]
Sharing of Verified Information about COVID-19 on Social Network Sites: A Social Exchange Theory Perspective
Authors: Xia Jiabei , Wu Tailai , Zhou Liqin
Published: January 2021

Background: Verified and authentic information about coronavirus disease (COVID-19) on social networking sites (SNS) could help people make appropriate decisions to protect themselves. However, little is known about what factors influence people’s sharing of verified information about COVID-19. Thus, the purpose of this study was to explore the factors that influence people’s sharing of verified information about COVID-19 on social networking sites. Methods: Based on social exchange theory, we explore the factors that influence sharing of verified information about COVID-19 from two perspectives: benefits and costs. We employed the survey method to validate our hypothesized relationships. By using our developed measurement instruments, we collected 347 valid responses from SNS users and utilized the partial least squares method to analyze the data. Results: Among the benefits of sharing verified information about COVID-19, enjoyment in helping (β = 0.357, p = 0.000), altruism (β = 0.133, p = 0.029) and reputation (β = 0.202, p = 0.000) were significantly associated with verified information sharing about COVID-19. Regarding the costs of sharing verified information about COVID-19, both verification cost (β = −0.078, p = 0.046) and executional cost (β = −0.126, p = 0.011) also significantly affect verified information sharing about COVID-19. All the proposed hypotheses were supported. Conclusions: By exploring factors from both benefits and costs perspectives, we could understand users’ intention to share verified information about COVID-19 comprehensively. This study not only contributes to the literature on information sharing, but also has implications concerning users’ behaviors on SNS.
Relation among Caregivers’ Burden, Abuse and Behavioural Disorder in People with Dementia
Authors: Gimeno Ignacio , Val Sonia , Cardoso Moreno María Jesús
Published: January 2021

Dementia produces a loss of independence to carry out the activities of daily life. The great demand for care that these people need usually falls on the family through informal care. This study aims to analyse the burden showed by the informal caregiver of a person with dementia. In addition, we analyse whether this burden present in informal caregivers could be related to abusive behaviour. We also study the relationship between the stage of the disease, the appearance of behavioural disorders and the level of burden in the caregiver using the Scales of Zarit, CASE and FAST. The data showed that 45.50 per cent of caregivers have light burden or burden. After the research, it was identified that the presence of behavioural disorders in patients with dementia showed a correlation with the increase in both the main caregiver burden and abuse. An increase in the level of burden is followed by an increase in the level of abuse (r = 0.844; p = 0.000). Furthermore, we analysed several conditions that could have a correlation with this burden and abuse. It was found that burden in the caregiver could be linked with the presence of behavioural disorders, like aggression (r = 0.577; p = 0.008) and irritability (r = 0.600; p = 0.005) at the moderate stage of the disease. On the other hand, there is a positive correlation between the probability that people with dementia suffer abuse in the moderate stage of the disease and the presence of aggression (r = 0.732; p = 0.000), lack of inhibition (r = 0.571; p = 0.009) and irritability (r = 0.827; p = 0.000). Taking this data into account, burden and abuse seem to be linked to the presence of behavioural disorders in patients with dementia in the moderate stage.
Subcritical Transmission in the Early Stage of COVID-19 in Korea
Authors: Won Yong Sul , Kim Jong-Hoon , Ahn Chi Young , Lee Hyojung
Published: January 2021

While the coronavirus disease 2019 (COVID-19) outbreak has been ongoing in Korea since January 2020, there were limited transmissions during the early stages of the outbreak. In the present study, we aimed to provide a statistical characterization of COVID-19 transmissions that led to this small outbreak. We collated the individual data of the first 28 confirmed cases reported from 20 January to 10 February 2020. We estimated key epidemiological parameters such as reporting delay (i.e., time from symptom onset to confirmation), incubation period, and serial interval by fitting probability distributions to the data based on the maximum likelihood estimation. We also estimated the basic reproduction number (R0) using the renewal equation, which allows for the transmissibility to differ between imported and locally transmitted cases. There were 16 imported and 12 locally transmitted cases, and secondary transmissions per case were higher for the imported cases than the locally transmitted cases (nine vs. three cases). The mean reporting delays were estimated to be 6.76 days (95% CI: 4.53, 9.28) and 2.57 days (95% CI: 1.57, 4.23) for imported and locally transmitted cases, respectively. The mean incubation period was estimated to be 5.53 days (95% CI: 3.98, 8.09) and was shorter than the mean serial interval of 6.45 days (95% CI: 4.32, 9.65). The R0 was estimated to be 0.40 (95% CI: 0.16, 0.99), accounting for the local and imported cases. The fewer secondary cases and shorter reporting delays for the locally transmitted cases suggest that contact tracing of imported cases was effective at reducing further transmissions, which helped to keep R0 below one and the overall transmissions small.
Moral Disengagement, Empathy, and Cybervictim’s Representation as Predictive Factors of Cyberbullying among Italian Adolescents
Authors: Mascia Maria Lidia , Agus Mirian , Zanetti Maria Assunta , Pedditzi Maria Luisa , Rollo Dolores , Lasio Mirko , Penna Maria Pietronilla
Published: January 2021

This study aimed to evaluate which aspects of moral disengagement (MD), empathy, and representations of the victim’s experience (VER) could be predictors of cyberbullying (CB). One hundred and eight-nine students (11–17 years old) completed 3 self-report questionnaires: An MD scale, an empathy scale, and a CB questionnaire. In relation to the personal experience of CB, four groups were identified: Victim, bully, bully/victim, and no experience with CB. The linear bivariate correlation analysis shows correlations between empathy and VER, between empathy and MD, and between MD and VER. A multinomial logistic regression identified which predictors could increase a subject’s probability of belonging to one of the four groups regarding the personal experience of CB (victim, bully, bully/victim, no experience). Findings highlighted that low cognitive empathy might increase the probability for a student to belong to the bullies’ group, rather than the victims’ group. Furthermore, low perception of the consequences of CB on the victim might increase the probability of belonging to the bully, bully/victim, and no experience groups. Then, a high score in the diffusion of responsibility was a significant predictor of belonging to the victim group rather than the no experience group. Results from this study confirm the need for preventive measures against CB, including the empowerment of cognitive empathy, decreasing the diffusion of responsibility, and increasing the awareness of the consequences of CB on the victim.
Sports Gamification: Evaluation of Its Impact on Learning Motivation and Performance in Higher Education
Authors: Liu Taofeng , Lipowski Mariusz
Published: January 2021

In this study, the impacts of sports gamification on college students’ learning motivation and learning performances were explored by training students majoring in physical education to play tennis. A total of 150 students from a physical education college were selected to participate in this experimental teaching, and they were divided into the experimental group (EG) and the control group (CG). Based on the above purposes, the differences in the teaching methods and teaching objectives of the EG and the CG is that the former uses games as a key method in tennis teaching. All participants were asked to complete questionnaires, with the purpose of evaluating the learning motivation of tennis before and after sports game intervention. Additionally, the differentiated learning motivation and learning performance between EG and CG before and after experimental teaching was tested and evaluated. Results demonstrate that students in the EG have significantly increased their intrinsic motivation and introjected regulation, thereby showing better results than CG in key test items. In addition, the above result reveals the positive role of sports gamification in promoting the learning motivation and performance of college students.
Risk Management and Treatment of Coagulation Disorders Related to COVID-19 Infection
Authors: Zanza Christian , Racca Fabrizio , Longhitano Yaroslava , Piccioni Andrea , Franceschi Francesco , Artico Marco , Abenavoli Ludovico , Maiese Aniello , Passaro Giovanna , Volonnino Gianpietro , La Russa Raffaele
Published: January 2021

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction and coagulation activation are key features of severe COVID-19. Fibrinogen and D-dimer levels are typically increased. The risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit despite prophylactic dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased while bleeding is less common than thrombosis, but it can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. The threshold for evaluation or diagnosis of thromboembolism should be low given the high frequency of these events. Management and treatment are new challenges due to the paucity of high-quality evidence regarding efficacy and safety of different approaches to prevent or treat thromboembolic complications of the disease. All inpatients should receive thromboprophylaxis unless contraindicated. Some institutional protocols provide more aggressive anticoagulation with intermediate or even therapeutic dose anticoagulation for COVID-19 patients admitted to ICU. Therapeutic dose anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19.
DNA Methylation in T-Cell Acute Lymphoblastic Leukemia: In Search for Clinical and Biological Meaning
Authors: Maćkowska Natalia , Drobna-Śledzińska Monika , Witt Michał , Dawidowska Małgorzata
Published: January 2021

Distinct DNA methylation signatures, related to different prognosis, have been observed across many cancers, including T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological neoplasm. By global methylation analysis, two major phenotypes might be observed in T-ALL: hypermethylation related to better outcome and hypomethylation, which is a candidate marker of poor prognosis. Moreover, DNA methylation holds more than a clinical meaning. It reflects the replicative history of leukemic cells and most likely different mechanisms underlying leukemia development in these T-ALL subtypes. The elucidation of the mechanisms and aberrations specific to (epi-)genomic subtypes might pave the way towards predictive diagnostics and precision medicine in T-ALL. We present the current state of knowledge on the role of DNA methylation in T-ALL. We describe the involvement of DNA methylation in normal hematopoiesis and T-cell development, focusing on epigenetic aberrations contributing to this leukemia. We further review the research investigating distinct methylation phenotypes in T-ALL, related to different outcomes, pointing to the most recent research aimed to unravel the biological mechanisms behind differential methylation. We highlight how technological advancements facilitated broadening the perspective of the investigation into DNA methylation and how this has changed our understanding of the roles of this epigenetic modification in T-ALL.
Therapeutic Agents for Oxaliplatin-Induced Peripheral Neuropathy; Experimental and Clinical Evidence
Authors: Kawashiri Takehiro , Mine Keisuke , Kobayashi Daisuke , Inoue Mizuki , Ushio Soichiro , Uchida Mayako , Egashira Nobuaki , Shimazoe Takao
Published: January 2021

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.
HPV Meets APOBEC: New Players in Head and Neck Cancer
Authors: Riva Giuseppe , Albano Camilla , Gugliesi Francesca , Pasquero Selina , Pacheco Sergio Fernando Castillo , Pecorari Giancarlo , Landolfo Santo , Biolatti Matteo , Dell’Oste Valentina
Published: January 2021

Besides smoking and alcohol, human papillomavirus (HPV) is a factor promoting head and neck squamous cell carcinoma (HNSCC). In some human tumors, including HNSCC, a number of mutations are caused by aberrantly activated DNA-modifying enzymes, such as the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. As the enzymatic activity of APOBEC proteins contributes to the innate immune response to viruses, including HPV, the role of APOBEC proteins in HPV-driven head and neck carcinogenesis has recently gained increasing attention. Ongoing research efforts take the cue from two key observations: (1) APOBEC expression depends on HPV infection status in HNSCC; and (2) APOBEC activity plays a major role in HPV-positive HNSCC mutagenesis. This review focuses on recent advances on the role of APOBEC proteins in HPV-positive vs. HPV-negative HNSCC.
The Progress of Stem Cell Technology for Skeletal Regeneration
Authors: Tani Shoichiro , Okada Hiroyuki , Chung Ung-il , Ohba Shinsuke , Hojo Hironori
Published: January 2021

Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To treat them, regenerative therapies using skeletal cells have been an attractive choice for patients with unmet clinical needs. Currently, there are two major strategies to prepare the cell sources. The first is to use induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), which can recapitulate the skeletal developmental process and differentiate into various skeletal cells. Skeletal tissues are derived from three distinct origins: the neural crest, paraxial mesoderm, and lateral plate mesoderm. Thus, various protocols have been proposed to recapitulate the sequential process of skeletal development. The second strategy is to extract stem cells from skeletal tissues. In addition to mesenchymal stem/stromal cells (MSCs), multiple cell types have been identified as alternative cell sources. These cells have distinct multipotent properties allowing them to differentiate into skeletal cells and various potential applications for skeletal regeneration. In this review, we summarize state-of-the-art research in stem cell differentiation based on the understanding of embryogenic skeletal development and stem cells existing in skeletal tissues. We then discuss the potential applications of these cell types for regenerative medicine.
MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori
Authors: Săsăran Maria Oana , Meliț Lorena Elena , Dobru Ecaterina Daniela
Published: January 2021

Helicobacter pylori (H. pylori) remains the most-researched etiological factor for gastric inflammation and malignancies. Its evolution towards gastric complications is dependent upon host immune response. Toll-like receptors (TLRs) recognize surface and molecular patterns of the bacterium, especially the lipopolysaccharide (LPS), and act upon pathways, which will finally lead to activation of the nuclear factor-kappa B (NF-kB), a transcription factor that stimulates release of inflammatory cytokines. MicroRNAs (MiRNAs) finely modulate TLR signaling, but their expression is also modulated by activation of NF-kB-dependent pathways. This review aims to focus upon several of the most researched miRNAs on this subject, with known implications in host immune responses caused by H. pylori, including let-7 family, miRNA-155, miRNA-146, miRNA-125, miRNA-21, and miRNA-221. TLR–LPS interactions and their afferent pathways are regulated by these miRNAs, which can be considered as a bridge, which connects gastric inflammation to pre-neoplastic and malignant lesions. Therefore, they could serve as potential non-invasive biomarkers, capable of discriminating H. pylori infection, as well as its associated complications. Given that data on this matter is limited in children, as well as for as significant number of miRNAs, future research has yet to clarify the exact involvement of these entities in the progression of H. pylori-associated gastric conditions.
lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway
Authors: Liu Hongxia , Zheng Wang , Chen Qianping , Zhou Yuchuan , Pan Yan , Zhang Jianghong , Bai Yang , Shao Chunlin
Published: January 2021

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.
Exploration of Bioengineered Scaffolds Composed of Thermo-Responsive Polymers for Drug Delivery in Wound Healing
Authors: Castillo-Henríquez Luis , Castro-Alpízar Jose , Lopretti-Correa Mary , Vega-Baudrit José
Published: January 2021

Innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan, polyvinylpyrrolidone, alginate, and poly(ε-caprolactone) can be used to create biocompatible and biodegradable scaffolds. These processed thermo-responsive biomaterials possess 3D architectures similar to human structures, providing physical support for cell growth and tissue regeneration. Furthermore, these structures are used as novel drug delivery systems. Locally heated tumors above the polymer lower the critical solution temperature and can induce its conversion into a hydrophobic form by an entropy-driven process, enhancing drug release. When the thermal stimulus is gone, drug release is reduced due to the swelling of the material. As a result, these systems can contribute to the wound healing process in accelerating tissue healing, avoiding large scar tissue, regulating the inflammatory response, and protecting from bacterial infections. This paper integrates the relevant reported contributions of bioengineered scaffolds composed of smart thermo-responsive polymers for drug delivery applications in wound healing. Therefore, we present a comprehensive review that aims to demonstrate these systems’ capacity to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to patient convenience and reduce drug toxicity and side effects.
Expression of Recombinant Human Octamer-Binding Transcription Factor 4 in Rice Suspension Cells
Authors: Huang Li-Fen , Sinaga Desyanti Saulina , Tan Chia-Chun , Hsieh Shu-Ju Micky , Huang Chi-Hung
Published: January 2021

The rice cell suspension culture system is a good way to produce recombinant human proteins, owing to its high biosafety and low production cost. Human Octamer-binding Transcription Factor 4 (Oct4) is a fundamental transcription factor responsible for maintaining human pluripotent embryonic stem cells. Recombinant Oct4 protein has been used to induce pluripotent stem cells. In this study, recombinant Oct4 proteins are produced via a sugar starvation-inducible αAmy3/RAmy3D promoter–signal peptide-based rice recombinant protein expression system. Oct4 mRNAs accumulate in the transgenic rice suspension cells under sugar starvation. The Oct4 recombinant protein is detected in the transgenic rice suspension cells, and its highest yield is approximately 0.41% of total cellular soluble proteins after one day of sugar starvation. The rice cell-synthesized recombinant human Oct4 protein show DNA-binding activity in vitro, which implies that the protein structure is correct for enabling specific binding to the target DNA motif.
A Closer Look at the Cellular and Molecular Components of the Deep/Muscular Fasciae
Authors: Fede Caterina , Pirri Carmelo , Fan Chenglei , Petrelli Lucia , Guidolin Diego , De Caro Raffaele , Stecco Carla
Published: January 2021

The fascia can be defined as a dynamic highly complex connective tissue network composed of different types of cells embedded in the extracellular matrix and nervous fibers: each component plays a specific role in the fascial system changing and responding to stimuli in different ways. This review intends to discuss the various components of the fascia and their specific roles; this will be carried out in the effort to shed light on the mechanisms by which they affect the entire network and all body systems. A clear understanding of fascial anatomy from a microscopic viewpoint can further elucidate its physiological and pathological characteristics and facilitate the identification of appropriate treatment strategies.
Function of Connexin-43 in Macrophages
Authors: Rodjakovic Daniel , Salm Lilian , Beldi Guido
Published: January 2021

Recent studies have helped to increase the understanding of the function of Connexin-43 (Cx43) in macrophages (Mφ). The various roles of Cx43 in Mφs range from migration, antigen-presentation and some forms of intercellular communication to more delicate processes, such as electrochemical support in the propagation of the heartbeat, immunomodulatory regulation in the lungs and in macrophage-differentiation. Its relevance in pathophysiology becomes evident in inflammatory bowel disease (IBD), tumours and HIV, in which aberrant functioning of Cx43 has been described. However, the involvement of Cx43 in other Mφ functions, such as phagocytosis and polarisation, and its involvement in other types of local and systemic inflammation, are still unclear and need further research.
Probiotic Activity of Staphylococcus epidermidis Induces Collagen Type I Production through FFaR2/p-ERK Signaling
Authors: Negari Indira Putri , Keshari Sunita , Huang Chun-Ming
Published: January 2021

Collagen type I is a key structural component of dermis tissue and is produced by fibroblasts and the extracellular matrix. The skin aging process, which is caused by intrinsic or extrinsic factors, such as natural aging or free radical exposure, greatly reduces collagen expression, thereby leading to obstructed skin elasticity. We investigated the effective fermentation of Cetearyl isononanoate (CIN), a polyethylene glycol (PEG) analog, as a carbon source with the skin probiotic bacterium Staphylococcus epidermidis (S.epidermidis) or butyrate, as their fermentation metabolites could noticeably restore collagen expression through phosphorylated extracellular signal regulated kinase (p-ERK) activation in mouse fibroblast cells and skin. Both the in vitro and in vivo knockdown of short-chain fatty acid (SCFA) or free fatty acid receptor 2 (FFaR2) considerably blocked the probiotic effect of S. epidermidis on p-ERK-induced collagen type I induction. These results demonstrate that butyric acid (BA) in the metabolites of fermenting skin probiotic bacteria mediates FFaR2 to induce the synthesis of collagen through p-ERK activation. We hereby imply that metabolites from the probiotic S. epidermidis fermentation of CIN as a potential carbon source could restore impaired collagen in the dermal extracellular matrix (ECM), providing integrity and elasticity to skin.
Transport Characteristics of CJMAED™ Homogeneous Anion Exchange Membranes in Sodium Chloride and Sodium Sulfate Solutions
Authors: Sarapulova Veronika , Pismenskaya Natalia , Titorova Valentina , Sharafan Mikhail , Wang Yaoming , Xu Tongwen , Zhang Yang , Nikonenko Victor
Published: January 2021

The interplay between the ion exchange capacity, water content and concentration dependences of conductivity, diffusion permeability, and counterion transport numbers (counterion permselectivity) of CJMA-3, CJMA-6 and CJMA-7 (Hefei Chemjoy Polymer Materials Co. Ltd., China) anion-exchange membranes (AEMs) is analyzed using the application of the microheterogeneous model to experimental data. The structure–properties relationship for these membranes is examined when they are bathed by NaCl and Na2SO4 solutions. These results are compared with the characteristics of the well-studied homogenous Neosepta AMX (ASTOM Corporation, Japan) and heterogeneous AMH-PES (Mega a.s., Czech Republic) anion-exchange membranes. It is found that the CJMA-6 membrane has the highest counterion permselectivity (chlorides, sulfates) among the CJMAED series membranes, very close to that of the AMX membrane. The CJMA-3 membrane has the transport characteristics close to the AMH-PES membrane. The CJMA-7 membrane has the lowest exchange capacity and the highest volume fraction of the intergel spaces filled with an equilibrium electroneutral solution. These properties predetermine the lowest counterion transport number in CJMA-7 among other investigated AEMs, which nevertheless does not fall below 0.87 even in 1.0 eq L−1 solutions of NaCl or Na2SO4. One of the reasons for the decrease in the permselectivity of CJMAED membranes is the extended macropores, which are localized at the ion-exchange material/reinforcing cloth boundaries. In relatively concentrated solutions, the electric current prefers to pass through these well-conductive but nonselective macropores rather than the highly selective but low-conductive elements of the gel phase. It is shown that the counterion permselectivity of the CJMA-7 membrane can be significantly improved by coating its surface with a dense homogeneous ion-exchange film.
Gut Microbiota–Host Interactions in Inborn Errors of Immunity
Authors: Castagnoli Riccardo , Pala Francesca , Bosticardo Marita , Licari Amelia , Delmonte Ottavia M. , Villa Anna , Marseglia Gian Luigi , Notarangelo Luigi Daniele
Published: January 2021

Inborn errors of immunity (IEI) are a group of disorders that are mostly caused by genetic mutations affecting immune host defense and immune regulation. Although IEI present with a wide spectrum of clinical features, in about one third of them various degrees of gastrointestinal (GI) involvement have been described and for some IEI the GI manifestations represent the main and peculiar clinical feature. The microbiome plays critical roles in the education and function of the host’s innate and adaptive immune system, and imbalances in microbiota-immunity interactions can contribute to intestinal pathogenesis. Microbial dysbiosis combined to the impairment of immunosurveillance and immune dysfunction in IEI, may favor mucosal permeability and lead to inflammation. Here we review how immune homeostasis between commensals and the host is established in the gut, and how these mechanisms can be disrupted in the context of primary immunodeficiencies. Additionally, we highlight key aspects of the first studies on gut microbiome in patients affected by IEI and discuss how gut microbiome could be harnessed as a therapeutic approach in these diseases.
A Cellular Assay for the Identification and Characterization of Connexin Gap Junction Modulators
Authors: Danish Azeem , Gedschold Robin , Hinz Sonja , Schiedel Anke C. , Thimm Dominik , Bedner Peter , Steinhäuser Christian , Müller Christa E.
Published: January 2021

Connexin gap junctions (Cx GJs) enable the passage of small molecules and ions between cells and are therefore important for cell-to-cell communication. Their dysfunction is associated with diseases, and small molecules acting as modulators of GJs may therefore be useful as therapeutic drugs. To identify GJ modulators, suitable assays are needed that allow compound screening. In the present study, we established a novel assay utilizing HeLa cells recombinantly expressing Cx43. Donor cells additionally expressing the Gs protein-coupled adenosine A2A receptor, and biosensor cells expressing a cAMP-sensitive GloSensor luciferase were established. Adenosine A2A receptor activation in the donor cells using a selective agonist results in intracellular cAMP production. The negatively charged cAMP migrates via the Cx43 gap junctions to the biosensor cells and can there be measured by the cAMP-dependent luminescence signal. Cx43 GJ modulators can be expected to impact the transfer of cAMP from the donor to the biosensor cells, since cAMP transit is only possible via GJs. The new assay was validated by testing the standard GJ inhibitor carbenoxolon, which showed a concentration-dependent inhibition of the signal and an IC50 value that was consistent with previously reported values. The assay was demonstrated to be suitable for high-throughput screening.
Pharmacological Approaches for the Modulation of the Potassium Channel KV4.x and KChIPs
Authors: Cercós Pilar , Peraza Diego A. , Benito-Bueno Angela de , Socuéllamos Paula G. , Aziz-Nignan Abdoul , Arrechaga-Estévez Dariel , Beato Escarle , Peña-Acevedo Emilio , Albert Armando , González-Vera Juan A. , Rodríguez Yoel , Martín-Martínez Mercedes , Valenzuela Carmen , Gutiérrez-Rodríguez Marta
Published: January 2021

Ion channels are macromolecular complexes present in the plasma membrane and intracellular organelles of cells. Dysfunction of ion channels results in a group of disorders named channelopathies, which represent an extraordinary challenge for study and treatment. In this review, we will focus on voltage-gated potassium channels (KV), specifically on the KV4-family. The activation of these channels generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current) and from the somata of hippocampal neurons (ISA). In the heart, KV4 dysfunctions are related to Brugada syndrome, atrial fibrillation, hypertrophy, and heart failure. In hippocampus, KV4.x channelopathies are linked to schizophrenia, epilepsy, and Alzheimer’s disease. KV4.x channels need to assemble with other accessory subunits (β) to fully reproduce the ITO and ISA currents. β Subunits affect channel gating and/or the traffic to the plasma membrane, and their dysfunctions may influence channel pharmacology. Among KV4 regulatory subunits, this review aims to analyze the KV4/KChIPs interaction and the effect of small molecule KChIP ligands in the A-type currents generated by the modulation of the KV4/KChIP channel complex. Knowledge gained from structural and functional studies using activators or inhibitors of the potassium current mediated by KV4/KChIPs will better help understand the underlying mechanism involving KV4-mediated-channelopathies, establishing the foundations for drug discovery, and hence their treatments.
A Study of Factors Affecting Intention to Adopt a Cloud-Based Digital Signature Service
Authors: Chong Kyung Won , Kim Yong Seok , Choi Jeongil
Published: January 2021

The electronic signature service has been causing various problems due to the rapid growth of e-commerce services. Therefore, in order to create an authentication service suitable for the era of the 4th Industrial Revolution, new security authentication technologies such as the cloud must be utilized. However, there is a lack of prior management studies on the intention to accept digital signatures. Therefore, this study conducted an empirical study to identify factors affecting the intention to adopt cloud-based digital signature services. This research proposed a model based on the technology–organization–environment framework and empirically analyzed the degree of mutual causality and influence between variables using the partial least squares structural equation model. The results show that technical characteristics, organizational characteristics, and environmental characteristics significantly affected the intention to adopt. However, there are still many concerns about the security of cloud-based services. It has been confirmed that solving this problem is the key to the activation of the electronic signature service.