bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavor Preference and Systemic Immunoglobulin Responses in E-Cigarette Users and Waterpipe and Tobacco Smokers: A Pilot Study
Authors: Jackson Monica , Singh Kameshwar P. , Lamb Thomas , McIntosh Scott , Rahman Irfan
Published: January 2020

Electronic cigarette (e-cigarette) use has had an exponential increase in popularity since the product was released to the public. Currently, there is a lack of human studies that assess different biomarker levels. This pilot study attempts to link e-cigarette and other tobacco product usage with clinical respiratory symptoms and immunoglobulin response. Subjects completed surveys in order to collect self-reported data on tobacco product flavor preferences. Along with this, plasma samples were collected to test for immunoglobulin G (IgG) and E (IgE) levels. Our pilot study’s cohort had a 47.9% flavor preference towards fruit flavors and a 63.1% preference to more sweet flavors. E-cigarette and traditional cigarette smokers were the two subject groups to report the most clinical symptoms. E-cigarette users also had a significant increase in plasma IgE levels compared to non-tobacco users 1, and dual users had a significant increase in plasma IgG compared to non-tobacco users 2, cigarette smokers, and waterpipe smokers. Our pilot study showed that users have a preference toward fruit and more sweet flavors and that e-cigarette and dual use resulted in an augmented systemic immune response.
Prevalence and Predictors of Burnout in Midwives: A Systematic Review and Meta-Analysis
Authors: Suleiman-Martos Nora , Albendín-García Luis , Gómez-Urquiza José L. , Vargas-Román Keyla , Ramirez-Baena Lucia , Ortega-Campos Elena , De La Fuente-Solana Emilia I.
Published: January 2020

The prevalence of burnout in midwives has been briefly studied. Given the negative effects of burnout syndrome in the physical and mental health, and also related to the quality of care provided, rates of absenteeism and sick leave; identifying related factors for the syndrome are needed. The aim was to determine the prevalence, levels, and factors related to the burnout syndrome, measured with the Copenhagen Burnout Inventory in midwives. A systematic review and meta-analysis were selected from CINAHL, LILACS, ProQuest, PsycINFO, PubMed, SciELO, and Scopus databases, with the search equation “burnout AND (midwife OR midwives OR nurses midwives)”. Fourteen articles were found with a total of 8959 midwives. Most of the studies showed moderate levels of personal burnout. The prevalence obtained was 50% (95% CI = 38–63) for personal burnout; 40% (95% CI = 32–49) for work-related burnout; and 10% (95% CI = 7–13) for client-related burnout. Midwives’ age, less experience, and living alone constitute the main related factors, as well as, the scarcity of resources, work environment, and the care model used. Most midwives present personal and work-related burnout, which indicates a high risk of developing burnout. Personal factors and working conditions should be taken into account when assessing burnout risk profiles of midwives.
The Effect of the Economic Crisis on Adolescents’ Perceived Health and Risk Behaviors: A Multilevel Analysis
Authors: Zozaya Néboa , Vallejo Laura
Published: January 2020

Background: Previous studies have analyzed the impact of economic crises on adult’s health and lifestyles, but evidence among children and adolescents is limited. The objective of this study was to analyze the impact of the economic crisis on self-perceived health and some risk behaviors in the Spanish adolescent population. Methods: We used data from four waves (2002, 2006, 2010, 2014) of the Health Behavior in School-Aged Children (HBSC) survey in Spain. Separate multilevel logistic and linear regression models were applied for health complaints, self-rated health, life satisfaction, smoking, alcohol consumption, and breakfast skipping. Annual change in Spanish regional unemployment rates was used as a proxy of the economic crisis. An increasing set of control variables were included, consisting of individual, socioeconomic, and family and peer relationships indicators. Median odds ratios were estimated to quantify the cross-region and cross-school variation. Results: Increases in unemployment rates were linked to a higher risk of poorer health and bad habits in the simplest models. The effect was no longer statistically significant when indicators of family and peer relationships were included, suggesting a protective effect against the impact of the economic crisis. Our findings also show that schools had a larger effect on health and lifestyles than regions. Conclusion: The child’s social context—family, peers, school, and region—play an important role on the effects of the economic crisis on health and risk behaviors.
Sustainable Development of Industry–Environmental System Based on Resilience Perspective
Authors: Wan Xue , Yang Xiaoning , Wen Quaner , Gang Jun , Gan Lu
Published: January 2020

The contradiction between industrial development and ecological environment pressure has been becoming progressively severe. Under this circumstance, more attention has been paid to the balance between industrial economic development and environmental deterioration and resource consumption. Thus, this study takes the development of industry and ecological environment change as an interactive system consideration, and comprehensively evaluates the changes of the industrial–environment system on resilience perspective with innovation. Accordingly, this paper establishes a comprehensive evaluation model. The Environmental Performance Index (EPI) and Industrial Structure Entropy (ISE) were applied to analyze the current environment pressure and industrial conditions. Then, the catastrophe theory was used to evaluate the reasonably established index system for the impact of various factors in the industrial–environment system on the resilience change. Next, the adaptive cycle model was used to analyze the evaluation results and reveals the dynamic change law of the system in the resilience range. Finally, Chengdu was selected as the research area to verify the validity of the whole study. It was found that the resilient change process of Chengdu industry–environmental system accord with the four-stage theory of adaptive cycle model. The resilient level of the city was also improved during the cycle. The result of the study can be useful to future plans and decisions. What is more, understanding the characteristics of each stage will be helpful to determine the reasonable implementation time of each key factor and improve its feedback ability.
Menstrual Hygiene Preparedness Among Schools in India: A Systematic Review and Meta-Analysis of System-and Policy-Level Actions
Authors: Sharma Shantanu , Mehra Devika , Brusselaers Nele , Mehra Sunil
Published: January 2020

With increasing girls’ enrolment in schools, school preparedness to ensure a menstrual friendly environment is crucial. The study aimed to conduct a systematic review regarding the existing evidence on menstrual hygiene management (MHM) across schools in India. It further aimed to highlight the actions that have been taken by the government to improve the MHM situation in India. We conducted the systematic literature search using PubMed, EMBASE, and Web of Science for searching the peer-reviewed articles and Google Scholar for anecdotal reports published from inception until 30 October 2019. Of 1125 publications retrieved through the search, 183 papers were included in this review, using a priori created data-extraction form. Meta-analysis was used to estimate the pooled prevalence (PP) of MHM practices in schools. Less than half of the girls were aware of menstruation before menarche (PP 0.45, 0.39 to 0.51, I2 = 100.0%, n = 122). Teachers were a less common source of information about menstruation to girls (PP 0.07, 0.05 to 0.08, I2 = 100.0%, n = 86). Separate toilets for girls were present in around half of the schools (PP 0.56, 0.42 to 0.75, I2 100.0%, n = 11). MHM in schools should be strengthened with convergence between various departments for explicit implementation of guidelines.
Evaluation of the Oxidative Stress Status in Zebrafish (Danio rerio) Liver Induced by Three Typical Organic UV Filters (BP-4, PABA and PBSA)
Authors: Huang Xinxin , Li Yuanyuan , Wang Tantan , Liu Hui , Shi Jiaqi , Zhang Xuesheng
Published: January 2020

Organic UV filters are a kind of emerging pollutants, which have been widely used in personal care products (PCPs). This study evaluated the effects of benzophenone-4 (BP-4), 4-aminobenzoic acid (PABA), and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) on the selected indices of antioxidative responses in zebrafish (Danio rerio) liver. Zebrafish were exposed to two different doses (i.e., 0.5 and 5 mg L−1) of semi-static water with three individual compounds. Liver samples were collected on 7 and 14 days to analyze biochemical indicators, including superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA). Oxidative stress occurred in zebrafish liver with significantly changed indicators during the whole exposure period. Different experimental groups could induce or inhibit the activity of antioxidant enzymes with varying degrees. With a prolonged exposure time and increased exposure dose, the hepatic lipid peroxidation was also obviously observed. Moreover, the toxicity order of three organic UV filters was analyzed using the integrated biomarker response (IBR) index and the results indicate that exposure to PABA for 7 days at 0.5 mg L−1 and PBSA for 7 days at 5 mg L−1 induced the most severe oxidative stress in the liver of zebrafish.
Cultural Adaptation and Psychometric Validation of the Standardised Nordic Questionnaire Spanish Version in Musicians
Authors: Gómez-Rodríguez Rosa , Díaz-Pulido Belén , Gutiérrez-Ortega Carlos , Sánchez-Sánchez Beatriz , Torres-Lacomba María
Published: January 2020

Background: The Standardised Nordic Questionnaire (SNQ) is an instrument to analyse the musculoskeletal symptoms in an ergonomic or occupational health context. We aimed to cross-culturally adapt and evaluate the psychometric properties of the SNQ among Spanish musicians. Methods: Cross-cultural adaptation and psychometric validation (reliability, validity, and feasibility) was performed. Reliability was analysed by test-retest reliability (Cohen’s Kappa) and internal consistency (Kuder–Richardson). Content and face validity were measured by the Expert Committee and the opinion of participants. Construct validity (Mann–Whitney U test) was measured by comparing with questionnaires used to assess pain and disability in neck, shoulders, upper back, and low back regions. Feasibility was calculated with the average response time. Results: A total of 312 Spanish musicians were included. The Spanish version of SNQ achieved good semantic, conceptual, idiomatic, and content equivalence. For most of the variables, test-retest reliability was good to very good (k = 0.60–0.81). The internal consistency showed good to acceptable (Kuder–Richardson 20 (KR20) = 0.737–0.873). Participants with versus without musculoskeletal problems in a related region showed significantly higher disability/pain, indicating a good construct validity. About the feasibility, the average response time of the questionnaire was 6 min (±2). Conclusions: The results show that the Spanish SNQ is reliable, valid, and feasible screening tool to assess musculoskeletal problems among musicians.
Fuzzy Logic-Based Risk Assessment of a Parallel Robot for Elbow and Wrist Rehabilitation
Authors: Tucan Paul , Gherman Bogdan , Major Kinga , Vaida Calin , Major Zoltan , Plitea Nicolae , Carbone Giuseppe , Pisla Doina
Published: January 2020

A few decades ago, robotics started to be implemented in the medical field, especially in the rehabilitation of patients with different neurological diseases that have led to neuromuscular disorders. The main concern regarding medical robots is their safety assurance in the medical environment. The goal of this paper is to assess the risk of a medical robotic system for elbow and wrist rehabilitation in terms of robot and patient safety. The approached risk assessment follows the ISO12100:2010 risk management chart in order to determine, identify, estimate, and evaluate the possible risk that can occur during the use of the robotic system. The result of the risk assessment process is further analyzed using a fuzzy logic system in order to determine the safety degree conferred during the use of the robotic system. The innovative process concerning the risk assessment allows the achievement of a reliable medical robotic system both for the patient and the clinicians as well. The clinical trials performed on a group of 18 patients validated the functionality and the safe behavior of the robotic system.
Platinum Mine Workers’ Exposure to Dust Particles Emitted at Mine Waste Rock Crusher Plants in Limpopo, South Africa
Authors: Sepadi Maasago M. , Chadyiwa Martha , Nkosi Vusumuzi
Published: January 2020

The South African mining industry is one of the largest producers of platinum (Pt) in the world. Workers in this industry are exposed to significant amounts of dust, and this dust consists of particles sizes that can penetrate deep inside the respiratory region. A cross-sectional study was conducted to evaluate dust exposure risk at two Pt mine waste rock crusher plants (Facility A and B) in Limpopo, South Africa. Workers’ demographic and occupational information was collected through a structured questionnaire, a walk-through observation on facilities’ processes, and static dust sampling for the collection of inhalable and respirable dust particles using the National Institute for Occupational Safety and Health (NIOH) 7602 and the Methods for Determination of Hazardous Substance (MDHS) 14/4 as guidelines. Only 79% of Pt mine workers, used their respiratory protective equipment (RPE), sixty-five percent were exposed to work shifts exceeding the recommended eight hours and 8.8% had been employed for more than ten years. The mean time-weighted average (TWA) dust concentrations between Facility A and B showed a significant difference (p < 0.026). The Pt mine’s inhalable concentrations (range 0.03–2.2 mg/m3) were higher than the respirable concentrations (range 0.02–0.7 mg/m3), however were all below the respective international and local occupational exposure limits (OELs). The Pt mine’s respirable crystalline silica (SiO2) quartz levels were all found below the detectable limit (<0.01 mg/m3). The Pt miners had increased health risks due to accumulated low levels of dust exposure and lack of usage of RPE. It is recommended that an improved dust control program be put in place which includes, but is not limited to, stockpile enclosures, tire stops with water sprays, and education on the importance of RPE usage.
Work Addiction, Obsessive-Compulsive Personality Disorder, Burn-Out, and Global Burden of Disease: Implications from the ICD-11
Authors: Atroszko Paweł A. , Demetrovics Zsolt , Griffiths Mark D.
Published: January 2020

Occupational stress and high workload are being increasingly recognized as significant contributors to the diseases and disorders constituting major components of the global burden of disease. A more detailed definition of burn-out was recently included by the World Health Organization (WHO) in the eleventh revision of the International Classification of Diseases (ICD-11) which reflects a growing acknowledgment of the role of professional work in mental health. One of the symptoms of obsessive-compulsive personality disorder/anankastic personality disorder (OCPD/APD) is an undue preoccupation with productivity to the exclusion of pleasure and interpersonal relationships. This compulsive overworking is closely related to the concept of work addiction, and OCPD/APD was suggested to be its major risk factor. OCPD/APD is the most prevalent personality disorder and one that appears to produce the highest direct and indirect medical costs. At the same time, it is vastly understudied. In recent years, it has been repeatedly emphasized that it requires consistent conceptualization and clarification of its overlapping with similar conditions. Even though the limited existing studies suggest its strong relationship with burn-out and depression among employed individuals, there has been no systematic effort to investigate its role in the consequences of occupational stress and high workload. This paper identifies several substantial gaps in the current understanding of the relationships between work addiction, OCPD/APD, burn-out, and the global burden of disease within the context of the WHO’s plan of developing evidence-based guidelines on mental wellbeing in the workplace.
Evidence in Asian Food Industry: Intellectual Capital, Corporate Financial Performance, and Corporate Social Responsibility
Authors: Tsai Cheng-Hung , Mutuc Eugene Burgos
Published: January 2020

Intellectual capital (IC) and corporate social responsibility (CSR) provide a strong link between the enterprise and stakeholders. These strategic approaches are responsible in value formation for better financial performance. This study investigates the mediating effects of corporate financial performance on the relationship between IC components (ICs) and CSR of firms from the food industry in Asia. We analyzed 308 firm-year observations of 44 listed firms from 2011 to 2017. The results of this study provided mixed findings regarding the effects of ICs and CSR. In addition, results vary from the disaggregated effects of each IC component on environmental, social, and governance pillars. The results also indicate that the combination of accounting and market-based estimates of financial performance was found to be significant mediating factor to explain the phenomenon which varies per ICs and dimensions of CSR. Lastly, the implications for sustainable business practices and investments in knowledge-based resources in the food industry are elaborated.
Detecting Intra-Urban Housing Market Spillover through a Spatial Markov Chain Model
Authors: Zhang Daijun , Zhang Xiaoqi , Zheng Yanqiao , Ye Xinyue , Li Shengwen , Dai Qiwen
Published: January 2020

This study analyzed the spillovers among intra-urban housing submarkets in Beijing, China. Intra-urban spillover imposes a methodological challenge for housing studies from the spatial and temporal perspectives. Unlike the inter-urban spillover, the range of every submarket is not naturally defined; therefore, it is impossible to evaluate the intra-urban spillover by standard time-series models. Instead, we formulated the spillover effect as a Markov chain procedure. The constrained clustering technique was applied to identify the submarkets as the hidden states of Markov chain and estimate the transition matrix. Using a day-by-day transaction dataset of second-hand apartments in Beijing during 2011–2017, we detected 16 submarkets/regions and the spillover effect among these regions. The highest transition probability appeared in the overlapped region of urban core and Tongzhou district. This observation reflects the impact of urban planning proposal initiated since early 2012. In addition to the policy consequences, we analyzed a variety of spillover “types” through regression analysis. The latter showed that the “ripple” form of spillover is not dominant at the intra-urban level. Other types, such as the spillover due to the existence of price depressed regions, play major roles. This observation reveals the complexity of intra-urban spillover dynamics and its distinct driving-force compared to the inter-urban spillover.
Specific Heat and Transport Functions of Water
Authors: Mallamace Francesco , Corsaro Carmelo , Mallamace Domenico , Fazio Enza , Chen Sow-Hsin , Cupane Antonio
Published: January 2020

Numerous water characteristics are essentially ascribed to its peculiarity to form strong hydrogen bonds that become progressively more stable on decreasing the temperature. However, the structural and dynamical implications of the molecular rearrangement are still subject of debate and intense studies. In this work, we observe that the thermodynamic characteristics of liquid water are strictly connected to its dynamic characteristics. In particular, we compare the thermal behaviour of the isobaric specific heat of water, measured in different confinement conditions at atmospheric pressure (and evaluated by means of theoretical studies) with its configurational contribution obtained from the values of the measured self-diffusion coefficient through the use of the Adam–Gibbs approach. Our results confirm the existence of a maximum in the specific heat of water at about 225 K and indicate that especially at low temperature the configurational contributions to the entropy are dominant.
Wound Dressing Selection Is Critical to Enhance Platelet-Rich Fibrin Activities in Wound Care
Authors: Del Amo Cristina , Perez-Valle Arantza , Perez-Zabala Elena , Perez-del-Pecho Karmele , Larrazabal Ainara , Basterretxea Andima , Bully Paola , Andia Isabel
Published: January 2020

The use of platelet-rich fibrin (PRF) is investigated in ulcer management because it provides a healing milieu rich in growth factors and cytokines. Although crucial, the relevance of secondary dressings is under-researched and no data support the use of any particular dressing in preference to another. We assessed the properties of different dressing categories, including alginates, hydrocolloids, foams, hydrofibers, films, meshes and gauzes, in terms of affinity for PRF, releasate management (retention/extrusion) and the kinetics of cytokine release as well as the influence of each combination product, [PRF + dressing], on dermal cell behaviour, aiming to provide useful information for choosing the most adequate dressing for each particular patient. Active dressings including alginates, hydrofibers, foams and hydrocolloids blend with PRF, creating a diverse combination of products with different performances. Alginate and hydrofiber showed the highest affinity but moderate retention of releasate, without interfering with cell functions. Instead, the foam sequestered the releasate and hindered the release of growth factors, thereby compromising cell activities. Film and mesh presented very poor releasate retention and performed similarly to PRF by itself. Affinity index and releasate management explained 79% of platelet-derived growth factor (PDGF-BB) concentration variability, p < 0.001. Cell proliferation depended on the ability of the combination product to retain/release supernatant, PDGF-BB concentration and cell adhesion R2 = 0.91, p = 0.014.
Age-Associated TET2 Mutations: Common Drivers of Myeloid Dysfunction, Cancer and Cardiovascular Disease
Authors: Ferrone Christina K. , Blydt-Hansen Mackenzie , Rauh Michael J.
Published: January 2020

Acquired, inactivating mutations in Tet methylcytosine dioxygenase 2 (TET2) are detected in peripheral blood cells of a remarkable 5%–10% of adults greater than 65 years of age. They impart a hematopoietic stem cell advantage and resultant clonal hematopoiesis of indeterminate potential (CHIP) with skewed myelomonocytic differentiation. CHIP is associated with an overall increased risk of transformation to a hematological malignancy, especially myeloproliferative and myelodysplastic neoplasms (MPN, MDS) and acute myeloid leukemia (AML), of approximately 0.5% to 1% per year. However, it is becoming increasingly possible to identify individuals at greatest risk, based on CHIP mutational characteristics. CHIP, and particularly TET2-mutant CHIP, is also a novel, significant risk factor for cardiovascular diseases, related in part to hyper-inflammatory, progeny macrophages carrying TET2 mutations. Therefore, somatic TET2 mutations contribute to myeloid expansion and innate immune dysregulation with age and contribute to prevalent diseases in the developed world—cancer and cardiovascular disease. Herein, we describe the impact of detecting TET2 mutations in the clinical setting. We also present the rationale and promise for targeting TET2-mutant and other CHIP clones, and their inflammatory environment, as potential means of lessening risk of myeloid cancer development and dampening CHIP-comorbid inflammatory diseases.
Drosophila as a Model Organism to Understand the Effects during Development of TFIIH-Related Human Diseases
Authors: Zurita Mario , Murillo-Maldonado Juan Manuel
Published: January 2020

Human mutations in the transcription and nucleotide excision repair (NER) factor TFIIH are linked with three human syndromes: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS). In particular, different mutations in the XPB, XPD and p8 subunits of TFIIH may cause one or a combination of these syndromes, and some of these mutations are also related to cancer. The participation of TFIIH in NER and transcription makes it difficult to interpret the different manifestations observed in patients, particularly since some of these phenotypes may be related to problems during development. TFIIH is present in all eukaryotic cells, and its functions in transcription and DNA repair are conserved. Therefore, Drosophila has been a useful model organism for the interpretation of different phenotypes during development as well as the understanding of the dynamics of this complex. Interestingly, phenotypes similar to those observed in humans caused by mutations in the TFIIH subunits are present in mutant flies, allowing the study of TFIIH in different developmental processes. Furthermore, studies performed in Drosophila of mutations in different subunits of TFIIH that have not been linked to any human diseases, probably because they are more deleterious, have revealed its roles in differentiation and cell death. In this review, different achievements made through studies in the fly to understand the functions of TFIIH during development and its relationship with human diseases are analysed and discussed.
Relaxin Positively Influences Ischemia—Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review
Authors: Jakubauskiene Lina , Jakubauskas Matas , Leber Bettina , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: January 2020

In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.
Review of Chitosan-Based Polymers as Proton Exchange Membranes and Roles of Chitosan-Supported Ionic Liquids
Authors: Rosli Nur Adiera Hanna , Loh Kee Shyuan , Wong Wai Yin , Yunus Rozan Mohamad , Lee Tian Khoon , Ahmad Azizan , Chong Seng Tong
Published: January 2020

Perfluorosulphonic acid-based membranes such as Nafion are widely used in fuel cell applications. However, these membranes have several drawbacks, including high expense, non-eco-friendliness, and low proton conductivity under anhydrous conditions. Biopolymer-based membranes, such as chitosan (CS), cellulose, and carrageenan, are popular. They have been introduced and are being studied as alternative materials for enhancing fuel cell performance, because they are environmentally friendly and economical. Modifications that will enhance the proton conductivity of biopolymer-based membranes have been performed. Ionic liquids, which are good electrolytes, are studied for their potential to improve the ionic conductivity and thermal stability of fuel cell applications. This review summarizes the development and evolution of CS biopolymer-based membranes and ionic liquids in fuel cell applications over the past decade. It also focuses on the improved performances of fuel cell applications using biopolymer-based membranes and ionic liquids as promising clean energy.
Genome-Wide Identification and Characterization of the NAC Transcription Factor Family in Musa Acuminata and Expression Analysis during Fruit Ripening
Authors: Li Bin , Fan Ruiyi , Yang Qiaosong , Hu Chunhua , Sheng Ou , Deng Guiming , Dong Tao , Li Chunyu , Peng Xinxiang , Bi Fangcheng , Yi Ganjun
Published: January 2020

Banana (Musa acuminata, AAA group) is a representative climacteric fruit with essential nutrients and pleasant flavors. Control of its ripening determines both the fruit quality and the shelf life. NAC (NAM, ATAF, CUC2) proteins, as one of the largest superfamilies of transcription factors, play crucial roles in various functions, especially developmental processes. Thus, it is important to conduct a comprehensive identification and characterization of the NAC transcription factor family at the genomic level in M. acuminata. In this article, a total of 181 banana NAC genes were identified. Phylogenetic analysis indicated that NAC genes in M. acuminata, Arabidopsis, and rice were clustered into 18 groups (S1–S18), and MCScanX analysis disclosed that the evolution of MaNAC genes was promoted by segmental duplication events. Expression patterns of NAC genes during banana fruit ripening induced by ethylene were investigated using RNA-Seq data, and 10 MaNAC genes were identified as related to fruit ripening. A subcellular localization assay of selected MaNACs revealed that they were all localized to the nucleus. These results lay a good foundation for the investigation of NAC genes in banana toward the biological functions and evolution.
Disulfide-Linked Peptides for Blocking BTLA/HVEM Binding
Authors: Spodzieja Marta , Kuncewicz Katarzyna , Sieradzan Adam , Karczyńska Agnieszka , Iwaszkiewicz Justyna , Cesson Valérie , Węgrzyn Katarzyna , Zhukov Igor , Maszota-Zieleniak Martyna , Michielin Olivier , Speiser Daniel E. , Zoete Vincent , Derré Laurent , Rodziewicz-Motowidło Sylwia
Published: January 2020

Immune checkpoints are crucial in the maintenance of antitumor immune responses. The activation or blockade of immune checkpoints is dependent on the interactions between receptors and ligands; such interactions can provide inhibitory or stimulatory signals, including the enhancement or suppression of T-cell proliferation, differentiation, and/or cytokine secretion. B-and T-lymphocyte attenuator (BTLA) is a lymphoid-specific cell surface receptor which is present on T-cells and interacts with herpes virus entry mediator (HVEM), which is present on tumor cells. The binding of HVEM to BTLA triggers an inhibitory signal which attenuates the immune response. This feature is interesting for studying the molecular interactions between HVEM and BTLA, as they may be targeted for novel immunotherapies. This work was based on the crystal structure of the BTLA/HVEM complex showing that BTLA binds the N-terminal cysteine-rich domain of HVEM. We investigated the amino acid sequence of HVEM and used molecular modeling methods to develop inhibitors of the BTLA/HVEM interaction. We synthesized novel compounds and determined their ability to interact with the BTLA protein and inhibit the formation of the BTLA/HVEM complex. Our results suggest that the HVEM (14–39) peptide is a potent inhibitor of the formation of the BTLA/HVEM protein complex.
Editing DNA Methylation in Mammalian Embryos
Authors: Yamazaki Taiga , Hatano Yu , Taniguchi Ryoya , Kobayashi Noritada , Yamagata Kazuo
Published: January 2020

DNA methylation in mammals is essential for numerous biological functions, such as ensuring chromosomal stability, genomic imprinting, and X-chromosome inactivation through transcriptional regulation. Gene knockout of DNA methyltransferases and demethylation enzymes has made significant contributions to analyzing the functions of DNA methylation in development. By applying epigenome editing, it is now possible to manipulate DNA methylation in specific genomic regions and to understand the functions of these modifications. In this review, we first describe recent DNA methylation editing technology. We then focused on changes in DNA methylation status during mammalian gametogenesis and preimplantation development, and have discussed the implications of applying this technology to early embryos.
Mitochondrial Quality Control in Age-Related Pulmonary Fibrosis
Authors: Roque Willy , Cuevas-Mora Karina , Romero Freddy
Published: January 2020

Idiopathic pulmonary fibrosis (IPF) is age-related interstitial lung disease of unknown etiology. About 100,000 people in the U.S have IPF, with a 3-year median life expectancy post-diagnosis. The development of an effective treatment for pulmonary fibrosis will require an improved understanding of its molecular pathogenesis and the “normal” and “pathological’ hallmarks of the aging lung. An important characteristic of the aging organism is its lowered capacity to adapt quickly to, and counteract, disturbances. While it is likely that DNA damage, chronic endoplasmic reticulum (ER) stress, and accumulation of heat shock proteins are capable of initiating tissue repair, recent studies point to a pathogenic role for mitochondrial dysfunction in the development of pulmonary fibrosis. These studies suggest that damage to the mitochondria induces fibrotic remodeling through a variety of mechanisms including the activation of apoptotic and inflammatory pathways. Mitochondrial quality control (MQC) has been demonstrated to play an important role in the maintenance of mitochondrial homeostasis. Different factors can induce MQC, including mitochondrial DNA damage, proteostasis dysfunction, and mitochondrial protein translational inhibition. MQC constitutes a complex signaling response that affects mitochondrial biogenesis, mitophagy, fusion/fission and the mitochondrial unfolded protein response (UPRmt) that, together, can produce new mitochondria, degrade the components of the oxidative complex or clearance the entire organelle. In pulmonary fibrosis, defects in mitophagy and mitochondrial biogenesis have been implicated in both cellular apoptosis and senescence during tissue repair. MQC has also been found to have a role in the regulation of other protein activity, inflammatory mediators, latent growth factors, and anti-fibrotic growth factors. In this review, we delineated the role of MQC in the pathogenesis of age-related pulmonary fibrosis.
Mechanisms of Disease in Sjögren Syndrome—New Developments and Directions
Authors: de Paiva Cintia S. , Pflugfelder Stephen C.
Published: January 2020

Sjögren Syndrome (SS) is an autoimmune disease that affects the exocrine glands, mainly salivary and lacrimal glands [...]
A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment
Authors: Merecz-Sadowska Anna , Sitarek Przemyslaw , Zielinska-Blizniewska Hanna , Malinowska Katarzyna , Zajdel Karolina , Zakonnik Lukasz , Zajdel Radoslaw
Published: January 2020

Worldwide use of electronic cigarettes has been rapidly expanding over recent years, but the long-term effect of e-cigarette vapor exposure on human health and environment is not well established; however, its mechanism of action entails the production of reactive oxygen species and trace metals, and the exacerbation of inflammation, which are associated with potential cytotoxicity and genotoxicity. The present study examines the effects of selected liquid chemicals used in e-cigarettes, such as propylene glycol/vegetable glycerin, nicotine and flavorings, on living organisms; the data collected indicates that exposure to e-cigarette liquid has potentially detrimental effects on cells in vitro, and on animals and humans in vivo. While e-liquid exposure can adversely influence the physiology of living organisms, vaping is recommended as an alternative for tobacco smoking. The study also compares the impact of e-cigarette liquid exposure and traditional cigarette smoke on organisms and the environmental impact. The environmental influence of e-cigarette use is closely connected with the emission of airborne particulate matter, suggesting the possibility of passive smoking. The obtained data provides an insight into the impact of nicotine delivery systems on living organisms and the environment.
Scenarios of Genes-to-Terpenoids Network Led to the Identification of a Novel α/β-Farnesene/β-Ocimene Synthase in Camellia sinensis
Authors: Jin Jieyang , Zhang Shangrui , Zhao Mingyue , Jing Tingting , Zhang Na , Wang Jingming , Wu Bin , Song Chuankui
Published: January 2020

Terpenoids play vital roles in tea aroma quality and plants defense performance determination, whereas the scenarios of genes to metabolites of terpenes pathway remain uninvestigated in tea plants. Here, we report the use of an integrated approach combining metabolites, target gene transcripts and function analyses to reveal a gene-to-terpene network in tea plants. Forty-one terpenes including 26 monoterpenes, 14 sesquiterpenes and one triterpene were detected and 82 terpenes related genes were identified from five tissues of tea plants. Pearson correlation analysis resulted in genes to metabolites network. One terpene synthases whose expression positively correlated with farnesene were selected and its function was confirmed involved in the biosynthesis of α-farnesene, β-ocimene and β-farnesene, a very important and conserved alarm pheromone in response to aphids by both in vitro enzymatic assay in planta function analysis. In summary, we provided the first reliable gene-to-terpene network for novel genes discovery.
Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria
Authors: Khumalo Makhosazana Jabulile , Nzuza Nomfundo , Padayachee Tiara , Chen Wanping , Yu Jae-Hyuk , Nelson David R. , Syed Khajamohiddin
Published: January 2020

The prokaryotic phylum Cyanobacteria are some of the oldest known photosynthetic organisms responsible for the oxygenation of the earth. Cyanobacterial species have been recognised as a prosperous source of bioactive secondary metabolites with antibacterial, antiviral, antifungal and/or anticancer activities. Cytochrome P450 monooxygenases (CYPs/P450s) contribute to the production and diversity of various secondary metabolites. To better understand the metabolic potential of cyanobacterial species, we have carried out comprehensive analyses of P450s, predicted secondary metabolite biosynthetic gene clusters (BGCs), and P450s located in secondary metabolite BGCs. Analysis of the genomes of 114 cyanobacterial species identified 341 P450s in 88 species, belonging to 36 families and 79 subfamilies. In total, 770 secondary metabolite BGCs were found in 103 cyanobacterial species. Only 8% of P450s were found to be part of BGCs. Comparative analyses with other bacteria Bacillus, Streptomyces and mycobacterial species have revealed a lower number of P450s and BGCs and a percentage of P450s forming part of BGCs in cyanobacterial species. A mathematical formula presented in this study revealed that cyanobacterial species have the highest gene-cluster diversity percentage compared to Bacillus and mycobacterial species, indicating that these diverse gene clusters are destined to produce different types of secondary metabolites. The study provides fundamental knowledge of P450s and those associated with secondary metabolism in cyanobacterial species, which may illuminate their value for the pharmaceutical and cosmetics industries.
Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials
Authors: Silvestro Serena , Bramanti Placido , Trubiani Oriana , Mazzon Emanuela
Published: January 2020

Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005–2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.
Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids—What Is the Relationship?
Authors: McCarthy Denis M.
Published: January 2020

Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin’s effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.
Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis
Authors: Li Ping , Fleischhauer Lutz , Nicolae Claudia , Prein Carina , Farkas Zsuzsanna , Saller Maximilian Michael , Prall Wolf Christian , Wagener Raimund , Heilig Juliane , Niehoff Anja , Clausen-Schaumann Hauke , Alberton Paolo , Aszodi Attila
Published: January 2020

Matrilins (MATN1, MATN2, MATN3 and MATN4) are adaptor proteins of the cartilage extracellular matrix (ECM), which bridge the collagen II and proteoglycan networks. In humans, dominant-negative mutations in MATN3 lead to various forms of mild chondrodysplasias. However, single or double matrilin knockout mice generated previously in our laboratory do not show an overt skeletal phenotype, suggesting compensation among the matrilin family members. The aim of our study was to establish a mouse line, which lacks all four matrilins and analyze the consequence of matrilin deficiency on endochondral bone formation and cartilage function. Matn1-4−/− mice were viable and fertile, and showed a lumbosacral transition phenotype characterized by the sacralization of the sixth lumbar vertebra. The development of the appendicular skeleton, the structure of the growth plate, chondrocyte differentiation, proliferation, and survival were normal in mutant mice. Biochemical analysis of knee cartilage demonstrated moderate alterations in the extractability of the binding partners of matrilins in Matn1-4−/− mice. Atomic force microscopy (AFM) revealed comparable compressive stiffness but higher collagen fiber diameters in the growth plate cartilage of quadruple mutant compared to wild-type mice. Importantly, Matn1-4−/− mice developed more severe spontaneous osteoarthritis at the age of 18 months, which was accompanied by changes in the biomechanical properties of the articular cartilage. Interestingly, Matn4−/− mice also developed age-associated osteoarthritis suggesting a crucial role of MATN4 in maintaining the stability of the articular cartilage. Collectively, our data provide evidence that matrilins are important to protect articular cartilage from deterioration and are involved in the specification of the vertebral column.