bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediterranean Diet Social Network Impact along 11 Years in the Major US Media Outlets: Thematic and Quantitative Analysis Using Twitter
Authors: Alvarez-Mon Miguel Angel , Fernandez-Lazaro Cesar I. , Llavero-Valero Maria , Alvarez-Mon Melchor , Mora Samia , Martínez-González Miguel A. , Bes-Rastrollo Maira
Published: January 2022

Background: Media outlets influence social attitudes toward health. Thus, it is important that they share contents which promote healthy habits. The Mediterranean diet (MedDiet) is associated with lower cardiovascular disease risk. Analysis of tweets has become a tool for understanding perceptions on health issues. Methods: We investigated tweets posted between January 2009 and December 2019 by 25 major US media outlets about MedDiet and its components as well as the retweets and likes generated. In addition, we measured the sentiment analysis of these tweets and their dissemination. Results: In total, 1608 tweets, 123,363 likes and 48,946 retweets about MedDiet or its components were analyzed. Dairy (inversely weighted in MedDiet scores) accounted for 45.0% of the tweets (723/1608), followed by nuts 19.7% (317/1608). MedDiet, as an overall dietary pattern, generated only 9.8% (157/1608) of the total tweets, while olive oil generated the least number of tweets. Twitter users’ response was quantitatively related to the number of tweets posted by these US media outlets, except for tweets on olive oil and MedDiet. None of the MedDiet components analyzed was more likely to be liked or retweeted than the MedDiet itself. Conclusions: The US media outlets analyzed showed reduced interest in MedDiet as a whole, while Twitter users showed greater interest in the overall dietary pattern than in its particular components.
Impacts of COVID-19 on the Education, Life and Mental Health of Students in Bangladesh
Authors: Piya Fahmida Liza , Amin Sumaiya , Das Anik , Kabir Muhammad Ashad
Published: January 2022

COVID-19’s unanticipated consequences have resulted in the extended closure of various educational institutions, causing significant hardship to students. Even though many institutions rapidly transitioned to online education programs, various issues have emerged that are impacting many aspects of students’ lives. An online survey was conducted with students of Bangladesh to understand how COVID-19 impacted their study, social and daily activities, plans, and mental health. A total of 409 Bangladeshi students took part in a survey. As a result of the COVID-19 pandemic, 13.7% of all participants are unable to focus on their studies, up from 1.2% previously. More than half of the participants (54%) have spent more time on social media than previously. We found that 45% of the participants have severe to moderate level depression. In addition, 48.6% of the students are experiencing severe to moderate level anxiety. According to our findings, students’ inability to concentrate on their studies, their increased use of social media and electronic communications, changing sleep hours during the pandemic, increased personal care time, and changes in plans are all correlated with their mental health.
Citizens’ Preparedness to Deal with Emergencies as an Important Component of Civil Protection
Authors: Kubás Jozef , Bugánová Katarína , Polorecká Mária , Petrlová Katarína , Stolínová Adéla
Published: January 2022

The main purpose of this paper is to point out a new approach in evaluating the preparedness of the population of a selected city for civil protection and its response to emergencies. Using new approaches, it evaluates a subjective questionnaire survey in combination with the objective state thanks to a mathematical approach and its subsequent verification on a specific example. The proposed approaches are then verified by experimental surveys in the selected city. The result is a highly adaptable tool that can be set up and adapted to different situations and different types of questionnaires to address the preparedness and safety of the population for emergencies. Thanks to this tool, it is possible to evaluate the subjective opinions of the population and thus gain insight into the assessment of the city’s preparedness for emergencies. Subsequently, we can set the prevention and preparedness of the population in the city on the basis of the obtained outputs, which potentially has a fundamental influence on the response after the occurrence of an emergency. Improving preparedness in the area of civil protection shall not only be reflected in the response and minimization of the consequences of the emergency, but also in the emotional security of the population.
A Qualitative Inquiry of a Three-Month Virtual Practicum Program on Youth with Visual Impairments and Their Coaches
Authors: Lieberman Lauren J. , Ball Lindsay , Beach Pamela , Perreault Melanie
Published: January 2022

Research has shown that the practicum experience for professional preparation students in physical education teacher education programs related to teaching youth with disabilities can improve self-efficacy. It is not currently known if a virtual program can be effective for the professional preparation students or the participants. The objective of this study was to determine the experiences of the participants of a three-month virtual practicum program. In this phenomenological study, thirty youth with visual impairments and 1:1 professional preparation students (coaches) took part in a three-month virtual physical activity program. A total of 11 coaches took part in 2 focus groups, and 10 of the participants were interviewed about their experiences in this unique practicum. Findings in this three-month program revealed four themes: (1) friendship, (2) self-determination, (3) goal setting, and (4) barriers. The results of the qualitative inquiry indicate that a virtual practicum program can have a positive effect on both the participants and the professional preparation students. Virtual programs should also be aware of barriers to implementing an effective program to benefit all parties.
Whether the Agricultural Insurance Policy Achieves Green Income Growth—Evidence from the Implementation of China’s Total Cost Insurance Pilot Program
Authors: Zhang Zhifeng , Xu Haodong , Shan Shuangshuang , Liu Qingzhi , Lu Yuqi
Published: January 2022

With the rise and popularization of the concept of green sustainable development, green income growth of agricultural insurance policies has attracted wide attention. Whether green income growth can be achieved has become an important criterion for measuring an agricultural insurance policy. In this context, this paper attempts to test whether the agricultural insurance policy achieves green income growth. Based on the panel data of 31 provinces (the research sample of this paper selects 31 provincial-level units (province for short) in China, including 22 provinces, 5 autonomous regions and 4 municipalities directly under the central government. Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan Province are not included in the research sample) from 2009 to 2020 in China, this paper empirically evaluates the triple-effect of total cost insurance pilot program (TCI) on farmers’ income, environment and public health by employing a difference-in-difference model (DID). The results show that TCI increases farmers’ income, but deteriorates the environment and residents’ health without achieving green income growth. In the analysis of heterogeneity, compared with central and western regions, farmers’ income is more likely to increase in the eastern regions. However, environmental pollution is more severe, and residents’ health deteriorates more, in eastern regions. In addition, the positive effect of TCI on farmers’ income and the deterioration of residents’ health is more obvious in areas with a higher degree of damage, while the negative effect of TCI on the environment is more obvious in areas with a lower degree of damage. Furthermore, the mechanism analysis shows that TCI not only promotes the increase in farmers’ income through insurance density, but also affects the environment and residents’ health through straw burning. Therefore, the government should raise the subsidy standard for farmers to use straw-processing equipment and also to implement differentiated subsidies in regions with different levels of economic development and areas with different degrees of damage.
Mental, Physical and Socio-Economic Status of Adults Living in Spain during the Late Stages of the State of Emergency Caused by COVID-19
Authors: Sánchez-Rodríguez Elisabet , Ferreira-Valente Alexandra , Pimenta Filipa , Ciaramella Antonella , Miró Jordi
Published: January 2022

Research has shown that the confinement measures implemented to curb the spread of COVID-19 can have negative effects on people’s lives at multiple levels. The objective of this cross-sectional study was to better understand the mental, physical, and socio-economic status of adults living in Spain during the late stages of the state of emergency caused by COVID-19. Five hundred and forty-four individuals responded to an online survey between 3 June and 30 July 2020. They were asked to report data about their mental and physical health, financial situation, and satisfaction with the information received about the pandemic. Means, percentages, t-test, ANOVAs, and logistic regressions were computed. A third of the participants reported symptoms of anxiety, depression, and stress, and worries about their health and the future. Participants also described mild levels of fatigue and pain during lockdown (66%), and a reduction in household income (39%). Respondents that were female, younger, single, and with lower levels of education reported experiencing a greater impact of the COVID-19 pandemic. The data showed that the negative effects of lockdown were present in the late stages of the state of emergency. The findings can be used to contribute to the development of programs to prevent or mitigate the negative impact of confinement measures.
Phytonutrients of Bitter Apricot Seeds Modulate Human Lipid Profile and LDL Subfractions in Adults with Elevated Cholesterol Levels
Authors: Kopčeková Jana , Kolesárová Anna , Schwarzová Marianna , Kováčik Anton , Mrázová Jana , Gažarová Martina , Lenártová Petra , Chlebo Peter , Kolesárová Adriana
Published: January 2022

The objective of the present study was to evaluate the effect of short-term consumption of bitter apricot seeds phytonutrients on cardiovascular risk factors with a special focus on LDL cholesterol subfractions using the Lipoprint system. A group of 34 adult volunteers (21 female/13 male) consumed 60 mg kg−1 of body weight of bitter apricot seeds daily for 42 days. Subjects were divided into two groups: one with normal cholesterol levels (NTC) and one with elevated total cholesterol levels (ETC). Blood serum levels of total cholesterol (T-C), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), and triglycerides (TG) did not change significantly (p > 0.05) in NTC group. However, there were significant decreasing of T-C (p ˂ 0.05) and LDL-C (p < 0.01) in ETC group. The LDL1, LDL2, and atherogenic LDL3−7 subfractions progressively decreased after 42 days of apricot seeds consumption in ETC group (p < 0.05). Apricot seeds consumption was associated with a significant increase in the mean LDL particle size especially in ETC group (p ˂ 0.01). The results of the present study support the hypothesis that daily consumption of bitter apricot seeds for 42 days positively modified the lipoprotein profile in the group with elevated total cholesterol.
Evolution of Legislation and Crimes Based on Sexual Identity or Orientation in Spain: A Retrospective Observational Study (2011–2021)
Authors: Ruiz-Azcona Laura , Pellico-López Amada , Manjón-Rodríguez Jimena B. , Sánchez Movellán Mar , Ajo Bolado Purificación , García-Vázquez José , Hernández-Aguado Ildefonso , Cayón-De las Cuevas Joaquín , Paz-Zulueta María
Published: January 2022

Respect for different sexual options and orientations prevents the occurrence of hate crimes against lesbian, gay, bisexual, trans and intersex (LGTBI) persons for this reason. Our aim was to review the legislation that protects the rights of LGTBI people and to quantify the victimization rates of hate crimes based on sexual identity and orientation. A retrospective observational study was conducted across all regions of Spain from 2011–2021. The laws on LGTBI rights in each region were identified. Hate crime victimization data on sexual identity and orientation were collected in annual rates per 100,000 inhabitants, annual percentage change and average change during the study period to assess the trend. The regulatory development of laws against discrimination against LGTBI individuals is heterogeneous across regions. Overall, in Spain there is an upward trend in the number of hate crime victimizations motivated by sexual identity or orientation. The effectiveness of data collection, thanks to better training and awareness of police forces regarding hate crimes and the processes of data cleansing and consolidation contributes to a greater visibility of hate crimes against LGTBI people.
Mental Well-Being: 2010–2018 Trends among Italian Adolescents
Authors: Bersia Michela , Berchialla Paola , Charrier Lorena , Lemma Patrizia , Borraccino Alberto , Nardone Paola , Pierannunzio Daniela , Ciardullo Silvia , Comoretto Rosanna Irene , Dalmasso Paola
Published: January 2022

(1) Aims: To explore temporal trends 2010–2018 of well-being among Italian adolescents and to evaluate potential explanatory factors. (2) Methods: Italian nationality representative samples of students aged 11, 13, and 15 years were recruited in 2010, 2014, and 2018; Health Behaviour in School-aged Children (HBSC), for an overall number of 165,000 teenagers. Multivariable logistic regression models were performed to fit the trends over time of life satisfaction (LS), psychological (PSY-HC) and somatic health complaints (SOM-HC) considering the contextual factors: school work pressure, social support (family, school, peers), socioeconomic status, geographic area, and immigration background; (3) Results: From 2010 to 2018 while LS was steady, health complaints increased, mainly for PSY-HC, in all age and gender groups. Trend of PSY-HC affected mainly 15-years-olds: rates among boys varied from 29.6% to 35.9% (OR: 1.13, 95%CI: 1.02–1.25); among girls from 49.1% to 63.3% (OR: 1.56, 95%CI: 1.42–1.72). High school work pressure and poor social support play a central role in worsening well-being outcomes; (4) Conclusions: Our findings pictured a remarkable worsening trend of teenagers’ well-being, especially among 15-year-old girls. Further research will be required to investigate this breaking up of the connection between psychophysical symptomatology and cognitive perception of life satisfaction.
Knowledge, Attitudes, and Practices on Tick-Borne Encephalitis Virus and Tick-Borne Diseases within Professionally Tick-Exposed Persons, Health Care Workers, and General Population in Serbia: A Questionnaire-Based Study
Authors: Vasić Ana , Bjekić Jovana , Veinović Gorana , Mihaljica Darko , Sukara Ratko , Poluga Jasmina , Filipović Saša R. , Tomanović Snežana
Published: January 2022

This study assessed the level of knowledge, attitudes, and practices (KAP) regarding tick-borne encephalitis virus (TBEV) and tick-borne diseases (TBDs) among different groups of people in Serbia. Professionally tick-exposed persons (PTEPs), health care workers (HCWs), and the general population (GP) were subjected to an anonymous, voluntary, online questionnaire using Microsoft Forms. A total of 663 questionnaire responses were collected (February–March 2021), while 642 were included in the analysis. The significant difference in knowledge in TBDs existed between GP and PTEPs, and HCWs (p < 0.001). The perception of risk-to-tick exposure and TBDs was generally high (42.4 (95% CI: 33.6–51.2) within GP, 44.9 (95% CI: 35.8–53.9) within PTEPs and 46.2 (95% CI: 38.0–54.5) within HCWs), while fear was low (13.7 (95% CI: 7.9–19.5) within GP, 12.6 (95% CI: 7.3–19.9) within PTEPs, and 13.5 (95% CI: 7.4–19.5) within HCWs). Protective practices differed across groups (F (2639) = 12.920, p < 0.001, η2 = 0.039), with both PTEPs (t = 3.621, Cohen d = 0.332, p < 0.001) and HCWs (t = 4.644, Cohen d = 0.468, p < 0.001) adhering to more protective practices than the GP, without differences between PTEPs and HCWs (t = 1.256, Cohen d = 0.137, p = 0.421). Further education about TBDs in Serbia is required and critical points were identified in this study.
Effect of Weight Self-Stigma and Self-Esteem on Aerobic Exercise Capacity in Adult Women with Different Body Compositions
Authors: Aldhahi Monira I. , Al Khalil Wafa K. , Almutiri Rawan B. , Alyousefi Mada M. , Alharkan Bayader S. , AnNasban Haya
Published: January 2022

Background: Overweight individuals face weight-related stigmatization, driving self-exclusion from exercise and physical activity. The extent to which weight self-stigma and self-esteem are associated with aerobic capacity remains unclear. Therefore, this study aimed to characterize the cardiopulmonary fitness, weight self-stigma, and self-esteem of overweight women and examine whether weight self-stigma and self-esteem predict cardiopulmonary aerobic capacity. Methods: A cross-sectional study was conducted with 66 women stratified into two groups: a normal weight (NW) group and an overweight (OW) group. The mean body mass indexes and ages of the NW and OW groups were 20.4 ± 0.36 kg/m2 and 29.5 ± 0.8 kg/m2, and 24 ± 7 years and 21 ± 3 years, respectively. Submaximal exercise testing using the modified Bruce treadmill protocol was conducted to measure the predicted oxygen uptake (VO2 peak) and energy expenditure. The Weight Self-Stigma Questionnaire and the Rosenberg Self-Esteem Scale were used. Results: Significantly lower mean of predicted VO2 peak and higher mean of energy expenditure were reported in the OW group compared with the NW group (25.8 ± 5.3 mL/kg/min vs. 28.7 ± 4.8 mL/kg/min, p = 0.001 and 9.7 ± 1.9 kcal/min vs. 7.5 ± 1.8 kcal, p = 0.03, respectively). There was a significant difference in weight self-stigma and self-esteem between the groups. Regression model analysis indicated that weight self-stigma and self-esteem explained 45% of the variance in the predicted VO2 peak. Conclusion: Strategies enhancing self-esteem and avoiding stigmatization should be embraced to promote fitness and engagement in physical activity among OW women.
Burden of Oral Cancer on the 10 Most Populous Countries from 1990 to 2019: Estimates from the Global Burden of Disease Study 2019
Authors: Zhang Shu-Zhen , Xie Long , Shang Zheng-Jun
Published: January 2022

Background: Oral cancer (OC) is a common tumour that poses a threat to human health and imposes a heavy burden on countries. This study assessed the burden imposed by OC on the 10 most populous countries from 1990 to 2019 on the basis of gender, age and socio-demographic index. Methods: Data on incidence, mortality, disability-adjusted life years (DALY) and corresponding age-standardised rates (ASR) for OC in the 10 most populous countries from 1990 to 2019 were derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes were calculated to assess the trends of morbidity, mortality and DALY. The indicator that served as a proxy for survival rate was the supplement of mortality-to-incidence ratio (SMIR) (1 − (M/I)). Results: The number of new cases, deaths and DALY have increased in all 10 countries in the past 30 years. Trends in age-standardised incidence rates (ASIR), age-standardised mortality rate (ASMR) and age-standardised DALY for OC in the 10 most populous countries varied. The SMIR increased in all countries, with most countries having an SMIR between 30% and 50%. In 2019, the United States had the highest SMIR at 76%, whereas Russia had the lowest at 21.7%. Incidence and mortality were close between male and female subjects in Japan, Indonesia, Mexico, India, Bangladesh and Pakistan. The incidence and mortality in male subjects in the United States, Russia, China and Brazil were two or more times those of female subjects. Gender difference was highest among patients aged 40–69 years. Conclusion: Trends and gender differences in ASIR, ASMR and age-standardised DALY for OC vary in the 10 most populous countries. Government cancer programs are often expensive to run, especially in countries with large populations. Policy makers need to take these differences into account when formulating policies.
Changing Attitudes towards Occupational Medicine with Blended Learning Methods Is Possible among Medical Students in Spain: A Longitudinal Study
Authors: Iguacel Isabel , Abecia Begoña , Bernal José Luis , Martínez-Jarreta Begoña
Published: January 2022

Medical students generally express a low interest in Occupational Medicine. We aimed to assess the attitudes and changes in attitudes of students towards this area after completing a course on Occupational Medicine in two Medical Universities in Spain (Zaragoza and Castilla-La Mancha). The teaching method included blended learning as a model that used online virtual patient platforms (CASUS) and/or EMUTOM, as well as traditional methods such as face-to-face teaching. A total of 526 students (98 of whom attended the University of Castilla-La Mancha) participated during three academic years (2015–2016, 2016–2017 and 2017–2018). The validation of the questionnaire was carried out using reliability, exploratory and confirmatory factor analysis. For the analysis of internal consistency and discrimination, Cronbach’s alpha was used. The adequacy of the factor analysis was measured by means of KMO, and a correlation matrix was examined by means of Bartlett’s test of sphericity. To identify differences between students before and after completing the course, the Mann–Whitney U-test for independent samples was used. Our results show that despite a negative or neutral attitude towards Occupational Medicine, the acquisition of competences and skills in this area and their training were recognized as fundamental for their future professional performance as doctors in any specialty.
The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of the Mycobacterium tuberculosis DprE1 Enzyme
Authors: Ezquerra-Aznárez José Manuel , Degiacomi Giulia , Gašparovič Henrich , Stelitano Giovanni , Sammartino Josè Camilla , Korduláková Jana , Governa Paolo , Manetti Fabrizio , Pasca Maria Rosalia , Chiarelli Laurent Roberto , Ramón-García Santiago
Published: January 2022

Avermectins are macrocyclic lactones with anthelmintic activity. Recently, they were found to be effective against Mycobacterium tuberculosis, which accounts for one third of the worldwide deaths from antimicrobial resistance. However, their anti-mycobacterial mode of action remains to be elucidated. The activity of selamectin was determined against a panel of M. tuberculosis mutants. Two strains carrying mutations in DprE1, the decaprenylphosphoryl-β-D-ribose oxidase involved in the synthesis of mycobacterial arabinogalactan, were more susceptible to selamectin. Biochemical assays against the Mycobacterium smegmatis DprE1 protein confirmed this finding, and docking studies predicted a binding site in a loop that included Leu275. Sequence alignment revealed variants in this position among mycobacterial species, with the size and hydrophobicity of the residue correlating with their MIC values; M. smegmatis DprE1 variants carrying these point mutations validated the docking predictions. However, the correlation was not confirmed when M. smegmatis mutant strains were constructed and MIC phenotypic assays performed. Likewise, metabolic labeling of selamectin-treated M. smegmatis and M. tuberculosis cells with 14C-labeled acetate did not reveal the expected lipid profile associated with DprE1 inhibition. Together, our results confirm the in vitro interactions of selamectin and DprE1 but suggest that selamectin could be a multi-target anti-mycobacterial compound.
Transcriptomic, Metabolomic and Ionomic Analyses Reveal Early Modulation of Leaf Mineral Content in Brassica napus under Mild or Severe Drought
Authors: D’Oria Aurélien , Jing Lun , Arkoun Mustapha , Pluchon Sylvain , Pateyron Stéphanie , Trouverie Jacques , Etienne Philippe , Diquélou Sylvain , Ourry Alain
Published: January 2022

While it is generally acknowledged that drought is one of the main abiotic factors affecting plant growth, how mineral nutrition is specifically and negatively affected by water deficit has received very little attention, other than being analyzed as a consequence of reduced growth. Therefore, Brassica napus plants were subjected to a gradual onset of water deficits (mild, severe, or severe extended), and leaves were analyzed at the ionomic, transcriptomic and metabolic levels. The number of Differentially Expressed Genes (DEGs) and of the most differentially accumulated metabolites increased from mild (525 DEGs, 57 metabolites) to severe (5454 DEGs, 78 metabolites) and severe extended (9346 DEGs, 95 metabolites) water deficit. Gene ontology enrichment analysis of the 11,747 DEGs identified revealed that ion transport was one of the most significant processes affected, even under mild water deficit, and this was also confirmed by the shift in ionomic composition (mostly micronutrients with a strong decrease in Mo, Fe, Zn, and Mn in leaves) that occurred well before growth reduction. The metabolomic data and most of the transcriptomic data suggested that well-known early leaf responses to drought such as phytohormone metabolism (ABA and JA), proline accumulation, and oxidative stress defense were induced later than repression of genes related to nutrient transport.
Effect of 1-Ethyl-3-methylimidazolium Tetrafluoroborate and Acetate Ionic Liquids on Stability and Amyloid Aggregation of Lysozyme
Authors: Fedunova Diana , Antosova Andrea , Marek Jozef , Vanik Vladimir , Demjen Erna , Bednarikova Zuzana , Gazova Zuzana
Published: January 2022

Amyloid fibrils draw attention as potential novel biomaterials due to their high stability, strength, elasticity or resistance against degradation. Therefore, the controlled and fast fibrillization process is of great interest, which raises the demand for effective tools capable of regulating amyloid fibrillization. Ionic liquids (ILs) were identified as effective modulators of amyloid aggregation. The present work is focused on the study of the effect of 1-ethyl-3-methyl imidazolium-based ILs with kosmotropic anion acetate (EMIM-ac) and chaotropic cation tetrafluoroborate (EMIM-BF4) on the kinetics of lysozyme amyloid aggregation and morphology of formed fibrils using fluorescence and CD spectroscopy, differential scanning calorimetry, AFM with statistical image analysis and docking calculations. We have found that both ILs decrease the thermal stability of lysozyme and significantly accelerate amyloid fibrillization in a dose-dependent manner at concentrations of 0.5%, 1% and 5% (v/v) in conditions and time-frames when no fibrils are formed in ILs-free solvent. The effect of EMIM-BF4 is more prominent than EMIM-ac due to the different specific interactions of the anionic part with the protein surface. Although both ILs induced formation of amyloid fibrils with typical needle-like morphology, a higher variability of fibril morphology consisting of a different number of intertwining protofilaments was identified for EMIM-BF4.
Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells
Authors: Yokoe Sho , Hasuike Akira , Watanabe Norihisa , Tanaka Hideki , Karahashi Hiroyuki , Wakuda Shin , Takeichi Osamu , Kawato Takayuki , Takai Hideki , Ogata Yorimasa , Sato Shuichi , Imai Kenichi
Published: January 2022

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem affecting more than half of the adult population worldwide. Recently, members of the herpes virus family, such as the Epstein–Barr virus (EBV), have been suggested to be involved in the etiology of periodontitis because bacterial activity alone does not adequately explain the clinical characteristics of periodontitis. However, the role of EBV in the etiology of periodontitis is unknown. This study aimed to examine the effect of inactivated EBV on the expression of inflammatory cytokines in human gingival fibroblasts (HGFs) and the induction of osteoclast differentiation. We found that extremely high levels of interleukin (IL)-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. The levels of IL-6 and IL-8 in HGFs were higher when the cells were treated with EBV than when treated with lipopolysaccharide and lipoteichoic acid. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. These findings suggest that even without infecting the cells, EBV contributes to inflammatory cytokine production and osteoclast differentiation by contact with oral cells or macrophage lineage, resulting in periodontitis onset and progression.
The SwissSimilarity 2021 Web Tool: Novel Chemical Libraries and Additional Methods for an Enhanced Ligand-Based Virtual Screening Experience
Authors: Bragina Maiia E. , Daina Antoine , Perez Marta A. S. , Michielin Olivier , Zoete Vincent
Published: January 2022

Hit finding, scaffold hopping, and structure–activity relationship studies are important tasks in rational drug discovery. Implementation of these tasks strongly depends on the availability of compounds similar to a known bioactive molecule. SwissSimilarity is a web tool for low-to-high-throughput virtual screening of multiple chemical libraries to find molecules similar to a compound of interest. According to the similarity principle, the output list of molecules generated by SwissSimilarity is expected to be enriched in compounds that are likely to share common protein targets with the query molecule and that can, therefore, be acquired and tested experimentally in priority. Compound libraries available for screening using SwissSimilarity include approved drugs, clinical candidates, known bioactive molecules, commercially available and synthetically accessible compounds. The first version of SwissSimilarity launched in 2015 made use of various 2D and 3D molecular descriptors, including path-based FP2 fingerprints and ElectroShape vectors. However, during the last few years, new fingerprinting methods for molecular description have been developed or have become popular. Here we would like to announce the launch of the new version of the SwissSimilarity web tool, which features additional 2D and 3D methods for estimation of molecular similarity: extended-connectivity, MinHash, 2D pharmacophore, extended reduced graph, and extended 3D fingerprints. Moreover, it is now possible to screen for molecular structures having the same scaffold as the query compound. Additionally, all compound libraries available for screening in SwissSimilarity have been updated, and several new ones have been added to the list. Finally, the interface of the website has been comprehensively rebuilt to provide a better user experience. The new version of SwissSimilarity is freely available starting from December 2021.
A Brief Review of In Vitro Models for Injury and Regeneration in the Peripheral Nervous System
Authors: Varier Parvathi , Raju Gayathri , Madhusudanan Pallavi , Jerard Chinnu , Shankarappa Sahadev A.
Published: January 2022

Nerve axonal injury and associated cellular mechanisms leading to peripheral nerve damage are important topics of research necessary for reducing disability and enhancing quality of life. Model systems that mimic the biological changes that occur during human nerve injury are crucial for the identification of cellular responses, screening of novel therapeutic molecules, and design of neural regeneration strategies. In addition to in vivo and mathematical models, in vitro axonal injury models provide a simple, robust, and reductionist platform to partially understand nerve injury pathogenesis and regeneration. In recent years, there have been several advances related to in vitro techniques that focus on the utilization of custom-fabricated cell culture chambers, microfluidic chamber systems, and injury techniques such as laser ablation and axonal stretching. These developments seem to reflect a gradual and natural progression towards understanding molecular and signaling events at an individual axon and neuronal-soma level. In this review, we attempt to categorize and discuss various in vitro models of injury relevant to the peripheral nervous system and highlight their strengths, weaknesses, and opportunities. Such models will help to recreate the post-injury microenvironment and aid in the development of therapeutic strategies that can accelerate nerve repair.
Dosing Therapeutic Radiopharmaceuticals in Obese Patients
Authors: van Nuland Merel , Ververs Tessa F. , Lam Marnix G. E. H.
Published: January 2022

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.
Schwannoma Gene Therapy via Adeno-Associated Viral Vector Delivery of Apoptosis-Associated Speck-like Protein Containing CARD (ASC): Preclinical Efficacy and Safety
Authors: Ahmed Sherif G. , Maguire Casey A. , Cao Shiliang Alice , Brenner Gary J.
Published: January 2022

Schwannomas are tumors derived from Schwann-lineage cells, cells that protect and support myelinated nerves in the peripheral nervous system. They are typically slow-growing, encapsulated and benign. These tumors develop along peripheral, spinal and cranial nerves causing pain, sensory-motor dysfunction and death. Primary treatment for schwannoma is operative resection which can be associated with significant morbidity. Pharmacotherapy is largely restricted to bevacizumab, which has minimal or no efficacy for many patients and can be associated with treatment-limiting adverse effects. Given the suffering and morbidity associated with schwannoma and the paucity of therapeutic options, there is an urgent need for safe and effective therapies for schwannomas. We previously demonstrated that adeno-associated virus serotype 1 (AAV1) vector mediated delivery of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) under the control of the P0 promoter, produced a prolonged reduction in tumor volume and tumor-associated pain in human xenograft and mouse syngeneic schwannoma models. Here, we present data essential for the translation of our AAV1-P0-ASC schwannoma gene therapy to clinical trials. We determine the minimum effective dose of AAV1-P0-hASC required to induce an anti-tumor effect in the xenograft human-schwannoma model. We also show that the presence of preexisting AAV1 immunity does not alter the antitumor efficacy of AAV-P0-mASC in a syngeneic mouse schwannoma model. Furthermore, the maximum deliverable intratumoral dose of AAV1-P0-ASC was not associated with neuronal toxicity in immunocompetent mice. Taken together, these safety and efficacy data support the translation of the AAV1-P0-ASC schwannoma gene therapy strategy to clinical trials.
Endoplasmic Reticulum Stress and Unfolded Protein Response Signaling in Plants
Authors: Manghwar Hakim , Li Jianming
Published: January 2022

Plants are sensitive to a variety of stresses that cause various diseases throughout their life cycle. However, they have the ability to cope with these stresses using different defense mechanisms. The endoplasmic reticulum (ER) is an important subcellular organelle, primarily recognized as a checkpoint for protein folding. It plays an essential role in ensuring the proper folding and maturation of newly secreted and transmembrane proteins. Different processes are activated when around one-third of newly synthesized proteins enter the ER in the eukaryote cells, such as glycosylation, folding, and/or the assembling of these proteins into protein complexes. However, protein folding in the ER is an error-prone process whereby various stresses easily interfere, leading to the accumulation of unfolded/misfolded proteins and causing ER stress. The unfolded protein response (UPR) is a process that involves sensing ER stress. Many strategies have been developed to reduce ER stress, such as UPR, ER-associated degradation (ERAD), and autophagy. Here, we discuss the ER, ER stress, UPR signaling and various strategies for reducing ER stress in plants. In addition, the UPR signaling in plant development and different stresses have been discussed.
CpG Island Methylator Phenotype—A Hope for the Future or a Road to Nowhere?
Authors: Paweł Karpiński , Maria Małgorzata Sąsiadek
Published: January 2022

The CpG island methylator phenotype (CIMP) can be regarded as the most notable emanation of epigenetic instability in cancer. Since its discovery in the late 1990s, CIMP has been extensively studied, mainly in colorectal cancers (CRC) and gliomas. Consequently, knowledge on molecular and pathological characteristics of CIMP in CRC and other tumour types has rapidly expanded. Concordant and widespread hypermethylation of multiple CpG islands observed in CIMP in multiple cancers raised hopes for future epigenetically based diagnostics and treatments of solid tumours. However, studies on CIMP in solid tumours were hampered by a lack of generalisability and reproducibility of epigenetic markers. Moreover, CIMP was not a satisfactory marker in predicting clinical outcomes. The idea of targeting epigenetic abnormalities such as CIMP for cancer therapy has not been implemented for solid tumours, either. Twenty-one years after its discovery, we aim to cover both the fundamental and new aspects of CIMP and its future application as a diagnostic marker and target in anticancer therapies.
Air-Liquid-Interface Differentiated Human Nose Epithelium: A Robust Primary Tissue Culture Model of SARS-CoV-2 Infection
Authors: Tran Bang M. , Grimley Samantha L. , McAuley Julie L. , Hachani Abderrahman , Earnest Linda , Wong Sharon L. , Caly Leon , Druce Julian , Purcell Damian F. J. , Jackson David C. , Catton Mike , Nowell Cameron J. , Leonie Laura , Deliyannis Georgia , Waters Shafagh A. , Torresi Joseph , Vincan Elizabeth
Published: January 2022

The global urgency to uncover medical countermeasures to combat the COVID-19 pandemic caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has revealed an unmet need for robust tissue culture models that faithfully recapitulate key features of human tissues and disease. Infection of the nose is considered the dominant initial site for SARS-CoV-2 infection and models that replicate this entry portal offer the greatest potential for examining and demonstrating the effectiveness of countermeasures designed to prevent or manage this highly communicable disease. Here, we test an air–liquid-interface (ALI) differentiated human nasal epithelium (HNE) culture system as a model of authentic SARS-CoV-2 infection. Progenitor cells (basal cells) were isolated from nasal turbinate brushings, expanded under conditionally reprogrammed cell (CRC) culture conditions and differentiated at ALI. Differentiated cells were inoculated with different SARS-CoV-2 clinical isolates. Infectious virus release into apical washes was determined by TCID50, while infected cells were visualized by immunofluorescence and confocal microscopy. We demonstrate robust, reproducible SARS-CoV-2 infection of ALI-HNE established from different donors. Viral entry and release occurred from the apical surface, and infection was primarily observed in ciliated cells. In contrast to the ancestral clinical isolate, the Delta variant caused considerable cell damage. Successful establishment of ALI-HNE is donor dependent. ALI-HNE recapitulate key features of human SARS-CoV-2 infection of the nose and can serve as a pre-clinical model without the need for invasive collection of human respiratory tissue samples.
Nutritional Approaches as a Treatment for Impaired Bone Growth and Quality Following the Consumption of Ultra-Processed Food
Authors: Griess-Fishheimer Shelley , Zaretsky Janna , Travinsky-Shmul Tamara , Zaretsky Irina , Penn Svetlana , Shahar Ron , Monsonego-Ornan Efrat
Published: January 2022

The severe impairment of bone development and quality was recently described as a new target for unbalanced ultra-processed food (UPF). Here, we describe nutritional approaches to repair this skeletal impairment in rats: supplementation with micro-nutrients and a rescue approach and switching the UPF to balanced nutrition during the growth period. The positive effect of supplementation with multi-vitamins and minerals on bone growth and quality was followed by the formation of mineral deposits on the rats’ kidneys and modifications in the expression of genes involved in inflammation and vitamin-D metabolism, demonstrating the cost of supplementation. Short and prolonged rescue improved trabecular parameters but incompletely improved the cortical parameters and the mechanical performance of the femur. Cortical porosity and cartilaginous lesions in the growth-plate were still detected one week after rescue and were reduced to normal levels 3 weeks after rescue. These findings highlight bone as a target for the effect of UPF and emphasize the importance of a balanced diet, especially during growth.
The Dynamics and Plasticity of Epigenetics in Diabetic Kidney Disease: Therapeutic Applications Vis-à-Vis
Authors: Kuo Feng-Chih , Chao Chia-Ter , Lin Shih-Hua
Published: January 2022

Chronic kidney disease (CKD) refers to the phenomenon of progressive decline in the glomerular filtration rate accompanied by adverse consequences, including fluid retention, electrolyte imbalance, and an increased cardiovascular risk compared to those with normal renal function. The triggers for the irreversible renal function deterioration are multifactorial, and diabetes mellitus serves as a major contributor to the development of CKD, namely diabetic kidney disease (DKD). Recently, epigenetic dysregulation emerged as a pivotal player steering the progression of DKD, partly resulting from hyperglycemia-associated metabolic disturbances, rising oxidative stress, and/or uncontrolled inflammation. In this review, we describe the major epigenetic molecular mechanisms, followed by summarizing current understandings of the epigenetic alterations pertaining to DKD. We highlight the epigenetic regulatory processes involved in several crucial renal cell types: Mesangial cells, podocytes, tubular epithelia, and glomerular endothelial cells. Finally, we highlight epigenetic biomarkers and related therapeutic candidates that hold promising potential for the early detection of DKD and the amelioration of its progression.
Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway
Authors: Kim Myun Soo , Park Dongmin , Lee Sora , Park Sunyoung , Kim Kyung Eun , Kim Tae Sung , Park Hyun Jeong , Cho Daeho
Published: January 2022

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.
Roles of Transcription Factors in the Development and Reprogramming of the Dopaminergic Neurons
Authors: Tian Lulu , Al-Nusaif Murad , Chen Xi , Li Song , Le Weidong
Published: January 2022

The meso-diencephalic dopaminergic (mdDA) neurons regulate various critical processes in the mammalian nervous system, including voluntary movement and a wide range of behaviors such as mood, reward, addiction, and stress. mdDA neuronal loss is linked with one of the most prominent human movement neurological disorders, Parkinson’s disease (PD). How these cells die and regenerate are two of the most hotly debated PD research topics. As for the latter, it has been long known that a series of transcription factors (TFs) involves the development of mdDA neurons, specifying cell types and controlling developmental patterns. In vitro and in vivo, TFs regulate the expression of tyrosine hydroxylase, a dopamine transporter, vesicular monoamine transporter 2, and L-aromatic amino acid decarboxylase, all of which are critical for dopamine synthesis and transport in dopaminergic neurons (DA neurons). In this review, we encapsulate the molecular mechanism of TFs underlying embryonic growth and maturation of mdDA neurons and update achievements on dopaminergic cell therapy dependent on knowledge of TFs in mdDA neuronal development. We believe that a deeper understanding of the extrinsic and intrinsic factors that influence DA neurons’ fate and development in the midbrain could lead to a better strategy for PD cell therapy.