bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Temporomandibular Joints’ Reciprocal Clicking Related to the Morphology and Position of the Mandible, as Well as to the Sagittal Position of Lower Incisors?—A Case-Control Study
Authors: Derwich Marcin , Mitus-Kenig Maria , Pawlowska Elzbieta
Published: May 2021

The number of patients diagnosed with temporomandibular joint (TMJ) internal derangements, who are seeking orthodontic treatment, is increasing. The aim of the study was to assess the relationship between the presence of TMJ reciprocal clicking and the morphology and position of the mandible, and position of lower incisors, examined on the lateral cephalograms. Fifty patients diagnosed with reciprocal clicking in at least one of the TMJs and 55 patients with no symptoms of TMJ dysfunction were included in the study. Cephalometric analysis was used for the assessment of: skeletal class, sagittal and vertical position of the mandible, angle of the mandible, inclination of the mandibular ramus and the mandibular corpus, as well as for the assessment of the position of the mandibular incisors. The statistical significance level was set at p = 0.05. There were no statistically significant differences between the examined groups regarding the sagittal and vertical position of the mandible, as well as regarding the sagittal position of the mandibular incisors. Presence of TMJ reciprocal clicking is not associated with the position and the morphology of the mandible, as well as with the sagittal position of the mandibular incisors. Patients with early stages of TMJ internal derangements do not present any significant changes in Cephalometrics. Patients diagnosed with TMJ internal derangements before orthodontic treatment require an interdisciplinary approach to the treatment, including physiotherapy.
The Effects of Group Art Therapy on the Primary Family Caregivers of Hospitalized Patients with Brain Injuries in South Korea
Authors: Kim Nayoung , Kim Shin-Jeong , Jeong Geum-Hee , Oh Younjae , Jang Heejung , Kim Aee-Lee
Published: May 2021

This study examined the effects of group art therapy on depression, burden, and self-efficacy in primary family caregivers of patients with brain injuries. This was a quasi-experimental, nonequivalent control group and a pre- and post-test design. This study was carried out in one national rehabilitation hospital targeting 41 primary family caregivers of patients with brain injuries. Group art therapy intervention was carried out three days per week comprising 12 sessions over four consecutive weeks. The experimental group (n = 20) received group art therapy, whereas the control group (n = 21) did not. We used a time difference method to minimize the risk of contaminating the control group by sampling sequentially. For depression, although there was a significant difference after the intervention (t = 3.296, p = 0.004), the mean difference score was not statistically significant between the experimental group and the control group (t = 0.861, p = 0.395). The experimental group showed a significantly greater decrease in burden (t = 2.462, p = 0.020) and significantly greater improvement in self-efficacy (t = −6.270, p < 0.001) than the control group. Group art therapy may be an effective nursing intervention for primary family caregivers of patients with brain injuries.
Impact of Social Media on Skin Cancer Prevention
Authors: De La Garza Henriette , Maymone Mayra B. C. , Vashi Neelam A.
Published: May 2021

Despite the increasing prevalence of social media usage in health care contexts, its impact on skin cancer prevention and awareness has not been largely investigated. We conducted a review of literature on this topic with the objective of summarizing and analyzing the role of social media in skin cancer and sun damage awareness and to identify the uses, benefits, and limitations of different social media platforms on skin cancer prevention. In today’s technological society, it is critical to understand and study the best form of communication. Specific platforms like Instagram, Twitter, Facebook, YouTube, and TikTok vary in originators of material, target demographics, messaging strategies, and reliability of information with regards to skin cancer, sun, and indoor tanning damage. Our results demonstrate that social media interventions have shown promise in skin cancer prevention and continue to escalate by the day. Dermatologists should keep pace with the latest dermatological content on social media and examine its evolution to target the right audience with the proper messages. Further research is needed to evaluate the effectiveness and true impact of social media on meaningful and lasting behavior change for skin cancer prevention.
The Use of Dietary Supplements in Fitness Practitioners: A Cross-Sectional Observation Study
Authors: Mazzilli Massimiliano , Macaluso Filippo , Zambelli Stefano , Picerno Pietro , Iuliano Enzo
Published: May 2021

This study was aimed at evaluating the prevalence of use of dietary supplements (DSs) among gym users and gym instructors involved in body shaping-oriented fitness training. Furthermore, this study aimed to verify whether differences existed in the prevalence and in the types of DSs used in both gym users and gym instructors involved in body shaping-oriented fitness competitions vs. those not involved in fitness competitions. A survey was distributed to 316 participants, composed of 89 gym instructors and 227 gym users of both genders aged 27.3 ± 7.7. Among these participants, 52 were involved in competitions and 248 were not, while 16 participants did not specify either way. The results showed a high prevalence in the use of DSs in the population considered, with 85.4% of the participants declaring they used DSs, with high heterogeneity in the numbers and in the combinations used. No differences were found between gym instructors and gym users, or between participants involved and those not involved in competitions. The results indicate that DSs are widely used by persons involved in body shaping-oriented fitness training. The results also suggest that the majority of the participants decided individually which DSs to use.
Effects of Sports Massage on the Physiological and Mental Health of College Students Participating in a 7-Week Intermittent Exercises Program
Authors: Shen Chih-Chien , Tseng Yi-Han , Shen Meng-Chun Susan , Lin Hsiao-Hsien
Published: May 2021

The purpose of the research is to analyze the improvement in the physical and mental health of college students after intermittent exercises are performed by massage. The present study employed a mixed research method. An experimental study was conducted to analyze the current status of the volunteers’ sports performance and body composition, and then a questionnaire was designed for the subjects’ physical and mental health. The data were then analyzed using SPSS 26.0 software for statistical analysis such as t-test and ANOVA. The subjects were then interviewed to collect their opinions on the study results, and finally, the results were explored by multivariate analysis. The study found that intermittent exercise can help university students develop physical fitness and performance, improve body composition, and regulate physical and mental health. The combination of intermittent exercise with sports massages further enhanced the performance of sit-ups and standing long jump, improve blood pressure, BMI, and self-confidence, as well as reducing suicidal tendencies (experimental group > control group). However, intermittent exercise participants still experienced fatigue, headache, emotional loss, and fear of depression, and the addition of sports massage did not significantly improve flexibility and cardiorespiratory endurance (control group > experimental group).
Exertional Heat Stroke Knowledge and Management among Emergency Medical Service Providers
Authors: Hirschhorn Rebecca , DadeMatthews Oluwagbemiga , Sefton JoEllen
Published: May 2021

This study evaluated emergency medical services (EMS) providers’ knowledge of exertional heat stroke (EHS) and assessed current EMS capabilities for recognizing and managing EHS. EMS providers currently practicing in the United States were recruited to complete a 25-item questionnaire. There were 216 questionnaire responses (183 complete) representing 28 states. On average, respondents were 42.0 ± 13.0 years old, male (n = 163, 75.5%), and white (n = 176, 81.5%). Most respondents were Paramedics (n = 110, 50.9%) and had ≥16 years of experience (n = 109/214, 50.9%) working in EMS. Fifty-five percent (n = 99/180) of respondents had previously treated a patient with EHS. The average number of correct answers on the knowledge assessment was 2.6 ± 1.2 out of 7 (~37% correct). Temporal (n = 79), tympanic (n = 76), and oral (n = 68) thermometers were the most prevalent methods of temperature assessment available. Chemical cold packs (n = 164) and air conditioning (n = 134) were the most prevalent cooling methods available. Respondents demonstrated poor knowledge regarding EHS despite years of experience, and over half stating they had previously treated EHS in the field. Few EMS providers reported having access to an appropriate method of assessing or cooling a patient with EHS. Updated, evidence-based training needs to be provided and stakeholders should ensure their EMS providers have access to appropriate equipment.
Modelling Farmers’ Watershed Ecological Protection Behaviour with the Value-Belief-Norm Theory: A Case Study of the Wei River Basin
Authors: Zhang Siyang , Zhao Minjuan , Ni Qi , Cai Yu
Published: May 2021

Encouraging farmers to protect their environment is of great significance in improving watershed ecological environments and promoting the sustainable development of the watershed economy. To explore the factors influencing farmers’ ecological protection behaviours in the river basin, we constructed a structural equation model to analyse the survey questionnaire responses of 719 farmers in the Wei River Basin, Shaanxi Province, China. The theoretical framework incorporated farmers’ watershed belonging and social capital into an extended value-belief-norm model. Robustness tests revealed that incorporating these variables was valid. Personality norms, watershed belonging, and social capital all had direct positive effects on farmers’ watershed ecological protection behaviour. Value orientation, environmental concern, consequences awareness, and responsibility attribution influenced the next variable in a causal chain and finally acted on watershed ecological protection behaviour indirectly through personality norms. Farmers’ watershed belonging and social capital positively impacted individual norm; through this, there was an indirect positive impact on their watershed ecological protection behaviour. Moreover, watershed belonging and social capital reinforced each other.
Physicians’ and Nurses’ Knowledge in Palliative Care: Multidimensional Regression Models
Authors: Martín-Martín Jaime , López-García Mónica , Medina-Abellán María Dolores , Beltrán-Aroca Cristina María , Martín-de-las-Heras Stella , Rubio Leticia , Pérez-Cárceles María Dolores
Published: May 2021

The increase in life expectancy has led to a growth in the number of people in need of palliative care. Health professionals must possess appropriate knowledge and skills. This study aimed to assess knowledge in palliative care through the Palliative Care Knowledge Test Spanish Version (PCKT-SV)®. A cross-sectional analytical study was conducted in 40 primary care health services. A total of 600 PCKT-SV questionnaires were distributed among health professionals; 561 of them (226 nurses and 335 physicians) were properly filled up. Sociodemographic information, education, and work experience were also recorded. A total of 34.41% of the nurses and 67.40% of the physicians showed good or excellent knowledge of palliative care. Physicians’ scores for pain, dyspnea, and psychiatric disorders were higher than those of the nurses. Nurses scored significantly better in philosophy. Professionals with continuous training in palliative care showed a higher level of knowledge. Age and work experience of physicians and undergraduate training in nurses had significant weight in knowledge. Developing continuous training and enhancing undergraduate training in palliative care will lead to improved patient care at the end of life.
Tooth Loss and Blood Pressure in Parkinson’s Disease Patients: An Exploratory Study on NHANES Data
Authors: Lyra Patrícia , Machado Vanessa , Proença Luís , Mendes José João , Botelho João
Published: May 2021

Objectives: To evaluate tooth loss severity in PD patients and the impact of missing teeth on blood pressure (BP) and glycated hemoglobin (Hba1c) levels. Methods: All adults reporting specific PD medication regimens with complete dental examinations were included from the NHANES 2001 to 2018 databases. Sociodemographic, systolic BP (SBP), diastolic BP (DBP) and Hba1c data were compared according to tooth loss severity, and linear regression analyses on the impact of tooth loss on SBP, DBP and Hba1c levels were conducted. Results: The 214 included participants presented 9.7 missing teeth, 23.8% severe tooth loss and 18.2% total edentulousness. Severe tooth loss cases were significantly older (p < 0.001), had higher smoking prevalence (p = 0.008), chronic medical conditions (p = 0.012) and higher Hba1c (p = 0.001), SBP (p = 0.015) and DBP (p < 0.001) levels. Crude and adjusted linear models revealed a relationship between SBP, DBP and missing teeth; however, age confounded these links (SBP: B = 0.10, SE = 0.16, p < 0.05; DBP: B = 0.16, SE = 0.10, p < 0.05). Tooth loss presented no significant relationship with Hba1c levels. Conclusions: Severe tooth loss is prevalent among PD patients. Blood pressure levels showed a positive linear relationship with the number of missing teeth, although age was a confounding factor. Furthermore, tooth loss and Hba1c levels revealed no significant linear relationship.
Explanatory Factors of Burnout in a Sample of Workers with Disabilities from the Special Employment Centres (SEC) of the Amica Association, Spain
Authors: Gutierrez-Martínez Isabel , González-Santos Josefa , Rodríguez-Fernández Paula , Jiménez-Eguizábal Alfredo , del Barrio-del Campo Jose Antonio , González-Bernal Jerónimo J.
Published: May 2021

Background: we have based our study on the fact that the labour market is progressively becoming more accessible for people with disabilities. This investigation aims to identify the factors that contribute to high levels of work-related stress in a group of disabled individuals in order to develop policies to prevent it and promote the health of the workforce. Methods: 131 workers from two Special Employment Centres (SECs) of the Amica Association in Cantabria (Spain) participated in the study. Sociodemographic and job-related variables were collected using a questionnaire. Work-related stress was evaluated using the Maslach Burnout Inventory General Survey (MBI-GS), which analyzes emotional exhaustion, cynicism and personal efficacy. Results: the main explanatory factors for higher levels of emotional exhaustion were more than 5 years of service in the company (OR 3.235–IC 95% 1.392–7.519; p = 0.006) and bad job satisfaction (OR 7.615–IC 95% 2.467–23.503; p = 0.0001); higher levels of cynicism were also explained by bad job satisfaction (OR 8.599–IC 95% 2.481–29.799; p = 0.001). Conclusions: future research is needed to facilitate the design of company policies and promote the well-being of the disabled population in the workplace, to avoid pathological conditions such as burnout syndrome.
Sagittal Integral Morphotype of Female Classical Ballet Dancers and Predictors of Sciatica and Low Back Pain
Authors: Cejudo Antonio , Gómez-Lozano Sebastián , Sainz de Baranda Pilar , Vargas-Macías Alfonso , Santonja-Medina Fernando
Published: May 2021

The aims of this study were to describe the sagittal integral morphotype (SIM) of classical ballet (CB) dancers, and to establish predictor factors and their cut off values for high risk of experiencing sciatica or low back pain (LBP). This retrospective cohort study was performed in 33 female professional CB dancers. Data related to anthropometric parameters, CB dance experience, sciatica or LBP history, and sagittal spine curvatures were collected. A binary logistic regression and receiver-operating characteristic analysis were performed. The main spine misalignments observed in the SIM of CB dancers were thoracic functional hyperkyphosis, hypomobile kyphosis, and hypokyphosis, and those for the lumbar curvature were hyperlordotic attitude and functional hyperkyphosis. The lumbar curvature in slump sitting and trunk forward bending positions, together with the stature, were significant predictor factors of sciatica history, while the years of dance experience was a significant predictor factor of LBP history. The cut off values analysis revealed that dancers with a stature of 161 cm or less, and those with 14 years of experience or more, have a greater probability of experiencing sciatica or LBP history, respectively.
Contamination of Foods from Cameroon with Residues of 20 Halogenated Pesticides, and Health Risk of Adult Human Dietary Exposure
Authors: Galani Yamdeu Joseph Hubert , Houbraken Michael , Wumbei Abukari , Djeugap Joseph Fovo , Fotio Daniel , Gong Yun Yun , Spanoghe Pieter
Published: May 2021

(1) Background: Halogenated pesticides are abundantly used in Cameroon, but there is no information on the health risk of consumers from exposure to their residues in foods. (2) Methods: Residues of 20 halogenated pesticides were determined in 11 agricultural products collected in the 3 largest cities of Cameroon using QuEChERS extraction and gas chromatography with electron capture detector (GC-ECD), and health risk from dietary exposure was assessed. (3) Results: Organochlorines pesticides aldrin, p,p’-dichlorodiphenyl-trichloroethane (DDT) and β-hexachlorocyclohexane (β-HCH) found in 85.0%, 81.9% and 72.5% of samples, respectively, were the most frequently detected. The highest average concentrations of residues were 1.12, 0.74 and 0.39 mg/kg for methoxychlor, alachlor and β-HCH, respectively, found in chilli pepper. Chili pepper (58.9%), cowpea (56.8%), black beans (56.5%) and kidney beans (54.0%) exhibited the highest residue occurrences. Levels above the European Union maximum residue limits (MRLs) were found for all the 20 pesticides, in 40.1% of the positive analyses, and the food samples contained 14 pesticides banned in Cameroon. Chronic, acute, cumulative and carcinogenic risk assessments revealed that lifetime consumption of maize, black beans, kidney beans, groundnuts and chili pepper contaminated with aldrin, dieldrin, endrin, HCB, heptachlor, o,p’-DDT, p,p’-DDD, p,p’-DDT, p,p’-DDE and β-HCH, could pose health risks. (4) Conclusion: These results show that there is an urgent need of pesticide usage regulation, effective application of pesticide bans and management of obsolete pesticide stocks in Cameroon.
Integration of Laser Scanner and Photogrammetry for Heritage BIM Enhancement
Authors: Alshawabkeh Yahya , Baik Ahmad , Miky Yehia
Published: May 2021

Digital 3D capture and reliable reproduction of architectural features is the first and most difficult step towards defining a heritage BIM. Three-dimensional digital survey technologies, such as TLS and photogrammetry, enable experts to scan buildings with a new level of detail. Challenges in the tracing of parametric objects in a TLS point cloud include the reconstruction of occluded parts, measurement of uncertainties relevant to surface reflectivity, and edge detection and location. In addition to image-based techniques being considered cost effective, highly flexible, and efficient in producing a high-quality 3D textured model, they also provide a better interpretation of surface linear characteristics. This article addresses an architecture survey workflow using photogrammetry and TLS to optimize a point cloud that is sufficient for a reliable HBIM. Fusion-based workflows were proposed during the recording of two heritage sites—the Matbouli House Museum in Historic Jeddah, a UNESCO World Heritage Site; and Asfan Castle. In the Matbouli House Museum building, which is rich with complex architectural features, multi-sensor recording was implemented at different resolutions and levels of detail. The TLS data were used to reconstruct the basic shape of the main structural elements, while the imagery’s superior radiometric data and accessibility were effectively used to enhance the TLS point clouds for improving the geometry, data interpretation, and parametric tracing of irregular objects in the facade. Furthermore, in the workflow that is considered to be the ragged terrain of the Castle of Asfan, here, the TLS point cloud was supplemented with UAV data in the upper building zones where the shadow data originated. Both datasets were registered using an ICP algorithm to scale the photogrammetric data and define their actual position in the construction system. The hybrid scans were imported and processed in the BIM environment. The building components were segmented and classified into regular and irregular surfaces, in order to perform detailed building information modeling of the architectural elements. The proposed workflows demonstrated an appropriate performance in terms of reliable and complete BIM mapping in the complex structures.
Mapping the Accessibility of Medical Facilities of Wuhan during the COVID-19 Pandemic
Authors: Zhou Zhenqi , Xu Zhen , Liu Anqi , Zhou Shuang , Mu Lan , Zhang Xuan
Published: May 2021

In December 2019, the coronavirus disease 2019 (COVID-19) pandemic attacked Wuhan, China. The city government soon strictly locked down the city, implemented a hierarchical diagnosis and treatment system, and took a series of unprecedented pharmaceutical and non-pharmaceutical measures. The residents’ access to the medical resources and the consequently potential demand–supply tension may determine effective diagnosis and treatment, for which travel distance and time are key indicators. Using the Application Programming Interface (API) of Baidu Map, we estimated the travel distance and time from communities to the medical facilities capable of treating COVID-19 patients, and we identified the service areas of those facilities as well. The results showed significant differences in service areas and potential loading across medical facilities. The accessibility of medical facilities in the peripheral areas was inferior to those in the central areas; there was spatial inequality of medical resources within and across districts; the amount of community healthcare centers was insufficient; some communities were underserved regarding walking distance; some medical facilities could be potentially overloaded. This study provides reference, in the context of Wuhan, for understanding the spatial aspect of medical resources and residents’ relevant mobility under the emergency regulation, and re-examining the coordination of emergency to improve future planning and utilization of medical facilities at various levels. The approach can facilitate policymakers to assess potential loading of medical facilities, identify low-accessibility areas, and deploy new medical facilities. It also implies that the accessibility analysis can be rapid and relevant even only with open-source data.
Are Electric Vehicles Reshaping the City? An Investigation of the Clustering of Electric Vehicle Owners’ Dwellings and Their Interaction with Urban Spaces
Authors: Kang Jing , Kan Changcheng , Lin Zhongjie
Published: May 2021

With the rapid development of electric vehicles (EVs) around the world, debates have arisen with regard to their impacts on people’s lifestyles and urban space. Mining spatio-temporal patterns from increasingly smart city sensors and personal mobile devices have become an important approach in understanding the interaction between human activity and urban space. In this study, we used location-based service data to identify EV owners and capture the distribution of home and charging stations. The research goal was to investigate that how the urban form in regions under rapid urbanization is driven by EV use, from a geographical perspective. Using a case study of the expanding metropolis of Beijing, GIS-based spatial statistical analysis was conducted to characterize the spatial-pattern of the homes of EV owners as well as their charging preferences. Our results indicate that the spatial clustering of the homes of EV owners in non-urban central areas—suburban areas—is significantly higher than that in urban central areas. According to the records of visits to charging stations, the spatial interaction distance between the dwellings of EV owners and their visits to charging stations exhibits significant distance attenuation characteristics. 88% of EV owners in this research travels within 40 km (Euclidean distance) between housing and charging stations. At the same time, there were significant differences in the spatial patterns between working days and non-working days which are affected by commuting activities. The three types of urban spatial interaction patterns were identified and categorized by visualization. This transformation to EV use in the city influences several aspects of people’s decisions and behaviors in life. Understanding the impacts will provide valuable information for the development of EVs and their implications in the electrification of transportation, smart planning, and sustainable urbanization.
Detecting Urban Events by Considering Long Temporal Dependency of Sentiment Strength in Geotagged Social Media Data
Authors: Jiang Wei , Wang Yandong , Xiong Zhengan , Song Xiaoqing , Long Yi , Cao Weidong
Published: May 2021

The development of location-based services facilitates the use of location data for detecting urban events. Currently, most studies based on location data model the pattern of an urban dynamic and then extract the anomalies, which deviate significantly from the pattern as urban events. However, few studies have considered the long temporal dependency of sentiment strength in geotagged social media data, and thus it is difficult to further improve the reliability of detection results. In this paper, we combined a sentiment analysis method and long short-term memory neural network for detecting urban events with geotagged social media data. We first applied a dictionary-based method to evaluate the positive and negative sentiment strength. Based on long short-term memory neural network, the long temporal dependency of sentiment strength in geotagged social media data was constructed. By considering the long temporal dependency, daily positive and negative sentiment strength are predicted. We extracted anomalies that deviated significantly from the prediction as urban events. For each event, event-related information was obtained by analyzing social media texts. Our results indicate that the proposed approach is a cost-effective way to detect urban events, such as festivals, COVID-19-related events and traffic jams. In addition, compared to existing methods, we found that accounting for a long temporal dependency of sentiment strength can significantly improve the reliability of event detection.
A Tryptophan-Deficient Diet Induces Gut Microbiota Dysbiosis and Increases Systemic Inflammation in Aged Mice
Authors: Yusufu Ibrahim , Ding Kehong , Smith Kathryn , Wankhade Umesh D. , Sahay Bikash , Patterson G. Taylor , Pacholczyk Rafal , Adusumilli Satish , Hamrick Mark W. , Hill William D. , Isales Carlos M. , Fulzele Sadanand
Published: May 2021

The gut microflora is a vital component of the gastrointestinal (GI) system that regulates local and systemic immunity, inflammatory response, the digestive system, and overall health. Older people commonly suffer from inadequate nutrition or poor diets, which could potentially alter the gut microbiota. The essential amino acid (AA) tryptophan (TRP) is a vital diet component that plays a critical role in physiological stress responses, neuropsychiatric health, oxidative systems, inflammatory responses, and GI health. The present study investigates the relationship between varied TRP diets, the gut microbiome, and inflammatory responses in an aged mouse model. We fed aged mice either a TRP-deficient (0.1%), TRP-recommended (0.2%), or high-TRP (1.25%) diet for eight weeks and observed changes in the gut bacterial environment and the inflammatory responses via cytokine analysis (IL-1a, IL-6, IL-17A, and IL-27). The mice on the TRP-deficient diets showed changes in their bacterial abundance of Coriobacteriia class, Acetatifactor genus, Lachnospiraceae family, Enterococcus faecalis species, Clostridium sp genus, and Oscillibacter genus. Further, these mice showed significant increases in IL-6, IL-17A, and IL-1a and decreased IL-27 levels. These data suggest a direct association between dietary TRP content, the gut microbiota microenvironment, and inflammatory responses in aged mice models.
One Raft to Guide Them All, and in Axon Regeneration Inhibit Them
Authors: Hernaiz-Llorens Marc , Martínez-Mármol Ramón , Roselló-Busquets Cristina , Soriano Eduardo
Published: May 2021

Central nervous system damage caused by traumatic injuries, iatrogenicity due to surgical interventions, stroke and neurodegenerative diseases is one of the most prevalent reasons for physical disability worldwide. During development, axons must elongate from the neuronal cell body to contact their precise target cell and establish functional connections. However, the capacity of the adult nervous system to restore its functionality after injury is limited. Given the inefficacy of the nervous system to heal and regenerate after damage, new therapies are under investigation to enhance axonal regeneration. Axon guidance cues and receptors, as well as the molecular machinery activated after nervous system damage, are organized into lipid raft microdomains, a term typically used to describe nanoscale membrane domains enriched in cholesterol and glycosphingolipids that act as signaling platforms for certain transmembrane proteins. Here, we systematically review the most recent findings that link the stability of lipid rafts and their composition with the capacity of axons to regenerate and rebuild functional neural circuits after damage.
PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial–Mesenchymal Transition
Authors: Bharath Kumar V. , Lin Jen-Tsun , Mahalakshmi B. , Chuang Yi-Ching , Ho Hsin-Yu , Lin Chia-Chieh , Lo Yu-Sheng , Hsieh Ming-Ju , Chen Mu-Kuan
Published: May 2021

Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial–mesenchymal transition process.
KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models
Authors: West James D. , Austin Eric D. , Rizzi Elise M. , Yan Ling , Tanjore Harikrishna , Crabtree Amber L. , Moore Christy S. , Muthian Gladson , Carrier Erica J. , Jacobson David A. , Hamid Rizwan , Kendall Peggy L. , Majka Susan , Rathinasabapathy Anandharajan
Published: May 2021

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.
Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC
Authors: Zhang Yueqi , Wang Hongbing , Xiao Hua
Published: May 2021

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models. This review focuses on the pathogenesis of NASH-related HCC and the mechanisms by which metformin inhibits the initiation and progression of NASH-related HCC. Since the functional role of immune cells in liver homeostasis and pathogenesis is increasingly appreciated in developing anti-cancer therapies on liver malignancies, we discuss both the traditional targets of metformin in hepatocytes and the recently defined effects of metformin on immune cells.
Fusicoccin (FC)-Induced Rapid Growth, Proton Extrusion and Membrane Potential Changes in Maize (Zea mays L.) Coleoptile Cells: Comparison to Auxin Responses
Authors: Polak Małgorzata , Karcz Waldemar
Published: May 2021

The fungal toxin fusicoccin (FC) induces rapid cell elongation, proton extrusion and plasma membrane hyperpolarization in maize coleoptile cells. Here, these three parameters were simultaneously measured using non-abraded and non-peeled segments with the incubation medium having access to their lumen. The dose–response curve for the FC-induced growth was sigmoidal shaped with the maximum at 10−6 M over 10 h. The amplitudes of the rapid growth and proton extrusion were significantly higher for FC than those for indole-3-acetic acid (IAA). The differences between the membrane potential changes that were observed in the presence of FC and IAA relate to the permanent membrane hyperpolarization for FC and transient hyperpolarization for IAA. It was also found that the lag times of the rapid growth, proton extrusion and membrane hyperpolarization were shorter for FC compared to IAA. At 30 °C, the biphasic kinetics of the IAA-induced growth rate could be changed into a monophasic (parabolic) one, which is characteristic for FC-induced rapid growth. It has been suggested that the rates of the initial phase of the FC- and IAA-induced growth involve two common mechanisms that consist of the proton pumps and potassium channels whose contribution to the action of both effectors on the rapid growth is different.
Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease
Authors: McKelvey Michael C. , Brown Ryan , Ryan Sinéad , Mall Marcus A. , Weldon Sinéad , Taggart Clifford C.
Published: May 2021

Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.
Mastocytosis, MCAS, and Related Disorders—Diagnosis, Classification, and Therapy
Authors: Niedoszytko Marek , Valent Peter , Nedoszytko Bogusław
Published: May 2021

Mastocytosis is a heterogeneous group of hematologic neoplasms defined by an accumulation of neoplastic mast cells (MC) in the skin, bone marrow, and other visceral organs [...]
In Pursuit of Healthy Aging: Effects of Nutrition on Brain Function
Authors: Melzer Thayza Martins , Manosso Luana Meller , Yau Suk-yu , Gil-Mohapel Joana , Brocardo Patricia S.
Published: May 2021

Consuming a balanced, nutritious diet is important for maintaining health, especially as individuals age. Several studies suggest that consuming a diet rich in antioxidants and anti-inflammatory components such as those found in fruits, nuts, vegetables, and fish may reduce age-related cognitive decline and the risk of developing various neurodegenerative diseases. Numerous studies have been published over the last decade focusing on nutrition and how this impacts health. The main objective of the current article is to review the data linking the role of diet and nutrition with aging and age-related cognitive decline. Specifically, we discuss the roles of micronutrients and macronutrients and provide an overview of how the gut microbiota-gut-brain axis and nutrition impact brain function in general and cognitive processes in particular during aging. We propose that dietary interventions designed to optimize the levels of macro and micronutrients and maximize the functioning of the microbiota-gut-brain axis can be of therapeutic value for improving cognitive functioning, particularly during aging.
Role of Carbonic Anhydrase in Cerebral Ischemia and Carbonic Anhydrase Inhibitors as Putative Protective Agents
Authors: Bulli Irene , Dettori Ilaria , Coppi Elisabetta , Cherchi Federica , Venturini Martina , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Nocentini Alessio , Supuran Claudiu T. , Pugliese Anna Maria , Pedata Felicita
Published: May 2021

Ischemic stroke is a leading cause of death and disability worldwide. The only pharmacological treatment available to date for cerebral ischemia is tissue plasminogen activator (t-PA) and the search for successful therapeutic strategies still remains a major challenge. The loss of cerebral blood flow leads to reduced oxygen and glucose supply and a subsequent switch to the glycolytic pathway, which leads to tissue acidification. Carbonic anhydrase (CA, EC 4.2.1.1) is the enzyme responsible for converting carbon dioxide into a protons and bicarbonate, thus contributing to pH regulation and metabolism, with many CA isoforms present in the brain. Recently, numerous studies have shed light on several classes of carbonic anhydrase inhibitor (CAI) as possible new pharmacological agents for the management of brain ischemia. In the present review we summarized pharmacological, preclinical and clinical findings regarding the role of CAIs in strokes and we discuss their potential protective mechanisms.
Targeting SIRT2 Sensitizes Melanoma Cells to Cisplatin via an EGFR-Dependent Mechanism
Authors: Karwaciak Iwona , Sałkowska Anna , Karaś Kaja , Dastych Jarosław , Ratajewski Marcin
Published: May 2021

Melanoma cells are resistant to most anticancer chemotherapeutics. Despite poor response rates and short-term efficacy, chemotherapy remains the main approach to treating this cancer. The underlying mechanisms of the intrinsic chemoresistance of melanoma remain unclear, but elucidating these mechanisms is important to improve the efficacy of chemotherapy regimens. Increasing evidence suggests that sirtuin 2 (SIRT2) plays a key role in the response of melanoma cells to chemotherapeutics; thus, in the present study, we evaluated the impact of shRNA-mediated and pharmacological inhibition of SIRT2 on the sensitivity of melanoma cells to cisplatin, which is used in several regimens to treat melanoma patients. We found that cells with SIRT2 inhibition revealed increased sensitivity to cisplatin and exhibited increased accumulation of γ-H2AX and reduced EGFR-AKT-RAF-ERK1/2 (epidermal growth factor receptor-protein B kinase–RAF kinase-extracellular signal-regulated kinase 1/2) pathway signaling compared to control cells. Thus, our results show that sirtuin 2 inhibition increased the in vitro efficacy of cisplatin against melanoma cells.
Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera
Authors: Stuckey Ruth , Gómez-Casares María Teresa
Published: May 2021

Genetic studies in the past decade have improved our understanding of the molecular basis of the BCR-ABL1-negative myeloproliferative neoplasm (MPN) polycythaemia vera (PV). Such breakthroughs include the discovery of the JAK2V617F driver mutation in approximately 95% of patients with PV, as well as some very rare cases of familial hereditary MPN caused by inherited germline mutations. Patients with PV often progress to fibrosis or acute myeloid leukaemia, both associated with very poor clinical outcome. Moreover, thrombosis and major bleeding are the principal causes of morbidity and mortality. As a result of increasingly available and economical next-generation sequencing technologies, mutational studies have revealed the prognostic relevance of a few somatic mutations in terms of thrombotic risk and risk of transformation, helping to improve the risk stratification of patients with PV. Finally, knowledge of the molecular basis of PV has helped identify targets for directed therapy. The constitutive activation of the tyrosine kinase JAK2 is targeted by ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor for PV patients who are resistant or intolerant to cytoreductive treatment with hydroxyurea. Other molecular mechanisms have also been revealed, and numerous agents are in various stages of development. Here, we will provide an update of the recent published literature on how molecular testing can improve the diagnosis and prognosis of patients with PV and present recent advances that may have prognostic value in the near future.
Impact of Differentiated Macrophage-Like Cells on the Transcriptional Toxicity Profile of CuO Nanoparticles in Co-Cultured Lung Epithelial Cells
Authors: Hufnagel Matthias , Neuberger Ronja , Wall Johanna , Link Martin , Friesen Alexandra , Hartwig Andrea
Published: May 2021

To mimic more realistic lung tissue conditions, co-cultures of epithelial and immune cells are one comparatively easy-to-use option. To reveal the impact of immune cells on the mode of action (MoA) of CuO nanoparticles (NP) on epithelial cells, A549 cells as a model for epithelial cells have been cultured with or without differentiated THP-1 cells, as a model for macrophages. After 24 h of submerged incubation, cytotoxicity and transcriptional toxicity profiles were obtained and compared between the cell culture systems. Dose-dependent cytotoxicity was apparent starting from 8.0 µg/cm2 CuO NP. With regard to gene expression profiles, no differences between the cell models were observed concerning metal homeostasis, oxidative stress, and DNA damage, confirming the known MoA of CuO NP, i.e., endocytotic particle uptake, intracellular particle dissolution within lysosomes with subsequent metal ion deliberation, increased oxidative stress, and genotoxicity. However, applying a co-culture of epithelial and macrophage-like cells, CuO NP additionally provoked a pro-inflammatory response involving NLRP3 inflammasome and pro-inflammatory transcription factor activation. This study demonstrates that the application of this easy-to-use advanced in vitro model is able to extend the detection of cellular effects provoked by nanomaterials by an immunological response and emphasizes the use of such models to address a more comprehensive MoA.
Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review
Authors: Ramzan Farha , Vickers Mark H. , Mithen Richard F.
Published: May 2021

Epigenetics refers to the DNA chemistry changes that result in the modification of gene transcription and translation independently of the underlying DNA coding sequence. Epigenetic modifications are reported to involve various molecular mechanisms, including classical epigenetic changes affecting DNA methylation and histone modifications and small RNA-mediated processes, particularly that of microRNAs. Epigenetic changes are reversible and are closely interconnected. They are recognised to play a critical role as mediators of gene regulation, and any alteration in these mechanisms has been identified to mediate various pathophysiological conditions. Moreover, genetic predisposition and environmental factors, including dietary alterations, lifestyle or metabolic status, are identified to interact with the human epigenome, highlighting the importance of epigenetic factors as underlying processes in the aetiology of various diseases such as MetS. This review will reflect on how both the classical and microRNA-regulated epigenetic changes are associated with the pathophysiology of metabolic syndrome. We will then focus on the various aspects of epigenetic-based strategies used to modify MetS outcomes, including epigenetic diet, epigenetic drugs, epigenome editing tools and miRNA-based therapies.