bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simulation-Based Multi-Objective Optimization Framework for the Production Planning in Energy Supply Chains
Authors: Chen Shiyu , Wang Wei , Zio Enrico
Published: May 2021

The work presents a simulation-based Multi-Objective Optimization (MOO) framework for efficient production planning in Energy Supply Chains (ESCs). An Agent-based Model (ABM) that is more comprehensive than others adopted in the literature is developed to simulate the agent’s uncertain behaviors and the transaction processes stochastically occurring in dynamically changing ESC structures. These are important realistic characteristics that are rarely considered. The simulation is embedded into a Non-dominated Sorting Genetic Algorithm (NSGA-II)-based optimization scheme to identify the Pareto solutions for which the ESC total profit is maximized and the disequilibrium among its agent’s profits is minimized, while uncertainty is accounted for by Monte Carlo (MC) sampling. An oil and gas ESC model with five layers is considered to show the proposed framework and its capability of enabling efficient management of the ESC sustained production while considering the agent’s uncertain interactions and the dynamically changing structure.
Cooling Design for PEM Fuel-Cell Stacks Employing Air and Metal Foam: Simulation and Experiment
Authors: Hmad Ali A. , Dukhan Nihad
Published: May 2021

A new study investigating the cooling efficacy of air flow inside open-cell metal foam embedded in aluminum models of fuel-cell stacks is described. A model based on a commercial stack was simulated and tested experimentally. This stack has three proton exchange membrane (PEM) fuel cells, each having an active area of 100 cm2, with a total output power of 500 W. The state-of-the-art cooling of this stack employs water in serpentine flow channels. The new design of the current investigation replaces these channels with metal foam and replaces the actual fuel cells with aluminum plates. The constant heat flux on these plates is equivalent to the maximum heat dissipation of the stack. Forced air is employed as the coolant. The aluminum foam used had an open-pore size of 0.65 mm and an after-compression porosity of 60%. Local temperatures in the stack and pumping power were calculated for various air-flow velocities in the range of 0.2–1.5 m/s by numerical simulation and were determined by experiments. This range of air speed corresponds to the Reynolds number based on the hydraulic diameter in the range of 87.6–700.4. Internal and external cells of the stack were investigated. In the simulations, and the thermal energy equations were solved invoking the local thermal non-equilibrium model—a more realistic treatment for airflow in a metal foam. Good agreement between the simulation and experiment was obtained for the local temperatures. As for the pumping power predicted by simulation and obtained experimentally, there was an average difference of about 18.3%. This difference has been attributed to the poor correlation used by the CFD package (ANSYS) for pressure drop in a metal foam. This study points to the viability of employing metal foam for cooling of fuel-cell systems.
A Decision-Making Approach Based on TOPSIS Method for Ranking Smart Cities in the Context of Urban Energy
Authors: Hajduk Sławomira , Jelonek Dorota
Published: May 2021

This paper presents the use of multi-criteria decision-making (MCDM) for the evaluation of smart cities. During the development of the method, the importance of the decision-making approach in the linear ordering of cities was presented. The method of using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) was proposed for the preparation of ranking. The method was verified by the application in the measurement of energy performance in smart cities. The authors conducted a literature review of research papers related to urban energy and MCDM published in the period from 2010 to 2020. The paper uses data from the World Council on City Data (WCCD). The research conducted allowed for the identification of the most popular MCDM techniques in the field of urban energy such as TOPSIS, AHP and DEA. The TOPSIS technique was used to organize and group the analyzed cities. Porto took the top position, whereas Buenos Aries was the last.
Determining the Seasonal Variability of the Territorial Sea Baseline in Poland (2018–2020) Using Integrated USV/GNSS/SBES Measurements
Authors: Specht Mariusz , Specht Cezary , Stateczny Andrzej , Marchel Łukasz , Lewicka Oktawia , Paliszewska-Mojsiuk Monika , Wiśniewska Marta
Published: May 2021

The Territorial Sea Baseline (TSB) allows coastal states to define the maritime boundaries, such as: contiguous zone, continental shelf, exclusive economic zone and territorial sea. Their delimitations determine what rights (jurisdiction and sovereignty) a given coastal state is entitled to. For many years, the problem of delimiting baseline was considered in two aspects: legal (lack of clear-cut regulations and different interpretations) and measurement (lack of research tools for precise and reliable depth measurement in ultra-shallow waters). This paper aimed to define the seasonal variability of the TSB in 2018–2020. The survey was conducted in three representative waterbodies of the Republic of Poland: open sea, river mouth and exit from a large port, differing between each other in seabed shape. Baseline measurements were carried out with Unmanned Surface Vehicles (USV), equipped with Global Navigation Satellite System (GNSS) geodetic receivers and miniature Single Beam Echo Sounders (SBES). The survey has shown that the smallest seasonal variability of TSB (1.86–3.00 m) was confirmed for the waterbody located near the Vistula Śmiała River mouth, which features steep shores. On the other hand, the greatest variability in the baseline (5.73–8.37 m) as observed in the waterbody adjacent to the public beach in Gdynia. Factors conditioning considerable changes in TSB determination were: periodically performed land reclamation works in the area and the fact that the depth of the waterbody increases slowly when moving away from the coastline.
Predicting Eucalyptus Diameter at Breast Height and Total Height with UAV-Based Spectral Indices and Machine Learning
Authors: da Silva Ana Karina Vieira , Borges Marcus Vinicius Vieira , Batista Tays Silva , da Silva Junior Carlos Antonio , Furuya Danielle Elis Garcia , Prado Osco Lucas , Teodoro Larissa Pereira Ribeiro , Baio Fábio Henrique Rojo , Ramos Ana Paula Marques , Gonçalves Wesley Nunes , Marcato Junior José , Teodoro Paulo Eduardo , Pistori Hemerson
Published: May 2021

Machine learning techniques (ML) have gained attention in precision agriculture practices since they efficiently address multiple applications, like estimating the growth and yield of trees in forest plantations. The combination between ML algorithms and spectral vegetation indices (VIs) from high-spatial-resolution line measurement, segment: 0.079024 m multispectral imagery, could optimize the prediction of these biometric variables. In this paper, we investigate the performance of ML techniques and VIs acquired with an unnamed aerial vehicle (UAV) to predict the diameter at breast height (DBH) and total height (Ht) of eucalyptus trees. An experimental site with six eucalyptus species was selected, and the Parrot Sequoia sensor was used. Several ML techniques were evaluated, like random forest (RF), REPTree (DT), alternating model tree (AT,) k-nearest neighbor (KNN), support vector machine (SVM), artificial neural network (ANN), linear regression (LR), and radial basis function (RBF). Each algorithm performance was verified using the correlation coefficient (r) and the mean absolute error (MAE). We used, as input, 34 VIs as numeric variables to predict DHB and Ht. We also added to the model a categorical variable as input identifying the different eucalyptus trees species. The RF technique obtained an overall superior estimation for all the tested configurations. Still, the RBF also showed a higher performance for predicting DHB, numerically surpassing the RF both in r and MAE, in some cases. For Ht variable, the technique that obtained the smallest MAE was SVM, though in a particular test. In this regard, we conclude that a combination of ML and VIs extracted from UAV-based imagery is suitable to estimate DBH and Ht in eucalyptus species. The approach presented constitutes an interesting contribution to the inventory and management of planted forests.
Advanced Methods of Thermal Petrophysics as a Means to Reduce Uncertainties during Thermal EOR Modeling of Unconventional Reservoirs
Authors: Chekhonin Evgeny , Romushkevich Raisa , Popov Evgeny , Popov Yury , Goncharov Alexander , Pchela Konstantin , Bagryantsev Maxim , Terentiev Alexey , Kireev Ivan , Demin Sergey
Published: May 2021

Within the vast category of unconventional resources, heavy oils play an essential role as related resources are abundant throughout the world and the amount of oil produced using thermal methods is significant. Simulators for thermo–hydro–dynamic modeling, as a mandatory tool in oilfield development, are continuously improving. However, the present paper shows that software capabilities for the integration of data on the rock thermal properties necessary for modeling are limited, outdated in some aspects, and require revision. In this paper, it is demonstrated that a characteristic lack of reliable data on rock thermal properties also leads to significant errors in the parameters characterizing oil recovery efficiency. A set of advanced methods and equipment for obtaining reliable data on thermal properties is presented, and a new, vast set of experimental data on formation thermal properties obtained from the Karabikulovskoye heavy oil field (Russia) is described. The time-dependent results of modeling oil recovery at the field segment using the steam-assisted gravity drainage method with both published and new data are discussed. It is shown that the lack of experimental data leads to significant errors in the evaluation of the cumulative oil production (up to 20%) and the cumulative steam/oil ratio (up to 52%).
Machine-Learning Techniques for Feature Selection and Prediction of Mortality in Elderly CABG Patients
Authors: Huang Yen-Chun , Li Shao-Jung , Chen Mingchih , Lee Tian-Shyug , Chien Yu-Ning
Published: May 2021

Coronary artery bypass surgery grafting (CABG) is a commonly efficient treatment for coronary artery disease patients. Even if we know the underlying disease, and advancing age is related to survival, there is no research using the one year before surgery and operation-associated factors as predicting elements. This research used different machine-learning methods to select the features and predict older adults’ survival (more than 65 years old). This nationwide population-based cohort study used the National Health Insurance Research Database (NHIRD), the largest and most complete dataset in Taiwan. We extracted the data of older patients who had received their first CABG surgery criteria between January 2008 and December 2009 (n = 3728), and we used five different machine-learning methods to select the features and predict survival rates. The results show that, without variable selection, XGBoost had the best predictive ability. Upon selecting XGBoost and adding the CHA2DS score, acute pancreatitis, and acute kidney failure for further predictive analysis, MARS had the best prediction performance, and it only needed 10 variables. This study’s advantages are that it is innovative and useful for clinical decision making, and machine learning could achieve better prediction with fewer variables. If we could predict patients’ survival risk before a CABG operation, early prevention and disease management would be possible.
Profiles of HIV Risk, Sexual Power, and Decision-Making among Sexual Minority Men of Color Who Engage in Transactional Sex: A Latent Profile Analysis
Authors: Ramos S. Raquel , Lardier David T. , Boyd Donte T. , Gutierrez José I. , Carasso Eliana , Houng David , Kershaw Trace
Published: May 2021

Though the transmission of HIV is preventable, there were still 37,968 new documented cases in the United States in 2018. HIV incidence is disproportionate in sexual minority men of color. The purpose of this study was to examine sexual relationship power risk profiles to identify distinct subgroups within the profiles who carry the highest HIV risk. Latent class profile analysis was used to identify subgroups of sexual minority men of color at the highest risk for contracting HIV based on their sexual power profiles. Among 322 sexual minority men, we identified four latent profiles. Profile 1: Low transactional sex and high power (n = 133; 14.3%); Profile 2: Transactional sex, high decision-making in sexual relationships, and low control in sexual relationship (n = 99; 30.7%); Profile 3: Low transactional sex, low decision-making, and moderate control (n = 43; 13.4%); Profile 4: High transactional sex and low power (n = 47; 14.6%). LPA was useful to identify distinct subgroups based on measures of sexual risk and relationship sexual power. Findings carry significant implications for developing tailored strategies to increase HIV knowledge and related HIV prevention and risk reduction services for sexual minority men of color who engage in transactional sex.
Regulation of Energy Substrate Metabolism in Endurance Exercise
Authors: Alghannam Abdullah F. , Ghaith Mazen M. , Alhussain Maha H.
Published: May 2021

The human body requires energy to function. Adenosine triphosphate (ATP) is the cellular currency for energy-requiring processes including mechanical work (i.e., exercise). ATP used by the cells is ultimately derived from the catabolism of energy substrate molecules—carbohydrates, fat, and protein. In prolonged moderate to high-intensity exercise, there is a delicate interplay between carbohydrate and fat metabolism, and this bioenergetic process is tightly regulated by numerous physiological, nutritional, and environmental factors such as exercise intensity and duration, body mass and feeding state. Carbohydrate metabolism is of critical importance during prolonged endurance-type exercise, reflecting the physiological need to regulate glucose homeostasis, assuring optimal glycogen storage, proper muscle fuelling, and delaying the onset of fatigue. Fat metabolism represents a sustainable source of energy to meet energy demands and preserve the ‘limited’ carbohydrate stores. Coordinated neural, hormonal and circulatory events occur during prolonged endurance-type exercise, facilitating the delivery of fatty acids from adipose tissue to the working muscle for oxidation. However, with increasing exercise intensity, fat oxidation declines and is unable to supply ATP at the rate of the exercise demand. Protein is considered a subsidiary source of energy supporting carbohydrates and fat metabolism, contributing to approximately 10% of total ATP turnover during prolonged endurance-type exercise. In this review we present an overview of substrate metabolism during prolonged endurance-type exercise and the regulatory mechanisms involved in ATP turnover to meet the energetic demands of exercise.
Prevalence and Factors for Anxiety during the COVID-19 Pandemic among College Students in China
Authors: Guan Jing , Wu Cuiping , Wei Dandan , Xu Qingqing , Wang Juan , Lin Hualiang , Wang Chongjian , Mao Zhenxing
Published: May 2021

Background: Knowledge of the impact of COVID-19 on the mental health of college students remains limited. Our aim is to investigate the prevalence of anxiety and explore the potential risk and protective factors of anxiety. Methods: A cross-sectional survey was adopted and a total of 24,678 college students were included from Zhengzhou, Henan Province, China, during February, 2020. Anxiety was assessed by using the Generalized Anxiety Disorder tool (GAD-7). Multiple logistic regression models were established for exploring potential factors of anxiety. Results: The overall prevalence of anxiety was 7.3%. After adjusting for potential confounders, sex, place of residence, worried level, fear level, cognitive levels, and behavior status were found to be associated with anxiety (p < 0.05). Students with positive preventive behaviors showed a protective effect against the anxiety symptoms compared to those with negative preventive behaviors. In contrast to the high-cognition category, participants at a low cognitive level were 14.9% more likely to present anxiety symptoms. Conclusion: This large-scale study assessed the prevalence of anxiety and its potential influencing factors among college students. It suggests that the government could strengthen health education related to COVID-19 and supervise the performance of preventive behaviors to handle anxiety.
Self-Perception and Self-Acceptance Are Related to Unhealthy Weight Control Behaviors in Catalan Adolescents: A Cross-Sectional Study
Authors: Pollina-Pocallet Mercè , Artigues-Barberà Eva , Tort-Nasarre Glòria , Sol Joaquim , Azlor Laura , Foguet-Boreu Quintí , Ortega-Bravo Marta
Published: May 2021

Adolescence is associated with a higher vulnerability that may result in a high dissatisfaction, the practice of unhealthy weight-control behaviors (UWCB) and, eventually, the onset of body image-related mental disorders. These factors are strongly associated with the social context, so it is important to characterize them in local or regional studies. To assess the relationship between body image and UWCB presence, a cross-sectional study was performed among 2496 schooled adolescents from Lleida (Spain) between 2017 and 2019. Their perceived and desired images were evaluated and compared with the real image in order to obtain the body distortion and the body dissatisfaction and relate them with UWCB. The studied individuals perceived themselves thinner than they actually were, with no differences between males and females. However, differences were found regarding body dissatisfaction, showing that females desired to be thinner, while males desired a more corpulent body image. Furthermore, one out of ten individuals reported UWCB, with higher prevalence among females. UWCB was associated with a desire to be thinner and with distorted body images. It is essential to work on self-perception and self-acceptance in early adolescence from an interdisciplinary perspective at educational, social and health levels to promote health in adolescence.
Psychosocial Correlates of Suicidal Behavior among Adolescents under Confinement Due to the COVID-19 Pandemic in Aguascalientes, Mexico: A Cross-Sectional Population Survey
Authors: Hermosillo-de-la-Torre Alicia Edith , Arteaga-de-Luna Stephania Montserrat , Acevedo-Rojas Denise Liliana , Juárez-Loya Angélica , Jiménez-Tapia José Alberto , Pedroza-Cabrera Francisco Javier , González-Forteza Catalina , Cano Manuel , Wagner Fernando A.
Published: May 2021

Background: Suicide and suicidal behaviors were already a global public health problem, producing preventable injuries and deaths. This issue may worsen due to the COVID-19 pandemic and may differentially affect vulnerable groups in the population, including children, adolescents, and young adults. The current study evaluated the association of affective variables (depression, hopelessness, and anxiety), drug use (alcohol, tobacco, and others), emotional intelligence, and attachment with suicidal behaviors. Methods: A state-wide survey included 8033 students (51% female, 49% male; mean age of 16 years) from science and technology high-schools using a standardized questionnaire that was distributed online. Multinomial logistic regression models tested associations between suicidal behaviors and several covariates. The analyses accommodated the complex structure of the sample. Results: Approximately 21% of all students reported a suicidal behavior (11% with a low-lethality suicide attempt, 6% with self-injuries, and 4% with a high-lethality suicide attempt). Variables associated with higher odds of suicidal behavior included: female sex, depression, hopelessness, anxiety, alcohol and tobacco use, childhood trauma, and having to self-rely as issues affecting attachment, and low self-esteem. Security of attachment was associated with lower odds of suicidal behavior. Conclusions: The complexity of suicidal behavior makes it clear that comprehensive programs need to be implemented.
Development and Validation of a Food Literacy Assessment Tool for Community-Dwelling Elderly People
Authors: So Hyeona , Park Dahyun , Choi Mi-Kyung , Kim Young-Sun , Shin Min-Jeong , Park Yoo-Kyoung
Published: May 2021

Food literacy refers to the knowledge, skills, and attitudes required for individuals to choose foods that promote health. As the rate of diet-related diseases increases, food literacy is becoming more important. However, there are no tools available to evaluate food literacy among the Korean elderly. We derived 547 questions from a literature review and, after three rounds of Delphi surveys, selected 33 preliminary questions. We calculated the content validity ratio of the questions and applied a face validity procedure. We then selected 32 questions, assessed their validity, and distributed them as a questionnaire to 205 elderly people. We then conducted exploratory factor analysis (EFA) to determine the validity of the questionnaire and used an internal consistency index (Cronbach’s α coefficient) to determine reliability. Based on the factor analysis, 13 questions were selected, distributed among three factors, and evaluated using the Kaiser–Meyer–Olkin (KMO) and Bartlett sphericity tests. The factor analysis showed that KMO was 0.872, which is a highly acceptable score, and the Bartlett sphericity test was χ2 = 1,374.69 at p = 0.00. The food literacy questionnaire developed in this study will likely be helpful for improving the healthcare of elderly people.
Online Attitudes and Information-Seeking Behavior on Autism, Asperger Syndrome, and Greta Thunberg
Authors: Skafle Ingjerd , Gabarron Elia , Dechsling Anders , Nordahl-Hansen Anders
Published: May 2021

The purpose of this study was to examine Internet trends data and sentiment in tweets mentioning autism, Asperger syndrome, and Greta Thunberg during 2019. We used mixed methods in analyzing sentiment and attitudes in viral tweets and collected 1074 viral tweets on autism that were published in 2019 (tweets that got more than 100 likes). The sample from Twitter was compared with search patterns on Google. In 2019, Asperger syndrome was closely connected to Greta Thunberg, as of the tweets specifically mentioning Asperger (from the total sample of viral tweets mentioning autism), 83% also mentioned Thunberg. In the sample of tweets about Thunberg, the positive sentiment expressed that Greta Thunberg was a role model, whereas the tweets that expressed the most negativity used her diagnosis against her and could be considered as cyberbullying. The Google Trends data also showed that Thunberg was closely connected to search patterns on Asperger syndrome in 2019. The study showed that being open about health information while being an active participant in controversial debates might be used against you but also help break stigmas and stereotypes.
Water–Food Nexus Assessment in Agriculture: A Systematic Review
Authors: Corona-López Evelyn , Román-Gutiérrez Alma D. , Otazo-Sánchez Elena M. , Guzmán-Ortiz Fabiola A. , Acevedo-Sandoval Otilio A.
Published: May 2021

The Water–Food Nexus (WF) has been proposed to reach equitable, balanced, and sustainable access to water and food resources in the face of the growing population demand. Therefore, developing models to assess them has become more relevant. This work systematically reviews the literature on the tools used to evaluate water and food resources between 2002 and 2020. Furthermore, it reports a critical analysis of the software used to assess the WF Nexus quantitatively. The models analyzed were Life Cycle Assessment (LCA), Common Agricultural Policy Regional Impact (CAPRI), Global Food and Water System (GFWS), Soil and Water Assessment Tool (SWAT), Water Evaluation And Planning system (WEAP), and Soil Water Atmosphere Plant (SWAP). We deduced that the following are necessary in evaluating the WF Nexus: (1) the capacity to generate future scenarios, (2) a global application, and (3) the application in case studies. The present paper is the first review to provide an overview of the software applied to evaluate WF Nexus, including the advantages and disadvantages of the tools found. They can help build sustainability criteria when designing policies that reduce water and food security risks and promote efficient water and food use.
Global Variation in Hand Hygiene Practices Among Adolescents: The Role of Family and School-Level Factors
Authors: Jatrana Santosh , Hasan Md. Mehedi , Mamun Abdullah A. , Fatima Yaqoot
Published: May 2021

While appropriate hand hygiene practices (HHP) are protective against infections, the paucity of evidence on global estimates and determinants of HHP in adolescents limits effective design and planning of intervention to improve HHP in young people. We examined the prevalence and correlates of HHP in adolescents. We used nationally representative data from the Global School-based Student Health Survey (2003–2017) from 92 countries. HHP were categorized as “appropriate”, “inappropriate” and “lacking” based on the information about “hand washing before eating”, “hand washing after using the toilet”, and “hand washing with soap”. Multinomial logistic regression analyses were used to assess the role of socio-demographic, health, lifestyle, school, and family-related variables in HHP. Among 354,422 adolescents (13–17 years), only 30.3% were found to practice appropriate hand hygiene. Multivariable models suggest that sedentary behavior (adjusted relative risk ratio (ARRR) 1.41, 95% CI 1.31–1.51)), and bullying victimization (ARRR 1.20, 95% CI 1.10–1.30) promoted inappropriate HHP. In contrast, parental supervision (ARRR 0.55, 95% CI 0.50–0.59) and parental bonding (ARRR 0.81, 95% CI 0.75–0.87) were protective against inappropriate HHP. From a policy perspective, hand hygiene promotion policies and programs should focus on both school (bullying, exercise) and family-level factors (parental supervision and parental bonding) factors.
Cellular Automata Based Land-Use Change Simulation Considering Spatio-Temporal Influence Heterogeneity of Light Rail Transit Construction: A Case in Nanjing, China
Authors: Na Jiaming , Zhu Jie , Zheng Jiazhu , Di Shaoning , Ding Hu , Ma Lingfei
Published: May 2021

Light rail transit (LRT), an essential urban public transport system in China, significantly reshaped the urban land-use (LU) pattern. Although the LRT impact and land-use change (LUC) analysis plays an essential role in urban planning policy, the spatiotemporal heterogeneity of LRT impacts have not been considered in LUC simulation studies. This study simulates the urban LU change, considering the spatiotemporal heterogeneity of LRT construction impacts on urban LUC. LUC from 1995 to 2005 in Nanjing, China, is chosen as a case study. At first, the distance decay function is employed to verify the quantitative impact of LRT construction on LU change. Accordingly, the variation trends of each LU type during different stages are described in time and space. A cellular automata model incorporated by the generated LRT impact is established and then implemented for simulation. According to model performance assessment results, the proposed model can produce a realistic urban pattern with Freedom of Movement (FoM) exceeding 24% and a significantly lower relative error than the CA simulation without considering LRT influence.
Exploring Spatial Patterns of Virginia Tornadoes Using Kernel Density and Space-Time Cube Analysis (1960–2019)
Authors: Allen Michael J. , Allen Thomas R. , Davis Christopher , McLeod George
Published: May 2021

This study evaluates the spatial-temporal patterns in Virginia tornadoes using the National Weather Service Storm Prediction Center’s Severe Weather GIS (SVRGIS) database. In addition to descriptive statistics, the analysis employs Kernel Density Estimation for spatial pattern analysis and space-time cubes to visualize the spatiotemporal frequency of tornadoes and potential trends. Most of the 726 tornadoes between 1960–2019 occurred in Eastern Virginia, along the Piedmont and Coastal Plain. Consistent with other literature, both the number of tornadoes and the tornado days have increased in Virginia. While 80% of the tornadoes occurred during the warm season, tornadoes did occur during each month including two deadly tornadoes in January and February. Over the 60-year period, a total of 28 people were killed in the Commonwealth. Most tornado activity took place in the afternoon and early evening hours drawing attention to the temporal variability of risk and vulnerability. Spatial analysis results identify significant, non-random clusters of tornado activity and increasing temporal frequency. While this study improves weather-related literacy and addresses a need in the Commonwealth, more research is necessary to further evaluate the synoptic and mesoscale mechanisms of Virginia tornadoes.
Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia
Authors: Dabrowski Maciej , Bukowy-Bieryllo Zuzanna , Jackson Claire L. , Zietkiewicz Ewa
Published: May 2021

Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.
Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function
Authors: Taylor Abigail , Warner Mark , Mendoza Christopher , Memmott Calvin , LeCheminant Tom , Bailey Sara , Christensen Colter , Keller Julie , Suli Arminda , Mizrachi Dario
Published: May 2021

The tight junction (TJ) is a structure composed of multiple proteins, both cytosolic and membranal, responsible for cell–cell adhesion in polarized endothelium and epithelium. The TJ is intimately connected to the cytoskeleton and plays a role in development and homeostasis. Among the TJ’s membrane proteins, claudins (CLDNs) are key to establishing blood–tissue barriers that protect organismal physiology. Recently, several crystal structures have been reported for detergent extracted recombinant CLDNs. These structural advances lack direct evidence to support quaternary structure of CLDNs. In this article, we have employed protein-engineering principles to create detergent-independent chimeric CLDNs, a combination of a 4-helix bundle soluble monomeric protein (PDB ID: 2jua) and the apical—50% of human CLDN1, the extracellular domain that is responsible for cell–cell adhesion. Maltose-binding protein-fused chimeric CLDNs (MBP-CCs) used in this study are soluble proteins that retain structural and functional aspects of native CLDNs. Here, we report the biophysical characterization of the structure and function of MBP-CCs. MBP-fused epithelial cadherin (MBP-eCAD) is used as a control and point of comparison of a well-characterized cell-adhesion molecule. Our synthetic strategy may benefit other families of 4-α-helix membrane proteins, including tetraspanins, connexins, pannexins, innexins, and more.
Ethanol Enhances Hyperthermia-Induced Cell Death in Human Leukemia Cells
Authors: Quintana Mercedes , Saavedra Ester , del Rosario Henoc , González Ignacio , Hernández Inmaculada , Estévez Francisco , Quintana José
Published: May 2021

Ethanol has been shown to exhibit therapeutic properties as an ablative agent alone and in combination with thermal ablation. Ethanol may also increase sensitivity of cancer cells to certain physical and chemical antitumoral agents. The aim of our study was to assess the potential influence of nontoxic concentrations of ethanol on hyperthermia therapy, an antitumoral modality that is continuously growing and that can be combined with classical chemotherapy and radiotherapy to improve their efficiency. Human leukemia cells were included as a model in the study. The results indicated that ethanol augments the cytotoxicity of hyperthermia against U937 and HL60 cells. The therapeutic benefit of the hyperthermia/ethanol combination was associated with an increase in the percentage of apoptotic cells and activation of caspases-3, -8 and -9. Apoptosis triggered either by hyperthermia or hyperthermia/ethanol was almost completely abolished by a caspase-8 specific inhibitor, indicating that this caspase plays a main role in both conditions. The role of caspase-9 in hyperthermia treated cells acquired significance whether ethanol was present during hyperthermia since the alcohol enhanced Bid cleavage, translocation of Bax from cytosol to mitochondria, release of mitochondrial apoptogenic factors, and decreased of the levels of the anti-apoptotic factor myeloid cell leukemia-1 (Mcl-1). The enhancement effect of ethanol on hyperthermia-activated cell death was associated with a reduction in the expression of HSP70, a protein known to interfere in the activation of apoptosis at different stages. Collectively, our findings suggest that ethanol could be useful as an adjuvant in hyperthermia therapy for cancer.
Production of Aldehydes by Biocatalysis
Authors: Kazimírová Veronika , Rebroš Martin
Published: May 2021

The production of aldehydes, highly reactive and toxic chemicals, brings specific challenges to biocatalytic processes. Absence of natural accumulation of aldehydes in microorganisms has led to a combination of in vitro and in vivo strategies for both, bulk and fine production. Advances in genetic and metabolic engineering and implementation of computational techniques led to the production of various enzymes with special requirements. Cofactor synthesis, post-translational modifications and structure engineering are applied to prepare active enzymes for one-step or cascade reactions. This review presents the highlights in biocatalytical production of aldehydes with the potential to shape future industrial applications.
IgM and IgG Immunoreactivity of SARS-CoV-2 Recombinant M Protein
Authors: Lopandić Zorana , Protić-Rosić Isidora , Todorović Aleksandra , Glamočlija Sofija , Gnjatović Marija , Ćujic Danica , Gavrović-Jankulović Marija
Published: May 2021

Diagnostic evaluation of specific antibodies against the SARS-CoV-2 virus is mainly based on spike (S) and nucleocapsid (N) proteins. Despite the critical functions in virus infection and contribution to the pattern of immunodominance in COVID-19, exploitation of the most abundant membrane (M) protein in the SARS-CoV-2 serology tests is minimal. This study investigated the recombinant M protein’s immunoreactivity with the sera from COVID-19 convalescents. In silico designed protein was created from the outer N-terminal part (19 aa) and internal C-terminal tail (101–222 aa) of the M protein (YP_009724393.1) and was recombinantly produced and purified. The designed M protein (16,498.74 Da, pI 8.79) revealed both IgM and IgG reactivity with serum samples from COVID-19 convalescents in Western blot. In ELISA, more than 93% (28/30) of COVID-19 sera were positive for IgM detection, and more than 96% (29/30) were positive for specific IgG detection to M protein. Based on the capacity to provoke an immune response and its strong antigenic properties, as shown here, and the fact that it is also involved in the virion entry into host cells, the M protein of the SARS-CoV-2 virus as a good antigen has the potential in diagnostic purposes and vaccine design.
Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity
Authors: Zahr Natalie M. , Pohl Kilian M. , Kwong Allison J. , Sullivan Edith V. , Pfefferbaum Adolf
Published: May 2021

Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.
Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
Authors: Kovalska Maria , Baranovicova Eva , Kalenska Dagmar , Tomascova Anna , Adamkov Marian , Kovalska Libusa , Lehotsky Jan
Published: May 2021

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.
Oxaliplatin Causes Transient Changes in TRPM8 Channel Activity
Authors: Rimola Vittoria , Osthues Tabea , Königs Vanessa , Geißlinger Gerd , Sisignano Marco
Published: May 2021

Oxaliplatin is a third-generation platinum-based anticancer drug that is widely used as first-line treatment for colorectal carcinoma. Patients treated with oxaliplatin develop an acute peripheral pain several hours after treatment, mostly characterized by cold allodynia as well as a long-term chronic neuropathy. These two phenomena seem to be causally connected. However, the underlying mechanisms that trigger the acute peripheral pain are still poorly understood. Here we show that the activity of the transient receptor potential melastatin 8 (TRPM8) channel but not the activity of any other member of the TRP channel family is transiently increased 1 h after oxaliplatin treatment and decreased 24 h after oxaliplatin treatment. Mechanistically, this is connected with activation of the phospholipase C (PLC) pathway and depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) after oxaliplatin treatment. Inhibition of the PLC pathway can reverse the decreased TRPM8 activity as well as the decreased PIP2-concentrations after oxaliplatin treatment. In summary, these results point out transient changes in TRPM8 activity early after oxaliplatin treatment and a later occurring TRPM8 channel desensitization in primary sensory neurons. These mechanisms may explain the transient cold allodynia after oxaliplatin treatment and highlight an important role of TRPM8 in oxaliplatin-induced acute and neuropathic pain.
Novel Seleno-Aspirinyl Compound AS-10 Induces Apoptosis, G1 Arrest of Pancreatic Ductal Adenocarcinoma Cells, Inhibits Their NF-κB Signaling, and Synergizes with Gemcitabine Cytotoxicity
Authors: Karelia Deepkamal N. , Kim Sangyub , K. Pandey Manoj , Plano Daniel , Amin Shantu , Lu Junxuan , Sharma Arun K.
Published: May 2021

Current available therapies for pancreatic ductal adenocarcinoma (PDAC) provide minimal overall survival benefits and cause severe adverse effects. We have identified a novel molecule AS-10, a selenazolidine-bis-aspirinyl derivative, that was two to three orders of magnitude more potent than aspirin and at least one to two orders of magnitude more potent than gemcitabine in inhibiting PDAC cancer cell growth/viability against three PDAC cell lines while sparing mouse embryonic fibroblasts in the same exposure range. In Panc-1 cells, AS-10 induced apoptosis without necrosis, principally through caspase-3/7 cascade and reactive oxygen species, in addition to an induction of G1 cell cycle block. Transcriptomic profiling with RNA-seq indicated the top responses to AS-10 exposure as CDKN1A (P21Cip1), CCND1, and nuclear transcription factor-kappa B (NF-κB) complex and the top functions as cell cycle, cell death, and survival without inducing the DNA damage gene signature. AS-10 pretreatment (6 h) decreased cytokine tumor necrosis factor-alpha (TNF-α)-stimulated NF-κB nuclear translocation, DNA binding activity, and degradation of cytosolic inhibitor of κB (IκB) protein. As NF-κB activation in PDAC cells confers resistance to gemcitabine, the AS-10 combination with gemcitabine increased the in vitro cytotoxicity more than the additivity of both compounds. Overall, our results suggest AS-10 may be a promising drug lead for PDAC, both as a single agent and in combination therapy.
High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia
Authors: Bai Gaowa , Furushima Daisuke , Niki Toshiro , Matsuba Takashi , Maeda Yosuke , Takahashi Atsushi , Hattori Toshio , Ashino Yugo
Published: May 2021

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.
The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension
Authors: Roger Inés , Milara Javier , Montero Paula , Cortijo Julio
Published: May 2021

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.