bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Evaluation of Meteorological Disaster Governance Capabilities in Mainland China Based on Generalized λ-Shapley Choquet Integral
Authors: Wang Yajun , Xiao Fang , Zhang Lijie , Gong Zaiwu
Published: April 2021

According to the United Nations report, climate disasters have intensified in the past 20 years, and China has the largest number of disasters in the world. So the study of meteorological disaster governance capacities is critically important for China. We designed a meteorological disaster governance capacity evaluation system to calculate the evaluation values by using the generalized λ-Shapley Choquet integral, a method that considers the interaction between indicators. We used various official statistical yearbooks and internal data of China Meteorological Administration (CMA) and weight intervals set by meteorologists for each level of indicators to calculate the evaluation values of meteorological disaster governance capacity in mainland provinces, from 2014 to 2018. We compared them with other methods (entropy weight method, Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), and Analytic Hierarchy Process (AHP)), and the results showed that the results calculated by the designed interaction method provided in this paper are more stable and differentiated. The results show that provincial meteorological disaster governance capacities in Mainland China are characterized by uneven development and a pro-slight polarization phenomenon. This leads to policy recommendations: Provinces should strengthen the construction of meteorological disaster information; provinces with outstanding capacity must strengthen the experience sharing with provinces with lower capacity.
Sleeping Duration, Napping and Snoring in Association with Diabetes Control among Patients with Diabetes in Qatar
Authors: Bawadi Hiba , Al Sada Asma , Al Mansoori Noof , Al Mannai Sharifa , Hamdan Aya , Shi Zumin , Kerkadi Abdelhamid
Published: April 2021

Background: Poor glycemic control is associated with chronic life-threatening complications. Several studies have revealed that sleep status is associated with glycemic control. Aim: to examine the association between sleep duration, quality and glycemic control among adults with diabetes. Methods: Data on 2500 participants aged 18–60 years were collected from the Qatar Biobank (QBB). Sleep duration and quality were assessed by a self-completed health and lifestyle questionnaire, and glycemic control was assessed using HbA1c. Logistic regression was used to assess the association between sleep duration, napping, snoring and poor glycemic control. Results: After adjusting for age and gender, sleep duration was not associated with poor glycemic control. Lack of association persisted after controlling for smoking, physical activity, education, BMI, fruit and vegetable intake, insulin and medication use. However, sleeping for long hours at night (≥8 h) had a trend in increasing the risk of poor glycemic control (OR = 1.28; 95% CI: 0.94–1.74). Napping was positively associated with poor glycemic control. After adjusting for age and gender, patients who reported “sometimes, frequently, or always” napping had more than 30% increased risk of poor control as compared to patients who reported “never/rarely” napping. Snoring was not associated with poor glycemic control among the study sample when adjusted for age and gender (p = 0.61). Other factors were found to be associated with a better glycemic control such as female, high educational and high physical activity level. Conclusions: our results suggest that napping may be an independent risk factor for a poor glycemic control in diabetes; further investigations are required.
Emission Variations of Primary Air Pollutants from Highway Vehicles and Implications during the COVID-19 Pandemic in Beijing, China
Authors: Cao Xizi , Tian Ye , Shen Yan , Wu Tongran , Li Renfei , Liu Xinyu , Yeerken Amanzheli , Cui Yangyang , Xue Yifeng , Lian Aiping
Published: April 2021

According to the traffic flow variation from January 2019 to August 2020, emissions of primary air pollutants from highway vehicles were calculated based on the emission factor method, which integrated the actual structure of on-road vehicles. The characteristics of on-highway traffic flow and pollution emissions were compared during various progression stages of coronavirus disease (COVID-19). The results showed that the average daily traffic volume decreased by 38.2% in 2020, with a decrease of 62% during the strict lockdown due to the impact of COVID-19. The daily emissions of primary atmospheric pollutants decreased by 29.2% in 2020 compared to the same period in 2019. As for the structure of on-highway vehicle types, the small and medium-sized passenger vehicles predominated, which accounted for 76.3% of traffic, while trucks and large passenger vehicles accounted for 19.7% and 4.0%, but contributed 58.4% and 33.9% of nitrogen oxide (NOx) emissions, respectively. According to the simulation results of the ADMS model, the average concentrations of NOx were reduced by 12.0 µg/m3 compared with the same period in 2019. As for the implication for future pollution control, it is necessary to further optimize the structure of on-highway and the road traffic vehicle types and increase the proportions of new-energy vehicles and vehicles with high emission standards.
Association between Triglyceride Glucose Index and Corrected QT Prolongation in Chinese Male Steelworkers
Authors: Lee Thung-Lip , Hsuan Chin-Feng , Wu Cheng-Ching , Hung Wei-Chin , Tsai I-Ting , Wei Ching-Ting , Yu Teng-Hung , Lu I-Cheng , Chung Fu-Mei , Lee Yau-Jiunn , Lu Yung-Chuan
Published: April 2021

Objectives: Increased triglyceride glucose (TyG) index appears to be linked to carotid and coronary atherosclerosis and calcifications and possesses an elevated future risk of developing cardiovascular disease. Corrected QT (QTc) interval prolongation is associated with ventricular arrhythmias and sudden cardiac death, and a high prevalence of prolonged QTc interval was previously reported in blue-collar workers. The purpose of this study was to find the possible causal inter-relationship between TyG index and QTc interval in a large population of Chinese male steelworkers. Methods: A total of 3189 male workers from two steel plants were enrolled. They responded to a cross-sectional questionnaire on basic attributes and lifestyle, including sleep patterns. All workers in the two plants underwent periodic health checkups, including twelve-lead electrocardiography. Structural equation modeling (SEM) was used to assess the direct and indirect effects of TyG index on QTc interval. Results: With increasing TyG index tertile, the male steelworkers had an increased QTc interval. Applying multivariate analysis, TyG index was associated independently with the odds of QTc prolongation (adjusted odds ratio = 2.73, 95% confidence interval = 1.39–5.24, p = 0.004). SEM revealed that TyG index, hypertension, obesity, lifestyle, white blood cell (WBC) count, and liver function had statistically significant direct effects on QTc interval. Furthermore, TyG index also had an indirect effect on QTc interval through hypertension, obesity, WBC count, and liver function. Moreover, lifestyle had an indirect effect on QTc interval through TyG index. The final model explained 14% of the variability in QTc interval. Conclusions: An increased TyG index was associated with QTc interval prolongation in this study, and SEM delineated possible causal pathways and inter-relationships of the risk factors contributing to the occurrence of QTc prolongation among Chinese male steelworkers.
Mindfulness at Methodist—A Prospective Pilot Study of Mindfulness and Stress Resiliency Interventions in Patients at a Tertiary Care Medical Center
Authors: Vivian Elaina , Oduor Hellen , Girisha Preeti , Mantry Parvez
Published: April 2021

Individuals with chronic medical conditions like cancer often experience heightened stress levels that can impact medical decision-making. The aim of this study was assess the impact of mindful stress-reduction interventions in cancer patients and support group participants (which included current and former cancer patients and their caregivers). A pilot study was conducted in which participants were provided a mindful stress-reduction intervention to determine whether they reduced stress, anxiety, and communication issues. Participants were provided a one-hour mindful stress-reduction intervention by a licensed physical therapist. Surveys were given to participants immediately before and after, and again 7-days after the intervention. Perceived stress was ascertained by asking participants: “Which emotional/mental state do you most frequently find yourself in?” Anxiety and communication abilities were measured using Neuro-QoL™ Anxiety and Communication v.1 instruments. Fifty-nine participants with a mean age of 60.6 years completed the study. Of these, 30.5%, 6.8%, 23.7%, and 39% were diagnosed (or were a caregiver to someone diagnosed) with pancreas, liver, breast, or unknown cancers, respectively. The surveys showed that participants’ perceived stress scores (p < 0.001), anxiety levels (p = 0.0067), and pain scores (p < 0.0001) were reduced after the mindful stress-reduction intervention. Larger studies with control groups are needed to confirm the interventions’ benefits.
Addendum: Shin, W.; et al. The Knowledge and Attitude of Patients Diagnosed with Epithelial Ovarian Cancer towards Genetic Testing. Int. J. Environ. Res. Public Health 2021, 18, 2312
Authors: Shin Wonkyo , Jeong Gowoon , Son Yedong , Seo Sang-Soo , Kang Sokbom , Park Sang-Yoon , Lim Myong Cheol
Published: April 2021

The authors would like to add the following information to the “Funding” section of their paper published in the International Journal of Environmental Research and Public Health [...]
Mental Health Problems and Needs among Transitional-Age Youth in Indonesia
Authors: Kaligis Fransiska , Ismail Raden Irawati , Wiguna Tjhin , Prasetyo Sabarinah , Indriatmi Wresti , Gunardi Hartono , Pandia Veranita , Magdalena Clarissa Cita
Published: April 2021

“Transitional-age youth” describes those whose ages range from 16–24 years old. In this phase, the youth face new challenges and new experiences which may increase the risk for having mental health problems, yet not very many seek help from mental health professionals. In Indonesia, no data are available about mental health problems and the needs of transitional-age youth. This study explores common mental health problems experienced during this stage and assesses how they cope with problems and their expectations from health services. This was a cross-sectional study involving 393 Indonesians aged 16–24 years in May 2020. More than 90% of students had financial and academic difficulties and felt lonely. The most prevalent mental health problem among students was anxiety (95.4%). Most of the students, ranging from 90% to 96.4%, had positive coping strategies. However, around 50% of respondents reported self-harming and having suicidal thoughts. The results of subcategories analysis between ages and faculties were similar. Their most important expectations from mental health services included confidentiality (99.2%) and being welcoming and friendly (99.2%). In conclusion, this study highlighted the most common problems transitional-age youth experience in Indonesia. While some of them already knew how to deal with their problems, not all the participants had good coping mechanisms. Their healthcare expectations were also explored, thereby providing a useful background to revise and amend the current conditions.
Hate Speech, Emotions, and Gender Identities: A Study of Social Narratives on Twitter with Trainee Teachers
Authors: Ortega-Sánchez Delfín , Blanch Joan Pagès , Quintana Jaime Ibáñez , Cal Esther Sanz de la , de la Fuente-Anuncibay Raquel
Published: April 2021

The objective of this study is, on the one hand, to analyse emotional responses to the construction of hate speech relating to gender identity on Twitter. On the other hand, the objective is to evaluate the capabilities of trainee primary education teachers at constructing alternative counter-narratives to this socially alive issue, surrounding the approval of the Ley de Identidad de Género [Gender Identity Law] in Chile, in 2018. With this two-fold objective in mind, quantitative, descriptive, and inferential analysis and qualitative analysis techniques are all applied. The results inform us of the influence of socially constructed emotions and feelings that are expressed in social narratives. However, the narratives of the participants neither appeared to reach satisfactory levels of reflection on the social issues that stirred their own emotional responses, nor on the conflict between reason and the value judgements that they expressed in the digital debate (counter-narratives). These results point to the need to consider both emotions and feelings, as categories of social analysis, and to reflect on their forms of expression within the framework of education for inclusive democratic citizenship.
Indoor Air Quality in Domestic Environments during Periods Close to Italian COVID-19 Lockdown
Authors: Pietrogrande Maria Chiara , Casari Lucia , Demaria Giorgia , Russo Mara
Published: April 2021

This paper describes the in situ monitoring of indoor air quality (IAQ) in two dwellings, using low-cost IAQ sensors to provide high-density temporal and spatial data. IAQ measurements were conducted over 2-week periods in the kitchen and bedroom of each home during the winter, spring, and summer seasons, characterized by different outside parameters, that were simultaneously measured. The mean indoor PM2.5 concentrations were about 15 μg m−3 in winter, they dropped to values close to 10 μg m−3 in spring and increased to levels of about 13 μg m−3 in summer. During the winter campaign, indoor PM2.5 was found mainly associated with particle penetration inside the rooms from outdoors, because of the high outdoor PM2.5 levels in the season. Such pollution winter episodes occur frequently in the study region, due to the combined contributions of strong anthropogenic emissions and stable atmospheric conditions. The concentrations of indoor volatile organic compounds (VOCs) and CO2 increased with the number of occupants (humans and pets), as likely associated with consequent higher emissions through breathing and metabolic processes. They also varied with occupants’ daily activities, like cooking and cleaning. Critic CO2 levels above the limit of 1000 ppm were observed in spring campaign, in the weeks close to the end of the COVID-19 quarantine, likely associated with the increased time that the occupants spent at home.
Utilizing Population Distribution Patterns for Disaster Vulnerability Assessment: Case of Foreign Residents in the Tokyo Metropolitan Area of Japan
Authors: Adu-Gyamfi Bismark , Shaw Rajib
Published: April 2021

Foreign residents in Japan are amongst the vulnerable groups at risk to disasters in the country. Improvement is crucial in meeting Japan’s vison of zero casualties in major disaster events. If the case of the 2005 Hurricane Katrina is to offer an insight into migrants’ characteristics in mega-disaster situations, then a broader analysis of vulnerabilities is needed to avoid mass casualties should the anticipated megathrust earthquake occur. Hence, this study analyzes the vulnerabilities of foreign residents by utilizing their spatial distribution attributes in the Tokyo metropolitan area. This study uses multiple approaches that combine geographic information systems to analyze secondary and primary datasets. The results reveal that foreign nationals are spatially clustered in some parts of the metropolis, especially within a 7 km radius of Minato city. The densities in these areas alter the earthquake community vulnerability levels from 1.23% to 2.8% and from 5.42% to 13.46%, respectively. Although only 11% of foreign residents are prepared for any disaster, there is a high sense of interaction amongst them and Japanese nationals, which almost eliminates isolation within communities. This study therefore proposes the utilization of some of these attributes in mobilizing specifically targeted evacuation procedures, management of evacuation centers, and disaster risk information dissemination.
The Moyamoya Health Behavior Scale for Adolescent Patients: Measurement Tool Development and Psychometric Evaluation
Authors: Oh Won-oak , Yeom Insun , Lim Sung-Hyun , Kim Dong-Seok , Shim Kyu-won
Published: April 2021

Clinical practitioners treating moyamoya disease recognize the need for a systematic approach to better manage the disease in adolescent patients with the disease. Methods: This study aimed to develop and evaluate the validity and reliability of a disease scale which measures the health-related behaviors of adolescents with moyamoya disease. Results: The final 12-item Moyamoya-HB Scale for adolescents was categorized by three sub-domains: implementation of treatment for moyamoya disease (four items); health promoting behavior for moyamoya disease (four items); and health coping behavior for moyamoya disease (four items). Overall, these factors explained 68.97% of the total variance. The results of the confirmative factor analysis supported the construct, convergent and discriminant validity of the three sub-domains. The Moyamoya-HB Scale for adolescents also demonstrated a concurrent validity with the Korean Adolescents’ Health Behaviors Tool (r = 0.59, p < 0.001). Reliability analysis showed an acceptable-to-high Cronbach’s alpha of 0.865 in total, and the subscales ranged from 0.800 to 0.841. Conclusions: Initial findings support the Moyamoya-HB Scale as a reliable and valid measure of health behaviors in adolescents with moyamoya disease.
Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study
Authors: Aminov Rustam
Published: April 2021

Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal.
Lithium Enhances the GABAergic Synaptic Activities on the Hypothalamic Preoptic Area (hPOA) Neurons
Authors: Rijal Santosh , Jang Seon Hui , Park Soo Joung , Han Seong Kyu
Published: April 2021

Lithium (Li+) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area contains GABAergic and glutamatergic neurons and their receptors, which regulate various hypothalamic functions such as the release of neurohormones, control circadian activities. At the neuronal level, several neurotransmitter systems are modulated by lithium exposure. However, the effect of Li+ on hypothalamic neuron excitability and the precise action mechanism involved in such an effect have not been fully understood yet. Therefore, Li+ action on hypothalamic neurons was investigated using a whole-cell patch-clamp technique. In hypothalamic neurons, Li+ increased the GABAergic synaptic activities via action potential independent presynaptic mechanisms. Next, concentration-dependent replacement of Na+ by Li+ in artificial cerebrospinal fluid increased frequencies of GABAergic miniature inhibitory postsynaptic currents without altering their amplitudes. Li+ perfusion induced inward currents in the majority of hypothalamic neurons independent of amino-acids receptor activation. These results suggests that Li+ treatment can directly affect the hypothalamic region of the brain and regulate the release of various neurohormones involved in synchronizing the neuroendocrine axis.
Agrobacterium-Mediated Capsicum annuum Gene Editing in Two Cultivars, Hot Pepper CM334 and Bell Pepper Dempsey
Authors: Park Sung-il , Kim Hyun-Bin , Jeon Hyun-Ji , Kim Hyeran
Published: April 2021

Peppers (Capsicum annuum L.) are the most widespread and cultivated species of Solanaceae in subtropical and temperate countries. These vegetables are economically attractive worldwide. Although whole-genome sequences of peppers and genome-editing tools are currently available, the precision editing of peppers is still in its infancy because of the lack of a stable pepper transformation method. Here, we employed three Agrobacterium tumefaciens strains—AGL1, EHA101, and GV3101—to investigate which Agrobacterium strain could be used for pepper transformation. Hot pepper CM334 and bell pepper Dempsey were chosen in this study. Agrobacterium tumefaciens GV3101 induced the highest number of calli in cv. Dempsey. All three strains generated similar numbers of calli for cv. CM334. We optimized a suitable concentration of phosphinothricin (PPT) to select a CRISPR/Cas9 binary vector (pBAtC) for both pepper types. Finally, we screened transformed calli for PPT resistance (1 and 5 mg/L PPT for cv. CM334 and Dempsey, respectively). These selected calli showed different indel frequencies from the non-transformed calli. However, the primary indel pattern was consistent with a 1-bp deletion at the target locus of the C. annuumMLO gene (CaMLO2). These results demonstrate the different sensitivity between cv. CM334 and Dempsey to A. tumefaciens-mediated callus induction, and a differential selection pressure of PPT via pBAtC binary vector.
Regulation of Flowering Timing by ABA-NnSnRK1 Signaling Pathway in Lotus
Authors: Cao Jing , Jin Qijiang , Kuang Jiaying , Wang Yanjie , Xu Yingchun
Published: April 2021

The lotus produces flower buds at each node, yet most of them are aborted because of unfavorable environmental changes and the mechanism remains unclear. In this work, we proposed a potential novel pathway for ABA-mediated flower timing control in the lotus, which was explored by combining molecular, genetic, transcriptomic, biochemical, and pharmacologic approaches. We found that the aborting flower buds experienced extensive programmed cell death (PCD). The hormonal changes between the normal and aborting flower buds were dominated by abscisic acid (ABA). Seedlings treated with increasing concentrations of ABA exhibited a differential alleviating effect on flower bud abortion, with a maximal response at 80 μM. Transcriptome analysis further confirmed the changes of ABA content and the occurrence of PCD, and indicated the importance of PCD-related SNF1-related protein kinase 1 (NnSnRK1). The NnSnRK1-silenced lotus seedlings showed stronger flowering ability, with their flower:leaf ratio increased by 40%. When seedlings were treated with ABA, the expression level and protein kinase activity of NnSnRK1 significantly decreased. The phenotype of NnSnRK1-silenced seedlings could also be enhanced by ABA treatment and reversed by tungstate treatment. These results suggested that the decline of ABA content in lotus flower buds released its repression of NnSnRK1, which then initiated flower bud abortion.
Mechanistic Insights into the Link between Obesity and Prostate Cancer
Authors: Adesunloye Bamidele A.
Published: April 2021

Obesity is a pandemic of increasing worldwide prevalence. There is evidence of an association between obesity and the risk of prostate cancer from observational studies, and different biologic mechanisms have been proposed. The chronic low-level inflammation within the adipose tissue in obesity results in oxidative stress, activation of inflammatory cytokines, deregulation of adipokines signaling, and increased circulating levels of insulin and insulin-like growth factors (IGF). These mechanisms may be involved in epithelial to mesenchymal transformation into a malignant phenotype that promotes invasiveness, aggressiveness, and metastatic potential of prostate cancer. A thorough understanding of these mechanisms may be valuable in the development of effective prostate cancer prevention strategies and treatments. This review provides an overview of these mechanisms.
Plants and Diabetes: Description, Role, Comprehension and Exploitation
Authors: Durazzo Alessandra , Lucarini Massimo , Santini Antonello
Published: April 2021

Many plants have been known for centuries to have medicinal importance with potential beneficial effects on health. Phytotherapeutic compounds are well known to play a globally significant role, in particular in the management and treatment of various chronic diseases. Among these, diabetes can cause long term damage to the body other than having a relevant economic burden on society being among the costliest chronic diseases. This motivated the focus of the proposed Special Issue, intended to develop and exploit the potential role of plants in the management and treatment of diabetes. The main topics included are: (i) description and use of medicinal plants for diabetes management; (ii) the elucidation and delineation of their main components, properties (anti-hyperglycaemic, hypoglicaemic, anti-infiammatory, apoptotic agents, etc.), (iii) the mechanism of action (in vitro and in vivo studies); (iv) formulation of nutraceuticals, botanicals, and dietary supplements useful as tools as an alternative or support to anti-diabetic pharmacological therapies; (v) development of new markers.
Current Understanding of the Relationship between Blood Donor Variability and Blood Component Quality
Authors: Hadjesfandiari Narges , Khorshidfar Mona , Devine Dana V.
Published: April 2021

While differences among donors has long challenged meeting quality standards for the production of blood components for transfusion, only recently has the molecular basis for many of these differences become understood. This review article will examine our current understanding of the molecular differences that impact the quality of red blood cells (RBC), platelets, and plasma components. Factors affecting RBC quality include cytoskeletal elements and membrane proteins associated with the oxidative response as well as known enzyme polymorphisms and hemoglobin variants. Donor age and health status may also be important. Platelet quality is impacted by variables that are less well understood, but that include platelet storage sensitive metabolic parameters, responsiveness to agonists accumulating in storage containers and factors affecting the maintenance of pH. An increased understanding of these variables can be used to improve the quality of blood components for transfusion by using donor management algorithms based on a donors individual molecular and genetic profile.
AKT Inhibitors: The Road Ahead to Computational Modeling-Guided Discovery
Authors: Halder Amit Kumar , Cordeiro M. Natália D. S.
Published: April 2021

AKT, is a serine/threonine protein kinase comprising three isoforms—namely: AKT1, AKT2 and AKT3, whose inhibitors have been recognized as promising therapeutic targets for various human disorders, especially cancer. In this work, we report a systematic evaluation of multi-target Quantitative Structure-Activity Relationship (mt-QSAR) models to probe AKT’ inhibitory activity, based on different feature selection algorithms and machine learning tools. The best predictive linear and non-linear mt-QSAR models were found by the genetic algorithm-based linear discriminant analysis (GA-LDA) and gradient boosting (Xgboost) techniques, respectively, using a dataset containing 5523 inhibitors of the AKT isoforms assayed under various experimental conditions. The linear model highlighted the key structural attributes responsible for higher inhibitory activity whereas the non-linear model displayed an overall accuracy higher than 90%. Both these predictive models, generated through internal and external validation methods, were then used for screening the Asinex kinase inhibitor library to identify the most potential virtual hits as pan-AKT inhibitors. The virtual hits identified were then filtered by stepwise analyses based on reverse pharmacophore-mapping based prediction. Finally, results of molecular dynamics simulations were used to estimate the theoretical binding affinity of the selected virtual hits towards the three isoforms of enzyme AKT. Our computational findings thus provide important guidelines to facilitate the discovery of novel AKT inhibitors.
Hemodynamic Forces Regulate Cardiac Regeneration-Responsive Enhancer Activity during Ventricle Regeneration
Authors: Geng Fang , Ma Jinmin , Li Xueyu , Hu Zhengyue , Zhang Ruilin
Published: April 2021

Cardiac regenerative capacity varies widely among vertebrates. Zebrafish can robustly regenerate injured hearts and are excellent models to study the mechanisms of heart regeneration. Recent studies have shown that enhancers are able to respond to injury and regulate the regeneration process. However, the mechanisms to activate these regeneration-responsive enhancers (RREs) remain poorly understood. Here, we utilized transient and transgenic analysis combined with a larval zebrafish ventricle ablation model to explore the activation and regulation of a representative RRE. lepb-linked enhancer sequence (LEN) directed enhanced green fluorescent protein (EGFP) expression in response to larval ventricle regeneration and such activation was attenuated by hemodynamic force alteration and mechanosensation pathway modulation. Further analysis revealed that Notch signaling influenced the endocardial LEN activity as well as endogenous lepb expression. Altogether, our work has established zebrafish models for rapid characterization of cardiac RREs in vivo and provides novel insights on the regulation of LEN by hemodynamic forces and other signaling pathways during heart regeneration.
Monoclonal Antibody Aggregation Associated with Free Radical Induced Oxidation
Authors: Zheng Kai , Ren Diya , Wang Y. John , Lilyestrom Wayne , Scherer Thomas , Hong Justin K. Y. , Ji Junyan A.
Published: April 2021

Oxidation is an important degradation pathway of protein drugs. The susceptibility to oxidation is a common concern for therapeutic proteins as it may impact product efficacy and patient safety. In this work, we used 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) as an oxidative stress reagent to evaluate the oxidation of therapeutic antibodies. In addition to the oxidation of methionine (Met) and tryptophan (Trp) residues, we also observed an increase of protein aggregation. Size-exclusion chromatography and multi-angle light scattering showed that the soluble aggregates induced by AAPH consist of dimer, tetramer, and higher-order aggregate species. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that inter-molecular disulfide bonds contributed to the protein aggregation. Furthermore, intrinsic fluorescence spectra suggested that dimerization of tyrosine (Tyr) residues could account for the non-reducible cross-links. An excipient screening study demonstrated that Trp, pyridoxine, or Tyr could effectively reduce protein aggregation due to oxidative stress. This work provides valuable insight into the mechanisms of oxidative-stress induced protein aggregation, as well as strategies to minimize such aggregate formation during the development and storage of therapeutic proteins.
Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function
Authors: Bálint László , Jakus Zoltán
Published: April 2021

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.
Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics
Authors: Li Yan , Tang Tianyu , Lee Hae June , Song Kiwon
Published: April 2021

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.
Where and Why Modeling Amyotrophic Lateral Sclerosis
Authors: Liguori Francesco , Amadio Susanna , Volonté Cinzia
Published: April 2021

Over the years, researchers have leveraged a host of different in vivo models in order to dissect amyotrophic lateral sclerosis (ALS), a neurodegenerative/neuroinflammatory disease that is heterogeneous in its clinical presentation and is multigenic, multifactorial and non-cell autonomous. These models include both vertebrates and invertebrates such as yeast, worms, flies, zebrafish, mice, rats, guinea pigs, dogs and, more recently, non-human primates. Despite their obvious differences and peculiarities, only the concurrent and comparative analysis of these various systems will allow the untangling of the causes and mechanisms of ALS for finally obtaining new efficacious therapeutics. However, harnessing these powerful organisms poses numerous challenges. In this context, we present here an updated and comprehensive review of how eukaryotic unicellular and multicellular organisms that reproduce a few of the main clinical features of the disease have helped in ALS research to dissect the pathological pathways of the disease insurgence and progression. We describe common features as well as discrepancies among these models, highlighting new insights and emerging roles for experimental organisms in ALS.
Hybrid Materials Based on Magnetic Iron Oxides with Benzothiazole Derivatives: A Plausible Potential Spectroscopy Probe
Authors: Corrêa Silviana , Rosa Isael Aparecido , Andolpho Gustavo A. , Assis Letícia Cristina de , Pires Maíra dos S. , Lacerda Lívia C. T. , Nogueira Francisco G. E. , Cunha Elaine F. F. da , Nepovimova Eugenie , Kuca Kamil , Ramalho Teodorico C.
Published: April 2021

Rare diseases affect a small part of the population, and the most affected are children. Because of the low availability of patients for testing, the pharmaceutical industry cannot develop drugs for the diagnosis of many of these orphan diseases. In this sense, the use of benzothiazole compounds that are highly selective and can act as spectroscopy probes, especially the compound 2-(4′-aminophenyl)benzothiazole (ABT), has been highlighted. This article reports the design of potential contrast agents based on ABT and iron to develop a new material with an efficient mechanism to raise the relaxation rate, facilitating diagnosis. The ABT/δ-FeOOH hybrid material was prepared by grafting (N-(4’-aminophenyl) benzothiazole-2-bromoacetamide) on the surface of the iron oxyhydroxide particles. FTIR spectra confirmed the material formations of the hybrid material ABT/δ-FeOOH. SEM analysis checked the covering of nanoflakes’ surfaces in relation to the morphology of the samples. The theoretical calculations test a better binding mode of compound with iron oxyhydroxide. Theoretical findings show the radical capture mechanism in the stabilization of this new material. In this context, Fe3+ ions are an electron acceptor from the organic phase.
Effects of COVID-19 Pandemic on University Students’ Learning
Authors: Ilieva Galina , Yankova Tania , Klisarova-Belcheva Stanislava , Ivanova Svetlana
Published: April 2021

The risk of COVID-19 in higher education has affected all its degrees and forms of training. To assess the impact of the pandemic on the learning of university students, a new reference framework for educational data processing was proposed. The framework unifies the steps of analysis of COVID-19 effects on the higher education institutions in different countries and periods of the pandemic. It comprises both classical statistical methods and modern intelligent methods: machine learning, multi-criteria decision making and big data with symmetric and asymmetric information. The new framework has been tested to analyse a dataset collected from a university students’ survey, which was conducted during the second wave of COVID-19 at the end of 2020. The main tasks of this research are as follows: (1) evaluate the attitude and the readiness of students in regard to distance learning during the lockdown; (2) clarify the difficulties, the possible changes and the future expectations from distance learning in the next few months; (3) propose recommendations and measures for improving the higher education environment. After data analysis, the conclusions are drawn and recommendations are made for enhancement of the quality of distance learning of university students.
A 2D Convolutional Gating Mechanism for Mandarin Streaming Speech Recognition
Authors: Wang Xintong , Zhao Chuangang
Published: April 2021

Recent research shows recurrent neural network-Transducer (RNN-T) architecture has become a mainstream approach for streaming speech recognition. In this work, we investigate the VGG2 network as the input layer to the RNN-T in streaming speech recognition. Specifically, before the input feature is passed to the RNN-T, we introduce a gated-VGG2 block, which uses the first two layers of the VGG16 to extract contextual information in the time domain, and then use a SEnet-style gating mechanism to control what information in the channel domain is to be propagated to RNN-T. The results show that the RNN-T model with the proposed gated-VGG2 block brings significant performance improvement when compared to the existing RNN-T model, and it has a lower latency and character error rate than the Transformer-based model.
Biofoam of Spittlebug, Poophilus costalis (Walker): Preferential Sites, Temperature Regulation, Chemical Composition and Antimicrobial Activity
Authors: Sahayaraj Kitherian , Saranya Balakrishnan , Sayed Samy , Estelle Loko Yêyinou Laura , Madasamy Koilraj
Published: April 2021

The foam produced by nymphs of Poophilus costalis on eleven different host plants belonging to eight families on St. Xavier’s College campus in India was studied over five months. The chemical composition and antimicrobial activity of these biofoams were investigated. The results revealed that P. costalis preferred Theporsia purpurea and Mimosa pudica for laying their eggs and producing foam, over the other tested plants. P. costalis produce their foam on either nodes or internodes on monocotyledons (30%) (p < 0.05), whereas on dicotyledons, they produce more foam on the stems (63.8%) than on the leaves (6.2%) (p < 0.01). The number of nymphs in each piece of foam from P. costalis varied from 1 to 3 (mean = 1.8 per plant). They produced their foam (5.7 to 45.2 cm) from the ground level on a plant. The length and breadth of a piece of foam ranged from 1.0 to 3.9 cm and 0.6 to 4.7 cm, respectively. The foam tended to be cooler than the environment. Qualitative profiling showed that the foam consists of carbohydrates, including maltose; trypsin; amino acids; protease. The foam was also analyzed using a spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), gas chromatography–mass spectroscopy (GC-MS), and high-performance liquid chromatography (HPLC). The antimicrobial activity of the biofoam was the greatest against Staphylococcus aureus, the growth of which was reduced by 55.9 ± 3.9%, suggesting that the foam could be used as an antimicrobial product. However, no activities were observed against Fusarium oxysporum and Candida albicans.
The Impact of Wave Model Source Terms and Coupling Strategies to Rapidly Developing Waves across the North-West European Shelf during Extreme Events
Authors: Valiente Nieves G. , Saulter Andrew , Edwards John M. , Lewis Huw W. , Castillo Sanchez Juan M. , Bruciaferri Diego , Bunney Christopher , Siddorn John
Published: April 2021

Prediction of severe natural hazards requires accurate forecasting systems. Recently, there has been a tendency towards more integrated solutions, where different components of the Earth system are coupled to explicitly represent the physical feedbacks between them. This study focuses on rapidly developing waves under extratropical storms to understand the impact of different wave source term parameterisations in the WAVEWATCH III (WWIII) model (ST4 and ST6) and coupling strategies (surface roughness closure versus surface stress closure) on the accuracy of the Met Office regional atmosphere-ocean-wave coupled research system for the north-west (NW) European shelf (UKC4). Results of a study focused on simulations during winter 2013/14 demonstrate that ST6 allows for a faster wave growth than the ST4 parameterisation but might degrade low to mid energy wave states. The difference between ST6 and ST4 in wave growth is larger for higher wind speeds and short fetches. The experiment with ST4 and roughness closure consistently under-predicts the wave growth in those locations where fetch dependence is an important factor (i.e., seas at the East (E) of Ireland and the UK for storms coming from the NW-WNW). The implementation in the wave model of ST6 physics with the stress closure coupling strategy appears to improve growth of young wind-seas, reducing bias in those locations where the storms are underestimated. The slower wave growth when using surface roughness closure seems to be related to an underestimation of the momentum transfer computed by the wave model when coupling the wind speeds. For very young to young wind seas, this can be overcome when the surface stress is computed by the atmospheric model and directly passed to the ocean.
Hybrid Modelling by Machine Learning Corrections of Analytical Model Predictions towards High-Fidelity Simulation Solutions
Authors: Bock Frederic E. , Keller Sören , Huber Norbert , Klusemann Benjamin
Published: April 2021

Within the fields of materials mechanics, the consideration of physical laws in machine learning predictions besides the use of data can enable low prediction errors and robustness as opposed to predictions only based on data. On the one hand, exclusive utilization of fundamental physical relationships might show significant deviations in their predictions compared to reality, due to simplifications and assumptions. On the other hand, using only data and neglecting well-established physical laws can create the need for unreasonably large data sets that are required to exhibit low bias and are usually expensive to collect. However, fundamental but simplified physics in combination with a corrective model that compensates for possible deviations, e.g., to experimental data, can lead to physics-based predictions with low prediction errors, also despite scarce data. In this article, it is demonstrated that a hybrid model approach consisting of a physics-based model that is corrected via an artificial neural network represents an efficient prediction tool as opposed to a purely data-driven model. In particular, a semi-analytical model serves as an efficient low-fidelity model with noticeable prediction errors outside its calibration domain. An artificial neural network is used to correct the semi-analytical solution towards a desired reference solution provided by high-fidelity finite element simulations, while the efficiency of the semi-analytical model is maintained and the applicability range enhanced. We utilize residual stresses that are induced by laser shock peening as a use-case example. In addition, it is shown that non-unique relationships between model inputs and outputs lead to high prediction errors and the identification of salient input features via dimensionality analysis is highly beneficial to achieve low prediction errors. In a generalization task, predictions are also outside the process parameter space of the training region while remaining in the trained range of corrections. The corrective model predictions show substantially smaller errors than purely data-driven model predictions, which illustrates one of the benefits of the hybrid modelling approach. Ultimately, when the amount of samples in the data set is reduced, the generalization of the physics-related corrective model outperforms the purely data-driven model, which also demonstrates efficient applicability of the proposed hybrid modelling approach to problems where data is scarce.