bluuebunny/crossref_metadata_2025 huggingface dataset:
A Literature Review of Emerging Research Needs for Micromobility—Integration through a Life Cycle Thinking Approach
Authors: Marques Daniel L. , Coelho Margarida C.
Published: February 2022

Micromobility is an increasingly attractive option, particularly over short distances. Walking, biking, and other modes of transport, such as e-scooters, are gaining popularity. Furthermore, a trend is emerging to introduce appealing items onto the market that incorporate new/more sustainable materials to improve wellbeing. Significant research questions concern the understanding of emerging research needs and the environmental, social, and economic effects of sustainability in the micromobility transport system, specifically because of developing and implementing new products, boosting the safety and comfort of ergonomic personal mobility devices (PMDs), and assuring security and privacy while digitalization arises. Such research topics can raise policymakers’ and the public’s awareness while providing impactful information for decision-makers. This paper provides a literature review of the most recent research on micromobility-related topics. It uses scientific databases, a keywords list, and defined inclusion criteria to select data, analyze content, and perform a bibliometric analysis. The findings highlight the significance of using Life Cycle Assessment (LCA) tools together with other methodologies to aid in the evaluation of urban complexity. Finally, using a life cycle thinking (LCT) approach, we propose a framework for comprehensively integrating identified research needs.
Emerging Roles of Non-Coding RNAs in the Feed Efficiency of Livestock Species
Authors: Hu Guoyu , Do Duy Ngoc , Davoudi Pourya , Miar Younes
Published: February 2022

A global population of already more than seven billion people has led to an increased demand for food and water, and especially the demand for meat. Moreover, the cost of feed used in animal production has also increased dramatically, which requires animal breeders to find alternatives to reduce feed consumption. Understanding the biology underlying feed efficiency (FE) allows for a better selection of feed-efficient animals. Non-coding RNAs (ncRNAs), especially micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), play important roles in the regulation of bio-logical processes and disease development. The functions of ncRNAs in the biology of FE have emerged as they participate in the regulation of many genes and pathways related to the major FE indicators, such as residual feed intake and feed conversion ratio. This review provides the state of the art studies related to the ncRNAs associated with FE in livestock species. The contribution of ncRNAs to FE in the liver, muscle, and adipose tissues were summarized. The research gap of the function of ncRNAs in key processes for improved FE, such as the nutrition, heat stress, and gut–brain axis, was examined. Finally, the potential uses of ncRNAs for the improvement of FE were discussed.
Characterization of the Complete Mitochondrial Genome of the Bromeliad Crab Metopaulias depressus (Rathbun, 1896) (Crustacea: Decapoda: Brachyura: Sesarmidae)
Authors: Rodriguez-Pilco Milena A. , Leśny Peter , Podsiadłowski Lars , Schubart Christoph D. , Baeza Juan Antonio
Published: February 2022

Metopaulias depressus is a non-marine crab endemic to Jamaica that dwells in rainforest bromeliads and exhibits elaborate active parental care behavior. Current genomic resources on M. depressus are rare, limiting the understanding of its adaptation to terrestrial life in species that evolved from marine ancestors. This study reports the complete mitochondrial genome of M. depressus assembled using Sanger sequencing. The AT-rich mitochondrial genome of M. depressus is 15,765 bp in length and comprises 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. A single 691 bp-long intergenic space is assumed to be the control region (CR) or D-loop. A set of selective pressure analyses indicate that the entirety of the PCGs experience purifying selection. Cox1, cox2, nad5, cox3, and atp6 experience strong purifying selection, and atp8 experiences weak purifying selection compared to the rest of the PCGs. The secondary structures of most tRNA genes exhibit a standard ‘cloverleaf’ structure, with the exception of trnS1, which lacks the dihydroxyuridine (DHU) arm but not the loop, the trnH gene, which lacks the thymine pseudouracil cytosine (T) loop but not the arm, and trnM, which exhibits an overly developed T loop. A maximum likelihood phylogenetic analysis based on all PCGs indicated that M. depressus is more closely related to the genera Clistocoeloma, Nanosesarma, and Parasesarma than to Chiromantes, Geosesarma, and Orisarma. This study contributes to deciphering the phylogenetic relationships within the family Sesarmidae and represents a new genomic resource for this iconic crab species.
Molecular Indicators of Sources and Biodegradation of Organic Matter in Sediments of Fluid Discharge Zones of Lake Baikal
Authors: Morgunova Inna , Semenov Petr , Kursheva Anna , Litvinenko Ivan , Malyshev Sergey , Bukin Sergey , Khlystov Oleg , Pavlova Olga , Zemskaya Tamara , Krylov Alexey A.
Published: February 2022

This paper performs a detailed study of a wide set of organic-geochemical proxies in 15 sediment cores collected from the main basins of Lake Baikal (the northern, the central and the southern) where processes of focused fluid discharge were detected. A variety of studied zones includes sites with gas and hydrothermal seepage, mud volcanoes with or without gas-oil fluid discharge, gas hydrates and authigenic carbonates. The composition of the dispersed organic matter and individual hydrocarbon molecular markers (n-alkanes, dimethyl alkanes, isoprenoids, steranes, terpanes and polycyclic aromatic hydrocarbons) testify to the input from predominantly allochthonous terrestrial and autochthonous microbial and algal sources. The studied sources, maturity and biodegradation parameters of organic matter vary significantly for areas with different fluid discharge. The composition of specific biomarkers including isoprenoids and immature hopanoids reflects the lateral and vertical changes of microbial activity in sediments associated with various environmental conditions. The identified types of terpanes distribution (mature, mixed and immature) correlate well with types of fluid discharge and attest to the development of various methanogenic and methanotrophic microbial communities in sediments. Moreover, the revealed specificity of microbial molecular markers distribution allowed us to suggest the fluid discharge processes in zones where they were not previously detected.
Establishing a Provenance Framework for Sandstones in the Greenland–Norway Rift from the Composition of Moraine/Outwash Sediments
Authors: Szulc Adam G. , Morton Andrew C. , Whitham Andrew G. , Hemming Sidney R. , Thomson Stuart N.
Published: February 2022

The crystalline basement and Caledonian orogenic belt of East Greenland between 70 and 78° N are divided into five source regions on the basis of heavy mineral assemblages, mineral geochemistry, and isotopic age data from 42 modern moraine/outwash samples. The sand types generated by the five source regions can be recognized in the Mesozoic sedimentary rocks of Mid-Norway, and are named, from south to north, MN7 (Gåseland), MN4i (Milne Land–Renland), MN2ii (Hinks Land–Suess Land), MN2iii (Payer Land–Dronning Louise Land), and MN6 (Germania Land). These provide a framework for interpreting the provenance of Greenland–Norway rift sedimentary deposits. The provenance characteristics of Liverpool Land have also been defined, but whether this relatively small region merits a separate provenance status is unclear. Provenance links can be made by comparing the source region sand types with the composition of onshore and offshore sediments from previous studies. Triassic sandstones of the Nordland Ridge and the far south of the Møre Basin, along with Jurassic sandstones of the Heidrun Field in the Haltenbanken area, were derived from the MN4i source region. The provenance of Cretaceous sandstones in East Greenland can be linked to the MN2ii source region. The source of Turonian sandstones on Traill Ø can be pinpointed by zircon U–Pb ages to the Neoproterozoic Lyell Land Group of the Franz Josef Allochthon. Cretaceous sandstones in the Vøring and Møre basins were derived from the MN2iii and MN4i source regions. In addition, some of the Cenomanian–Campanian sedimentary rocks of East Greenland and Mid-Norway contain Permian–Cretaceous-aged zircon grains that are absent from the moraine/outwash samples. The most likely source of these zircon grains is the circum-Arctic region, implying the existence of a long-lived axial drainage system that entered the Greenland–Norway rift from the north.
Inline Skating as an Additional Activity for Alpine Skiing: The Role of the Outside Leg in Short Turn Performance
Authors: Cigrovski Vjekoslav , Očić Mateja , Bon Ivan , Matković Branka , Šagát Peter
Published: February 2022

The complexity of skiing movements urges recreational alpine skiers and competitors to undertake many specific skill trainings not only during the season but also during the off-season using alternative sports. In AS, the role of the outside leg is crucial for successful turn performance. By measuring kinematic and kinetic parameters, we could define whether there is an objective similarity of the role and the movements of the outside leg while performing a turn in AS to those in the most used additional activity, IS. The sample consisted of ten female alpine ski instructors (age 31.6 ± 8.23, height 170.66 ± 7.32 cm, weight 60.16 ± 7.58 kg). Overall, 280 turns were analyzed (140 for AS and 140 for IS). For the purposes of this study, the variable sample consisted of 14 variables in total. For the detection of differences between short turn performance in AS and IS, MANOVA was used. The main findings of our study are defined similarities in pressure distribution during IS and AS and noticeable differences in the kinematic parameters of the outside leg between the mentioned activities. Based on the gathered results, recreational alpine skiers should be aware that IS cannot be used for the purpose of AS adoption, but rather as a dry-land additional activity for AS preparation.
Examining Whistleblowing Intention: The Influence of Rationalization on Wrongdoing and Threat of Retaliation
Authors: Khan Jawad , Saeed Imran , Zada Muhammad , Ali Amna , Contreras-Barraza Nicolás , Salazar-Sepúlveda Guido , Vega-Muñoz Alejandro
Published: February 2022

Whistleblowers who expose wrongdoing often face several concerns, pressures, and threats of retaliation before reaching a final decision. Specifically, this study examines the effects of perceived seriousness of wrongdoing (PSW) and perceived threat of retaliation (PTR), as well as the impact of rationalization (RNL), comparing perceived seriousness of wrongdoing, perceived threat of retaliation and whistleblowing intention. Furthermore, this study aims to determine the mediating effect of anticipated regret (AR) on the relationship between perceived seriousness of wrongdoing and whistleblowing intention. We validated our model by analyzing data gathered across three stages from employees in the telecom sector in Pakistan. The key findings of our research may be summarized as follows: (i) individuals’ willingness to ‘blow the whistle’ increases as a result of perceived seriousness of wrongdoing; (ii) whistleblowers are more likely to opt to remain silent if they anticipate a greater threat of retaliation, and (iii) our study establishes a positive connection between perceived seriousness of wrongdoing and whistleblowing intention, indicating that perceived seriousness of wrongdoing enhances people’s willingness to blow the whistle, and whistleblowers are more likely to choose to emerge if the behaviour is more serious in nature; (iv) the data we have uncovered indicates a moderating role of rationalization in regulating the connections between perceived seriousness of wrongdoing, perceived threat of retaliation, and whistleblowing intention; and (v) the findings demonstrate that anticipated regret mediates the connection between perceived seriousness of wrongdoing and the intention to report wrongdoing. Additionally, the results are discussed in terms of their significance for corporate ethics researchers and managers, as well as for end-users who are interested in whistleblowing.
The Impact of Compensation Gap on Corporate Innovation: Evidence from China’s Pharmaceutical Industry
Authors: Fu Liping , Zhang Shan , Wu Fan
Published: February 2022

The pharmaceutical industry is typically driven by innovation, and is relevant to people’s livelihoods. How to effectively motivate pharmaceutical enterprises to engage in innovative activities is a hot topic. On the basis of the perspective of the combined effect of tournament theory and social comparison theory, this study explored the impact of internal compensation gap on corporate innovation by using data from China’s listed pharmaceutical enterprises during 2011–2018. The findings show a nonlinear (inverted-U-shaped) relationship between compensation gap and corporate innovation within the pharmaceutical industry, which illustrates that the role of the compensation gap is not endless. We also find the optimal compensation gap between executives and employees. Further analyses indicate that this association is more pronounced in regions with low marketization levels, and in large enterprises. Moreover, the practical significance of the results is explored with an expectation of providing theoretical references for the pharmaceutical industry to establish reasonable incentive mechanisms and promote innovative development, and for the government to introduce innovation incentive policies.
High Incidence of Atopic Dermatitis among Children Whose Fathers Work in Primary Industry: The Japan Environment and Children’s Study (JECS)
Authors: Yokomichi Hiroshi , Mochizuki Mie , Kojima Reiji , Horiuchi Sayaka , Ooka Tadao , Akiyama Yuka , Miyake Kunio , Kushima Megumi , Otawa Sanae , Shinohara Ryoji , Yamagata Zentaro ,   on behalf of the Japan Environment and Children’s Study Group
Published: February 2022

The hygiene hypothesis assumes a low incidence of allergic diseases in families engaging in farming work. However, a few studies have indicated rural life as a potential risk factor for atopic dermatitis (AD). Using a large Japanese birth cohort dataset, we calculated the accumulated incidence of AD in children aged 6 months and 1, 2, and 3 years by family business and the hazard ratio. We adjusted for confounding factors. The father’s job was considered the family business. We analysed data on 41,469 father–child pairs at 6 months of age, 40,067 pairs at 1 year, 38,286 pairs at 2 years, and 36,570 pairs at 3 years. We found the highest accumulated incidence of AD among children with fathers engaged in primary industry, with 2.5% at the age of 6 months, 6.6% at 1 year, 12.0% at 2 years, and 15.4% at 3 years. Among primary industry occupations, forestry was associated with the highest incidence of AD across these ages. The hazard ratio of AD was also highest for children whose family business was primary industry. In conclusion, the highest incidence and hazard ratio of AD were observed among children whose fathers worked in primary industry.
A Comparative Cross-Sectional Study of the Prevalence and Determinants of Health Insurance Coverage in Nigeria and South Africa: A Multi-Country Analysis of Demographic Health Surveys
Authors: Akokuwebe Monica Ewomazino , Idemudia Erhabor Sunday
Published: February 2022

Background: The core Universal Health Coverage (UHC) objectives are to ensure universal access to healthcare services by reducing all forms of inequalities. However, financial constraints are major barriers to accessing healthcare, especially in countries such as Nigeria and South Africa. The findings of this study may aid in informing and communicating health policy to increase financial access to healthcare and its utilization in South Africa and Nigeria. Nigeria-South Africa bilateral relations in terms of politics, economics and trade are demonstrated in the justification of the study setting selection. The objectives were to estimate the prevalence of health insurance coverage, and to explore the socio-demographic factors associated with health insurance in South Africa and Nigeria. Methods: This was a cross-sectional study using the 2018 Nigeria Demographic Health Survey and the 2016 South Africa Demographic Health Survey. The 2018 Nigeria Demographic Health Survey data on 55,132 individuals and the 2016 South Africa Demographic Health Survey on 12,142 individuals were used to investigate the prevalence of health insurance associated with socio-demographic factors. Percentages, frequencies, Chi-square and multivariate logistic regression were e mployed, with a significance level of p < 0.05. Results: About 2.8% of the Nigerian population and 13.3% of the South African population were insured (Nigeria: males—3.4%, females—2.7% vs. South Africa: males—13.9%, females—12.8%). The multivariate logistic regression analyses showed that higher education was significantly more likely to be associated with health insurance, independent of other socio-demographic factors in Nigeria (Model I: OR: 1.43; 95% CI: 0.34–1.54, p < 0.05; Model II: OR: 1.34; 95% CI: 0.28–1.42, p < 0.05) and in South Africa (Model I: OR: 1.33; 95% CI: 0.16–1.66, p < 0.05; Model II: OR: 1.76; 95% CI: 0.34–1.82, p < 0.05). Respondents with a higher wealth index and who were employed were independently associated with health insurance uptake in Nigeria and South Africa (p < 0.001). Females were more likely to be insured (p < 0.001) than males in both countries, and education had a significant impact on the likelihood of health insurance uptake in high wealth index households among both male and females in Nigeria and South Africa. Conclusion: Health insurance coverage was low in both countries and independently associated with socio-demographic factors such as education, wealth and employment. There is a need for continuous sensitization, educational health interventions and employment opportunities for citizens of both countries to participate in the uptake of wide health insurance coverage.
Effect of Elevated Ambient Temperature on Maternal, Foetal, and Neonatal Outcomes: A Scoping Review
Authors: Dalugoda Yohani , Kuppa Jyothi , Phung Hai , Rutherford Shannon , Phung Dung
Published: February 2022

This scoping review provides an overview of the published literature, identifies research gaps, and summarises the current evidence of the association between elevated ambient temperature exposure during pregnancy and adverse maternal, foetal, and neonatal outcomes. Following the PRISMA extension for scoping reviews reporting guidelines, a systematic search was conducted on CINAHL, PubMed, and Embase and included original articles published in the English language from 2015 to 2020 with no geographical limitations. A total of seventy-five studies were included, conducted across twenty-four countries, with a majority in the USA (n = 23) and China (n = 13). Study designs, temperature metrics, and exposure windows varied considerably across studies. Of the eighteen heat-associated adverse maternal, foetal, and neonatal outcomes identified, pre-term birth was the most common outcome (n = 30), followed by low birth weight (n = 11), stillbirth (n = 9), and gestational diabetes mellitus (n = 8). Overall, papers reported an increased risk with elevated temperature exposures. Less attention has been paid to relationships between heat and the diverse range of other adverse outcomes such as congenital anomalies and neonatal mortality. Further research on these less-reported outcomes is needed to improve understanding and the effect size of these relationships with elevated temperatures, which we know will be exacerbated by climate change.
ICU-Associated Costs during the Fourth Wave of the COVID-19 Pandemic in a Tertiary Hospital in a Low-Vaccinated Eastern European Country
Authors: Popescu Mihai , Ştefan Oana Mara , Ştefan Mihai , Văleanu Liana , Tomescu Dana
Published: February 2022

The COVID-19 pandemic has been associated with a tremendous financial and social impact. The pressure on healthcare systems worldwide has increased with each pandemic wave. The present study assesses the impact of the COVID-19 pandemic on healthcare-derived costs of critically ill patients during the fourth wave of the COVID-19 pandemic in a tertiary hospital in Romania. We prospectively included patients admitted to a single-centre intensive care unit (ICU) during the fourth wave of the COVID-19 pandemic. Median daily costs were calculated from financial records and divided in three groups: administrative costs, treatment costs and investigation costs. These were then compared to two retrospective cohorts of non-COVID-19 patients admitted to the same ICU during the same time interval in 2020 and 2019. Demographic data and the management of SARS-CoV-2 infection and of associated organ dysfunctions were recorded to identify risk factors for higher costs. Our results show that the COVID-19 pandemic has been associated with a 70.8% increase in total costs compared to previous years. This increase was mainly determined by an increase in medication and medical-device-related costs. We identified the following as risk factors for increased costs: higher degrees of lung involvement, severity of respiratory dysfunction, need for renal replacement therapy and the use of antiviral or immunomodulatory therapy. Costs were higher in patients who had a shorter duration of hospitalization. In conclusion, the COVID-19 pandemic is associated with increased costs for patients, and rapid measures need to be taken to ensure adequate financial support during future pandemic waves, especially in developing countries.
Ambulances Deployment Problems: Categorization, Evolution and Dynamic Problems Review
Authors: Neira-Rodado Dionicio , Escobar-Velasquez John Wilmer , McClean Sally
Published: February 2022

In this paper, an analytic review of the recent methodologies tackling the problem of dynamic allocation of ambulances was carried out. Considering that state-of-the-art is moving to deal with more extensive and dynamic problems to address in a better way real-life instances, this research looks to identify the evolution and recent applications of this kind of problem once the basic models are explored. This extensive review allowed us to identify the most recent developments in this problem and the most critical gaps to be addressed. In this sense, it is essential to point out that the dynamic location of emergency medical services (EMS) is nowadays a relevant topic considering its impact on the healthcare system outcomes. Issues related to forecasting, simulation, heterogeneous fleets, robustness, and solution speed for real-life problems, stand out in the identified gaps. Applications of machine learning the deployment challenges during epidemic outbreaks such as SARS and COVID-19 were also explored. At the same time, a proposed notation tries to tackle the fact that the word problem in this kind of work refers to a model on many occasions. The proposed notation eases the comparison between the different model proposals found in the literature.
Fire Scenario Zone Construction and Personnel Evacuation Planning Based on a Building Information Model and Geographical Information System
Authors: Yang Qiang , Zhang Xu , Zhang Zhongren , He Longjiang , Yan Xiaojie , Na Jiaming
Published: February 2022

The spatial–temporal simulation of fire disasters and evacuation route planning are important research fields for urban emergency responses and are primary tasks that answer complex questions after fires break out. The increasing demand for refined building information models will sharply increase the calculated and analyzed quantity. This demand presents a challenge for fire emergency responses based on massive building information. In this paper, the principle of the realistic worst case (RWC) is introduced into fire simulation and evacuation route planning. Taking the library of the Nanjing Forestry University as the study object, the spatial–temporal characteristics of the influential environmental factors of the fire are simulated, such as the meteorological elements, building structure, and building skin. The scenario zones that are relatively prone to fire are selected using an overlay analysis across the four seasons. Then, the risk threshold for evacuating personnel is analyzed in the fire zone according to international standards and firefighting criteria. Specific parameters are determined based on the analysis of the above. The growing trends for fires across the four seasons are simulated with scenario zones as the starting positions and incorporate factors such as temperature, carbon monoxide, and smoke. Lastly, a life safety assurance path (LSAP) for personnel evacuation is designed based on an indoor road network and path search algorithm. The evacuation planning result is compared with the traditional shortest-time path and shortest-distance path. Based on the study results, fire scenario zones can improve the speed and operating efficiency of spatial–temporal simulation models of fire and can also support path planning and design for emergency responses.
Spectral Index for Mapping Topsoil Organic Matter Content Based on ZY1-02D Satellite Hyperspectral Data in Jiangsu Province, China
Authors: Yang Yayu , Shang Kun , Xiao Chenchao , Wang Changkun , Tang Hongzhao
Published: February 2022

Estimation of soil organic matter content (SOMC) is essential for soil quality evaluation. Compared with traditional multispectral remote sensing for SOMC mapping, the distribution of SOMC in a certain area can be obtained quickly by using hyperspectral remote sensing data. The Advanced Hyper-Spectral Imager (AHSI) onboard the ZY1-02D satellite can simultaneously obtain spectral information in 166 bands from visible (400 nm) to shortwave infrared (2500 nm), providing an important data source for SOMC mapping. In this study, SOMC-related spectral indices (SIs) suitable for this satellite were analyzed and evaluated in Shuyang County, Jiangsu Province. A series of SIs were constructed for the bare soil and vegetation-covered (mainly rice crops and tree seedlings) areas by combining spectral transformations (such as reciprocal and square root) and dual-band index formulas (such as ratio and difference), respectively. The optimal SIs were determined based on Pearson’s correlation coefficient (ρ) and satellite data quality, and applied to SOMC level mapping and estimation. The results show that: (1) The SI with the highest ρ in the bare soil area is the ratio index of original reflectance at 654 and 679 nm (OR-RI(654,679)), whereas the SI in the vegetation area is the square root of the difference between the reciprocal reflectance at 551 and 1998 nm (V-RR-DSI(551,1998)); (2) the spatial distribution trend of regional SOMC results obtained by linear regression models of OR-RI(654,679) and V-RR-DSI(551,1998) is consistent with the samples; (3) based on the optimal SIs, support vector machine and tree ensembles were used to predict the SOMC of bare soil and vegetation-covered areas of Shuyang County, respectively. The determination coefficient of the soil–vegetation combined prediction results is 0.775, the root mean square error is 3.72 g/kg, and the residual prediction deviation is 2.12. The results show that the proposed SIs for ZY1-02D satellite hyperspectral data are of great potential for SOMC mapping.
FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story
Authors: Chambraud Béatrice , Byrne Cillian , Meduri Geri , Baulieu Etienne Emile , Giustiniani Julien
Published: February 2022

The FK506-binding protein 52 (FKBP52) belongs to a large family of ubiquitously expressed and highly conserved proteins (FKBPs) that share an FKBP domain and possess Peptidyl-Prolyl Isomerase (PPIase) activity. PPIase activity catalyzes the isomerization of Peptidyl-Prolyl bonds and therefore influences target protein folding and function. FKBP52 is particularly abundant in the nervous system and is partially associated with the microtubule network in different cell types suggesting its implication in microtubule function. Various studies have focused on FKBP52, highlighting its importance in several neuronal microtubule-dependent signaling pathways and its possible implication in neurodegenerative diseases such as tauopathies (i.e., Alzheimer disease) and alpha-synucleinopathies (i.e., Parkinson disease). This review summarizes our current understanding of FKBP52 actions in the microtubule environment, its implication in neuronal signaling and function, its interactions with other members of the FKBPs family and its involvement in neurodegenerative disease.
Conversion of Human Fibroblasts into Induced Neural Stem Cells by Small Molecules
Authors: Liu Donghui , Rychkov Grigori , Hurtado Plinio , Luo Hai-Yun , Zhang Tao , Bobrovskaya Larisa , Zhou Xin-Fu
Published: February 2022

Induced neural stem cells (iNSCs) reprogrammed from somatic cells hold great potentials for drug discovery, disease modelling and the treatment of neurological diseases. Although studies have shown that human somatic cells can be converted into iNSCs by introducing transcription factors, these iNSCs are unlikely to be used for clinical application due to the safety concern of using exogenous genes and viral transduction vectors. Here, we report the successful conversion of human fibroblasts into iNSCs using a cocktail of small molecules. Furthermore, our results demonstrate that these human iNSCs (hiNSCs) have similar gene expression profiles to bona fide NSCs, can proliferate, and are capable of differentiating into glial cells and functional neurons. This study collectively describes a novel approach based on small molecules to produce hiNSCs from human fibroblasts, which may be useful for both research and therapeutic purposes.
A Transfer-Learning-Based Deep Convolutional Neural Network for Predicting Leukemia-Related Phosphorylation Sites from Protein Primary Sequences
Authors: He Jian , Wu Yanling , Pu Xuemei , Li Menglong , Guo Yanzhi
Published: February 2022

As one of the most important post-translational modifications (PTMs), phosphorylation refers to the binding of a phosphate group with amino acid residues like Ser (S), Thr (T) and Tyr (Y) thus resulting in diverse functions at the molecular level. Abnormal phosphorylation has been proved to be closely related with human diseases. To our knowledge, no research has been reported describing specific disease-associated phosphorylation sites prediction which is of great significance for comprehensive understanding of disease mechanism. In this work, focusing on three types of leukemia, we aim to develop a reliable leukemia-related phosphorylation site prediction models by combing deep convolutional neural network (CNN) with transfer-learning. CNN could automatically discover complex representations of phosphorylation patterns from the raw sequences, and hence it provides a powerful tool for improvement of leukemia-related phosphorylation site prediction. With the largest dataset of myelogenous leukemia, the optimal models for S/T/Y phosphorylation sites give the AUC values of 0.8784, 0.8328 and 0.7716 respectively. When transferred learning on the small size datasets, the models for T-cell and lymphoid leukemia also give the promising performance by common sharing the optimal parameters. Compared with other five machine-learning methods, our CNN models reveal the superior performance. Finally, the leukemia-related pathogenesis analysis and distribution analysis on phosphorylated proteins along with K-means clustering analysis and position-specific conversation profiles on the phosphorylation site all indicate the strong practical feasibility of our easy-to-use CNN models.
Gene Transfer of Skeletal Muscle-Type Myosin Light Chain Kinase via Adeno-Associated Virus 6 Improves Muscle Functions in an Amyotrophic Lateral Sclerosis Mouse Model
Authors: Oya Ryohei , Tsukamoto Osamu , Hitsumoto Tatsuro , Nakahara Naoya , Okamoto Chisato , Matsuoka Ken , Kato Hisakazu , Inohara Hidenori , Takashima Seiji
Published: February 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that shows progressive muscle weakness. A few treatments exist including symptomatic therapies, which can prolong survival or reduce a symptom; however, no fundamental therapies have been found. As a therapeutic strategy, enhancing muscle force is important for patients’ quality of life. In this study, we focused on skeletal muscle-specific myosin regulatory light chain kinase (skMLCK), which potentially enhances muscle contraction, as overexpression of skMLCK was thought to improve muscle function. The adeno-associated virus serotype 6 encoding skMLCK (AAV6/skMLCK) and eGFP (control) was produced and injected intramuscularly into the lower limbs of SOD1G37R mice, which are a familial ALS model. AAV6/skMLCK showed the successful expression of skMLCK in the muscle tissues. Although the control did not affect the muscle force in both of the WT and SOD1G37R mice, AAV6/skMLCK enhanced the twitch force of SOD1G37R mice and the tetanic force of WT and SOD1G37R mice. These results indicate that overexpression of skMLCK can enhance the tetanic force of healthy muscle as well as rescue weakened muscle function. In conclusion, the gene transfer of skMLCK has the potential to be a new therapy for ALS as well as for other neuromuscular diseases.
The Role of AGE-RAGE Signalling as a Modulator of Gut Permeability in Diabetes
Authors: Snelson Matthew , Lucut Elisa , Coughlan Melinda T.
Published: February 2022

There is increasing evidence for the role of intestinal permeability as a contributing factor in the pathogenesis of diabetes; however, the molecular mechanisms are poorly understood. Advanced glycation endproducts, of both exogenous and endogenous origin, have been shown to play a role in diabetes pathophysiology, in part by their ligation to the receptor for advanced glycation endproducts (RAGE), leading to a proinflammatory signalling cascade. RAGE signalling has been demonstrated to play a role in the development of intestinal inflammation and permeability in Crohn’s disease and ulcerative colitis. In this review, we explore the role of AGE-RAGE signalling and intestinal permeability and explore whether activation of RAGE on the intestinal epithelium may be a downstream event contributing to the pathogenesis of diabetes complications.
Identification of Potential Antiviral Inhibitors from Hydroxychloroquine and 1,2,4,5-Tetraoxanes Analogues and Investigation of the Mechanism of Action in SARS-CoV-2
Authors: Ramos Ryan S. , Borges Rosivaldo S. , de Souza João S. N. , Araujo Inana F. , Chaves Mariana H. , Santos Cleydson B. R.
Published: February 2022

This study aimed to identify potential inhibitors and investigate the mechanism of action on SARS-CoV-2 ACE2 receptors using a molecular modeling study and theoretical determination of biological activity. Hydroxychloroquine was used as a pivot structure and antimalarial analogues of 1,2,4,5 tetraoxanes were used for the construction and evaluation of pharmacophoric models. The pharmacophore-based virtual screening was performed on the Molport® database (~7.9 million compounds) and obtained 313 structures. Additionally, a pharmacokinetic study was developed, obtaining 174 structures with 99% confidence for human intestinal absorption and penetration into the blood–brain barrier (BBB); posteriorly, a study of toxicological properties was realized. Toxicological predictions showed that the selected molecules do not present a risk of hepatotoxicity, carcinogenicity, mutagenicity, and skin irritation. Only 54 structures were selected for molecular docking studies, and five structures showed binding affinity (ΔG) values satisfactory for ACE2 receptors (PDB 6M0J), in which the molecule MolPort-007-913-111 had the best ΔG value of −8.540 Kcal/mol, followed by MolPort-002-693-933 with ΔG = −8.440 Kcal/mol. Theoretical determination of biological activity was realized for 54 structures, and five molecules showed potential protease inhibitors. Additionally, we investigated the Mpro receptor (6M0K) for the five structures via molecular docking, and we confirmed the possible interaction with the target. In parallel, we selected the TopsHits 9 with antiviral potential that evaluated synthetic accessibility for future synthesis studies and in vivo and in vitro tests.
EZH2–CCF–cGAS Axis Promotes Breast Cancer Metastasis
Authors: Duan Dandan , Shang Mengjie , Han Yanxu , Liu Jiayuan , Liu Jiwei , Kong Sun Hyok , Hou Jingyao , Huang Baiqu , Lu Jun , Zhang Yu
Published: February 2022

Cytoplasmic chromatin fragments (CCF) are recognized by the cytoplasmic DNA sensor cyclic GMP-AMP synthase (cGAS), which activates the cGAS–STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway and promotes the production of inflammatory factors and breast cancer metastasis. However, the mechanisms by which CCF are formed in tumor cells and CCF activation cGAS promotes breast cancer metastasis remain unclear. Here, we report that the enhancer of zeste homolog 2 (EZH2) can promote the formation of CCF and activate the cGAS–STING pathway to promote breast cancer metastasis. Further research found that the EZH2-mediated CCF formation depended on high mobility group A1 (HMGA1), while the stability of EZH2 required ubiquitin-specific peptidase 7 (USP7), indicating that the EZH2–HMGA1–USP7 complex regulated CCF formation. Moreover, EZH2 can activate cGAS through CCF, requiring USP7 to deubiquitinate cGAS and stabilize cGAS. In vivo experimental results showed that EZH2 could promote breast cancer metastasis through CCF. Our findings highlight a new target for breast cancer metastasis. Targeting the EZH2–CCF–cGAS axis may be a potential therapeutic strategy for inhibiting breast cancer metastasis.
Enhanced Expression of TRAP1 Protects Mitochondrial Function in Motor Neurons under Conditions of Oxidative Stress
Authors: Clarke Benjamin E. , Kalmar Bernadett , Greensmith Linda
Published: February 2022

TNF-receptor associated protein (TRAP1) is a cytoprotective mitochondrial-specific member of the Hsp90 heat shock protein family of protein chaperones that has been shown to antagonise mitochondrial apoptosis and oxidative stress, regulate the mitochondrial permeability transition pore and control protein folding in mitochondria. Here we show that overexpression of TRAP1 protects motor neurons from mitochondrial dysfunction and death induced by exposure to oxidative stress conditions modelling amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease in which motor neurons degenerate, leading to muscle weakness and atrophy and death, typically within 3 years of diagnosis. In primary murine motor neurons, shRNA-mediated knockdown of TRAP1 expression results in mitochondrial dysfunction but does not further exacerbate damage induced by oxidative stress alone. Together, these results show that TRAP1 may be a potential therapeutic target for neurodegenerative diseases such as ALS, where mitochondrial dysfunction has been shown to be an early marker of pathogenesis.
Trapped Acoustic Modes in an Axial Multi-Stage Compressor Leading to Non-Synchronous Blade Vibrations
Authors: Fiquet Anne-Lise , Aubert Stéphane , Buffaz Nicolas , Vercoutter Agathe , Brandstetter Christoph
Published: February 2022

Non-synchronous blade vibrations have been observed in an experimental multi-stage high-speed compressor setup at part-speed conditions. A detailed numerical study has been carried out to understand the observed phenomenon by performing unsteady full-annulus Reynolds-Averaged Navier–Stokes (RANS) simulations of the whole setup using the solver elsA. Several operating conditions have been simulated to observe this kind of phenomena along a speedline of interest. Based on the simulation results, the physical source of the non-synchronous blade vibration is identified: An aerodynamic disturbance appears in a highly loaded downstream rotor and excites a spinning acoustic mode. A “lock-in” phenomenon occurs between the blade boundary layer oscillations and the spinning acoustic mode. The establishment of axially propagating acoustic waves can lead to a complex coupling mechanism and this phenomenon is highly relevant in understanding the multi-physical interactions appearing in modern compressors. It is shown that aerodynamic disturbances occurring downstream can lead to critical excitation of rotor blades in upstream stages due to an axially propagating acoustic wave. The paper includes the analysis of a relevant transient test and a detailed analysis of the numerical results. The study shows the capability and necessity of a full-annulus multistage simulation to understand the phenomenon.
DOA Estimation Algorithm for Reconfigurable Intelligent Surface Co-Prime Linear Array Based on Multiple Signal Classification Approach
Authors: Lan Tianyu , Huang Kaizhi , Jin Liang , Xu Xiaoming , Sun Xiaoli , Zhong Zhou
Published: February 2022

Co-prime linear arrays (CLAs) provide an additional degree of freedom (DOF) with a limited number of physical sensors, and thus help to improve the resolution of direction of arrival (DOA) estimation algorithms. However, the DOF of traditional CLA is restrained by the structure of the array, which cannot be adjusted after deployment. In this paper, we propose a DOA estimation algorithm for reconfigurable intelligent surface co-prime linear array (RIS CLA) based on the multiple signal classification approach. Specifically, an RIS CLA is first constructed on the ground of RIS antenna, by turning on/off specific elements at different times. Then, the covariance matrix of the received signal is vectorized, so as to construct a virtual difference array, whose aperture is considerably expanded. Finally, a spectral peak search on the noise subspace of the received signal of the difference array is conducted to obtain the DOA estimation result. Simulations verify the improvement of the proposed algorithm in terms of DOF and resolution. To be specific, the DOF provided by RIS CLA outnumbers that of CLA by more than 30%, and the resolution of the proposed DOA estimation algorithm is effectively improved, with its accuracy increased up to 70% under the low signal-noise-ratio (SNR) scenario, compared with existing algorithms.
Application and Investigation of Multimedia Design Principles in Augmented Reality Learning Environments
Authors: Krüger Jule M. , Bodemer Daniel
Published: February 2022

Digital media have changed the way educational instructions are designed. Learning environments addressing different presentation modes, sensory modalities and realities have evolved, with augmented reality (AR) as one of the latest developments in which multiple aspects of all three dimensions can be united. Multimedia learning principles can generally be applied to AR scenarios that combine physical environments and virtual elements, but their AR-specific effectiveness is unclear so far. In the current paper, we describe two studies examining AR-specific occurrences of two basic multimedia learning principles: (1) the spatial contiguity principle with visual learning material, leveraging AR-specific spatiality potentials, and (2) the coherence principle with audiovisual learning material, leveraging AR-specific contextuality potentials. Both studies use video-based implementations of AR experiences combining textual and pictorial representation modes as well as virtual and physical visuals. We examine the effects of integrated and separated visual presentations of virtual and physical elements (study one, N = 80) in addition to the effects of the omission of or the addition of matching or non-matching sounds (study two, N = 130) on cognitive load, task load and knowledge. We find only few significant effects and interesting descriptive results. We discuss the results and the implementations based on theory and make suggestions for future research.
Imported Dengue Case Numbers and Local Climatic Patterns Are Associated with Dengue Virus Transmission in Florida, USA
Authors: Stephenson Caroline , Coker Eric , Wisely Samantha , Liang Song , Dinglasan Rhoel R. , Lednicky John A.
Published: February 2022

Aedes aegypti mosquitoes are the main vector of dengue viruses globally and are present throughout much of the state of Florida (FL) in the United States of America. However, local transmission of dengue viruses in FL has mainly occurred in the southernmost counties; specifically Monroe and Miami-Dade counties. To get a better understanding of the ecologic risk factors for dengue fever incidence throughout FL, we collected and analyzed numerous environmental factors that have previously been connected to local dengue cases in disease-endemic regions. We analyzed these factors for each county-year in FL, between 2009–2019, using negative binomial regression. Monthly minimum temperature of 17.5–20.8 °C, an average temperature of 26.1–26.7 °C, a maximum temperature of 33.6–34.7 °C, rainfall between 11.4–12.7 cm, and increasing numbers of imported dengue cases were associated with the highest risk of dengue incidence per county-year. To our knowledge, we have developed the first predictive model for dengue fever incidence in FL counties and our findings provide critical information about weather conditions that could increase the risk for dengue outbreaks as well as the important contribution of imported dengue cases to local establishment of the virus in Ae. aegypti populations.
Systematic Studies on the Antioxidant Capacity and Volatile Compound Profile of Yellow Mealworm Larvae (T. molitor L.) under Different Drying Regimes
Authors: Keil Claudia , Grebenteuch Sandra , Kröncke Nina , Kulow Fenja , Pfeif Sebastian , Kanzler Clemens , Rohn Sascha , Boeck Georg , Benning Rainer , Haase Hajo
Published: February 2022

The yellow mealworm (Tenebrio molitor L., Coleoptera: Tenebrionidae) is an edible insect and due to its ubiquitous occurrence and the frequency of consumption, a promising candidate for the cultivation and production on an industrial scale. Moreover, it is the first insect to be approved by EFSA 2021 following the Novel Food Regulation. Industrial production of mealworms necessitates optimized processing techniques, where drying as the first postharvest procedure is of utmost importance for the quality of the final product. The focus of the present study was to analyse the chemical composition, antioxidant capacity, volatile compound profile and colouring of mealworm larvae dried in various regimes (freeze-drying, microwave drying, infrared drying, rack-oven drying and high-frequency drying). Proximate composition and fatty acid profile were similar for all dried larvae. Freeze dried larvae were predominantly marked by lipid oxidation with significantly higher peroxide values, secondary/tertiary oxidation products in the headspace GC-MS profiles and lower antioxidant capacity. High-temperature treatment in the rack oven—and to some extent also infrared or microwave drying—led to mealworm larvae darkening and the appearance of volatile Maillard secondary products such as 2-methylpropanoic acid, 2-/3-methylbutanoic acid and alkylpyrazines. High-frequency drying as a new emerging technology in insect processing was the most cost-effective method with energy costs of solely 0.09 Є/kg T. molitor L. leading to final larval material characterized by both lipid oxidation and nonenzymatic Maillard-browning.