bluuebunny/crossref_metadata_2025 huggingface dataset:
RAD50 Loss of Function Variants in the Zinc Hook Domain Associated with Higher Risk of Familial Esophageal Squamous Cell Carcinoma
Authors: Ko Josephine Mun Yee , Lam Shiu Yeung , Ning Lvwen , Chai Annie Wai Yeeng , Lei Lisa Chan , Choi Sheyne Sta Ana , Wong Carissa Wing Yan , Lung Maria Li
Published: September 2021

Unbiased whole-exome sequencing approaches in familial esophageal squamous cell carcinoma (ESCC) initially prioritized RAD50 as a candidate cancer predisposition gene. The combined study with 3289 Henan individuals from Northern China identified two pathogenic RAD50 protein truncation variants, p.Q672X and a recurrent p.K722fs variant at the zinc hook domain significantly conferring increased familial ESCC risk. Effects of ~10-fold higher familial ESCC risk were observed, when compared to East Asians from the gnomAD database. Functional characterization suggested that the RAD50Q672X mutation contributes a dominant-negative effect in DNA repair of double-stranded breaks. Overexpression of the RAD50Q672X and RAD50L1264F missense mutation also sensitized cell death upon replication stress stimuli induced by formaldehyde treatment and the CHK1 inhibitor, AZD7762. Our study suggested the novel insight of the potential for synthetic lethal therapeutic options for RAD50Q672X and the East-Asian-specific RAD50L1264F variants and CHK1 inhibitors. Our study also suggested the association of RAD50 LOF variants in the zinc hook domain with a higher risk of familial ESCC in Chinese.
The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis
Authors: Asif Paris Jabeen , Longobardi Ciro , Hahne Michael , Medema Jan Paul
Published: September 2021

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.
Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled
Authors: Sionov Ronit Vogt
Published: September 2021

Neutrophils are the most abundant immune cell in the circulation of human and act as gatekeepers to discard foreign elements that have entered the body. They are essential in initiating immune responses for eliminating invaders, such as microorganisms and alien particles, as well as to act as immune surveyors of cancer cells, especially during the initial stages of carcinogenesis and for eliminating single metastatic cells in the circulation and in the premetastatic organs. Since neutrophils can secrete a whole range of factors stored in their many granules as well as produce reactive oxygen and nitrogen species upon stimulation, neutrophils may directly or indirectly affect carcinogenesis in both the positive and negative directions. An intricate crosstalk between tumor cells, neutrophils, other immune cells and stromal cells in the microenvironment modulates neutrophil function resulting in both anti- and pro-tumor activities. Both the anti-tumor and pro-tumor activities require chemoattraction towards the tumor cells, neutrophil activation and ROS production. Divergence is seen in other neutrophil properties, including differential secretory repertoire and membrane receptor display. Many of the direct effects of neutrophils on tumor growth and metastases are dependent on tight neutrophil–tumor cell interactions. Among them, the neutrophil Mac-1 interaction with tumor ICAM-1 and the neutrophil L-selectin interaction with tumor-cell sialomucins were found to be involved in the neutrophil-mediated capturing of circulating tumor cells resulting in increased metastatic seeding. On the other hand, the anti-tumor function of neutrophils was found to rely on the interaction between tumor-surface-expressed receptor for advanced glycation end products (RAGE) and Cathepsin G expressed on the neutrophil surface. Intriguingly, these two molecules are also involved in the promotion of tumor growth and metastases. RAGE is upregulated during early inflammation-induced carcinogenesis and was found to be important for sustaining tumor growth and homing at metastatic sites. Cathepsin G was found to be essential for neutrophil-supported lung colonization of cancer cells. These data level up the complexity of the dual role of neutrophils in cancer.
Presence and Biomass Information Extraction from Highly Uncertain Data of an Experimental Low-Range Insect Radar Setup
Authors: Noskov Alexey , Achilles Sebastian , Bendix Jörg
Published: September 2021

Systematic, practicable, and global solutions are required for insect monitoring to address species decline and pest management concerns. Compact frequency-modulated continuous-wave (FMCW) radar can facilitate these processes. In this work, we evaluate a 60 GHz low-range FMCW radar device for its applicability to insect monitoring. Initial tests showed that radar parameters should be carefully selected. We defined optimal radar configuration during the first experiment and developed a methodology for individual target observation. In the second experiment, we tried various individual-insect targets, including small ones. The third experiment was devoted to mass-insect-target detection. All experiments were intentionally conducted in very uncertain conditions to make them closer to a real field situation. A novel parameter, the Sum of Sequential Absolute Magnitude Differences (SSAMD), has been proposed for uncertainty reduction and noisy data processing. SSAMD enables insect target presence detection and biomass estimation. We have defined ranges of SSAMD for distinguishing noise, insects, and other larger targets (e.g., bats, birds, or other larger objects). We have provided evidence of the high correlation between insect numbers and the average of SSAMD values proving the biomass estimation possibility. This work confirms that such radar devices can be used for insect monitoring. We plan to use the evaluated system assembled with a light trap for real fieldwork in the future.
Concurrent Butterfly, Bat and Small Mammal Monitoring Programmes Using Citizen Science in Catalonia (NE Spain): A Historical Review and Future Directions
Authors: Torre Ignasi , López-Baucells Adrià , Stefanescu Constantí , Freixas Lídia , Flaquer Carles , Bartrina Carme , Coronado Alba , López-Bosch David , Mas Maria , Míguez Sílvia , Muñoz Joaquim , Páramo Ferran , Puig-Montserrat Xavier , Tuneu-Corral Carme , Ubach Andreu , Arrizabalaga Antoni
Published: September 2021

The Biodiversity and Bioindicators research group (BiBIO), based at the Natural Sciences Museum of Granollers, has coordinated four long-term faunal monitoring programmes based on citizen science over more than two decades in Catalonia (NE Spain). We summarize the historical progress of these programmes, describing their main conservation outputs, the challenges overcome, and future directions. The Catalan Butterfly Monitoring Scheme (CBMS) consists of a network of nearly 200 recording sites where butterfly populations have been monitored through visual censuses along transects for nearly three decades. This programme provides accurate temporal and spatial changes in the abundance of butterflies and relates them to different environmental factors (e.g., habitat and weather conditions). The Bat Monitoring Programme has progressively evolved to include passive acoustic monitoring protocols, as well as bat box-, underground- and river-bat surveys, and community ecological indices have been developed to monitor bat responses at assemblage level to both landscape and climatic changes. The Monitoring of common small mammals in Spain (SEMICE), a common small mammal monitoring programme with almost 80 active live-trapping stations, provides information to estimate population trends and has underlined the relevance of small mammals as both prey (of several predators) and predators (of insect forest pests). The Dormouse Monitoring Programme represents the first monitoring programme in Europe using specific nest boxes for the edible dormouse, providing information about biological and demographic data of the species at the southern limit of its distribution range. The combination and complementarity of these monitoring programmes provide crucial data to land managers to improve the understanding of conservation needs and develop efficient protection laws.
Comparisons on Different Innovative Cascode GaN HEMT E-Mode Power Modules and Their Efficiencies on the Flyback Converter
Authors: Wu Chih-Chiang , Liu Ching-Yao , Anand Sandeep , Chieng Wei-Hua , Chang Edward-Yi , Sarkar Arnab
Published: September 2021

The conventional cascode structure for driving depletion-mode (D-mode) gallium nitride (GaN) high electron mobility transistors (HEMTs) raises reliability concerns. This is because of the possibility of the gate to source voltage of the GaN HEMT surging to a negative voltage during the turn off transition. The existing solutions for this problem in the literature produce additional drawbacks such as reducing the switching frequency or introducing many additional components. These drawbacks may outweigh the advantages of using a GaN HEMT over its silicon (Si) alternative. This paper proposes two innovative gate drive circuits for D-mode GaN HEMTs—namely the GaN-switching based cascode GaN HEMT and the modified GaN-switching based cascode GaN HEMT. In these schemes, the Si MOSFET in series with the D-mode GaN HEMT is always turned on during regular operation. The GaN HEMT is then switched on and off by using a charge pump based circuit and a conventional gate driver. Since the GaN HEMT is driven independently, the highly negative gate-to-source voltage surge during turn off is avoided, and in addition, high switching frequency operation is made possible. Only two diodes and one capacitor are used in each of the schemes. The application of the proposed circuits is experimentally demonstrated in a high voltage flyback converter, where more than 96% efficiency is obtained for 60 W output load.
Experimental Investigation on Flow Boiling Heat Transfer and Pressure Drop of a Low-GWP Refrigerant R1234ze(E) in a Horizontal Minichannel
Authors: Xu Yu , Yan Zihao , Li Ling
Published: September 2021

To protect the environment, a new low-GWP refrigerant R1234ze(E) was created to substitute R134a. However, its flow boiling performances have not received sufficient attention so far, which hinders its popularization to some extent. In view of this, an experimental investigation was carried out in a 1.88 mm horizontal circular minichannel. The saturation pressures were maintained at 0.6 and 0.7 MPa, accompanied by mass flux within 540–870 kg/m2 s and heat flux within 25–65 kW/m2. For nucleate boiling, a larger heat flux brings about a larger heat transfer coefficient (HTC), while for convective boiling, the mass flux and vapor quality appear to take the lead role. The threshold vapor quality of different heat transfer mechanisms is around 0.4. Additionally, larger saturation pressure results in large HTC. As for the frictional pressure drop (FPD), it is positively influenced by mass flux and vapor quality, while negatively affected by saturation pressure, and the influence of heat flux is negligible. Furthermore, with the measured data, several existing correlations are compared. The results indicate that the correlations of Saitoh et al. (2007) and Müller-Steinhagen and Heck (1986) perform best on flow boiling HTC and FPD with mean absolute deviations of 5.4% and 10.9%.
Possibilities of Upgrading Warsaw Existing Residential Area to Status of Positive Energy Districts
Authors: Jędrzejuk Hanna , Chwieduk Dorota
Published: September 2021

This paper analyses possibilities of refurbishment of Warsaw’s residential buildings towards standards of the Positive Energy District. The annual final energy consumption in the city in 2019 for the district heating was 8668 GWh, gas (pipelines) was 5300 GWh, electricity from the grid was 7500 GWh, while the emission of the carbon dioxide was 5.62 × 109 kg. The city consists of 18 districts, which are heterogeneous in terms of typology and structure of buildings. The great variety of buildings can be seen, for example, by the annual final energy demand for space heating and hot water preparation per unit of room area. This annual index ranges from over 400 kWh/m2 in historic buildings to 60 kWh/m2 in modern buildings. A reduction in the consumption of non-renewable energy sources and carbon dioxide emissions can be achieved by improving the energy standard of residential buildings and by using renewable energy sources: solar energy, geothermal energy and biogas. The potential barriers for achieving the status of a positive energy district, for example, problems connected with ownership, financing new investments and refurbishment and legal boundaries, have been identified. Moreover, changing the existing electrical grid and district heating systems in urban areas in Warsaw requires comprehensive modernization of practically the entire city’s infrastructure.
Impact of Quadrature Booster on Power-System State Estimation in Polar Coordinates
Authors: Okon Tomasz , Wilkosz Kazimierz
Published: September 2021

The paper concerns the estimation of the state of a power system in which there is a phase shifter called a quadrature booster. The aim of the paper is a comparative analysis of two different cases including the quadrature booster in the state estimation. In the first case, the quadrature booster is represented by a model consisting of two real voltage sources, one in series with a power line and the other in a shunt branch. In the second case, in the power system model, the real branch with the quadrature booster is represented as off at the end where the considered quadrature booster is actually installed. The state estimation is assumed to be carried out in the polar coordinate system. The properties of the state estimation are characterized by: the number of iterations in the calculation process, the index of conditioning of the matrix of coefficients in the equations to be solved (cond(G)), and ratio Je/Jm, which is a measure of the accuracy of the estimation. Using IEEE 14-bus test system, investigations are carried out in such a way as to cover the entire state space of the power system as possible. In the investigations, Monte Carlo experiments are carried out for each of the considered cases of the state estimation. Each of these cases is also analyzed from the point of view of the assumed definition of the state estimation. Investigations show that in the first of the previously described cases, the state estimation is more accurate, but there are more iterations in the calculations and worse conditioning of the estimation process. The comparative analysis also shows that, the accuracy of the results obtained in each of the considered cases is practically independent of the coordinate system in which the estimation calculations are performed. Taking into account the number of iterations in the estimation process and index cond(G), it can be concluded that the implementation of each of the above-mentioned estimation cases in the rectangular coordinate system is more reasonable.
The Environmental Aspect in the Concept of Corporate Social Responsibility in the Energy Industry and Sustainable Development of the Economy
Authors: Huk Katarzyna , Kurowski Mateusz
Published: September 2021

Sustainable development is now an important direction for the further development of all economies in the world. It is important to balance economic development with the impact on the environment and our planet. Another direction in the development of management sciences is the emergence of the concept of Corporate Social Responsibility, which considers this impact in three key aspects—economic, environmental and social—in terms of microeconomics. This concept gives companies specific guidelines and tools that minimize their negative impact on the environment. Reducing the negative impact of companies influences the environment and this is what is mainly associated with them. However, companies should also pay attention to internal consistency and caring for employees. Company practices such as the exploitation of people, including children, and injustice in the workplace are some of the factors that can be observed in less developed countries. The article focuses on the presentation of the environmental aspect in the context of the concept of corporate social responsibility. We analyzed individual sectors of the economy in terms of the environmental aspect, with particular emphasis on the energy industry. The study is based on a statistical analysis taking into account data from 1718 companies from all over the world. The aim of the article is to present the environmental aspect in the context of corporate social responsibility in the energy industry as a direction for sustainable development of the economy. The article is based on the analysis of the literature and databases presenting CSR, which was created on the basis of questionnaire research. The article shows which regions of the world are worse and which are better in terms of the environmental aspects of CSR. Conclusions on the main CSR guidelines for the environment are also presented. We analyzed factors such as environmental routines, policies and targets, implementation of environmental management systems, ISO 14001/EMAS certification, environmental reporting, environmental requirements inside the supply chain, the trend of GHG emissions and the trend of energy consumption for their environmental impact. The analysis was carried out on the basis of given regions of the world and individual sectors of the economy, especially the energy industry.
A Comparison of Methods for Determining Forest Composition from High-Spatial-Resolution Remotely Sensed Imagery
Authors: Fraser Benjamin T. , Congalton Russell G.
Published: September 2021

Remotely sensed imagery has been used to support forest ecology and management for decades. In modern times, the propagation of high-spatial-resolution image analysis techniques and automated workflows have further strengthened this synergy, leading to the inquiry into more complex, local-scale, ecosystem characteristics. To appropriately inform decisions in forestry ecology and management, the most reliable and efficient methods should be adopted. For this reason, our research compares visual interpretation to digital (automated) processing for forest plot composition and individual tree identification. During this investigation, we qualitatively and quantitatively evaluated the process of classifying species groups within complex, mixed-species forests in New England. This analysis included a comparison of three high-resolution remotely sensed imagery sources: Google Earth, National Agriculture Imagery Program (NAIP) imagery, and unmanned aerial system (UAS) imagery. We discovered that, although the level of detail afforded by the UAS imagery spatial resolution (3.02 cm average pixel size) improved the visual interpretation results (7.87–9.59%), the highest thematic accuracy was still only 54.44% for the generalized composition groups. Our qualitative analysis of the uncertainty for visually interpreting different composition classes revealed the persistence of mislabeled hardwood compositions (including an early successional class) and an inability to consistently differentiate between ‘pure’ and ‘mixed’ stands. The results of digitally classifying the same forest compositions produced a higher level of accuracy for both detecting individual trees (93.9%) and labeling them (59.62–70.48%) using machine learning algorithms including classification and regression trees, random forest, and support vector machines. These results indicate that digital, automated, classification produced an increase in overall accuracy of 16.04% over visual interpretation for generalized forest composition classes. Other studies, which incorporate multitemporal, multispectral, or data fusion approaches provide evidence for further widening this gap. Further refinement of the methods for individual tree detection, delineation, and classification should be developed for structurally and compositionally complex forests to supplement the critical deficiency in local-scale forest information around the world.
Wireless Internet, Multimedia, and Artificial Intelligence: New Applications and Infrastructures
Authors: Saia Roberto , Carta Salvatore , Bergmann Olaf
Published: September 2021

The potential offered by the Internet, combined with the enormous number of connectable devices, offers benefits in many areas of our modern societies, both public and private. The possibility of making heterogeneous devices communicate with each other through the Internet has given rise to a constantly growing scenario, which was unthinkable not long ago. This unstoppable growth takes place thanks to the continuous availability of increasingly sophisticated device features, an ever-increasing bandwidth and reliability of the connections, and the ever-lower consumption of the devices, which grants them long autonomy. This scenario of exponential growth also involves other sectors such as, for example, that of Artificial Intelligence (AI), which offers us increasingly sophisticated approaches that can be synergistically combined with wireless devices and the Internet in order to create powerful applications for everyday life. Precisely for the aforementioned reasons, the community of researchers, year by year, dedicates more time and resources in this direction. It should be observed that this happens in an atypical way concerning the other research fields, and this is because the achieved progress and the developed applications have practical applications in numerous and different domains.
Lactose Residual Content in PDO Cheeses: Novel Inclusions for Consumers with Lactose Intolerance
Authors: Facioni Maria Sole , Dominici Simona , Marescotti Francesca , Covucci Rosanna , Taglieri Isabella , Venturi Francesca , Zinnai Angela
Published: September 2021

Lactose intolerance (LI) is the symptomatic condition that characterizes subjects unable to digest lactose. The main solution consists of reducing or eliminating lactose from one’s diet, and so dairy products, particularly cheeses, are often the first foods excluded. The purpose of this study is to contribute to this topic by creating an updated list of naturally lactose-free (NLF) cheeses. Twenty-five PDO (Protected Designation of Origin) cheeses were selected and analyzed to determine their lactose content. At the same time, interviews with the PDO quality control consortia were carried out to understand which parameters are involved in lactose reduction, based on the cheeses’ product specifications. The analytical techniques used here for lactose determination are the most sensitive (HPAEC-PAD and LC/MS-MS), given their low limit of quantification (LOQ) of less than 10 mg/kg. The majority of selected PDO cheeses resulted in a lactose content less than the LOQ. Because of the high variability allowed in PDO cheeses’ operative conditions, it would be better to case-by-case examine the PDO cheese specification and declare the product as NLF after repeated analysis. The results of the chemical determination of this research allowed to draw up a very useful list of PDO cheeses for both consumers and nutritionists that could be identified as NLF.
Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)
Authors: Schierbaum Luca M. , Schneider Sophia , Herms Stefan , Sivalingam Sugirthan , Fabian Julia , Reutter Heiko , Weber Stefanie , Merz Waltraut M. , Tkaczyk Marcin , Miklaszewska Monika , Sikora Przemyslaw , Szmigielska Agnieszka , Krzemien Grazyna , Zachwieja Katarzyna , Szczepanska Maria , Taranta-Janusz Katarzyna , Kroll Pawel , Polok Marcin , Zaniew Marcin , Hilger Alina C.
Published: September 2021

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.
Genetic Diversity and Population Structure of Cowpea [Vigna unguiculata (L.) Walp.] Germplasm Collected from Togo Based on DArT Markers
Authors: Gbedevi Kodjo M. , Boukar Ousmane , Ishikawa Haruki , Abe Ayodeji , Ongom Patrick O. , Unachukwu Nnanna , Rabbi Ismail , Fatokun Christian
Published: September 2021

Crop genetic diversity is a sine qua non for continuous progress in the development of improved varieties, hence the need for germplasm collection, conservation and characterization. Over the years, cowpea has contributed immensely to the nutrition and economic life of the people in Togo. However, the bulk of varieties grown by farmers are landraces due to the absence of any serious genetic improvement activity on cowpea in the country. In this study, the genetic diversity and population structure of 255 cowpea accessions collected from five administrative regions and the agricultural research institute of Togo were assessed using 4600 informative diversity array technology (DArT) markers. Among the regions, the polymorphic information content (PIC) ranged from 0.19 to 0.27 with a mean value of 0.25. The expected heterozygosity (He) varied from 0.22 to 0.34 with a mean value of 0.31, while the observed heterozygosity (Ho) varied from 0.03 to 0.07 with an average of 0.05. The average inbreeding coefficient (FIS) varied from 0.78 to 0.89 with a mean value of 0.83, suggesting that most of the accessions are inbred. Cluster analysis and population structure identified four groups with each comprising accessions from the six different sources. Weak to moderate differentiation was observed among the populations with a genetic differentiation index varying from 0.014 to 0.117. Variation was highest (78%) among accessions within populations and lowest between populations (7%). These results revealed a moderate level of diversity among the Togo cowpea germplasm. The findings of this study constitute a foundation for genetic improvement of cowpea in Togo.
Improved Large-Scale Homology Search by Two-Step Seed Search Using Multiple Reduced Amino Acid Alphabets
Authors: Takabatake Kazuki , Izawa Kazuki , Akikawa Motohiro , Yanagisawa Keisuke , Ohue Masahito , Akiyama Yutaka
Published: September 2021

Metagenomic analysis, a technique used to comprehensively analyze microorganisms present in the environment, requires performing high-precision homology searches on large amounts of sequencing data, the size of which has increased dramatically with the development of next-generation sequencing. NCBI BLAST is the most widely used software for performing homology searches, but its speed is insufficient for the throughput of current DNA sequencers. In this paper, we propose a new, high-performance homology search algorithm that employs a two-step seed search strategy using multiple reduced amino acid alphabets to identify highly similar subsequences. Additionally, we evaluated the validity of the proposed method against several existing tools. Our method was faster than any other existing program for ≤120,000 queries, while DIAMOND, an existing tool, was the fastest method for >120,000 queries.
Effect of Triweekly Interdental Brushing on Bleeding Reduction in Adults: A Six-Month Retrospective Study
Authors: Lee Jae-Young , Kim Seon-Jip , Lee Hyo-Jin , Cho Hyun-Jae
Published: September 2021

This study assessed the effect of triweekly interdental brushing for a period of 6 months using the bleeding on full-mouth interdental brushing (BOFIB) index. All participants answered questionnaires and were instructed to clean all interdental areas using an interdental brush at least every second day. A dentist assessed the BOFIB index of 28 participants at baseline and at 3- and 6-month follow-up visits. We stratified the participants into three groups: IB-NN, those who used the interdental brush less than three times per week both before and after this program; IB-NY, those who used the interdental brush less than three times per week before the program but at least three times per week after the program; and IB-YY, those who used it at least three times per week both before and after the program. Owing to the weekly number of interdental brushings, the IB-YY and the other two groups showed a significant difference at baseline. At the 6-month follow-up, the weekly number of interdental brushings led to a significant difference between the IB-NN and the other two groups. The BOFIB index was lower among the compliant participants than among the noncompliant participants after 3 and 6 months of triweekly interdental brushing.
Under-5 Mortality and Its Associated Factors in Northern Nigeria: Evidence from 22,455 Singleton Live Births (2013–2018)
Authors: Ezeh Osita K. , Ogbo Felix A. , Odumegwu Anastasia O. , Oforkansi Gladys H. , Abada Uchechukwu D. , Goson Piwuna C. , Ishaya Tanko , Agho Kingsley E.
Published: September 2021

The northern geopolitical zones (NGZs) continue to report the highest under-5 mortality rates (U5MRs) among Nigeria’s six geopolitical zones. This study was designed to identify factors related to under-5 mortality (U5M) in the NGZs. The NGZ populations extracted from the 2018 Nigeria Demographic and Health Survey were explored to assess the factors associated with U5M using logistic regression, generalised linear latent, and mixed models. Between 2013 and 2018, the northwest geopolitical zone reported the highest U5MR (179 deaths per 1000 live births; 95% confidence interval [CI]: 163–194). The adjusted model showed that geopolitical zone, poor household, paternal occupation, perceived children’s body size at birth, caesarean delivery, and mothers and fathers’ education were highly associated with increased odds of U5M. Other significant factors that influenced U5M included children of fourth or higher birth order with shorter interval ≤ 2 years (adjusted odds ratio [aOR] = 1.68; CI: 1.42–1.90) and mothers who did not use contraceptives (aOR = 1.41, CI: 1.13–1.70). Interventions are needed and should primarily spotlight children residing in low-socioeconomic households. Educating mothers on the benefits of contraceptive use, child spacing, timely and safe caesarean delivery and adequate care for small-sized babies may also reduce U5M in Nigeria, particularly in the NGZs.
Method for Determining Regional Reference Values of Metal Content in Biological Substrates and Their Intake into the Body via Drinking Water
Authors: Tunakova Yulia , Shagidullin Artur , Valiev Vsevolod , Novikova Svetlana , Faizullin Rashat
Published: September 2021

Natural and manmade flows of matter form complex metal associations in the body of residents living in certain territories, which leads to functional disorders in their bodies and the depletion of adaptive reserves. It is possible to assess the distribution of metals in the body only taking into account its biogeochemical localization. The question arises about the methodological approach to the determination of regional reference values of the concentrations of metals in biosubstrates of residents of different territories, to which this study was devoted. A designed and trained neural network was used, reflecting the relationship between the concentrations of metals in consumed drinking water and biosubstrates of the body, taking into account the physiological characteristics of the tested group of children and adolescents, based on the regional reference values obtained. Neural network regression methods allowed the calculation of nonlinear dependences of indicators of the state of the internal environment of an organism with external factors, and localized reference values determined in such calculations the indicators of the base state, being guided by the intensity of external factors, which should be assessed. The results of this study are intended for patient-oriented diagnosis and the treatment of eco-conditioned microelementosis in individual locations.
A Dynamic Analysis of Air Pollution: Implications of Economic Growth and Renewable Energy Consumption
Authors: Xie Jia Yu , Suh Dong Hee , Joo Sung-Kwan
Published: September 2021

This paper examines how economic growth and renewable energy consumption are associated with air pollution using a dynamic panel approach. Focusing on several major air pollutants, namely, particulate matter, sulfur dioxide, nitrogen oxide, and carbon monoxide, this paper tests the environmental Kuznets hypothesis and determines whether the use of renewable energy sources contributes to a reduction in air pollution. Data from a balanced panel of 145 countries for the period between 2000 and 2014 was used for the estimation of the dynamic panel model. The results of the dynamic panel model showed inverted U-shaped curves for the relationship between economic development and particulate matter and sulfur dioxide emissions. The results also revealed that increasing renewable energy consumption contributes to an improvement in air quality. Moreover, it was found that urbanization tends to decrease sulfur dioxide and nitrogen oxide emissions, while trade openness reduces particulate matter and carbon monoxide emissions but increases sulfur dioxide emissions.
In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts
Authors: Ramírez-Villalobos Jesica M. , Romo-Sáenz César I. , Morán-Santibañez Karla S. , Tamez-Guerra Patricia , Quintanilla-Licea Ramiro , Orozco-Flores Alonso A. , Romero-Arguelles Ricardo , Tamez-Guerra Reyes , Rodríguez-Padilla Cristina , Gomez-Flores Ricardo
Published: September 2021

Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.
Biomolecular Markers of Recurrent Implantation Failure—A Review
Authors: Mrozikiewicz Aleksandra E. , Ożarowski Marcin , Jędrzejczak Piotr
Published: September 2021

Currently, infertility affects 8–12% of reproductive age couples worldwide, a problem that also affects women suffering from recurrent implantation failure (RIF). RIF is a complex condition resulting from many physiological and molecular mechanisms involving dynamic endometrium–blastocyst interaction. The most important are the endometrial receptivity process, decidualization, trophoblast invasion, and blastocyst nesting. Although the exact multifactorial pathogenesis of RIF remains unclear, many studies have suggested the association between hormone level imbalance, disturbances of angiogenic and immunomodulatory factors, certain genetic polymorphisms, and occurrence of RIF. These studies were performed in quite small groups. Additionally, the results are inconsistent between ethnicities. The present review briefly summarizes the importance of factors involved in RIF development that could also serve as diagnostic determinants. Moreover, our review could constitute part of a new platform for discovery of novel diagnostic and therapeutic solutions for RIF.
Serum Albumin: A Multifaced Enzyme
Authors: De Simone Giovanna , di Masi Alessandra , Ascenzi Paolo
Published: September 2021

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.
Design and Engineering of “Green” Nanoemulsions for Enhanced Topical Delivery of Bakuchiol Achieved in a Sustainable Manner: A Novel Eco-Friendly Approach to Bioretinol
Authors: Lewińska Agnieszka , Domżał-Kędzia Marta , Maciejczyk Ewa , Łukaszewicz Marcin , Bazylińska Urszula
Published: September 2021

In the present work, we establish novel “environmentally-friendly” oil-in-water nanoemulsions to enhance the transdermal delivery of bakuchiol, the so-called “bioretinol” obtained from powdered Psoralea corylifolia seeds via a sustainable process, i.e., using a supercritical fluid extraction approach with pure carbon dioxide (SC-CO2). According to Green Chemistry principles, five novel formulations were stabilized by “green” hybrid ionic surfactants such as coco-betaine—surfactin molecules obtained from coconut and fermented rapeseed meal. Preliminary optimization studies involving three dispersion stability tests, i.e., centrifugation, heating, and cooling cycles, indicated the most promising candidates for further physicochemical analysis. Finally, nanoemulsion colloidal characterization provided by scattering (dynamic and electrophoretic light scattering as well as backscattering), microscopic (transmission electron and confocal laser scanning microscopy), and spectroscopic (UV–Vis spectroscopy) methods revealed the most stable nanocarrier for transdermal biological investigation. In vitro, topical experiments provided on human skin cell line HaCaT keratinocytes and normal dermal NHDF fibroblasts indicated high cell viability upon treatment of the tested formulation with a final 0.02–0.2 mg/mL bakuchiol concentration. This excellent biocompatibility was confirmed by ex vivo and in vivo tests on animal and human skin tissue. The improved permeability and antiaging potential of the bakuchiol-encapsulated rich extract were observed, indicating that the obtained ecological nanoemulsions are competitive with commercial retinol formulations.
Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model
Authors: Paradiso Francesca , Serpelloni Stefano , Francis Lewis W. , Taraballi Francesca
Published: September 2021

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform’s level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements.
Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms
Authors: Alsherbiny Muhammad A. , Bhuyan Deep J. , Low Mitchell N. , Chang Dennis , Li Chun Guang
Published: September 2021

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of CBD and its synergistic combination with SN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.
Actions and Roles of FSH in Germinative Cells
Authors: Recchia Kaiana , Jorge Amanda Soares , Pessôa Laís Vicari de Figueiredo , Botigelli Ramon Cesar , Zugaib Vanessa Cristiane , de Souza Aline Fernanda , Martins Daniele dos Santos , Ambrósio Carlos Eduardo , Bressan Fabiana Fernandes , Pieri Naira Caroline Godoy
Published: September 2021

Follicle stimulating hormone (FSH) is produced by the pituitary gland in a coordinated hypothalamic–pituitary–gonadal (HPG) axis event, plays important roles in reproduction and germ cell development during different phases of reproductive development (fetal, neonatal, puberty, and adult life), and is consequently essential for fertility. FSH is a heterodimeric glycoprotein hormone of two dissociable subunits, α and β. The FSH β-subunit (FSHβ) function starts upon coupling to its specific receptor: follicle-stimulating hormone receptor (FSHR). FSHRs are localized mainly on the surface of target cells on the testis and ovary (granulosa and Sertoli cells) and have recently been found in testicular stem cells and extra-gonadal tissue. Several reproduction disorders are associated with absent or low FSH secretion, with mutation of the FSH β-subunit or the FSH receptor, and/or its signaling pathways. However, the influence of FSH on germ cells is still poorly understood; some studies have suggested that this hormone also plays a determinant role in the self-renewal of germinative cells and acts to increase undifferentiated spermatogonia proliferation. In addition, in vitro, together with other factors, it assists the process of differentiation of primordial germ cells (PGCLCs) into gametes (oocyte-like and SSCLCs). In this review, we describe relevant research on the influence of FSH on spermatogenesis and folliculogenesis, mainly in the germ cell of humans and other species. The possible roles of FSH in germ cell generation in vitro are also presented.