bluuebunny/crossref_metadata_2025 huggingface dataset:
Employing Bibliometric Analysis to Identify the Current State of the Art and Future Prospects of Electric Vehicles
Authors: Ullah Irfan , Safdar Muhammad , Zheng Jianfeng , Severino Alessandro , Jamal Arshad
Published: March 2023

Electric vehicles (EVs) are rapidly becoming a sustainable and viable mode of future transportation due to their multitude of advantages, such as reduced CO2 emissions, local air pollutants, and vehicular noise. This study aims to identify and analyze the scientific literature using bibliometric analysis to determine the main topics of authors, their sources, and the most-cited articles, countries, journals, and institutes in the literature on EVs. This bibliometric analysis included scientific work that was published from 2011 to 2022 to provide a thorough analysis of EVs, which will assist researchers and policymakers in understanding the most current global EV advancements. This analysis extracted all bibliometric information about EVs from the Scopus database, collecting 17,150 articles published between 2011 and 2022. The data were sorted for analysis by publication year, document type, author, institute, country, cited author, keyword, and keyword co-occurrence of the EVs. The VOSviewer software was employed to examine the sorted data due to its excellent analysis and visualization capabilities. We used VOSviewer to graphically represent the density, co-occurrence, trends, and linkage of the aforementioned data comprehensibly. The publishing patterns of EVs indicate that the research field is evolving, with a yearly increase in the number of publications. The analysis showed that China, the United States, and the United Kingdom are leading in EV research and large-scale applications. Furthermore, China is the leading country in terms of research institutions and authors involved in EVs. The journal Energies is the most prominent publication periodical. Keyword analysis revealed that during the past decade, EV research has concentrated on battery-management systems, energy storage, charging infrastructure, environmental concerns, etc. The bibliometric study offered pertinent details on the main themes explored concerning EVs and current technological developments.
An Analysis of Dynamic Correlations among Oil, Natural Gas and Ethanol Markets: New Evidence from the Pre- and Post-COVID-19 Crisis
Authors: Quintino Derick , Ogino Cristiane , Haq Inzamam Ul , Ferreira Paulo , Oliveira Márcia
Published: March 2023

After the economic shock caused by COVID-19, with relevant effects on both the supply and demand for energy assets, there was greater interest in understanding the relationships between key energy prices. In order to contribute to a deeper understanding of energy price relationships, this paper analyzes the dynamics between the weekly spot prices of oil, natural gas and benchmark ethanol in the US markets. The analysis period started on 23 June 2006 and ended on 10 June 2022. This study used the DMCA cross-correlation coefficient in a dynamic way, using sliding windows. Among the main results, it was found that: (i) in the post-pandemic period, oil and natural gas were not correlated, in both short- and long-term timescales; and (ii) ethanol was negatively associated with natural gas in the most recent post-pandemic period, especially in short-term scales. The results of the present study are potentially relevant for both market and public agents regarding investment diversification strategies and can aid public policies due to the understanding of the interrelationship between energy prices.
Modification Model of Glued-In Rods Splice Connection Using Statistical Analysis for Mengkulang Glulam Timber
Authors: Raja Hussin Tengku Anita , Hassan Rohana , Anshari Buan , Md Nor Azman , Sapuan S. M.
Published: March 2023

The statistical study of the glued-in rod splice connection for Mengkulang glulam timber is presented in this research. This type of connection is used in many applications, such as bridge construction and wide hall, besides becoming increasingly popular due to its cost-effectiveness and ease of installation. Using statistical analysis to evaluate the performance of glued-in rod splice connections is relatively new. Statistical analysis can assess the connection’s performance by examining the glued-in rod splice connection’s strength, stiffness, and durability. Glued-in rods have several advantages over traditional mechanical connections generally used in beam design, such as higher stiffness, more uniform stress distribution, fewer rod corrosion problems and better appearance. Due to this limitation, the standard design for glued-in rods using glulam is the estimated extrapolation for solid timber guidelines. The main objectives of this research were to develop the pull-out model and validate the effectiveness of the model equation for glued-in rods parallel (GRPS0°) and perpendicular (GRPS90°) to the grain directions using a statistical package for the social sciences (SPSS). The variables examined were the number of rods, diameter, length, spacing, the kind of glue utilised, and the number of adhesive layers. In conclusion, the model development clearly shows that most of the parameters achieved the R2 more than 80% accurate for both parallel (GRPS0°) and perpendicular (GRPS90°) to the grain directions.
Matrix-Based Method for the Analysis and Control of Networked Evolutionary Games: A Survey
Authors: Yang Xinrong , Geng Zhenping , Li Haitao
Published: March 2023

In this paper, a detailed survey is presented for the analysis and control of networked evolutionary games via the matrix method. The algebraic form of networked evolutionary games is firstly recalled. Then, some existing results on networked evolutionary games are summarized. Furthermore, several generalized forms of networked evolutionary games are reviewed, including networked evolutionary games with time delay, networked evolutionary games with bankruptcy mechanism, networked evolutionary games with time-varying networks, and random evolutionary Boolean games. The computational complexity of general networked evolutionary games is still challenging, which limits the application of the matrix method to large-scale networked evolutionary games. Future works are finally presented in the conclusion.
Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy
Authors: Elek Zsuzsanna , Losoncz Eszter , Maricza Katalin , Fülep Zoltán , Bánlaki Zsófia , Kovács-Nagy Réka , Keszler Gergely , Rónai Zsolt
Published: March 2023

COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.
Microsatellite Genome-Wide Database Development for the Commercial Blackhead Seabream (Acanthopagrus schlegelii)
Authors: Luo Xinhui , Zhang Lichun , Chen Songlin
Published: March 2023

Simple sequence repeats (SSRs), the markers with the highest polymorphism and co-dominance degrees, offer a crucial genetic research resource. Limited SSR markers in blackhead seabream have been reported. The availability of the blackhead seabream genome assembly provided the opportunity to carry out genome-wide identification for all microsatellite markers, and bioinformatic analyses open the way for developing a microsatellite genome-wide database in blackhead seabream. In this study, a total of 412,381 SSRs were identified in the 688.08 Mb genome by Krait software. Whole-genome sequences (10×) of 42 samples were aligned against the reference genome and genotyped using the HipSTR tools by comparing and counting repeat number variation across the SSR loci. A total of 156,086 SSRs with a 2–4 bp repeat were genotyped by HipSTR tools, which accounted for 55.78% of the 2–4 bp SSRs in the reference genome. High accuracy of genotyping was observed by comparing HipSTR tools and PCR amplification. A set of 109,131 loci with a number of alleles ≥ 3 and with a number of genotyped individuals ≥ 6 were reserved to constitute the polymorphic SSR database. Fifty-one polymorphic SSR loci were identified through PCR amplification. This strategy to develop polymorphic SSR markers not only obtained a large set of polymorphic SSRs but also eliminated the need for laborious experimental screening. SSR markers developed in this study may facilitate blackhead seabream research, which lays a certain foundation for further gene tagging and genetic linkage analysis, such as marker-assisted selection, genetic mapping, as well as comparative genomic analysis.
Late Mesozoic and Cenozoic Geodynamics of the Arctic Region: Implications for Abiogenic Generation of Hydrocarbons
Authors: Sorokhtin Nickolay , Lobkovsky Leopold , Semiletov Igor , Shipilov Eduard , Nikiforov Sergey , Kozlov Nikolay , Shakhova Natalia , Ananiev Roman , Alekseev Dmitry
Published: March 2023

Late Mesozoic and Cenozoic geodynamics of the Arctic region is discussed in the context of possible mechanisms which provide multistage cyclic transformations and transport of carbon through crust and mantle. Geodynamic processes control the abiogenic generation of hydrocarbons and the patterns of their localization. Possible mechanisms of abiotic hydrocarbon generation are explained in the context of carbon transport from subduction zones to rifts and serpentinization of ultramafic rocks in the rifts in the case of the Laptev Sea and Gakkel Ridge areas. The carbon of shallow crust origin migrates with encapsulated fragments of marine sediments which are consumed in the Pacific subduction zone where they become destroyed and transformed by different chemical and physical processes. The resulting C-species are involved in mantle convection flows and reach the continental rifts of the Laptev Sea and the Gakkel mid-ocean ridge. Thus, the hydrocarbons formed in the crust and in the mantle acquire signatures of abiotic origin. According to the authors, the scale of manifestation of abiogenic methanogenesis in the lower parts of the lithosphere and in the upper mantle is not so wide. Numerous small (mm and fractions of the mm) particles of exogenous matter and dispersed carbon pulled into the mantle can only form a stable crustal geochemical plume that propagates in the plane of movement of convective flows. Indirectly, the scale of manifestation of this process can be judged by the volumes of degassing of hydrocarbon and carbon dioxide gases, as well as hydrogen and its compounds in the rift systems of the earth’s crust, which are extremely insignificant. However, in the cold seas of the Eastern Arctic, massive emissions of bubble methane of mixed genesis were found. As shown in the literature, the range of variability of stable isotopes of carbon and 14C of methane in certain areas of discharge associated with rifting demonstrates values (anomalously heavy 13C, and young 14C) that can be considered as examples of presumably abiogenic origin. Our work is mostly theoretical and suggests further discussion and improvement of the mechanism of formation of abiogenic hydrocarbons and the processes of their transformation.
Potential Exposure to Respiratory and Enteric Bacterial Pathogens among Wastewater Treatment Plant Workers, South Africa
Authors: Poopedi Evida , Singh Tanusha , Gomba Annancietar
Published: March 2023

Wastewater handling has been associated with an increased risk of developing adverse health effects, including respiratory and gastrointestinal illnesses. However, there is a paucity of information in the literature, and occupational health risks are not well quantified. Grab influent samples were analysed using Illumina Miseq 16S amplicon sequencing to assess potential worker exposure to bacterial pathogens occurring in five municipal wastewater treatment plants (WWTPs). The most predominant phyla were Bacteroidota, Campilobacterota, Proteobacteria, Firmicutes, and Desulfobacterota, accounting for 85.4% of the total bacterial community. Taxonomic analysis showed a relatively low diversity of bacterial composition of the predominant genera across all WWTPs, indicating a high degree of bacterial community stability in the influent source. Pathogenic bacterial genera of human health concern included Mycobacterium, Coxiella, Escherichia/Shigella, Arcobacter, Acinetobacter, Streptococcus, Treponema, and Aeromonas. Furthermore, WHO-listed inherently resistant opportunistic bacterial genera were identified. These results suggest that WWTP workers may be occupationally exposed to several bacterial genera classified as hazardous biological agents for humans. Therefore, there is a need for comprehensive risk assessments to ascertain the actual risks and health outcomes among WWTP workers and inform effective intervention strategies to reduce worker exposure.
HIV-Related Knowledge and Practices among Asian and African Migrants Living in Australia: Results from a Cross-Sectional Survey and Qualitative Study
Authors: Vujcich Daniel , Reid Alison , Brown Graham , Durham Jo , Guy Rebecca , Hartley Lisa , Mao Limin , Mullens Amy B. , Roberts Meagan , Lobo Roanna
Published: March 2023

Australian HIV notification rates are higher for people born in Northeast Asia, Southeast Asia and sub-Saharan Africa compared to Australian-born people. The Migrant Blood-Borne Virus and Sexual Health Survey represents the first attempt to build the national evidence base regarding HIV knowledge, risk behaviors and testing among migrants in Australia. To inform survey development, preliminary qualitative research was conducted with a convenience sample of n = 23 migrants. A survey was developed with reference to the qualitative data and existing survey instruments. Non-probability sampling of adults born in Northeast Asia, Southeast Asia and sub-Saharan Africa was undertaken (n = 1489), and descriptive and bivariate analyses of data were conducted. Knowledge of pre-exposure prophylaxis was low (15.59%), and condom use at last sexual encounter was reported by 56.63% of respondents engaging in casual sex, and 51.80% of respondents reported multiple sexual partners. Less than one-third (31.33%) of respondents reported testing for any sexually transmitted infection or blood-borne virus in the previous two years and, of these, less than half (45.95%) tested for HIV. Confusion surrounding HIV testing practices was reported. These findings identify policy interventions and service improvements critically needed to reduce widening disparities regarding HIV in Australia.
Knowledge, Attitude, and Practices toward Hepatitis B Infection among Healthcare Students—A Nationwide Cross-Sectional Study in Jordan
Authors: Alaridah Nader , Joudeh Rayan M. , Al-Abdallat Haneen , Jarrar Raba’a F. , Ismail Layan , Jum’ah Mohammad , Alnajjar Zaina , Alzyoud Eman , Battah Zaina , Battah Aya , Alshami Manar , Abu-Humaidan Anas H. A.
Published: March 2023

The World Health Organization has estimated that around 66 thousand HBV infection cases are caused by needlestick injuries annually. Healthcare students should be aware of HBV transmission routes and preventive measures. This study assessed the knowledge, attitudes, and practices toward HBV among Jordanian healthcare students and its associated factors. A cross-national study was conducted from March to August 2022. The questionnaire was composed of four sections: participants’ sociodemographics, knowledge, attitudes, and practices about HBV, and 2322 participants were enrolled. The collected responses were analyzed with SPSS software (version 25 (IBM Corp., Armonk, NY, USA)) using descriptive statistics, unpaired t-tests, chi-square tests, and multivariate regression analyses. A p-value ≤ 0.05 was considered statistically significant. The results showed that 67.9% were females, 26.4% were medical students, and 35.9% were in their 3rd year. Overall, 40% of the participants held high levels of knowledge and attitudes. Further, 63.9% of participants had good practices toward HBV. Gender, year of study, encountering HBV patients, college, and having extra HBV courses were associated with high levels of KAP. This study demonstrated insufficient knowledge and attitudes toward HBV; however, the practice level toward HBV among healthcare students was promising. Therefore, public health efforts should modify the knowledge and attitude gaps to reinforce awareness and minimize the risk of infection.
24-Hour Movement Behaviours (Physical Activity, Sedentary Behaviour and Sleep) Association with Glycaemic Control and Psychosocial Outcomes in Adolescents with Type 1 Diabetes: A Systematic Review of Quantitative and Qualitative Studies
Authors: Patience Mhairi , Janssen Xanne , Kirk Alison , McCrory Stephanie , Russell Eilidh , Hodgson William , Crawford Megan
Published: March 2023

Type 1 Diabetes (T1D) is a condition requiring 24-hour management. The way in which an individual combines their 24-hour movement behaviours (24-h MBs), which is comprised of physical activity (PA), sedentary behaviour (SB), and sleep, throughout the day can have a significant impact on physical and mental health. This mixed methods systematic review aimed to investigate 24-h MBs’ relationship with glycaemic control and psychosocial outcomes in adolescents (11–18 years) with T1D. Ten databases were searched for quantitative and qualitative English language articles reporting at least one of the behaviours and their relationship with outcomes. There were no restrictions on article publication dates or study design. Articles were subjected to title and abstract screening, full text screening, data extraction and quality assessment. Data were summarised narratively, and a meta-analysis was conducted where possible. From 9922 studies, 84 were included for data extraction (quantitative (n = 76), qualitative (n = 8)). Meta-analyses revealed a significant favourable association between PA and HbA1c (−0.22 [95% CI: −0.35, −0.08; I2 = 92.7%; p = 0.001). SB had an insignificant unfavourable association with HbA1c (0.12 [95% CI: −0.06, 0.28; I2 = 86.1%; p = 0.07]) and sleep had an insignificant favourable association (−0.03 [95% CI: −0.21, 0.15; I2 = 65.9%; p = 0.34]). Importantly, no study investigated how combinations of behaviours collectively interacted and impacted on outcomes.
My Family Accounts Much for Me: How Does Work-to-Family Conflict Lead to Unethical Pro-Family Behavior
Authors: Wang Yuming , Hu Wenan , Liu Zhaopeng , Luo Jinlian
Published: March 2023

Although unethical behaviors are prevalent in the workplace, little is known about the unethical behavior aiming at benefiting one’s family (unethical pro-family behavior, UPFB). In this paper, we leverage self-determination theory to explore the association between work-to-family conflict and UPFB. Specifically, we hypothesize and corroborate a positive relationship between work-to-family conflict and UPFB, and such relationship is mediated by family motivation. Moreover, we identify two conditional factors, guilt proneness (at first stage) and ethical leadership (at second stage), in moderating the proposed relationship. In study 1 (scenario-based experiment, N = 118), we tested the causality of work-to-family conflict and intention to perform UPFB. In study 2 (field study, N = 255), we tested our hypotheses by employing a three-wave time-lagged survey design. As expected, results from two studies fully supported our predictions. Overall, we explain whether, how, and when work-to-family conflict will lead to UPFB. Implications of theory and practice are then discussed.
Digital Maturity and Its Measurement of General Practitioners: A Scoping Review
Authors: Neunaber Timo , Meister Sven
Published: March 2023

The work of general practitioners (GPs) is increasingly characterized by digitalization. Their progress in digitalization can be described by the concept of digital maturity and measured using maturity models. The aim of this scoping review is to provide an overview of the state of research on digital maturity and its measurement in primary care, specifically for GPs. The scoping review was conducted according to Arksey and O’Malley, considering the reporting scheme for PRISMA-ScR. For the literature search, we used PubMed and Google Scholar as the main sources of information. A total of 24 international, mostly Anglo-American studies, were identified. The understanding of digital maturity varied widely. In most studies, it was understood in a highly technical way and associated with the adoption of electronic medical records. More recent, but mostly unpublished, studies have attempted to capture overall digital maturity. So far, the understanding of digital maturity of GPs is still very diffuse—the research literature is still in its infancy. Future research should therefore aim to explore the dimensions of digital maturity of GPs to be able to develop a consistent and validated model for measuring digital maturity.
“The Feeling Is What Counts”: Fathers’ Perspectives on Child Risk and Protection within the Ultra-Orthodox Context
Authors: Gemara Netanel
Published: March 2023

Context is known to have substantial influence on issues pertaining to child development. Nevertheless, the field of child well-being, risk, and protection is rooted in Western modernized research and experience, often overlooking contextual dissimilarity. The present study aimed to explore risk and protection for children in a distinct context: the Ultra-Orthodox community, which is an insular and religiously close-knit society. Fifteen in-depth interviews with Ultra-Orthodox fathers dealing with issues of child risk and protection were conducted and thematically analyzed. Analysis of the findings revealed two major areas that fathers viewed as posing potential risk for children: poverty and a lack of paternal presence. In both cases, the fathers emphasized that appropriate mediation of these circumstances can diffuse their potential harm. The discussion outlines the different ways fathers proposed mediating potential risk situations, highlighting distinct religion-related methods. It then considers specific, context-informed ramifications and recommendations and notes limitations and directions for future study.
Intra-Articular Collagen Injections for Osteoarthritis: A Narrative Review
Authors: Tarantino Domiziano , Mottola Rosita , Palermi Stefano , Sirico Felice , Corrado Bruno , Gnasso Rossana
Published: March 2023

Osteoarthritis (OA) is the most frequent degenerative progressive joint disease worldwide, with the hand, hip, and knee being the most-affected joints. Actually, no treatment can alter the course of OA, and therapy is directed at reducing pain and improving function. The exogenous administration of collagen has been investigated as a possible symptomatic adjuvant or stand-alone treatment for OA. The aim of this review is to assess if intra-articular collagen administration can be considered as a valid and safe therapeutic option for OA. A search in the main scientific electronic databases to identify the available scientific articles about the effects of intra-articular collagen as an OA treatment was performed. The results of the seven included studies showed that the intra-articular administration of collagen may stimulate chondrocytes to produce hyaline cartilage and hinder the normal inflammatory response leading to fibrous tissue formation, reducing symptoms, and improving functionality. The use of type-I collagen as an intra-articular treatment for knee OA was found not only to be effective, but also safe with negligible side effects. The reported findings are strongly promising, highlighting the need for further high-quality research to confirm the consistency of these findings.
The Evolution of Landscape Patterns and Its Ecological Effects of Open-Pit Mining: A Case Study in the Heidaigou Mining Area, China
Authors: Zhao Yuxia , Wang Yang , Zhang Zifan , Zhou Yi , Huang Haoqing , Chang Ming
Published: March 2023

This paper investigates the impact of land use/cover type changes in the Haideigou open-pit coal mine on the evolution of the landscape patterns and ecological and environmental quality in the mine area, based on medium- and high-resolution remote sensing images in 2006, 2011, 2016, and 2021 using ArcGIS 10.5, Fragstats 4.2, and the Google Earth Engine platform. The results show that: (1) From 2006 to 2021, the area of cropland and waste dumps in the Heidaigou mining area changed significantly, the land use shifted in a single direction, and the overall land use change was unbalanced. (2) Through the analysis of landscape indicators, it was shown that the diversity of the landscape patches in the study area increased, connectivity decreased, and the patches became more fragmented. (3) Based on the changes in the mean value of the RSEI over the past 15 years, the ecological environment quality of the mining area deteriorated first and then improved. The quality of the ecological environment in the mining area was significantly affected by human activities. This study provides an important basis for achieving the sustainability and stability of ecological environmental development in mining areas.
Structural and Serological Characterization of the O Antigen of Proteus mirabilis Clinical Isolates Classified into a New Proteus Serogroup, O84
Authors: Drzewiecka Dominika , Siwińska Małgorzata , Senchenkova Sof’ya N. , Levina Evgeniya A. , Shashkov Alexander S. , Knirel Yuriy A.
Published: March 2023

Two closely related Proteus mirabilis smooth strains, Kr1 and Ks20, were isolated from wound and skin samples, respectively, of two infected patients in central Poland. Serological tests, using the rabbit Kr1-specific antiserum, revealed that both strains presented the same O serotype. Their O antigens are unique among the Proteus O serotypes, which had been described earlier, as they were not recognized in an enzyme-linked immunosorbent assay (ELISA) by a set of Proteus O1-O83 antisera. Additionally, the Kr1 antiserum did not react with O1-O83 lipopolysaccharides (LPSs). The O-specific polysaccharide (OPS, O antigen) of P. mirabilis Kr1 was obtained via the mild acid degradation of the LPSs, and its structure was established via a chemical analysis and one- and two-dimensional 1H and 13C nuclear magnetic resonance (NMR) spectroscopy applied to both initial and O-deacetylated polysaccharides, where most β-2-acetamido-2-deoxyglucose (N-acetylglucosamine) (GlcNAc) residues are non-stoichiometrically O-acetylated at positions 3, 4, and 6 or 3 and 6, and a minority of α-GlcNAc residues are 6-O-acetylated. Based on the serological features and chemical data, P. mirabilis Kr1 and Ks20 were proposed as candidates to a new successive O-serogroup in the genus Proteus, O84, which is another example of new Proteus O serotypes identified lately among serologically differentiated Proteus bacilli infecting patients in central Poland.
Osteogenic and Adipogenic Differentiation Potential of Oral Cancer Stem Cells May Offer New Treatment Modalities
Authors: Karisik Milica Jaksic , Lazarevic Milos , Mitic Dijana , Nikolic Nadja , Markovic Maja Milosevic , Jelovac Drago , Milasin Jelena
Published: March 2023

(1) Treatment failure of oral squamous cell carcinoma (OSCC) is generally due to the development of therapeutic resistance caused by the existence of cancer stem cells (CSCs), a small cell subpopulation with marked self-renewal and differentiation capacity. Micro RNAs, notably miRNA-21, appear to play an important role in OSCC carcinogenesis. Our objectives were to explore the multipotency of oral CSCs by estimating their differentiation capacity and assessing the effects of differentiation on stemness, apoptosis, and several miRNAs’ expression. (2) A commercially available OSCC cell line (SCC25) and five primary OSCC cultures generated from tumor tissues obtained from five OSCC patients were used in the experiments. Cells harboring CD44, a CSC marker, were magnetically separated from the heterogeneous tumor cell populations. The CD44+ cells were then subjected to osteogenic and adipogenic induction, and the specific staining was used for differentiation confirmation. The kinetics of the differentiation process was evaluated by qPCR analysis of osteogenic (Bone Morphogenetic Protein—BMP4, Runt-related Transcription Factor 2—RUNX2, Alkaline Phosphatase—ALP) and adipogenic (Fibroblast Activation Protein Alpha—FAP, LIPIN, Peroxisome Proliferator-activated Receptor Gamma—PPARG) markers on days 0, 7, 14, and 21. Embryonic markers (Octamer-binding Transcription Factor 4—OCT4, Sex Determining Region Y Box 2—SOX2, and NANOG) and micro RNAs (miRNA-21, miRNA-133, and miRNA-491) were also correspondingly evaluated by qPCR. An Annexin V assay was used to assess the potential cytotoxic effects of the differentiation process. (3) Following differentiation, the levels of markers for the osteo/adipo lineages showed a gradual increase from day 0 to day 21 in the CD44+ cultures, while stemness markers and cell viability decreased. The oncogenic miRNA-21 also followed the same pattern of gradual decrease along the differentiation process, while tumor suppressor miRNA-133 and miRNA-491 levels increased. (4) Following induction, the CSCs acquired the characteristics of the differentiated cells. This was accompanied by loss of stemness properties, a decrease of the oncogenic and concomitant, and an increase of tumor suppressor micro RNAs.
Structural Characterization of Hypoxia Inducible Factor α—Prolyl Hydroxylase Domain 2 Interaction through MD Simulations
Authors: Camagni Giorgia F. , Minervini Giovanni , Tosatto Silvio C. E.
Published: March 2023

The Prolyl Hydroxylases (PHDs) are an enzymatic family that regulates cell oxygen-sensing. PHDs hydroxylate hypoxia-inducible transcription factors α (HIFs-α) driving their proteasomal degradation. Hypoxia inhibits PHDs activity, inducing HIFs-α stabilization and cell adaptation to hypoxia. As a hallmark of cancer, hypoxia promotes neo-angiogenesis and cell proliferation. PHD isoforms are thought to have a variable impact on tumor progression. All isoforms hydroxylate HIF-α (HIF-1,2,3α) with different affinities. However, what determines these differences and how they pair with tumor growth is poorly understood. Here, molecular dynamics simulations were used to characterize the PHD2 binding properties in complexes with HIF-1α and HIF-2α. In parallel, conservation analysis and binding free energy calculations were performed to better understand PHD2 substrate affinity. Our data suggest a direct association between the PHD2 C-terminus and HIF-2α that is not observed in the PHD2/HIF-1α complex. Furthermore, our results indicate that phosphorylation of a PHD2 residue, Thr405, causes a variation in binding energy, despite the fact that this PTM has only a limited structural impact on PHD2/HIFs-α complexes. Collectively, our findings suggest that the PHD2 C-terminus may act as a molecular regulator of PHD’s activity.
Framing Heartaches: The Cardiac ECM and the Effects of Age
Authors: Ringström Nathalie , Edling Charlotte , Nalesso Giovanna , Jeevaratnam Kamalan
Published: March 2023

The cardiac extracellular matrix (ECM) is involved in several pathological conditions, and age itself is also associated with certain changes in the heart: it gets larger and stiffer, and it develops an increased risk of abnormal intrinsic rhythm. This, therefore, makes conditions such as atrial arrythmia more common. Many of these changes are directly related to the ECM, yet the proteomic composition of the ECM and how it changes with age is not fully resolved. The limited research progress in this field is mainly due to the intrinsic challenges in unravelling tightly bound cardiac proteomic components and also the time-consuming and costly dependency on animal models. This review aims to give an overview of the composition of the cardiac ECM, how different components aid the function of the healthy heart, how the ECM is remodelled and how it is affected by ageing.
Metal-Responsive Transcription Factors Co-Regulate Anti-Sigma Factor (Rsd) and Ribosome Dimerization Factor Expression
Authors: Yoshida Hideji , Shimada Tomohiro , Ishihama Akira
Published: March 2023

Bacteria exposed to stress survive by regulating the expression of several genes at the transcriptional and translational levels. For instance, in Escherichia coli, when growth is arrested in response to stress, such as nutrient starvation, the anti-sigma factor Rsd is expressed to inactivate the global regulator RpoD and activate the sigma factor RpoS. However, ribosome modulation factor (RMF) expressed in response to growth arrest binds to 70S ribosomes to form inactive 100S ribosomes and inhibit translational activity. Moreover, stress due to fluctuations in the concentration of metal ions essential for various intracellular pathways is regulated by a homeostatic mechanism involving metal-responsive transcription factors (TFs). Therefore, in this study, we examined the binding of a few metal-responsive TFs to the promoter regions of rsd and rmf through promoter-specific TF screening and studied the effects of these TFs on the expression of rsd and rmf in each TF gene-deficient E. coli strain through quantitative PCR, Western blot imaging, and 100S ribosome formation analysis. Our results suggest that several metal-responsive TFs (CueR, Fur, KdpE, MntR, NhaR, PhoP, ZntR, and ZraR) and metal ions (Cu2+, Fe2+, K+, Mn2+, Na+, Mg2+, and Zn2+) influence rsd and rmf gene expression while regulating transcriptional and translational activities.
Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells
Authors: Ptacek Jakub , Snajdr Ivan , Schimer Jiri , Kutil Zsofia , Mikesova Jana , Baranova Petra , Havlinova Barbora , Tueckmantel Werner , Majer Pavel , Kozikowski Alan , Barinka Cyril
Published: March 2023

Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family of enzymes due to its complex domain organization and cytosolic localization. Experimental data point toward the therapeutic use of HDAC6-selective inhibitors (HDAC6is) for use in both neurological and psychiatric disorders. In this article, we provide side-by-side comparisons of hydroxamate-based HDAC6is frequently used in the field and a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function as an alternative zinc-binding group (compound 7). In vitro isotype selectivity screening uncovered HDAC10 as a primary off-target for the hydroxamate-based HDAC6is, while compound 7 features exquisite 10,000-fold selectivity over all other HDAC isoforms. Complementary cell-based assays using tubulin acetylation as a surrogate readout revealed approximately 100-fold lower apparent potency for all compounds. Finally, the limited selectivity of a number of these HDAC6is is shown to be linked to cytotoxicity in RPMI-8226 cells. Our results clearly show that off-target effects of HDAC6is must be considered before attributing observed physiological readouts solely to HDAC6 inhibition. Moreover, given their unparalleled specificity, the oxadiazole-based inhibitors would best be employed either as research tools in further probing HDAC6 biology or as leads in the development of truly HDAC6-specific compounds in the treatment of human disease states.
DNA Damage and Its Role in Cancer Therapeutics
Authors: Moon Jaeyoung , Kitty Ichiwa , Renata Kusuma , Qin Sisi , Zhao Fei , Kim Wootae
Published: March 2023

DNA damage is a double-edged sword in cancer cells. On the one hand, DNA damage exacerbates gene mutation frequency and cancer risk. Mutations in key DNA repair genes, such as breast cancer 1 (BRCA1) and/or breast cancer 2 (BRCA2), induce genomic instability and promote tumorigenesis. On the other hand, the induction of DNA damage using chemical reagents or radiation kills cancer cells effectively. Cancer-burdening mutations in key DNA repair-related genes imply relatively high sensitivity to chemotherapy or radiotherapy because of reduced DNA repair efficiency. Therefore, designing specific inhibitors targeting key enzymes in the DNA repair pathway is an effective way to induce synthetic lethality with chemotherapy or radiotherapy in cancer therapeutics. This study reviews the general pathways involved in DNA repair in cancer cells and the potential proteins that could be targeted for cancer therapeutics.
Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models
Authors: Fang Xinru , Gao Feiqiong , Yao Qigu , Xu Haoying , Yu Jiong , Cao Hongcui , Li Shibo
Published: March 2023

Background: Although increasing preclinical studies have emphasized the benefits of exosome-related therapies, the efficacy of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) for liver injury is unclear. In this work, a pooled analysis was conducted to explore the overall effect of MSC-EV in animal models. Methods: A systematic search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases was performed, from initiation to February 2022, for preclinical studies with liver disease models. The treatment outcomes were evaluated based on liver function, histological analysis, and inflammatory cytokines. Results: After screening, 39 studies were included. Pooled analyses demonstrated that MSC-EV therapy significantly improved liver functions (ALB, ALT, AST, ALP, and γ-GT), promoted the repair of injured liver tissue (damaged area, Ishak’s score), reduced inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), and increased an anti-inflammatory cytokine (IL-10) compared to the placebo control group. Subgroup analyses indicated that MSC-EV had therapeutic effects on liver fibrosis (n = 16), acute liver injury (n = 11), non-alcoholic fatty liver disease (n = 3), autoimmune hepatitis (n = 4), and hepatic ischemia-reperfusion injury (n = 6). Additionally, the therapeutic effect of EV was comparable to that of MSCs. Conclusion: MSC-EV have therapeutic potential for acute and chronic liver diseases.
Construction of Osteosarcoma Diagnosis Model by Random Forest and Artificial Neural Network
Authors: Li Sheng , Que Yukang , Yang Rui , He Peng , Xu Shenglin , Hu Yong
Published: March 2023

Osteosarcoma accounts for 28% of primary bone malignancies in adults and up to 56% in children and adolescents (<20 years). However, early diagnosis and treatment are still inadequate, and new improvements are still needed. Missed diagnoses exist due to fewer traditional diagnostic methods, and clinical symptoms are often already present before diagnosis. This study aimed to develop novel and efficient predictive models for the diagnosis of osteosarcoma and to identify potential targets for exploring osteosarcoma markers. First, osteosarcoma and normal tissue expression microarray datasets were downloaded from the Gene Expression Omnibus (GEO). Then we screened the differentially expressed genes (DEGs) in the osteosarcoma and normal groups in the training group. Next, in order to explore the biologically relevant role of DEGs, Metascape and enrichment analyses were also performed on DEGs. The “randomForest” and “neuralnet” packages in R software were used to select representative genes and construct diagnostic models for osteosarcoma. The next step is to validate the model of the artificial neural network. Then, we performed an immune infiltration analysis by using the training set data. Finally, we constructed a prognostic model using representative genes for prognostic analysis. The copy number of osteosarcoma was also analyzed. A random forest classifier identified nine representative genes (ANK1, TGFBR3, RSF21, HSPB8, ITGA7, RHD, AASS, GREM2, NFASC). HSPB8, RHD, AASS, and NFASC were genes we identified that have not been previously reported to be associated with osteosarcoma. The osteosarcoma diagnostic model we constructed has good performance with areas under the curves (AUCs) of 1 and 0.987 in the training and validation groups, respectively. This study opens new horizons for the early diagnosis of osteosarcoma and provides representative markers for the future treatment of osteosarcoma. This is the first study to pioneer the establishment of a genetic diagnosis model for osteosarcoma and advance the development of osteosarcoma diagnosis and treatment.
Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues
Authors: Kartti Souad , Bendani Houda , Boumajdi Nasma , Bouricha El Mehdi , Zarrik Oumaima , EL Agouri Hajar , Fokar Mohamed , Aghlallou Youssef , EL Jaoudi Rachid , Belyamani Lahcen , Elkhannoussi Basma , Ibrahimi Azeddine
Published: March 2023

Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.
Cytotoxic Lymphocyte-Related Gene Signature in Triple-Negative Breast Cancer
Authors: Han Yiqun , Wang Jiayu , Xu Binghe
Published: March 2023

To curate the signature genes of cytotoxic lymphocytes (CLs) and explore the heterogeneity based on the CL-related (CLR) gene signature, we analyzed the gene expression of 592 patients with histologically diagnosed triple-negative breast cancer. Based on the 13-gene panel, CLR signatures were curated and associated with the stage of tumor size. Patients in the CLR-low group exhibited the worse overall survival (OS) (median OS, 75.23 months vs. 292.66 months, p < 0.0001) and were characterized by the upregulation of the NF-κB, Wnt, and p53 pathways, the positive regulation of angiogenesis, and a higher expression of immune checkpoints including CTLA4, LAG3, CD86, ICOS, ICOSLG, and TNFSF9. In cancer immunotherapy cohorts (GSE157284, GSE35640, IMvigor210), a higher CLR signature score was remarkably associated with greater tumor shrinkage and immune characteristics consisting of higher PD-L1 and neoantigen expression, as well as an inflamed tumor microenvironment. In the pan-cancer atlas, the CLR signature was notably associated with patient survival and revealed a profound heterogeneity across the malignancy types. In sum, the CLR signature is a promising indicator for immune characteristics, tumor shrinkage, and survival outcomes following cancer immunotherapy in addition to the prognostic heterogeneity in the pan-cancer atlas.
Chatbot-Based Services: A Study on Customers’ Reuse Intention
Authors: Silva Filipe Araújo , Shojaei Alireza Shabani , Barbosa Belem
Published: March 2023

The main objective of this article is to investigate the factors that influence customers’ intention to reuse chatbot-based services. The study employs a combination of the technology acceptance model (TAM) with other contributions in the literature to develop a theoretical model that predicts and explains customers’ intention to reuse chatbots. The research uses structural equation modeling (PLS-SEM) to test the proposed hypotheses. Data collected from 201 chatbot users among Portuguese consumers were analyzed, and the results showed that user satisfaction, perceived usefulness, and subjective norm are significant predictors of chatbot reuse intentions. Additionally, the findings indicated that perceived usefulness, perceived ease of use, and trust have a positive impact on attitudes toward using chatbots. Trust was found to have a significant impact on perceived usefulness, user satisfaction, and attitudes toward using chatbots. However, there was no significant effect of attitude toward using chatbots, perceived ease of use, trust, and perceived social presence on reuse intentions. The article concludes with theoretical contributions and recommendations for managers.
Process Optimization of Dual-Liquid Casting and Interfacial Strength–Toughness of the Produced LAS/HCCI Bimetal
Authors: Xing Zhen-Guo , He Li-Xin , Liang Shun-Xing , Chang Lian-Bo , Xiao Zhi-Xia , Xing Wan-Li , Shen Hai-Bin , Cao Jing-Jing , Liu Hong-Ji
Published: March 2023

The pouring time interval is the decisive factor of dual-liquid casting for bimetallic productions. Traditionally, the pouring time interval is fully determined by the operator’s experience and on-site observation. Thus, the quality of bimetallic castings is unstable. In this work, the pouring time interval of dual-liquid casting for producing low alloy steel/high chromium cast iron (LAS/HCCI) bimetallic hammerheads is optimized via theoretical simulation and experimental verification. The relevancies of interfacial width and bonding strength to pouring time interval are, respectively, established. The results of bonding stress and interfacial microstructure indicate that 40 s is the optimum pouring time interval. The effects of interfacial protective agent on interfacial strength–toughness are also investigated. The addition of the interfacial protective agent yields an increase of 41.5% in interfacial bonding strength and 15.6% in toughness. The optimum dual-liquid casting process is used to produce LAS/HCCI bimetallic hammerheads. Samples cut from these hammerheads show excellent strength–toughness (1188 Mpa for bonding strength and 17 J/cm2 for toughness). The findings could be a reference for dual-liquid casting technology. They are also helpful for understanding the formation theory of the bimetal interface.