bluuebunny/crossref_metadata_2025 huggingface dataset:
UPAYA MENINGKATKAN HASIL BELAJAR MATEMATIKA MELALUI PENERAPAN STRATEGI PEMBELAJARAN KOOPERATIF TIPE QUICK ON THE DRAW
Authors: Wirahmad Ika , Iwansyah Iwansyah , Dusalan Dusalan
Published: February 2021

ABSTRAK

 Tujuan penelitian ini adalah Untuk mengetahui meningkatnya hasil belajar matematika siswa kelas VIII.A SMP Negeri 3 Wera setelah diterapkan strategi pembelajaran Kooperatif tipe Quick On The Draw.

Penelitian ini adalah penelitian tindakan kelas (PTK). Pendekatan ini menerapkan dua pendekatan yaitu kualitatif dan kuantitatif. Data kualitatifnya adalah data aktivitas siswa dan aktivitas guru sedangkan data kuantitatifnya adalah data hasil belajar siswa.Penelitian ini dilakukan sebanyak dua siklus.Siklus I hasil belajarnya73,08% siswa mendapat nilai minimal 65, aktivitas belajar siswa berada pada skor 22 dengan kategori kurang aktif dan aktivitas guru berada pada skor 19 dengan kategori aktif. Sedangkan siklus II hasil belajarnya 88,64% siswa mendapat nilai minimal 65, aktivitas belajar siswa berada pada skor 31 dengan kategori sangat aktif dan aktivitas guru berada pada skor 23 sangat aktif. Hal ini menunjukkan adanya peningkatan secara signifikan dari siklus I kesiklus II.Jadi penerapan strategi pembelajaran kooperatif tipe Quick On The Draw dapat meningkatkan aktivitas dan hasil belajar siswa pada materi Relasi dan Fungsi di kelas VIII.A SMP Negeri 3 Wera tahun pelajaran 2020/2021.

 Kata Kunci : Penerapan Quick On The Draw, Hasil belajar, Relasi dan Fungsi.
The process of marketing research in the tourism sector
Authors: Litovka  , Demenina
Published: February 2021

The subject of the research is a set of theoretical and practical aspects of the use of basic marketing research in planning the work of a tourist organization.
The purpose of the article is to clarify and improve the basic theoretical approaches in the use of marketing research, to offer them systematically at each stage of developing the marketing strategy of a tourism enterprise.
The research methodology consists in the application of methods of analysis, synthesis, comparison, generalization, forecasting, as well as in the use of systemic, activity, historical approaches.
The results of the work – presented proposals for solving problems in the field of tourism, in particular in conducting marketing research at travel agencies. The problematic issues in the field of tourism from the point of view of the analysis of the market of specific services arecovered.
Conclusions. Tourism organizations need market monitoring, constant andconsistent marketing research due to high competitiveness and time challenges.
ANALYSIS OF TRENDS IN THE DEVELOPMENT OF STARTUP ENVIRONMENT IN UKRAINE
Authors: Hromozdova  , Ablova  , Studennikova  , Hromozdov  , Maliarevsky  , Smirnova
Published: February 2021

The purpose of the article is presentation of research results of the tourism potential in Ukraine, analysis of trends in the development of startup environment, definition of measures, directions to ensure the development of startups in the tourism business. The object of study is the process of organizing startups in the tourism business. The subject of research is theoretical and practical aspects of the organization and prospects of development of startups in the tourism business of Ukraine. The methodological basis of the study is a system-analytical method that contributes to the theoretical generalization of scientific concepts, developments, proposals of leading domestic and foreign scientists on the problems of forming startups in tourism. Methods of economic and statistical analysis are used to study the current state and trends of startups in the tourism business of Ukraine. The scientific novelty of the article is that startup technologies are considered as an effective form of implementing innovative ideas in the tourism industry. Conclu- sions. Thus, today startup technologies in the tourism business are a key tool for effective communication of local authorities, public and business structures with a global audience of potential tourists. It is determined that tourism startup proj- ects are an effective tool for establishing partnerships between Ukrainian and international companies, which intensifies grants and direct investments, promotes the entry of Ukrainian tourism enterprises into world markets, is an effective mechanism for international presentation of new tourism products in Ukraine. The scientific results of the study serve as a theoretical and methodological, informa- tion-analytical and practical basis for streamlining the organization of startups in the tourism business of Ukraine. In general, the work provides an opportunity to assess the potential of the country, as well as to identify measures to ensure the development of startups in the tourism business.
Theoretical and methodological fundamentals of marketing functioning in the hospitality industry of tourism enterprises
Authors: Ablova  , Hromozdova  , Studennikova  , Hromozdov  , Boichenko  , Smirnova  , Shvydka
Published: February 2021

The purpose of the article is to study the world marketing experience of the hospitality industry, to define the concept of hospitality and the hospitality indus- try. The object of research is the hospitality of the company’s tourism activities. The subject of research is marketing in the hospitality industry. The method- ological foundations of the study are the following methods: historicism, systems approach, analysis and synthesis. The scientific novelty is that in this article the marketing of the hospitality industry is defined as a set of initiated and controlled marketing tools that are used to provide an atmosphere of hospitality as part of the market attractiveness of the service. Conclusions. Thanks to the study of the terms “hospitality industry”, it can be argued that the scientific literature provides many definitions, but a consensual, single definition has not yet been formulated. It is also determined that the marketing complex for hospitality companies should be understood as a set of basic elements involved in the formation of marketing programs of enterprises, which can be key factors in the success of the institution and which must be controlled to respond to target markets, achieve competitive advantage and increase demand hospitality services.
Audit of production enterprises inventories
Authors: Bunda  , Vityuk
Published: February 2021

The purpose of the article is to generalize and improve the organizational and methodological aspects of the audit of production enterprise inventories. The re- search methodology is to use the following methods: analysis, synthesis, induction, deduction, analogy, modeling, formalization. The scientific novelty of the article lies in the substantiation of the algorithm of decisions during the audit of stocks in the information environment of the production enterprise. Conclusions. The application of the algorithm of decisions in the audit of stocks in the information environment of the production enterprise will significantly increase the efficiency of the stocks usage at the production enterprise, which will directly affect the results of financial and economic activities of the enterprise. The proposed plan and program of audit of stocks of the production enterprise will allow to carry out qualitative and detailed audit of stocks of the production enterprise, to form the audit conclusion and to give recommendations concerning stocks of the production enterprise.
An Examination of the Gust Effect Factor for Rigid High-Rise Buildings
Authors: Liu Yi , Kopp Gregory A. , Chen Shui-fu
Published: February 2021

In order to systematically investigate the gust effect factor for rigid buildings, the derivation of the gust effect factor in ASCE 7–16 is carefully reviewed and scale model pressure tests were carried out for rectangular-plan high-rise buildings with plan aspect ratios ranging from 0.11 to 9. The gust effect factor and the aerodynamic admittance function (AAF) for area-averaged pressure coefficients and base drag coefficients were obtained and discussed in detail. The results show that the AAF has direct influence on the value of the gust effect factor, depending on whether effects of non-contemporaneous gust actions or body-generated turbulence are playing a leading role. The ASCE 7–16 gust effect factor for rigid buildings underestimates the measured values for individual walls due to differences in the AAF, peak factors, and the employment of the 3 s moving average filter. However, the ASCE 7–16 gust factor for overall drag is estimated within 5% or better.
A Comparative Study on Na2Fe0.6Mn0.4PO4F/C Cathode Materials Synthesized With Various Carbon Sources for Na-ion Batteries
Authors: Tang Shibao , Zhang Xiaoping , Sui Yulei , Wang Bingjue , Li Jiangpeng , Wu Ling
Published: February 2021

Na2Fe0.6Mn0.4PO4F/C composite materials are synthesized with various carbon sources via a simple spray-drying method in this study, and the effect of carbon sources on structure, morphology, and electrochemical properties of Na2Fe0.6Mn0.4PO4F/C materials are investigated in detail. XRD and SEM results indicate that the reduction ability of carbon sources has a key impact on the structure and morphology of Na2Fe0.6Mn0.4PO4F/C composite materials. Among these Na2Fe0.6Mn0.4PO4F/C materials, the sample prepared with ascorbic acid presents a uniform hollow spherical architecture. Electrochemical analysis demonstrates that the Na2Fe0.6Mn0.4PO4F/C sample prepared with ascorbic acid has optimal electrochemical performance. The sample shows high discharge capacities of 95.1 and 48.1 mAh g−1 at 0.05C and 1C rates, respectively, and it exhibits an improved cycle stability (91.7% retention after 100 cycles at 0.5C), which are superior to Na2Fe0.6Mn0.4PO4F/C materials prepared with other carbon sources. This study demonstrates that the reduction ability of carbon sources significantly influences the electrochemical properties of fluorophosphate/C composite materials. This work also provides a promising strategy to obtain high performance cathode materials for sodium-ion batteries.
Synergism of Streptococcus mutans and Candida albicans Reinforces Biofilm Maturation and Acidogenicity in Saliva: An In Vitro Study
Authors: Kim Hye-Eun , Liu Yuan , Dhall Atul , Bawazir Marwa , Koo Hyun , Hwang Geelsu
Published: February 2021

Early childhood caries, a virulent-form of dental caries, is painful, difficult, and costly to treat that has been associated with high levels ofStreptococcus mutans(Sm) andCandida albicans(Ca) in plaque-biofilms on teeth. These microorganisms appear to develop a symbiotic cross-kingdom interaction that amplifies the virulence of plaque-biofilms. Although biofilm studies reveal synergistic bacterial-fungal association, how these organisms modulate cross-kingdom biofilm formation and enhance its virulence in the presence of saliva remain largely unknown. Here, we compared the properties of Sm and Sm-Ca biofilms cultured in saliva by examining the biofilm structural organization and capability to sustain an acidic pH environment conducive to enamel demineralization. Intriguingly, Sm-Ca biofilm is rapidly matured and maintained acidic pH-values (~4.3), while Sm biofilm development was retarded and failed to create an acidic environment when cultured in saliva. In turn, the human enamel slab surface was severely demineralized by Sm-Ca biofilms, while there was minimal damage to the enamel surface by Sm biofilm. Interestingly, Sm-Ca biofilms exhibited an acidic environment regardless of their hyphal formation ability. Our data reveal the critical role of symbiotic interaction betweenS. mutansandC. albicansin human saliva in the context of pathogenesis of dental caries, which may explain how the cross-kingdom interaction contributes to enhanced virulence of plaque-biofilm in the oral cavity.
A Theoretical and Evidence-Based Conceptual Design of MetaDash: An Intelligent Teacher Dashboard to Support Teachers' Decision Making and Students’ Self-Regulated Learning
Authors: Wiedbusch Megan D. , Kite Vance , Yang Xi , Park Soonhye , Chi Min , Taub Michelle , Azevedo Roger
Published: February 2021

Teachers’ ability to self-regulate their own learning is closely related to their competency to enhance self-regulated learning (SRL) in their students. Accordingly, there is emerging research for the design of teacher dashboards that empower instructors by providing access to quantifiable evidence of student performance and SRL processes. Typically, they capture evidence of student learning and performance to be visualized through activity traces (e.g., bar charts showing correct and incorrect response rates, etc.) and SRL data (e.g., eye-tracking on content, log files capturing feature selection, etc.) in order to provide teachers with monitoring and instructional tools. Critics of the current research on dashboards used in conjunction with advanced learning technologies (ALTs) such as simulations, intelligent tutoring systems, and serious games, argue that the state of the field is immature and has 1) focused only on exploratory or proof-of-concept projects, 2) investigated data visualizations of performance metrics or simplistic learning behaviors, and 3) neglected most theoretical aspects of SRL including teachers’ general lack of understanding their’s students’ SRL. Additionally, the work is mostly anecdotal, lacks methodological rigor, and does not collect critical process data (e.g. frequency, duration, timing, or fluctuations of cognitive, affective, metacognitive, and motivational (CAMM) SRL processes) during learning with ALTs used in the classroom. No known research in the areas of learning analytics, teacher dashboards, or teachers’ perceptions of students’ SRL and CAMM engagement has systematically and simultaneously examined the deployment, temporal unfolding, regulation, and impact of all these key processes during complex learning. In this manuscript, we 1) review the current state of ALTs designed using SRL theoretical frameworks and the current state of teacher dashboard design and research, 2) report the important design features and elements within intelligent dashboards that provide teachers with real-time data visualizations of their students’ SRL processes and engagement while using ALTs in classrooms, as revealed from the analysis of surveys and focus groups with teachers, and 3) propose a conceptual system design for integrating reinforcement learning into a teacher dashboard to help guide the utilization of multimodal data collected on students’ and teachers’ CAMM SRL processes during complex learning.
Thyroid Function Abnormalities in COVID-19 Patients
Authors: Wang Weibin , Su Xingyun , Ding Yongfeng , Fan Weina , Zhou Weibin , Su Junwei , Chen Zhendong , Zhao Hong , Xu Kaijin , Ni Qin , Xu Xiaowei , Qiu Yunqing , Teng Lisong
Published: February 2021

Purpose

The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown.

Methods

Eighty-four hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were retrospectively enrolled in this study, among which 22 cases had complete records of thyroid hormones. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls.

Results

We found that levels of total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were lower in COVID-19 patients than healthy group (p < 0.001). Besides, TSH level in COVID-19 patients was obviously lower than non-COVID-19 patients (p < 0.001). Within the group of COVID-19, 61.9% (52/84) patients presented with thyroid function abnormalities and the proportion of thyroid dysfunction was higher in severe cases than mild/moderate cases (74.6 vs. 23.8%, p < 0.001). Patients with thyroid dysfunction tended to have longer viral nucleic acid cleaning time (14.1 ± 9.4 vs. 10.6 ± 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time.

Conclusion

Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be partially explained by nonthyroidal illness syndrome.
Massively Parallel Sequencing for Rare Genetic Disorders: Potential and Pitfalls
Authors: McInerney-Leo Aideen M. , Duncan Emma L.
Published: February 2021

There have been two major eras in the history of gene discovery. The first was the era of linkage analysis, with approximately 1,300 disease-related genes identified by positional cloning by the turn of the millennium. The second era has been powered by two major breakthroughs: the publication of the human genome and the development of massively parallel sequencing (MPS). MPS has greatly accelerated disease gene identification, such that disease genes that would have taken years to map previously can now be determined in a matter of weeks. Additionally, the number of affected families needed to map a causative gene and the size of such families have fallen: de novo mutations, previously intractable by linkage analysis, can be identified through sequencing of the parent–child trio, and genes for recessive disease can be identified through MPS even of a single affected individual. MPS technologies include whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing, each with their strengths. While WES has been responsible for most gene discoveries through MPS, WGS is superior in detecting copy number variants, chromosomal rearrangements, and repeat-rich regions. Panels are commonly used for diagnostic purposes as they are extremely cost-effective and generate manageable quantities of data, with no risk of unexpected findings. However, in instances of diagnostic uncertainty, it can be challenging to choose the right panel, and in these circumstances WES has a higher diagnostic yield. MPS has ethical, social, and legal implications, many of which are common to genetic testing generally but amplified due to the magnitude of data (e.g., relationship misattribution, identification of variants of uncertain significance, and genetic discrimination); others are unique to WES and WGS technologies (e.g., incidental or secondary findings). Nonetheless, MPS is rapidly translating into clinical practice as an extremely useful part of the clinical armamentarium.
Will Public Environmental Concerns Foster Green Innovation in China’s Automotive Industry? An Empirical Study Based on Multi-Sourced Data Streams
Authors: Li Yan , Wang Zhicheng
Published: February 2021

This study explores the impact of public concerns on green innovation in China’s automotive industry and examines whether the effect varies based on firm size, ownership, and time phase. The study investigates 151 automobile enterprises and provides a novel, large-scale, and data-based perspective and estimation method for exploring critical factors of green innovation. By applying transition probabilities matrix (TPM) model, this paper finds that for different-sizes automotive enterprises there are significant differences in innovation sustainability, non-innovation sustainability, and liquidity between innovation and non-innovation, and such differences also exist for state-owned and non-state-owned enterprises. Then, based on the dynamic panel random probit (DPRP) model, the paper further analyzes the possible reasons for these differences, and particularly focuses on exploring the impact of public environmental concern on the environmental technology innovation. The empirical results show: 1) public concerns encourages green innovation emerging in all automotive firms, but only affects innovation persistence in medium and large companies. 2) public concerns encourages non-innovator state-owned companies to become innovators and motivates them to maintain continuous innovation. 3) the impact of public concerns changes over time. In the periods of 2002–2007 and 2012–2013, the role of public concerns is not significant. However, in the 2007–2012 period, public concerns significantly stimulate enterprises to move from non-innovators to innovators and promotes continuous innovation.
DriverSubNet: A Novel Algorithm for Identifying Cancer Driver Genes by Subnetwork Enrichment Analysis
Authors: Zhang Di , Bin Yannan
Published: February 2021

Identification of driver genes from mass non-functional passenger genes in cancers is still a critical challenge. Here, an effective and no parameter algorithm, named DriverSubNet, is presented for detecting driver genes by effectively mining the mutation and gene expression information based on subnetwork enrichment analysis. Compared with the existing classic methods, DriverSubNet can rank driver genes and filter out passenger genes more efficiently in terms of precision, recall, and F1 score, as indicated by the analysis of four cancer datasets. The method recovered about 50% more known cancer driver genes in the top 100 detected genes than those found in other algorithms. Intriguingly, DriverSubNet was able to find these unknown cancer driver genes which could act as potential therapeutic targets and useful prognostic biomarkers for cancer patients. Therefore, DriverSubNet may act as a useful tool for the identification of driver genes by subnetwork enrichment analysis.
Whole-Exome Sequencing and hiPSC Cardiomyocyte Models Identify MYRIP, TRAPPC11, and SLC27A6 of Potential Importance to Left Ventricular Hypertrophy in an African Ancestry Population
Authors: Irvin Marguerite R. , Aggarwal Praful , Claas Steven A. , de las Fuentes Lisa , Do Anh N. , Gu C. Charles , Matter Andrea , Olson Benjamin S. , Patki Amit , Schwander Karen , Smith Joshua D. , Srinivasasainagendra Vinodh , Tiwari Hemant K. , Turner Amy J. , Nickerson Deborah A. , Rao Dabeeru C. , Broeckel Ulrich , Arnett Donna K.
Published: February 2021

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven procedure to prioritize and select genes for functional validation using a human induced pluripotent stem cell cardiomyocyte (hiPSC-CM) model. Three genes [myosin VIIA and Rab interacting protein (MYRIP), trafficking protein particle complex 11 (TRAPPC11), and solute carrier family 27 member 6 (SLC27A6)] were prioritized based on statistical significance, variant functional annotations, gene expression in the hiPSC-CM model, and prior biological evidence and were subsequently knocked down in the hiPSC-CM model. Expression profiling of hypertrophic gene markers in the knockdowns suggested a decrease in hypertrophic expression profiles. MYRIP knockdowns showed a significant decrease in atrial natriuretic factor (NPPA) and brain natriuretic peptide (NPPB) expression. Knockdowns of the heart long chain fatty acid (FA) transporter SLC27A6 resulted in downregulated caveolin 3 (CAV3) expression, which has been linked to hypertrophic phenotypes in animal models. Finally, TRAPPC11 knockdown was linked to deficient calcium handling.

Conclusions: The three genes are biologically plausible candidates that provide new insight to hypertrophic pathways.
FANCA Gene Mutations in North African Fanconi Anemia Patients
Authors: Ben Haj Ali Abir , Messaoud Olfa , Elouej Sahar , Talmoudi Faten , Ayed Wiem , Mellouli Fethi , Ouederni Monia , Hadiji Sondes , De Sandre-Giovannoli Annachiara , Delague Valérie , Lévy Nicolas , Bogliolo Massimo , Surrallés Jordi , Abdelhak Sonia , Amouri Ahlem
Published: February 2021

Populations in North Africa (NA) are characterized by a high rate of consanguinity. Consequently, the proportion of founder mutations might be higher than expected and could be a major cause for the high prevalence of recessive genetic disorders like Fanconi anemia (FA). We report clinical, cytogenetic, and molecular characterization ofFANCAin 29 North African FA patients from Tunisia, Libya, and Algeria. Cytogenetic tests revealed high rates of spontaneous chromosome breakages for all patients except two of them.FANCAmolecular analysis was performed using three different molecular approaches which allowed us to identify causal mutations as homozygous or compound heterozygous forms. It included a nonsense mutation (c.2749C > T; p.Arg917Ter), one reported missense mutation (c.1304G > A; p.Arg435His), a novel missense variant (c.1258G > A; p.Asp409Glu), and theFANCAmost common reported mutation (c.3788_3790delTCT; p.Phe1263del). Furthermore, three founder mutations were identified in 86.7% of the 22 Tunisian patients: (1) a deletion of exon 15, in 36.4% patients (8/22); (2), a deletion of exons 4 and 5 in 23% (5/22) and (3) an intronic mutation c.2222 + 166G > A, in 27.3% (6/22). Despite the relatively small number of patients studied, our results depict the mutational landscape of FA among NA populations and it should be taken into consideration for appropriate genetic counseling.
Case Report: A Novel Deletion in the 11p15 Region Causing a Familial Beckwith–Wiedemann Syndrome
Authors: Chen Juan , Xu Jian , Yu Yang , Sun Ling
Published: February 2021

Beckwith–Wiedemann syndrome (BWS; OMIM 130650) is a human overgrowth and cancer susceptibility disorder with a wide clinical spectrum, which cannot be predicted based on genomic variants alone. Most reports on BWS cases focus on childhood patients. Studies on adult BWS patients are scarce. Our study reports a BWS family in which the disorder appears to be caused by deletion of H19 and its upstream regulatory elements. Genetic analysis showed a heterozygous microdeletion (~chr11:2009895-2070570 (GRCh37)) in the patients. Maternal deletion in H19 can result in loss of function of the IGF2-H19 imprinting control element, which leads to BWS. The male proband in this family was affected by the testicular anomaly and cryptorchidism. Early orchidopexy did not rescue his azoospermia, which might be not the consequence of cryptorchidism, but due to genetic defects associated with H19 deletion. In summary, our study gives some insights on the presentation of BWS in adulthood.
Recent Advances in the Application of CRISPR/Cas9 Gene Editing System in Poultry Species
Authors: Khwatenge Collins N. , Nahashon Samuel N.
Published: February 2021

CRISPR/Cas9 system genome editing is revolutionizing genetics research in a wide spectrum of animal models in the genetic era. Among these animals, is the poultry species. CRISPR technology is the newest and most advanced gene-editing tool that allows researchers to modify and alter gene functions for transcriptional regulation, gene targeting, epigenetic modification, gene therapy, and drug delivery in the animal genome. The applicability of the CRISPR/Cas9 system in gene editing and modification of genomes in the avian species is still emerging. Up to date, substantial progress in using CRISPR/Cas9 technology has been made in only two poultry species (chicken and quail), with chicken taking the lead. There have been major recent advances in the modification of the avian genome through their germ cell lineages. In the poultry industry, breeders and producers can utilize CRISPR-mediated approaches to enhance the many required genetic variations towards the poultry population that are absent in a given poultry flock. Thus, CRISPR allows the benefit of accessing genetic characteristics that cannot otherwise be used for poultry production. Therefore CRISPR/Cas9 becomes a very powerful and robust tool for editing genes that allow for the introduction or regulation of genetic information in poultry genomes. However, the CRISPR/Cas9 technology has several limitations that need to be addressed to enhance its use in the poultry industry. This review evaluates and provides a summary of recent advances in applying CRISPR/Cas9 gene editing technology in poultry research and explores its potential use in advancing poultry breeding and production with a major focus on chicken and quail. This could aid future advancements in the use of CRISPR technology to improve poultry production.
Monotherapy With Anti-CD70 Antibody Causes Long-Term Mouse Cardiac Allograft Acceptance With Induction of Tolerogenic Dendritic Cells
Authors: Zhao Jing , Que Weitao , Du Xiaoxiao , Fujino Masayuki , Ichimaru Naotsugu , Ueta Hisashi , Tokuda Nobuko , Guo Wen-zhi , Zabrocki Piotr , de Haard Hans , Nonomura Norio , Li Xiao-Kang
Published: February 2021

Allograft rejection has been an obstacle for the long-term survival of patients. CD70, a tumor necrosis factor (TNF) family member critically expressed on antigen-presenting cells and strongly but transiently up-regulated during lymphocyte activation, represents an important co-stimulatory molecule that induces effective T cell responses. We used a mouse heterotopic cardiac transplantation model to evaluate the effects of monotherapy with the antibody targeting mouse CD70 (FR70) on transplantation tolerance and its immunoregulatory activity. FR70-treated C3H recipient mice permanently accepted B6 fully mismatched cardiac allografts. Consistent with the graft survival, the infiltration of CD8+ T cells in the graft was reduced, dendritic cells were differentiated into a tolerogenic status, and the number of regulatory T cells was elevated both in the graft and the recipient’s spleen. In addition, naïve C3H given an adoptive transfer of spleen cells from the primary recipients with FR70 treatment accepted a heart graft from a matching B6 donor but not third-party BALB/c mice.　Our findings show that treatment with FR70 induced regulatory cells and inhibited cytotoxic T cell proliferation, which led to long-term acceptance of mouse cardiac allografts. These findings highlight the potential role of anti-CD70 antibodies as a clinically effective treatment for allograft rejection.
Serum Amyloid A in Inflammatory Rheumatic Diseases: A Compendious Review of a Renowned Biomarker
Authors: Sorić Hosman Iva , Kos Ivanka , Lamot Lovro
Published: February 2021

Serum amyloid A (SAA) is an acute phase protein with a significant importance for patients with inflammatory rheumatic diseases (IRD). The central role of SAA in pathogenesis of IRD has been confirmed by recent discoveries, including its involvement in the activation of the inflammasome cascade and recruitment of interleukin 17 producing T helper cells. Clinical utility of SAA in IRD was originally evaluated nearly half a century ago. From the first findings, it was clear that SAA could be used for evaluating disease severity and monitoring disease activity in patients with rheumatoid arthritis and secondary amyloidosis. However, cost-effective and more easily applicable markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), overwhelmed its use in clinical practice. In the light of emerging evidences, SAA has been discerned as a more sensitive biomarker in a wide spectrum of IRD, especially in case of subclinical inflammation. Furthermore, a growing number of studies are confirming the advantages of SAA over many other biomarkers in predicting and monitoring response to biological immunotherapy in IRD patients. Arising scientific discoveries regarding the role of SAA, as well as delineating SAA and its isoforms as the most sensitive biomarkers in various IRD by recently developing proteomic techniques are encouraging the revival of its clinical use. Finally, the most recent findings have shown that SAA is a biomarker of severe Coronavirus disease 2019 (COVID-19). The aim of this review is to discuss the SAA-involving immune system network with emphasis on mechanisms relevant for IRD, as well as usefulness of SAA as a biomarker in various IRD. Therefore, over a hundred original papers were collected through an extensive PubMed and Scopus databases search. These recently arising insights will hopefully lead to a better management of IRD patients and might even inspire the development of new therapeutic strategies with SAA as a target.
Use of Flow Cytometry to Evaluate Phagocytosis of Staphylococcus aureus by Human Neutrophils
Authors: Boero Elena , Brinkman Iris , Juliet Thessely , van Yperen Eline , van Strijp Jos A. G. , Rooijakkers Suzan H. M. , van Kessel Kok P. M.
Published: February 2021

Neutrophils play a key role in the human immune response to Staphylococcus aureus infections. These professional phagocytes rapidly migrate to the site of infection to engulf bacteria and destroy them via specialized intracellular killing mechanisms. Here we describe a robust and relatively high-throughput flow cytometry assay to quantify phagocytosis of S. aureus by human neutrophils. We show that effective phagocytic uptake of S. aureus is greatly enhanced by opsonization, i.e. the tagging of microbial surfaces with plasma-derived host proteins like antibodies and complement. Our rapid assay to monitor phagocytosis can be used to study neutrophil deficiencies and bacterial evasion, but also provides a powerful tool to assess the opsonic capacity of antibodies, either in the context of natural immune responses or immune therapies.
AhR Ligands Differentially Regulate miRNA-132 Which Targets HMGB1 and to Control the Differentiation of Tregs and Th-17 Cells During Delayed-Type Hypersensitivity Response
Authors: Abdulla Osama A. , Neamah Wurood , Sultan Muthanna , Chatterjee Saurabh , Singh Narendra , Nagarkatti Mitzi , Nagarkatti Prakash
Published: February 2021

Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through induction of Tregs and Th-17 cells, respectively. In the current study, we investigated whether the differential effects of AhR ligands on T cell differentiation are mediated by miRNA during delayed-type hypersensitivity (DTH) reaction against methylated Bovine Serum Albumin (mBSA). Treatment of C57BL/6 mice with TCDD attenuated mBSA-mediated DTH response, induced Tregs, decreased Th-17 cells, and caused upregulation of miRNA-132. TCDD caused an increase in several Treg subsets including inducible peripheral, natural thymic, and Th3 cells. Also, TCDD increased TGF-β and Foxp3 expression. In contrast, treating mice with FICZ exacerbated the DTH response, induced inflammatory Th17 cells, induced IL-17, and RORγ. Analysis of miRNA profiles from draining lymph nodes showed that miR-132 was upregulated in the TCDD group and downregulated in the FICZ group. Transfection studies revealed that miRNA-132 targeted High Mobility Group Box 1 (HMGB1). Downregulation of HMGB1 caused an increase in FoxP3+ Treg differentiation and suppression of Th-17 cells while upregulation of HMGB1 caused opposite effects. Moreover, TCDD was less effective in suppressing DTH response and induction of Tregs in mice that were deficient in miR-132. In summary, this study demonstrates that TCDD and FICZ have divergent effects on DTH response and T cell differentiation, which is mediated through, at least in part, regulation of miRNA-132 that targets HMGB1.
The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis
Authors: Zou Xueyang , Zhang Yi , Wang Xiaoya , Zhang Rongchao , Yang Wei
Published: February 2021

The increasing number of patients with infertility is recognized as an emerging problem worldwide. However, little is known about the cause of infertility. At present, it is believed that infertility may be related to genetic or abnormal immune responses. It has long been indicated that autoimmune regulator (AIRE), a transcription factor, participates in immune tolerance by regulating the expression of thousands of promiscuous tissue-specific antigens in medullary thymic epithelial cells (mTECs), which play a pivotal role in preventing autoimmune diseases. AIRE is also expressed in germ cell progenitors. Importantly, the deletion of AIRE leads to severe oophoritis and age-dependent depletion of follicular reserves and causes altered embryonic development in female mice. AIRE-deficient male mice exhibit altered apoptosis during spermatogenesis and have a significantly decreased breeding capacity. These reports suggest that AIRE deficiency may be responsible for infertility. The causes may be related to the production of autoantibodies against sperm, poor development of germ cells, and abnormal ovarian function, which eventually lead to infertility. Here, we focus on the potential associations of AIRE deficiency with infertility as well as the possible pathogenesis, providing insight into the significance of AIRE in the development of infertility.
On the Impact of the Caribbean Counter Current in the Guajira Upwelling System
Authors: Orfila Alejandro , Urbano-Latorre Claudia P. , Sayol Juan M. , Gonzalez-Montes Stephanie , Caceres-Euse Alejandro , Hernández-Carrasco Ismael , Muñoz Ángel G.
Published: February 2021

The variability of La Guajira upwelling system, in the south-central Caribbean Sea, is strongly influenced by the intensity and location of the atmospheric Caribbean Low-Level Jet (CLLJ), a near-surface branch of the easterlies, as well as by the regional ocean circulation. During favorable conditions (i.e., strong easterlies blowing almost parallel to the coast), upwelling is enhanced and a large amount of primary productivity occurs in La Guajira area. In contrast, during relatively mild wind conditions, the CLLJ is misaligned to the coast and the Caribbean Counter Current (CCC, locally also known as the Darien Current), which forms as a branch from the Panama-Colombia Gyre, flows northeastward over the continental shelf advecting waters from the southwestern Caribbean basin toward La Guajira. The CCC has a clear signature at the surface layer that extends from the Darien Gulf toward La Guajira peninsula during mild wind periods, while disappears during the months of strong winds. The direction and the magnitude of the easterlies, and more specifically of the CLLJ, control the position and pathway of the CCC, which extends more than 900 km in the southern Caribbean Sea during May, June, August, September, and October. The high concentration of chlorophyll-a at the sea surface evidenced by satellite-based color images is semi-seasonally modulated by the CLLJ, which during its relaxation phase allows the irruption of the CCC toward the east up to La Guajira.
Impact of Plastic Debris on the Gut Microbiota of Caretta caretta From Northwestern Adriatic Sea
Authors: Biagi Elena , Musella Margherita , Palladino Giorgia , Angelini Valeria , Pari Sauro , Roncari Chiara , Scicchitano Daniel , Rampelli Simone , Franzellitti Silvia , Candela Marco
Published: February 2021

Plastic pollution is nowadays a relevant threat for the ecological balance in marine ecosystems. Small plastic debris (PD) can enter food webs through various marine organisms, with possible consequences on their physiology and health. The loggerhead sea turtle (Caretta caretta), widespread across the whole Mediterranean Sea, is a “flagship species,” useful as indicator of the general pollution level of marine ecosystems. Ingested PD accumulate in the final section of turtles’ digestive tract before excretion. During their transit and accumulation, PD also interact with the residing microbial community, with possible feedback consequences on the host’s health. To explore the possible relationship between fecal microbial composition and PD ingestion, we collected fecal samples from 45 turtles rescued between 2017 and 2019 in the Northwestern Adriatic Sea (Italy), assessing occurrence and content of PD in the samples and in parallel the microbiome structure by 16S rRNA gene sequencing. According to our findings, almost all samples contained PD, mirroring the high level of plastic pollution in the area. We identified phylotypes associated to a high amount of PD, namelyCetobacterium someraeand other taxa, possibly responding to contamination by plastic-associated chemicals. Furthermore, putative marine pathogens were found associated to higher plastic contamination, supporting the hypothesis that PD can act as a carrier for environmental pathogenic bacteria into marine organisms. Besides confirming the role of the sea turtle as relevant flagship species for plastic pollution of the marine environment, our study paves the way to the exploration of the impact that PD ingestion can have on the microbial counterpart of large marine organisms, with potential feedback consequences on the animal and ecosystem health.
Modeling the Electrostatic Actuation of Nanomechanical Pillar Dimers
Authors: Kainz Andreas , Beigelbeck Roman , Schmid Silvan
Published: February 2021

With their unparalleled mass sensitivity, enabling single-molecule mass spectrometry, nanomechanical resonators have the potential to considerably improve existing sensor technology. Vertical pillar resonators are a promising alternative to the existing lateral resonator designs. However, one major obstacle still stands in the way of their practical use: The efficient transduction (actuation & detection) of the vibrational motion of such tiny structures, even more so when large arrays of such nanopillars need to be driven. While electrostatic forces are typically weak and, on the nanoscale even weaker when compared to a cantilever-like stiffness, it is worth revisiting the possibility of electrostatic actuation of nanomechanical pillars and other nanomechanical structures. In this paper, these forces produced by an external field are studied both analytically and numerically, and their dependencies on the geometric dimensions are discussed. Furthermore, the expected deflections for different configurations of pillar geometries are calculated and compared.
Assessment of Immunotoxicity and Oxidative Stress Induced by Zinc Selenium/Zinc Sulphide Quantum Dots
Authors: Reshma V. G. , Mohanan P. V.
Published: February 2021

Although ZnSe/ZnS quantum dots (QDs) have emerged as apparently less hazardous substitute to cadmium-based QDs, their toxicity has not been fully understood. Huge levels of ROS production and associated difficulties comprise the underlying reason for nanomaterial toxicity in cells. This will cause both immunotoxicity and genotoxicity. In the current work, Zinc Selenium/Zinc Sulphide (ZnSe/ZnS) QDs was synthesized, characterized and analyzed for its role in oxidative stress induction in two cell lines (HepG2 and HEK) and Swiss Albino mice. ROS production and influence of catalase activity in ROS production measured by DCFHDA assay in both HepG2 and HEK cells after exposure to ZnSe/ZnS QDs. Assessment of nitrile radical formation carried out by griess reagent. Level of GSH is assessed as a marker for oxidative stress induced by QDs. Cell death induced after exposure to ZnSe/ZnS QDs investigated by Calcein AM-PI live dead assay. Apoptotic DNA ladder assay carried out for studying the potential of ZnSe/ZnS QDs to induce DNA fragmentation. In vivo bio-nano interaction was studied by exposing Swiss Albino mice to ZnSe/ZnS QDs via i.v. and i.p. injection. Antioxidant assays were carried out in brain and liver homogenates to study the oxidative stress. LPO, GSH, GPx, GR and SOD are considered as biomarkers for the stress analysis. Blood brain barrier (BBB) integrity also studied. Spleenocytes proliferation assay was carried out to study the immunotoxicity response. ZnSe/ZnS QDs do not induce visible oxidative stress upto a concentration of 50 μg/ml. Cell death occurs at higher concentration (100 μg/ml) caused by ROS production. Overall study apparently provide attentive information that ZnSe/ZnS QDs is not capable of eliciting any serious damages to liver and brain tissues which in turn substantiates its applicability in biomedical applications.
Neurological Disorders Associated With COVID-19 Hospital Admissions: Experience of a Single Tertiary Healthcare Center
Authors: Dhillon Permesh Singh , Dineen Robert A. , Morris Haley , Tanasescu Radu , Nikfekr Esmaeil , Evans Jonathan , Constantinescu Cris S. , Hosseini Akram A.
Published: February 2021

Background: Early reports have detailed a range of neurological symptoms in patients with the SARS-CoV-2 infection. However, there is a lack of detailed description and incidence of the neurological disorders amongst hospitalized COVID-19 patients. We describe a range of neurological disorders (other than non-specific neurological symptoms), including their clinical, radiological, and laboratory findings, encountered in our cohort of COVID-19 patients admitted to a large tertiary institution.

Methods: We reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke admissions and Neurological multi-disciplinary team meetings for all hospitalized patients with suspected or proven COVID-19 from 17 March 2020 to 31 August 2020.

Results: Twenty-nine of 1,243 COVID-19 inpatients (2.3%) presented with COVID-19-related neurological disorders. The mean age was 68.9 ± 13.5(SD) years, age range of 34–97 years, and there were 16 males. Twenty two patients had confirmed, five were probable and two had suspected COVID-19 infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms at presentation included acute confusion and delirium, seizures, and new focal neurological deficits. Based on the pre-defined neurological phenotype, COVID-19 patients were grouped into four main categories. Sixteen patients had cerebrovascular events (13 with acute ischemic stroke and three had hemorrhagic features), seven patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy (including two with known Multiple Sclerosis), whilst disorders of movement and peripheral nervous system were diagnosed in three patients each.

Conclusion: Although the exact prevalence and etiology remain unclear, new onset of neurological disorders, in addition to anosmia, is non-sporadic during the acute COVID-19-infection. Longitudinal follow-up of these patients is required to determine the clinical and functional outcome, treatment response and long-term effects of the SARS-CoV-2 infection.
Neuroimage Biomarker Identification of the Conversion of Mild Cognitive Impairment to Alzheimer’s Disease
Authors: Kung Te-Han , Chao Tzu-Cheng , Xie Yi-Ru , Pai Ming-Chyi , Kuo Yu-Min , Lee Gwo Giun Chris
Published: February 2021

An efficient method to identify whether mild cognitive impairment (MCI) has progressed to Alzheimer’s disease (AD) will be beneficial to patient care. Previous studies have shown that magnetic resonance imaging (MRI) has enabled the assessment of AD progression based on imaging findings. The present work aimed to establish an algorithm based on three features, namely, volume, surface area, and surface curvature within the hippocampal subfields, to model variations, including atrophy and structural changes to the cortical surface. In this study, a new biomarker, the ratio of principal curvatures (RPC), was proposed to characterize the folding patterns of the cortical gyrus and sulcus. Along with volumes and surface areas, these morphological features associated with the hippocampal subfields were assessed in terms of their sensitivity to the changes in cognitive capacity by two different feature selection methods. Either the extracted features were statistically significantly different, or the features were selected through a random forest model. The identified subfields and their structural indices that are sensitive to the changes characteristic of the progression from MCI to AD were further assessed with a multilayer perceptron classifier to help facilitate the diagnosis. The accuracy of the classification based on the proposed method to distinguish whether a MCI patient enters the AD stage amounted to 79.95%, solely using the information from the features selected by a logical feature selection method.