bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodological approaches to estimating the efficiency and effectiveness of research activities: world practice
Authors:   SESE “The Academy of Financial Management”, KLYMENKO Kateryna , SAVOSTIANENKO Maksym ,   SESE “The Academy of Financial Management”
Published: December 2020

The article discusses methodological approaches to assessing the effectiveness and efficiency of research activities used in world practice, in particular, such OECD standards as Oslo Manual, Frascati Manual, Using Patent Data as Science and Technology Indikators – Patent Manual, The Measurement of Human Resources Devoted to S&T – Canberra Manual and Guide for the Measurement and Interpretation of Balance of Payments Data, Hong Kong Principles etc. The assessment of the scientific sphere in international comparisons is given according to the following world rankings: The Global Innovation Index (GII, Global Innovation Index), the Global Competitiveness Index (GCІ, The Global Competitiveness Index) and the European Innovation Scoreboard (EIS, European Innovation Scoreboard). To compare world practice, the article presents the indicators used in Ukraine for grouping statistical data on scientific activity, which are covered by the State Statistics Service and the Ministry of Education and Science. The article emphasizes the importance of adopting the Concept of the State Program for the Development of Research Infrastructures in Ukraine until 2026, proposed by the Ministry of Education and Science. The adoption of such a Concept is extremely important, as its implementation will contribute to the effective and balanced development of research infrastructures and will ensure the functioning of the research infrastructure system at the appropriate level. Scientists will be provided with access to a competitive research infrastructure and motivated to engage in high-level scientific and scientific-technical activities. The effectiveness of the Concept implementation measures will be ensured by optimizing logistical, financial and labor costs aimed at improving the quality of Ukrainian research infrastructures.
The sustainable human capital development and financing of education in Europe and Ukraine
Authors:   Academician Stepan Demianchuk International University of Economics and Humanities, OLIEVSKA Myroslava , ROMANOV Arthur ,   Academician Stepan Demianchuk International University of Economics and Humanities, BONDARENKO Dmytro ,   SESE “The Academy of Financial Management”
Published: December 2020

Human capital is a key to unlocking a child’s potential and to improving economic growth in every country. But the COVID-19 pandemic threatens hard-won gains in health and education over the past decade, especially in the developing countries. The research is devoted to the analysis of the European experience of financing education for sustainable human capital development and provides practical recommendations for implementing tools for financing education for sustainable human capital development in Ukraine. In order to achieve the stated purpose theoretical bases, legislative and regulatory official documents were analyzed. The main problematic areas are: participation of adults in learning; the share of employed graduates; the low level average expenditure per pupil/student and others. The review shows that the most perspective approaches to financing education for sustainable human capital development are partnership of governments, local authorities, educational, business and household institutions; reform the mechanism of education funding. As a result, the roles of the EU and international organizations in the development of mechanisms and tools for financing education at all levels by different groups of actors have been identified. The objective need for cooperation of international organizations, state institutions, economic entities and human capital carriers to finance quality and affordable education is substantiated. The results of the study can be used in governance models. The study actualizes the value of human capital development and financing of education, and proves their impact on the sustainable growth.
Improvement of tax control in Ukraine on the basis of implementing BEPS plan tools and automatic information exchange
Authors:   SESE “The Academy of Financial Management”, OLEYNIKOVA Liudmyla , DOLZHENKO Inna ,   Improvement of tax control in Ukraine on the basis of implementing BEPS plan tools and automatic information exchange
Published: December 2020

The article is devoted to substantiating the need to develop and strengthening the competencies and capabilities of tax services to identify and stop tax evasion in the global economic space characterized by the use of aggressive tax planning schemes related to the taxation of cross-border companies. The aim of the article is to determine the procedures and consequences of the introduction in Ukraine of the standard of automatic exchange of information for tax purposes, the advantages of which are its potential to curb significant tax evasion offshore. Research methods: methods used in this research goes as following: comparative analysis, systematic analysis, cognitive-analytical, data base analysis etc. It is established that the exchange of information between the tax authorities of different countries is the most important among the international instruments to combat cross-border tax evasion schemes, and the main international tool for cooperation in overcoming the asymmetry of tax information is the introduction of a standard for automatic exchange of information for tax purposes. Emphasis is placed on the parameters set by the CRS standard for the identification and exchange of information and the steps that need to be taken to implement it in Ukraine. Research methods: methods used in this research goes as following: comparative analysis, systematic analysis, cognitive-analytical, data base analysis etc. Author arrives at the conclusion that the dates of establishment of the automatic taxation and financial information exchange system in Ukraine (in accordance with CRS standards) are not being followed sufficiently. In this paper author discusses the importance of systematic and methodological establishment of the automatic taxation and financial information exchange system in Ukraine (in accordance with CRS standards) as well as suggests the methods that would efficiently speed up the process of law enforcement project development in Ukraine as well as other normative acts.
Analysis of Japan’s and Ukraine’s sectoral structure of the economy within the framework of the aggregated input-output models
Authors:   SESE “The Academy of Financial Management”, KULYK Volodymyr
Published: December 2020

The sectoral structure of the economies of Japan and Ukraine is studied. The aggregation of the input-output table of Japan’s economy (2015) to 13 constipated industries, which have traditionally been used for a long time for the analysis of the Japanese economic structure, and the input-output table of Ukraine’s economy (2018) to 10 sectors were carried out. For a more comparable comparison of the input-output tables of both economies was aggregated to the level of 3 constipated sectors (primary, secondary and tertiary). The analysis of production processes for the economy as a whole and in terms of sectors was conducted, the structure of sectoral costs and generateable income (gross value added, factor income) was investigated. The author worked out a matrix of direct costs, built heat maps, etc. Analysis based on aggregated release cost tables, including 3 sectoral input-output tables, is useful for initial familiarization with the peculiarities of inter-sectoral relationships, final demand structure and added value, peculiarities of production processes. Being quite simplified, they reflect the basic content of processes in the production sphere, can be used for educationally methodical purposes, in the development of a strategy for modernization of production, to be the basis for comparing production systems of different national economies. Further research is appropriate within more detailed input-output tables, where the classification of types of economic activity and the degree of data aggregation meets international standards.
Evaluating the system of factors influencing the investment decision under postindustrial transformations
Authors:   SESE “The Academy of Financial Management”, KORNIEIEVA Iuliia
Published: December 2020

The article analyzes the prerequisites for systematic use of Big Data sources by government agencies as a tool for forecasting systemic financial risks during investment decision processes at the state level as well as for the formation of public investment policy. The author made a comprehensive assessment of the system of factors that influence the investment decision-making process in terms of post-industrial transformations. The author proposes to solve the problem of forming investment activity information risks based on empowerment of big data analytics. The proposed model assesses the institutional framework by analyzing a wide range of factors such as the level of shadow economy, corruption and economic freedom, including government integrity, property rights, investment freedom, that influence the process of investment decision. Based on indices analysis expands the limited capabilities of risk assessment models of financial instruments based on market data, that reflect the components of expectations, covering the behavioral factor - speculative behavior. Cluster assessment of investment inflows to Ukraine was conducted based on econometric modeling using VAR analysis revealed no significant impact of indicators that reflect the presence of institutional barriers for investors concerning FDI from offshore countries (Cyprus, British Virgin Islands), the impact was limited to an average of 5%. Along with economic factors, the determinants of FDI inflows from developed countries (Germany, Great Britain, United States of America, Austria, the Netherlands) were institutional ones influencing the formation of compliance risks, the impact of which ranged within 30%.
THE ROLE OF LAW IN ECONOMIC GLOBALIZATION IN INDONESIA
Authors: Ukas Ukas , Arman Zuhdi
Published: December 2020

Legal development has a more comprehensive and basic meaning compared to the promotion and renewal of law in the context of increasing the nation's competitiveness, legal politics in Indonesia directs legal development to encourage economic growth. The research objective is to determine economic growth, especially in the business world and in the industrial world which determines investment capacity, especially law enforcement and protection. The method used is normative juridical. The results of this study see Law as a social engineering tool that was born because the concept of law is taught to direct people to better understand change. Law as an instrument of development control includes development in the economic field. Enforcement of law and justice in particular in the economic development of activities and developing development in accordance with long-term government programs. The role of law in economic globalization in the 21st century is certainly expected aspects of globalization in legal and economic growth, the development of economic law also includes investment law, which of course must run in accordance with long-term development tools.
Shapley Value Confidence Intervals for Attributing Variance Explained
Authors: Fryer Daniel , Strümke Inga , Nguyen Hien
Published: December 2020

The coefficient of determination, the R2, is often used to measure the variance explained by an affine combination of multiple explanatory covariates. An attribution of this explanatory contribution to each of the individual covariates is often sought in order to draw inference regarding the importance of each covariate with respect to the response phenomenon. A recent method for ascertaining such an attribution is via the game theoretic Shapley value decomposition of the coefficient of determination. Such a decomposition has the desirable efficiency, monotonicity, and equal treatment properties. Under a weak assumption that the joint distribution is pseudo-elliptical, we obtain the asymptotic normality of the Shapley values. We then utilize this result in order to construct confidence intervals and hypothesis tests for Shapley values. Monte Carlo studies regarding our results are provided. We found that our asymptotic confidence intervals required less computational time to competing bootstrap methods and are able to exhibit improved coverage, especially on small samples. In an expository application to Australian real estate price modeling, we employ Shapley value confidence intervals to identify significant differences between the explanatory contributions of covariates, between models, which otherwise share approximately the same R2 value. These different models are based on real estate data from the same periods in 2019 and 2020, the latter covering the early stages of the arrival of the novel coronavirus, COVID-19.
Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine
Authors: Assunção Marisa , Dehghan-Baniani Dorsa , Yiu Chi Him Kendrick , Später Thomas , Beyer Sebastian , Blocki Anna
Published: December 2020

Cell-derived extracellular matrices (CD-ECMs) captured increasing attention since the first studies in the 1980s. The biological resemblance of CD-ECMs to their in vivo counterparts and natural complexity provide them with a prevailing bioactivity. CD-ECMs offer the opportunity to produce microenvironments with costumizable biological and biophysical properties in a controlled setting. As a result, CD-ECMs can improve cellular functions such as stemness or be employed as a platform to study cellular niches in health and disease. Either on their own or integrated with other materials, CD-ECMs can also be utilized as biomaterials to engineer tissues de novo or facilitate endogenous healing and regeneration. This review provides a brief overview over the methodologies used to facilitate CD-ECM deposition and manufacturing. It explores the versatile uses of CD-ECM in fundamental research and therapeutic approaches, while highlighting innovative strategies. Furthermore, current challenges are identified and it is accentuated that advancements in methodologies, as well as innovative interdisciplinary approaches are needed to take CD-ECM-based research to the next level.
CircAMOTL1 Promotes Tumorigenesis Through miR-526b/SIK2 Axis in Cervical Cancer
Authors: Sun Zhengwei , Niu Sanqiang , Xu Fuxia , Zhao Weidong , Ma Rong , Chen Mingwei
Published: December 2020

Background

Cervical cancer is one of the most common malignancies in women, leading to major health problems for its high morbidity and mortality. Numerous studies have demonstrated that circular RNAs (circRNAs) could be participated in the progression of multifarious diseases, especially plentiful carcinomas. CircAMOTL1 (angiomotin-like1, ID: hsa_circ_0004214), which is located on human chromosome 11:9 4532555-94533477, is involved in the occurrence of breast cancer, etc. However, the intrinsic and concrete molecular mechanism of circAMOTL1 in cervical carcinomas remained thoroughly unclear, which was also the bottleneck of circRNAs studies in cancer.

Methods

The relative expression levels of circAMOTL1 and miR-526b in cervical carcinoma patients’ specimens and cervical carcinoma cell lines were detected by RT-qPCR. Through experiments including loss-function and overexpression, the biological effects of circAMOTL1 and miR-526b on the proliferation, migration, apoptosis, and tumorigenicity were explored in cervical carcinomas. Dual luciferase reporter gene analysis, western blot, and other methods were adopted to explore the circAMOTL1 potential mechanism in cervical carcinomas.

Results

In our experiments, our researches displayed that circAMOTL1 was significantly higher expression in cervical carcinomas specimens and cell lines. Further experiments illustrated that the knockdown of circAMOTL1 could restrain the malignant phenotype, AKT signaling, and epithelial–mesenchymal transition (EMT) of in cervical carcinomas cells. Meanwhile miR-526b was downregulated in cervical carcinomas and even miR-526b could partially reverse circAMOTL1 function in malignant cervical tumor cells. CircAMOTL1 acts as a microRNA (miRNA) sponge that actively regulates the expression of salt-inducible kinase 2 (SIK2) to sponge miR-526b and subsequently increases malignant phenotypes of cervical carcinomas cells. In a word, circAMOTL1 acts a carcinogenic role and miR-526b serves as the opposite function of antioncogene in the cervical carcinoma pathogenesis.

Conclusion

CircAMOTL1-miR-526b-SIK2 axis referred to the malignant progression and development of cervical carcinomas. CircAMOTL1 expression was inversely correlated with miR-526b and positively correlated with SIK2 mRNA in cervical cancer tissues. Thus, circAMOTL1 exerted an oncogenic role in cervical cancer progression through sponging miR-526b. Taken together, our study revealed that circAMOTL1 acted as an oncogene and probably was a potential therapeutic target for the cervical cancer.
Super-Enhancer Associated Five-Gene Risk Score Model Predicts Overall Survival in Multiple Myeloma Patients
Authors: Qi Tingting , Qu Jian , Tu Chao , Lu Qiong , Li Guohua , Wang Jiaojiao , Qu Qiang
Published: December 2020

Multiple myeloma (MM) is a malignant plasma cell tumor with high heterogeneity, characterized by anemia, hypercalcemia, renal failure, and lytic bone lesions. Although various powerful prognostic factors and models have been exploited, the development of more accurate prognosis and treatment for MM patients is still facing many challenges. Given the essential roles of super-enhancer (SE) associated genes in the tumorigenesis of MM, we tried to initially screen and identify the significant prognostic factors from SE associated genes in MM by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis using GSE24080 and GSE9782 datasets. Risk score model of five genes including CSGALNACT1, FAM53B, TAPBPL, REPIN1, and DDX11, was further constructed and the Kaplan-Meier (K-M) curves showed that the low-risk group seems to have better clinical outcome of survival compared to the high-risk group. Time-dependent receiver operating characteristic (ROC) curves presented the favorable performance of the model. An interactive nomogram consisting of the five-gene risk group and eleven clinical traits was established and identified by calibration curves. Therefore, the risk score model of SE associated five genes developed here could be used to predict the prognosis of MM patients, which may assist the clinical treatment of MM patients in the future.
Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic Signature in Kidney Renal Papillary Cell Carcinoma
Authors: He Ruyi , Wang Longyu , Li Juan , Ma Lixin , Wang Fei , Wang Yang
Published: December 2020

The kidney renal papillary cell carcinoma (KIRP) is a relatively rare type of renal cell carcinoma (RCC). Currently, most kidney cancer studies primarily focus on RCC, and there has been no investigation to find a robust signature to predict the survival outcome of KIRP patients. In this study, we constructed a competing endogenous RNA (ceRNA) network, including 1,251 lncRNA–miRNA–mRNA interactions. Eight differentially expressed genes (IGF2BP3, PLK1, LINC00200, NCAPG, CENPF, miR-217, GAS6-As1, and LRRC4) based on the TCGA database were selected. The prognostic signature was established by combining the univariate Cox regression method and a stepwise regression method, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. In conclusion, we identified eight prognostic signatures with using ceRNA networks. Our study provided a global view and a systematic dissection on KIRP prognosis biomarkers, and the eight identified genes might be used as new and important prognostic factors involved in KIRP pathogenesis.
Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology
Authors: Carrasco Elisa , Stockert Juan Carlos , Juarranz Ángeles , Blázquez-Castro Alfonso
Published: December 2020

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O2) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like per se chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to in situ ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry. The effect takes advantage of the photoexcitation of plasmonic resonances in metal nanoparticles to induce a new cohort of photochemical and redox reactions. These metal photo-transducers are considered chemically inert and can undergo billions of photoexcitation rounds without bleaching or suffering significant oxidative alterations. Also, their optimal absorption band can be shape- and size-tailored in order to match any of the near infrared (NIR) biological windows, where undesired absorption/scattering are minimal. In this mini review, the basic mechanisms and principal benefits of this light-driven approach to generate ROS will be discussed. Additionally, some significant experiments in vitro and in vivo will be presented, and tentative new avenues for further research will be advanced.
Lipid Profile Features and Their Associations With Disease Severity and Mortality in Patients With COVID-19
Authors: Sun Jia Teng , Chen Zhongli , Nie Peng , Ge Heng , Shen Long , Yang Fan , Qu Xiao Long , Ying Xiao Ying , Zhou Yong , Wang Wei , Zhang Min , Pu Jun
Published: December 2020

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality.

Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020.

Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456–0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456–0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70–0.85) and 0.85 (95% CI, 0.76–0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61–0.88) and 0.74 (95% CI, 0.61–0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (<0.95 g/L) or HDL-C (<0.84 mmol/l) had higher mortality rates during hospitalization (log-rank p < 0.001). Notably, levels of apoA-1 and HDL-C were inversely proportional to disease severity. The survivors of severe cases showed significant recovery of apoA-1 levels at the end of hospitalization (vs. midterm apoA-1 levels, p = 0.02), whereas the mortality cases demonstrated continuously lower apoA-1 levels throughout hospitalization. Correlation analysis revealed that apoA-1 and HDL-C levels were negatively correlated with both admission levels and highest concentrations of C-reactive protein and interleukin-6.

Conclusions: Severely ill COVID-19 patients featured low HDL-C and apoA-1 levels, which were strongly correlated with inflammatory states. Thus, low apoA-1 and HDL-C levels may be promising predictors for severe disease and in-hospital mortality in patients suffering from COVID-19.
Quantitative Magnetic Resonance Imaging of the Pancreas of Individuals With Diabetes
Authors: Virostko John
Published: December 2020

Magnetic resonance imaging (MRI) has the potential to improve our understanding of diabetes and improve both diagnosis and monitoring of the disease. Although the spatial resolution of MRI is insufficient to directly image the endocrine pancreas in people, the increasing awareness that the exocrine pancreas is also involved in diabetes pathogenesis has spurred new MRI applications. These techniques build upon studies of exocrine pancreatic diseases, for which MRI has already developed into a routine clinical tool for diagnosis and monitoring of pancreatic cancer and pancreatitis. By adjusting the imaging contrast and carefully controlling image acquisition and processing, MRI can quantify a variety of tissue pathologies. This review introduces a number of quantitative MRI techniques that have been applied to study the diabetic pancreas, summarizes progress in validating and standardizing each technique, and discusses the need for image analyses that account for spatial heterogeneity in the pancreas.
Strategies Using Genomic Selection to Increase Genetic Gain in Breeding Programs for Wheat
Authors: Tessema Biructawit Bekele , Liu Huiming , Sørensen Anders Christian , Andersen Jeppe Reitan , Jensen Just
Published: December 2020

Conventional wheat-breeding programs involve crossing parental lines and subsequent selfing of the offspring for several generations to obtain inbred lines. Such a breeding program takes more than 8 years to develop a variety. Although wheat-breeding programs have been running for many years, genetic gain has been limited. However, the use of genomic information as selection criterion can increase selection accuracy and that would contribute to increased genetic gain. The main objective of this study was to quantify the increase in genetic gain by implementing genomic selection in traditional wheat-breeding programs. In addition, we investigated the effect of genetic correlation between different traits on genetic gain. A stochastic simulation was used to evaluate wheat-breeding programs that run simultaneously for 25 years with phenotypic or genomic selection. Genetic gain and genetic variance of wheat-breeding program based on phenotypes was compared to the one with genomic selection. Genetic gain from the wheat-breeding program based on genomic estimated breeding values (GEBVs) has tripled compared to phenotypic selection. Genomic selection is a promising strategy for improving genetic gain in wheat-breeding programs.
The Genetic Status of the Critically Endangered Hainan Gibbon (Nomascus hainanus): A Species Moving Toward Extinction
Authors: Guo Yanqing , Chang Jiang , Han Ling , Liu Tao , Li Gang , Garber Paul A. , Xiao Ning , Zhou Jiang
Published: December 2020

The Hainan gibbon (Nomascus hainanus), once widespread across Hainan, China, is now found only in the Bawangling National Nature Reserve. With a remaining population size of 33 individuals, it is the world’s rarest primate. Habitat loss and fragmentation are the primary drivers of Hainan gibbon population decline. In this study, we integrated data based on field investigations and genotype analyses of 10 microsatellite loci (from fecal samples) to assess genetic diversity in this Critically Endangered primate species. We found that the genetic diversity of the Hainan gibbon is extremely low, with 7 of 8 microsatellite loci exhibiting decreased diversity. Additional molecular analyses are consistent with field observations indicating that individuals in groups A, B, and C are closely related, the female–male sex ratios of the offspring deviates significantly from 1:1, and the world’s remaining Hainan gibbon population is expected to experience continued high levels of inbreeding in the future. Given extensive habitat loss (99.9% of its natural range has been deforested) and fragmentation, this rarest ape species faces impending extinction unless corrective measures are implemented immediately.
Higher Cytokine and Opsonizing Antibody Production Induced by Bovine Serum Albumin (BSA)-Conjugated Tetrasaccharide Related to Streptococcus pneumoniae Type 3 Capsular Polysaccharide
Authors: Kurbatova Ekaterina A. , Akhmatova Nelli K. , Zaytsev Anton E. , Akhmatova Elina A. , Egorova Nadezhda B. , Yastrebova Natalya E. , Sukhova Elena V. , Yashunsky Dmitriy V. , Tsvetkov Yury E. , Nifantiev Nikolay E.
Published: December 2020

A number of studies have demonstrated the limited efficacy ofS. pneumoniaetype 3 capsular polysaccharide (CP) in the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal diseases and carriage. Synthetic oligosaccharides (OSs) may provide an alternative to CPs for development of novel conjugated pneumococcal vaccines and diagnostic test systems. A comparative immunological study of di–, tri–, and tetra–bovine serum albumin (BSA) conjugates was performed. All oligosaccharides conjugated with biotin and immobilized on streptavidin-coated plates stimulated production of IL-1α, IL-2, IL-4, IL-5, IL-10, IFNγ, IL-17A, and TNFα, but not IL-6 and GM-CSF in monocultured mice splenocytes. The tetrasaccharide–biotin conjugate stimulated the highest levels of IL-4, IL-5, IL-10, and IFNγ, which regulate expression of specific immunoglobulin isotypes. The tetra–BSA conjugate adjuvanted with aluminum hydroxide elicited high levels of IgM, IgG1, IgG2a, and IgG2b antibodies (Abs). Anti-CP-induced Abs could only be measured using the biotinylated tetrasaccharide. The tetrasaccharide ligand possessed the highest binding capacity for anti-OS and antibacterial IgG Abs in immune sera. Sera to the tetra–BSA conjugate promoted greater phagocytosis of bacteria by neutrophils and monocytes than the CRM197-CP-antisera. Sera of mice immunized with the tetra–BSA conjugate exhibited the highest titer of anti-CP IgG1 Abs compared with sera of mice inoculated with the same doses of di– and tri–BSA conjugates. Upon intraperitoneal challenge with lethal doses ofS. pneumoniaetype 3, the tri– and tetra–BSA conjugates protected mice more significantly than the di–BSA conjugate. Therefore, it may be concluded that the tetrasaccharide ligand is an optimal candidate for development of a semi-synthetic vaccine againstS. pneumoniaetype 3 and diagnostic test systems.
IL4I1 Accelerates the Expansion of Effector CD8+ T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation
Authors: Puiffe Marie-Line , Dupont Aurélie , Sako Nouhoum , Gatineau Jérôme , Cohen José L. , Mestivier Denis , Lebon Agnès , Prévost-Blondel Armelle , Castellano Flavia , Molinier-Frenkel Valérie
Published: December 2020

IL4I1 is an immunoregulatory enzyme that inhibits CD8 T-cell proliferation in vitro and in the tumoral context. Here, we dissected the effect of IL4I1 on CD8 T-cell priming by studying the differentiation of a transgenic CD8 T-cell clone and the endogenous repertoire in a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection. Unexpectedly, we show that IL4I1 accelerates the expansion of functional effector CD8 T cells during the first several days after infection and increases the average affinity of the elicited repertoire, supporting more efficient LCMV clearance in WT mice than IL4I1-deficient mice. Conversely, IL4I1 restrains the differentiation of CD8 T-cells into long-lived memory precursors and favors the memory response to the most immunodominant peptides. IL4I1 expression does not affect the phenotype or antigen-presenting functions of dendritic cells (DCs), but directly reduces the stability of T-DC immune synapses in vitro, thus dampening T-cell activation. Overall, our results support a model in which IL4I1 increases the threshold of T-cell activation, indirectly promoting the priming of high-affinity clones while limiting memory T-cell differentiation.
The Roles of Inflammation in Keloid and Hypertrophic Scars
Authors: Wang Zheng-Cai , Zhao Wan-Yi , Cao Yangyang , Liu Yan-Qi , Sun Qihang , Shi Peng , Cai Jia-Qin , Shen Xiao Z. , Tan Wei-Qiang
Published: December 2020

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.
Broad Neutralization Responses Against Oncogenic Human Papillomaviruses Induced by a Minor Capsid L2 Polytope Genetically Incorporated Into Bacterial Ferritin Nanoparticles
Authors: Yang Fan , Mariz Filipe C. , Zhao Xueer , Spagnoli Gloria , Ottonello Simone , Müller Martin
Published: December 2020

Cervical cancer remains a global health burden despite the introduction of highly effective vaccines for the prophylaxis of causative human papillomavirus infection (HPV). Current efforts to eradicate cervical cancer focus on the development of broadly protective, cost-effective approaches. HPV minor capsid protein L2 is being recognized as a promising alternative to the major capsid protein L1 because of its ability to induce responses against a wider range of different HPV types. However, a major limitation of L2 as a source of cross-neutralizing epitopes is its lower immunogenicity compared to L1 when assembled into VLPs. Various approaches have been proposed to overcome this limitation, we developed and tested ferritin-based bio-nanoparticles displaying tandemly repeated L2 epitopes from eight different HPV types grafted onto the surface of Pyrococcus furiosus thioredoxin (Pf Trx). Genetic fusion of the Pf Trx-L2(8x) module to P. furiosus ferritin (Pf Fe) did not interfere with ferritin self-assembly into an octahedral structure composed by 24 protomers. In guinea pigs and mice, the ferritin super-scaffolded, L2 antigen induced a broadly neutralizing antibody response covering 14 oncogenic and two non-oncogenic HPV types. Immune-responsiveness lasted for at least one year and the resulting antibodies also conferred protection in a cervico-vaginal mouse model of HPV infection. Given the broad organism distribution of thioredoxin and ferritin, we also verified the lack of cross-reactivity of the antibodies elicited against the scaffolds with human thioredoxin or ferritin. Altogether, the results of this study point to P. furiosus ferritin nanoparticles as a robust platform for the construction of peptide-epitope-based HPV vaccines.
Predicting Geographic Ranges of Marine Animal Populations Using Stable Isotopes: A Case Study of Great Hammerhead Sharks in Eastern Australia
Authors: Raoult Vincent , Trueman Clive N. , Kingsbury Kelsey M. , Gillanders Bronwyn M. , Broadhurst Matt K. , Williamson Jane E. , Nagelkerken Ivan , Booth David J. , Peddemors Victor , Couturier Lydie I. E. , Gaston Troy F.
Published: December 2020

Determining the geographic range of widely dispersed or migratory marine organisms is notoriously difficult, often requiring considerable costs and typically extensive tagging or exploration programs. While these approaches are accurate and can reveal important information on the species, they are usually conducted on only a small number of individuals and can take years to produce relevant results, so alternative approaches may be preferable. The presence of latitudinal gradients in stable carbon isotope compositions of marine phytoplankton offers a means to quickly determine likely geographic population ranges of species that rely on productivity from these resources. Across sufficiently large spatial and temporal scales, the stable carbon isotopes of large coastal or pelagic marine species should reflect broad geographic patterns of resource use, and could be used to infer geographic ranges of marine populations. Using two methods, one based on a global mechanistic model and the other on targeted low-cost latitudinal sampling of fishes, we demonstrate and compare these stable isotope approaches to determine the core population geography of an apex predator, the great hammerhead (Sphyrna mokarran). Both methods indicated similar geographic ranges and suggested thatS. mokarranrecorded in south-eastern Australia are likely to be from more northern Australian waters. These approaches could be replicated in other areas where coastlines span predictable geographic gradients in isotope values and be used to determine the core population geography of highly mobile species to inform management decisions.
Refractory Celiac Disease Type II: A Case Report and Literature Review
Authors: Chibbar Richa , Nostedt Jordan , Mihalicz Dana , Deschenes Jean , McLean Ross , Dieleman Levinus A.
Published: December 2020

We present an unusual case of 68-year-old male, who presented with acute abdomen, ulcerative jejunitis with perforation, and 2 months later with perforation of the sigmoid colon. We will also discuss difficulties in the delay in diagnosis of refractory celiac disease (RCD), specifically the atypical presentation, multiple surgeries, the consecutive failure of distinct therapeutic options, and multiple complications that occurred within the 3 months since first presentation.
Classification of Patients With Sepsis According to Immune Cell Characteristics: A Bioinformatic Analysis of Two Cohort Studies
Authors: Zhang Shi , Wu Zongsheng , Chang Wei , Liu Feng , Xie Jianfeng , Yang Yi , Qiu Haibo
Published: December 2020

Background: Sepsis is well-known to alter innate and adaptive immune responses for sustained periods after initiation by an invading pathogen. Identification of immune cell characteristics may shed light on the immune signature of patients with sepsis and further indicate the appropriate immune-modulatory therapy for distinct populations. Therefore, we aimed to establish an immune model to classify sepsis into different immune endotypes via transcriptomics data analysis of previously published cohort studies.

Methods: Datasets from two observational cohort studies that included 585 consecutive sepsis patients admitted to two intensive care units were downloaded as a training cohort and an external validation cohort. We analyzed genome-wide gene expression profiles in blood from these patients by using machine learning and bioinformatics.

Results: The training cohort and the validation cohort had 479 and 106 patients, respectively. Principal component analysis indicated that two immune subphenotypes associated with sepsis, designated the immunoparalysis endotype, and immunocompetent endotype, could be distinguished clearly. In the training cohort, a higher cumulative 28-day mortality was found in patients classified as having the immunoparalysis endotype, and the hazard ratio was 2.32 (95% CI: 1.53–3.46 vs. the immunocompetent endotype). External validation further demonstrated that the present model could categorize sepsis into the immunoparalysis and immunocompetent type precisely and efficiently. The percentages of 4 types of immune cells (M0 macrophages, M2 macrophages, naïve B cells, and naïve CD4 T cells) were significantly associated with 28-day cumulative mortality (P < 0.05).

Conclusion: The present study developed a comprehensive tool to identify the immunoparalysis endotype and immunocompetent status in hospitalized patients with sepsis and provides novel clues for further targeting of therapeutic approaches.
Serous Effusions Diagnostic Accuracy for Hematopoietic Malignancies: A Cyto-Histological Correlation
Authors: Li Jinnan , Zhao Sha , Zhang Wenyan , Jiang Yong , Zhu Xianglan , Den Xueqin , Liu Weiping , Su Xueying
Published: December 2020

Background: The aim of this study was to establish the liability of cytological diagnostic and, along with ancillary techniques, to sub-classify hematopoietic malignancies in serous effusions.

Methods: We retrospectively reviewed the serous effusions of hematopoietic malignancies over an 11-year period, along with ancillary studies, clinical and histological data. We compared cytological along with histological diagnosis to evaluate the value of cytology itself. Furthermore, the discrepant cases were reviewed.

Results: In this study, a total of 242 cases were identified as hematopoietic malignancies. Ancillary technologies were performed: in 24 cases FCM, 242 cases ICC, 35 cases ISH, 81 cases PCR and 10 cases FISH. Cyto-histological correlation was available for 122 cases. The subtyping of hematopoietic malignancies was achieved using cytological material in 65/122 cases (53.3%). Of the 65 cases, T-Acute lymphoblastic leukemia/lymphoma (22.1%) was the leading subtype, followed by Burkitt lymphoma (5.7%), plasmacytoma (5.7%). Cyto-histological correlation showed a 100% concordant rate of diagnosis for hematopoietic malignancies and a high degree of agreement on sub-classification (51.6%). In this regard, T-acute lymphoblastic leukemia/lymphoma, plasmacytoma, extranodal NK/T-cell lymphoma, nasal type, anaplastic large cell lymphoma, myeloid sarcoma, and follicular lymphoma showed the highest degree of agreement (100%). The sub-classification on cytology was achieved in 53 out of the remaining 120 cases without histological diagnosis (44.2%). T-acute lymphoblastic leukemia/lymphoma (20.8%) was again the most frequently encountered subtype, followed by plasmacytoma (5.8%) and Burkitt lymphoma (4.2%).

Conclusions: This large series study provided evidence that combining cytology and ancillary studies enabled the accurate serous effusions cytological diagnoses and subsequent sub-classification for the described malignancies.
Treatment of Whole-Plant Corn Silage With Lactic Acid Bacteria and Organic Acid Enhances Quality by Elevating Acid Content, Reducing pH, and Inhibiting Undesirable Microorganisms
Authors: Jiang Fu-gui , Cheng Hai-jian , Liu Dong , Wei Chen , An Wen-juan , Wang Ya-fang , Sun Hai-tao , Song En-liang
Published: December 2020

We investigated the variation in microbial community and fermentation characteristics of whole-plant corn silage after treatment with lactic acid bacteria (LAB) and organic acids. The fresh corn forages were treated with a combination of L. acidophilus and L. plantarum (106 CFU/g fresh material) or a 7:1:2 ratio of formic acid, acetic acid, and propionic acid (6 mL/g fresh material) followed by 45 or 90 days of ensiling. Silages treated with LAB showed increased lactic acid content and decreased pH after 45 days. Although treatment with LAB or organic acids decreased the common and unique operational taxonomic units, indicating a reduction in microbial diversity, the relative abundance of Lactobacillus was elevated after 45 and 90 days compared with control, which was more distinct in the organic acid groups. Moreover, we found higher levels of acetic acid and increased abundance of Acetobacter in silages treated with organic acids whereas undesirable microorganisms such as Klebsiella, Paenibacillus, and Enterobacter were reduced. In summary, the quality of corn silages was improved by LAB or organic acid treatment in which LAB more effectively enhanced lactic acid content and reduced pH while organic acid inhibited the growth of undesirable microorganisms.
How do Planktonic Particle Collection Methods Affect Bacterial Diversity Estimates and Community Composition in Oligo-, Meso- and Eutrophic Lakes?
Authors: Xie Guijuan , Tang Xiangming , Gong Yi , Shao Keqiang , Gao Guang
Published: December 2020

Particles are hotspots of bacterial growth and nutrient recycling in aquatic ecosystems. In the study of particle-attached (PA) and/or free-living (FL) microbial assemblages, the first step is to separate particles from their surrounding water columns. Widely used collection techniques are filtration using different pore size filters, and centrifugation; however, it is unclear how the bacterial diversity, bacterial community structure (BCS) and taxonomic composition of PA assemblages are affected by different particle collection methods. To address this knowledge gap, we collected planktonic particles from eutrophic Lake Taihu, mesotrophic Lake Tianmu, and oligotrophic Lake Fuxian in China, using filtration with five pore size of filters (20, 10, 8.0, 5.0, and 3.0 μm), and centrifugation. Bacterial communities were then analyzed using Illumina MiSeq sequencing of the 16S rRNA gene. We found that PA collection method affected BCS significantly in all lakes. Centrifugation yielded the highest species diversity and lowest mean percentage of photoautotrophic Cyanobacteria in Lake Taihu, but not in the other two lakes, thus highlighting the potential compatibility of this method in the study of PA assemblage in eutrophic lakes. The high bacterial diversity and low relative percentage of Cyanobacteria was in samples retained on 5.0 μm filters in all lakes. These results suggest that collecting PA samples in lakes using filters with 5.0 μm pore size is the preferred protocol, if species diversity and heterotrophic bacteria are the top research priorities, when comparing bacterial communities in different trophic lakes at the same time. The present study offers the possibility of collecting PA samples using unified methods in oligotrophic to eutrophic lakes.
Unveiling the Biogeography and Potential Functions of the Intestinal Digesta- and Mucosa-Associated Microbiome of Donkeys
Authors: Zhang Ruiyang , Zhang Junpeng , Dang Wanyi , Irwin David M. , Wang Zhe , Zhang Shuyi
Published: December 2020

The intestinal microbial composition and metabolic functions under normal physiological conditions in the donkey are crucial for health and production performance. However, compared with other animal species, limited information is currently available regarding the intestinal microbiota of donkeys. In the present study, we characterized the biogeography and potential functions of the intestinal digesta- and mucosa-associated microbiota of different segments of the intestine (jejunum, ileum, cecum, and colon) in the donkey, focusing on the differences in the microbial communities between the small and large intestine. Our results show that, Firmicutes and Bacteroidetes dominate in both the digesta- and mucosa-associated microbiota in different intestinal locations of the donkey. Starch-degrading and acid-producing (butyrate and lactate) microbiota, such as Lactobacillus and Sarcina, were more enriched in the small intestine, while the fiber- and mucin-degrading bacteria, such as Akkermansia, were more enriched in the large intestine. Furthermore, metabolic functions in membrane transport and lipid metabolism were more enriched in the small intestine, while functions for energy metabolism, metabolism of cofactors and vitamins, amino acid metabolism were more enriched in the large intestine. In addition, the microbial composition and functions in the digesta-associated microbiota among intestinal locations differed greatly, while the mucosal differences were smaller, suggesting a more stable and consistent role in the different intestinal locations. This study provides us with new information on the microbial differences between the small and large intestines of the donkey and the synergistic effects of the intestinal microbiota with host functions, which may improve our understanding the evolution of the equine digestive system and contribute to the healthy and efficient breeding of donkeys.