bluuebunny/crossref_metadata_2025 huggingface dataset:
FROM INCREDIBLE TO A NEW NORM: DELUSIONS AND REALITIES IN WORLD POLITICS
Authors:   Institute of Europe of the Russian Academy of Sciences, Moscow, Russian Federation, GROMYKO ALEXEY
Published: September 2022

The article explores a phenomenon of events in political history, which in the course of time evolve from a category of incredible to a New Norm. An emphasis is made on the topic of European security. The role of objective and subjective factors is dwelt upon. The author analyses several key trends in contemporary international relations, distinguishes between virtual and real processes, discusses ideas of a “New Bipolarity” and a “New Cold War”. Significant attention is paid to the main divides in the system of global governance and regulation - some of them invented and some natural. A conclusion is drawn on the indispensable role of international analytics in providing the science-based foresight of future developments and the think-tank support of the state foreign policy.
ORGANIZATIONAL AND LEGAL ASPECTS OF THE EUROPEAN COMMUNITIES MEMBERSHIP IN THE WORLD CUSTOMS ORGANIZATION AS A PRECEDENT FOR CUSTOMS AND ECONOMIC UNIONS
Authors:   Research Institute of the Russian Customs Academy, Lyubertsy, Moscow region, Russian Federation, MOZER SERGEI
Published: September 2022

A task. To systematize the EC (EU) experience in terms of obtaining rights and obligations akin to those enjoyed by the WCO members, including highlighting the actions and stages in connection with the consideration of the EC application for membership in the World Customs Organization. Conclusions. The research article is devoted to the issues of the EC (EU) legal status of in the WCO and the use of the EC precedent for the implementation of the Strategic Directions for the Development of Eurasian Economic Integration until 2025 (Strategic Directions) in terms of joint actions with Member States aimed at obtaining the Union’s membership status in the WCO. The subject of the study is the activities and stages passed by the EC in the framework of interaction with the WCO to change the legal status from an observer to akin to the WCO membership. The research paper presents in abstract form the legal instruments and legal structures that have been developed at the expert level to satisfy the EC application. The identified activities, by analogy, can be used to develop an action plan (roadmap) for the Eurasian Economic Union (EEU) to obtain the WCO member status. Based on the results of the study, conclusions and recommendations were formed within the framework of cooperation between the Eurasian Economic Commission and the WCO. Social consequences. Conducting a study of the legal status of customs and economic unions in the WCO is associated with the implementation of paragraph 11.7.5. of Strategic Directions [6] in terms of cooperation with this international organization. Practical value. The results of the study are of interest to the customs cooperation block of the Eurasian Economic Commission (EEC), and can be used by specialists from customs and other executive authorities in the EEU member states, EEC experts to organize and implement mutually beneficial customs cooperation between the EEC and the WCO. The article is recommended to researchers, teachers, students, graduate students and other categories of students in the Russian Customs Academy, in other universities and the WCO regional training centers in the specialties “Customs” and “Jurisprudence”. Originality/value. The research material is based on an analysis of the practical aspects of the activities of the EEC, the WCO and is the result of a comprehensive study of the issue of the legal and organizational basis for obtaining the WCO member status by economic and customs unions.
ANALYSIS OF THE FORMATION OF THE SUBSYSTEM OF INTERNATIONAL RELATIONS IN NORTHEAST ASIA FROM THE POINT OF VIEW OF THE CIVILIZATIONAL APPROACH. PART 1
Authors:   Moscow International University, Moscow, Russian Federation, NIKIFOROV SVYATOSLAV
Published: September 2022

The purpose and objectives. The purpose of the article is to analyze the formation of the subsystem of international relations in Northeast Asia from the point of view of the civilizational approach. The following tasks are being solved: the study of the configuration of the acting forces of the superethnic level and the activity of non-ethnic systems of the subsystem of international relations in Northeast Asia and the compilation of the periodization of models of international relations on the cross-section of the ethnosphere in this region. Methodological approach. The methodology of L.N. Gumilev is the main one in the work, as well as the systematic approach developed in Oriental political science by A.D. Voskresensky, general scientific methods of cognition and the comparative historical method are also used. Results and conclusions. The article proposes the author’s periodization of models of international relations on the cross-section of the ethnosphere in Northeast Asia from the point of view of the civilizational approach. Originality and value. The research is valuable in view of its relevance and originality of the work, which focuses on obtaining new knowledge about the configuration of the acting forces of the superethnic level and the activity of non-ethnic systems of the subsystem of international relations in Northeast Asia and about the periodization of models of international relations in the ethnosphere in this region.
COMPARATIVE ANALYSIS OF THE DEVELOPMENT OF ETHNOPOLITICAL SYSTEMS OF KOREAN AND JAPANESE CIVILIZATION IN THE SUBSYSTEM OF INTERNATIONAL RELATIONS OF NORTHEAST ASIA
Authors:   Moscow International University, Moscow, Russian Federation, NIKIFOROV SVYATOSLAV
Published: September 2022

The purpose and objectives. The main goal is a comparative analysis of the development of the ethnopolitical systems of Korean and Japanese civilization in the subsystem of international relations in Northeast Asia. Methodological approach. The L.N. Gumilev’s methodology takes first place in the work, as well as the systematic approach developed in oriental political science by A.D. Voskresensky. The Reasearch is also based on general scientific methods of cognition and political forecasting. Results and conclusions. The article briefly analyzes the development of the Korean and Japanese ethnosystems in the region, and gives a forecast of the further development of political processes in these countries. Originality and value. The research is valuable in view of its relevance and originality of the work, which focuses on obtaining new knowledge about the nature of the Japanese and Korean ethnic systems and studying the features of the development of these ethnogenesis in the context of the political development of the subsystem of international relations in Northeast Asia.
SOCIOLOGICAL ANALYSIS OF THE FACTORS OF THE FORMATION OF THE MONETARY CULTURE OF THE RUSSIAN POPULATION
Authors:   Financial University under the government of the Russian Federation, Moscow, Russian Federation, RAZOV PAVEL , POPOV SERGEY ,   Moscow Financial and Industrial University “Synergy”, Moscow, Russian Federation
Published: September 2022

This article discusses the issue related to the sociological analysis of the factors of the formation of the monetary culture of the Russian population. The author studied the main elements of such a phenomenon as monetary culture, considered the current state of monetary culture in Russian society. This article also examines the concept of monetary behavior, which is in a special relationship with such a phenomenon as monetary culture. An important place in this work is devoted to the analysis of factors influencing the formation of the monetary culture of the Russian population. Among them, the author identified 2 large groups: objective and subjective factors. In this article, both groups are considered, while it is revealed that the factors cannot be abstracted from each other, but are in a state of interdependence. In addition, the author determined the relationship between the factors of the formation of monetary culture and the key values that can be distinguished in the monetary culture of the Russian population. In the final part of the article, the author offers recommendations for improving the monetary culture of the Russian population, as well as for further studying the factors influencing the formation of the monetary culture of the Russian population.
STRATEGIC INSTABILITY AS A RESULT OF MODERN INFORMATION AND COMMUNICATION STRATEGIES FUNCTIONING
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, MOLODTSOV IGOR , OSMOLOVSKAYA DARIA
Published: September 2022

The purpose of the research. The article is about the phenomenon of “strategic instability” as a result of the implementation of various information and communication technologies in the modern media space. Considering strategic instability as a state of existing social systems, the authors subject the ideas and concepts of “controlled chaos”, “new normal” and “end of history” to a socio-philosophical analysis. Conclusions. Modern information and communication strategies have a negative impact on the functioning of various social structures (the creation of “new”, deconstruction, decomposition, destruction), the formation of public consciousness, the construction of the agenda and the geopolitical situation on the world stage, etc., as a result of which strategic instability is comprehended society as the norm of modern life, and the existing threats to state are not perceived at the proper level. It seems that the way out of this situation is to use the methodology of information and strategic modeling (creation of virtual projects of “state systems as a future reality”).
BUSINESS JUDGEMENT OF MAJORITY SHAREHOLDER RULE IN CONTEXT OF LEGAL NATURE OF NON-PUBLIC COMMERCIAL CORPORATION
Authors:   Kutafin Moscow State Law University (MSAL), Moscow, Russian Federation, LEDENEV VIKTOR
Published: September 2022

Goal. In the article we research applicability of business judgement rule to actions of a majority shareholder taking in the account specificities of non-public commercial corporations. Analysis of application of the rule to a majority shareholder’s actions in view of non-public corporation’s legal nature was conducted only in the Peeples’ paper [13]. However, this analysis fails to take into the account ability of shareholders of corporations to apply informal sanctions against each other. The goal of this article is to supplement current understanding of legal nature of non-public corporation and to elaborate additional grounds for application of the rule. Inferences. In the article we confirm the conclusion that justification of application of the rule in non-public corporations has specificities derivative from the legal nature of such corporations. Besides that, we conclude that the rule’s application may depend upon ability of shareholders to deter opportunistic behavior by informal sanctions. Value. The article for the first time proves that the legal nature of non-public corporations depends not only upon trust between shareholders, but from their ability to apply informal sanctions as a mean of protection from opportunistic behavior of a counteragent. Given this, we suppose that the state’s role in protection of rights and interests of minority shareholders may be decreased.
Investigation of the Effects of Whey Powder on Haematococcus pluvialis Cell Growth Kinetics
Authors: AYDOĞDU Büşra , FAKIOĞLU Özden
Published: September 2022

This study was carried out to examine the effect on the growth of Haematococcus pluvialis using low-cost whey powder (WP). The H. pluvialis used in this study were from Çukurova University, Faculty of Fisheries, and 70% demineralized WP from Cici Dairy Industry Trade Inc. The experiment was conducted under laboratory conditions with 3 replications. During this experiment, cell numbers and biomass were analyzed every day. In addition, the specific growth rate of H. pluvialis was calculated according to the Monod Equivalence. The mean values of the cell number following the WP application were calculated according to the groups (C, W5, W10 and W15) as 763.34±419.62 cells/ml, 951.60±388.20 cells/ml, 1105.27±380.35 cells/ml and 978.63±411.07 cells/ml, respectively. The mean biomass value has been found the lowest in the control group (0.84±0.36 g/l), and the highest value in the W15 group (1.26±0.55 gl-1). The mean specific growth rate was determined as 0.52±0.09 day-1 in the control group, 0.56±0.1 day-1 in the W5 group, 0.56±0.14 day-1 in the W10 group, and as 0.61±0,09 day-1 in the W15 group. In accordance with the data obtained, both the biomass and the specific growth rate of H. pluvialis were observed to increase in the W15 group. The use of WP as a nutrient medium is recommended due to its low-cost as well as increasing biomass.
Rapid metabolism and increased expression of CYP81E8 gene confer high level of resistance to tembotrione in a multiple-resistant Palmer amaranth (Amaranthus palmeri S. Watson)
Authors: Aarthy Thiagarayaselvam , Shyam Chandrima , Jugulam Mithila
Published: September 2022

Herbicides, such as tembotrione, that inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) enzyme are used to control broad spectrum of weeds, primarily in corn, as this crop can metabolize these herbicides via cytochrome P450 activity. In 2018, a Palmer amaranth (Amaranthus palmeri) population, KCTR was found to be resistant to multiple herbicides including, tembotrione in Kansas (KS), USA. However, the mechanism of tembotrione resistance in KCTR is not known. The objective of this study was to characterize the level of tembotrione resistance and investigate the mechanism of resistance to this herbicide in KCTR using a known susceptible Palmer amaranth population (KSS). Tembotrione dose response experiments revealed that KCTR Palmer amaranth is 23 times more resistant to this herbicide, than KSS. No difference in absorption or translocation of [14C] tembotrione between KSS and KCTR was found. However, the time required to metabolize 50% of tembotrione was shorter in KCTR than in KSS. More than 95% of tembotrione was metabolized at 6 hours after treatment (HAT) in the KCTR, compared to only 50% in KSS plants. Application of cytochrome P450-inhibitors (e.g., malathion or piperonyl butoxide), along with tembotrione reversed the resistance in KCTR. Furthermore, the KCTR plants showed 35-fold increase in constitutive expression of CYP81E8 gene compared to KSS. Nonetheless, the HPPD gene expression was not altered in KCTR Palmer amaranth. Our results suggest that enhanced metabolism of tembotrione possibly due to increased expression of CYP81E8 gene contribute to tembotrione resistance in KCTR. Metabolic resistance to herbicides is a challenge for weed management as such resistance predisposes weeds to evolve resistance to unknown herbicides even without selection.
The three-dimension preclinical models for ferroptosis monitoring
Authors: Meng Yiming , Sun Jing , Zhang Guirong , Yu Tao , Piao Haozhe
Published: September 2022

As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.
Multimodal imaging of nano-assembled microspheres loaded with doxorubicin and Cisplatin for liver tumor therapy
Authors: He Yiwei , Zhang Yuqing , Gong Yuanchuan , Zhang Zhewei , Xu Tiancheng , Tian Liqiang , Pan Ting , Yang Hong , Pan Hao , Kou Quanming , Wang Hao , Shao Guoliang
Published: September 2022

Currently, clinically available drug-loaded embolic microspheres have some shortcomings, such as being invisible with standard medical imaging modalities and only being able to carry positively charged drugs. The visualization of drug-loaded microspheres is very important for real-time monitoring of embolic position to improve the therapeutic effect. Meanwhile, the visualization of microspheres can enable postoperative reexamination, which is helpful for evaluating the embolization area and guiding the subsequent treatment. In addition, microspheres capable of loading different charged drugs can increase the choice of chemotherapeutic drugs and provide more possibilities for treatment. Therefore, it is of great importance to explore drug-loaded microspheres capable of multimodal imaging and loading drugs with different charges for transarterial chemoembolization (TACE) treatment of liver tumors. In our study, we designed a kind of nano-assembled microspheres (NAMs) that can realize computer X-ray tomography (CT)/magnetic resonance imaging (MRI)/Raman multimodal imaging, be loaded with positively and negatively charged drugs and test their imaging ability, drug loading and biological safety. The microspheres have strong attenuation performance for CT, high T2 relaxation for MRI and good sensitivity for surface enhanced Raman spectroscopy (SERS). At the same time, our microspheres can also load the positively charged drug, doxorubicin (DOX), and negatively charged drug Cisplatin. One gram of NAMs can hold 168 mg DOX or 126 mg Cisplatin, which has good drug loading and sustained-release capacity. Cell experiments also showed that the nano-assembled microspheres had good biocompatibility. Therefore, as multimodal developed drug loaded microspheres, nano assembled microspheres have great potential in TACE treatment of liver cancer.
Integrated Kinetic Modelling and Microbial Profiling Provide Insights Into Biological Sulfate-Reducing Reactor Design and Operation
Authors: Hessler Tomas , Harrison Susan T. L. , Huddy Robert J.
Published: September 2022

Biological sulfate reduction (BSR) is an attractive approach for the bioremediation of sulfate-rich wastewater streams. Many sulfate-reducing microorganisms (SRM), which facilitate this process, have been well-studied in pure culture. However, the role of individual members of microbial communities within BSR bioreactors remains understudied. In this study we investigated the performance of two up-flow anaerobic packed bed reactors (UAPBRs) supplemented primarily with acetate and with lactate, respectively, during a hydraulic retention time (HRT) study set up to remediate sulfate-rich synthetic wastewater over the course of 1,000 + days. Plug-flow hydrodynamics led to a continuum of changing volumetric sulfate reduction rates (VSRRs), available electron donors, degrees of biomass retention and compositions of microbial communities throughout these reactors. Microbial communities throughout the successive zones of the reactors were resolved using 16S rRNA gene amplicon sequencing which allowed the association of features of performance with discrete microorganisms. The acetate UAPBR achieved a maximum VSRR of 23.2 mg.L−1. h−1 at a one-day HRT and a maximum sulfate conversion of the 1 g/L sulfate of 96% at a four-day HRT. The sulfate reduction reactions in this reactor could be described with a reaction order of 2.9, an important observation for optimisation and future scale-up. The lactate UAPBR achieved a 96% sulfate conversion at one-day HRT, corresponding with a VSRR of 40.1 mg.L−1. h−1. Lactate was supplied in this reactor at relatively low concentrations necessitating the subsequent use of propionate and acetate, by-products of lactate fermentation with acetate also a by-product of incomplete lactate oxidation, to achieve competitive performance. The consumption of these electron donors could be associated with specific SRM localised within biofilms of discrete zones. The sulfate reduction rates in the lactate UAPBR could be modelled as first-order reactions, indicating effective rates were conferred by these propionate- and acetate-oxidising SRM. Our results demonstrate how acetate, a low-cost substrate, can be used effectively despite low associated SRM growth rates, and that lactate, a more expensive substrate, can be used sparingly to achieve high VSRR and sulfate conversions. We further identified the preferred environment of additional microorganisms to inform how these microorganisms could be enriched or diminished in BSR reactors.
Femtosecond laser treatment promotes the surface bioactivity and bone ingrowth of Ti6Al4V bone scaffolds
Authors: Wang Su , Zhang Miao , Liu Linlin , Xu Rongwei , Huang Zhili , Shi Zhang’ao , Liu Juncai , Li Zhong , Li Xiaohong , Hao Peng , Hao Yongqiang
Published: September 2022

In this study, a femtosecond laser with a wavelength of 800 nm was used to modify the surface of a titanium alloy bone scaffold created via selective laser melting (SLM). The outcomes demonstrated that the surface morphology of the bone scaffold after femtosecond laser treatment was micro-nano morphology. The hydrophobic structure of the scaffold was changed into a super-hydrophilic structure, improving the surface roughness, which was highly helpful for osteoblast adhesion and differentiation. The femtosecond laser surface treatment in vitro samples produced a thick layer of hydroxyapatite (HAP) with improved surface bioactivity. The effectiveness of osseointegration and interstitial growth of the specimens treated with the femtosecond laser surface were found to be better when bone scaffolds were implanted into the epiphysis of the tibia of rabbits. As a result, femtosecond laser therapy dramatically enhanced the surface activity of bone scaffolds and their capacity to integrate with the surrounding bone tissues, serving as a trustworthy benchmark for future biological scaffold research.
Mild cold stress specifically disturbs clustering movement of DFCs and sequential organ left-right patterning in zebrafish
Authors: Liu Min , Zou Xinyu , Fu Mao , Bai Xinping , Zhao Yongyan , Chen Xin , Wang Xiaoyu , Wang Peijian , Huang Sizhou
Published: September 2022

In poikilothermic animals, the distinct acclimatization ability of different organs has been previously addressed, while the tissue-specific role of cold stress in early development is largely unknown. In this study, we discovered that despite its role in delaying embryonic development, mild cold stress (22°C) does not disturb multiple-organ progenitor specification, but does give rise to organ left-right (LR) patterning defects. Regarding the mechanism, the data showed that mild cold stress downregulated the expression of cell-adhesion genes cdh1 and cdh2 during gastrulation, especially in dorsal forerunner cells (DFCs), which partially disturbed the clustering movement of DFCs, Kupffer’s vesicle (KV) morphogenesis, and ciliogenesis. As a result, the defects of KV/cilia disrupted asymmetric nodal signaling and subsequent heart and liver LR patterning. In conclusion, our data novelly identified that, in early development, DFCs are more sensitive to mild cold stress, and mild cold stress repressed the expression of cell adhesion-related gene cdh1 and cdh2. This role partially disturbed the clustering movement of DFCs, which resulted in defective KV/cilia development and sequential organ LR patterning defects.
Compressive properties of self-healing microcapsule-based cementitious composites subjected to freeze-thaw cycles using acoustic emission
Authors: Hao Wenfeng , Hao Hao , Kanwal Humaira , Jiang Shiping
Published: September 2022

Microcapsule self-healing technology is an effective scheme to improve the durability of cementitious composites. In this paper, the compressive properties of microcapsule-based self-healing cementitious composites after freeze-thaw cycles were studied using acoustic emission (AE), and the changes in AE characteristics, compressive strength, mass loss rate, and electric flux of microcapsule-based self-healing cementitious composites with different microcapsule contents and freeze-thaw cycles were studied. The results show that if the content of the microcapsule is appropriate, with the increase in the number of freeze-thaw cycles, the AE hits will generally increase first and then decrease, and the early AE events will also decrease. Because of the different contents of microcapsules, the improvement effect and defect effect change dynamically with the number of freeze-thaw cycles, which is also reflected in the dynamic process of compressive strength. After 100 freeze-thaw cycles, the compressive strength of self-healing cementitious composite samples with 5% content of microcapsules and 3% content of microcapsules is the highest. The changes in mass loss rate and electric flux are similar to the AE characteristic parameters, which further verifies the results of AE. The research results of this paper provide experimental data and experimental methods for the engineering application of microcapsule self-healing cement-based composites in cold areas.
Adenoviral delivery of soluble ovine OX40L or CD70 costimulatory molecules improves adaptive immune responses to a model antigen in sheep
Authors: Rojas José M. , Mancho Carolina , Louloudes-Lázaro Andrés , Rodríguez-Martín Daniel , Avia Miguel , Moreno Santiago , Sevilla Noemí , Martín Verónica
Published: September 2022

The tumour necrosis factor superfamily OX40L and CD70 and their receptors are costimulatory signalling axes critical for adequate T and B cell activation in humans and mice. In this work we inoculated groups of sheep with human recombinant adenovirus type 5 (Ad) expressingOvis aries(Oa)OX40L orOaCD70 or a control adenoviral vector to determine whether they could improve the immune response to the model antigen OVA. PBMCs and serum samples were obtained for analysis of the adaptive immune response to OVA at days 0, 15, 30 and 90 post-inoculation (pi). Recall responses to OVA were assessed at day 7 and 30 after the second antigen inoculation (pb) at day 90. Administration of these immunomodulatory molecules did not induce unspecific PBMC stimulation. WhileOaOX40L administration mainly increased TNF-α and IL-4 in PBMC at day 15 pi concomitantly with a slight increase in antibody titer and the number of IFN-γ producing cells, we detected greater effects on adaptive immunity afterOaCD70 administration. AdOaCD70 inoculation improved antibody titers to OVA at days 30 and 90 pi, and increased anti-OVA-specific IgG-secreting B cell counts when compared to control. Moreover, higher IFN-γ production was detected on days 7 pi, 7 pb and 30 pb in PBMCs from this group. Phenotypic analysis of T cell activation showed an increase in effector CD8+T cells (CD8+CD62L-CD27-) at day 15 pi in AdOaCD70 group, concurrent with a decrease in early activated cells (CD8+CD62L-CD27+). Moreover, recall anti-OVA CD8+T cell responses were increased at 7 pb in the AdOaCD70 group. AdOaCD70 administration could therefore promote CD8+T cell effector differentiation and long-term activity. In this work we characterized thein vivoadjuvant potential on the humoral and cellular immune response ofOaOX40L andOaCD70 delivered by non-replicative adenovirus vectors using the model antigen OVA. We present data highlighting the potency of these molecules as veterinary vaccine adjuvant.
Efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations: Results from phase II and III trials
Authors: Yu Wei , Shen Ping , Luo Qixia , Xiong Luying , Xiao Yonghong
Published: September 2022

Objectives

The addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.

Methods

We conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).

Results

A total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.

Conclusions

ICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.
Engineering recombinantly expressed lectin-based antiviral agents
Authors: Maier Irene
Published: September 2022

Cyanovirin-N (CV-N), a lectin from Nostoc ellipsosporum was found an infusion inhibitory protein for human immunodeficiency virus (HIV)-1. A tandem-repeat of the engineered domain-swapped dimer bound specific sites at hemagglutinin (HA), Ebola and HIV spike glycoproteins as well as dimannosylated HA peptide, N-acetyl-D-glucosamine and high-mannose containing oligosaccharides. Among these, CV-N bound the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein at a dissociation constant (KD) of 18.6 µM (and KD=260 µM to RBD), which was low-affinity carbohydrate-binding as compared with the recognition of the other viral spikes. Binding of dimannosylated peptide to homo-dimeric CVN2 and variants of CVN2 that were pairing Glu-Arg residues sterically located close to its high-affinity carbohydrate binding sites, was measured using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Binding affinity increased with polar interactions, when the mutated residues were used to substitute a single, or two disulfide bonds, in CVN2. Site-specific N-linked glycans on spikes were mediating the infection with influenza virus by broadly neutralizing antibodies to HA and lectin binding to HA was further investigated via modes of saturation transfer difference (STD)-NMR. Our findings showed that stoichiometry and the lectin’s binding affinity were revealed by an interaction of CVN2 with dimannose units and either the high- or low-affinity binding site. To understand how these binding mechanisms add to viral membrane fusion we compare our tested HA-derived peptides in affinity with SARS-CoV-2 glycoprotein and review lectins and their mechanisms of binding to enveloped viruses for a potential use to simulate neutralization ability.
Meglumine antimoniate was associated with a higher cure rate than liposomal amphotericin B in the treatment of American tegumentary leishmaniasis: A retrospective cohort study from a Leishmania braziliensis-endemic area
Authors: Barroso Daniel Holanda , Gonçalves Renata Trindade , Barbosa Joadyson Silva , da Motta Jorgeth de Oliveira Carneiro , Freire Gustavo Subtil Magalhães , Gomes Ciro Martins , Sampaio Raimunda Nonata Ribeiro
Published: September 2022

Background

Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established.

Objective

This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates.

Methods

This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results.

Results

Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61).

Conclusions

We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis.
Human Rickettsia felis infections in Mainland China
Authors: Teng Zhongqiu , Zhao Na , Ren Ruotong , Zhang Xue , Du Zhenshan , Wang Pengfei , Qin Tian
Published: September 2022

We identified four flea-borne spotted fever cases caused by Rickettsia felis in a retrospective survey of 182 patients with fever of unknown origin (FUO) in China between 2021 and 2022. The clinical signs and symptoms of the patients were similar to those of other rickettsioses, including fever, rash, and liver and kidney dysfunction. All four patients in the present study developed pneumonia or lung lesions after R. felis infection. The cases of R. felis infection, a neglected infectious disease, were sporadic in multiple provinces of the country. The high prevalence (2.14%, 4/187) of R. felis among patients with FUO highlights the risk posed by this pathogen to public health in China.
Can signal-to-noise ratio indicate prediction skill? Based on skill assessment of 1-month lead prediction of monthly temperature anomaly over Japan
Authors: Doi Takeshi , Nonaka Masami , Behera Swadhin
Published: September 2022

We present a skill assessment of 1-month lead deterministic predictions of monthly surface air temperature anomalies over most part of Japan based on a large-ensemble climate model, SINTEX-F. We found that September is the most predictable and the only month in which the prediction skill beats the persistence. Interestingly, however, prediction of December becomes skillful (correlation skill: 0.67) when we select only years in which the signal-to-noise ratio of the predictions is relatively high. This means that the signal-to-noise ratio can partly indicate the prediction skill. The inter-member co-variability suggests that a combination of the tropical Pacific and western Indian Ocean surface temperature is the key for the prediction. Although seasonal climate prediction in the mid-latitude regions, such as Japan, is still challenging in general, providing the signal-to-noise ratio and the inter-member co-variability in addition to the real-time prediction might be useful for stakeholders to know how confident the individual prediction is, as well as its potential sources of predictability. Such information can be helpful to take necessary mitigation measures to reduce socio-economic losses associated with extreme climate.
Critical research gaps in understanding Southeast Asian women’s wildlife trade and use practices
Authors: Davis Elizabeth Oneita
Published: September 2022

The hunting and consumption of wildlife is a global practice with practices that are socially nested, mediated, and shared across social categories, including gender. Research into wildlife trade increasingly recognizes the importance of understanding and investigating social drivers and processes of hunting and consumption. However, studies of social norms, motivations, and actions specific to women are still lacking within wildlife trade literature, particularly within Southeast Asia. Women are central to how a society operates and to societal practices, and they are fundamental actors in initiating change in these practices. In Southeast Asia, women are especially powerful actors within resident matrilineal and bilateral societies. This article will reflect on wildlife trafficking through the roles and activities of women. While women’s narratives are lacking across all current wildlife trade research, I will highlight in this article critical research gaps, gender-specific issues in methodology, and important research opportunities.
Substrate specificity of branched chain amino acid aminotransferases: The substitution of glycine to serine in the active site determines the substrate specificity for α-ketoglutarate
Authors: Sutter Jan-Moritz , Mitchell Daniel E. , Schmidt Marcel , Isupov Michail N. , Littlechild Jennifer A. , Schönheit Peter
Published: September 2022

A branched chain aminotransferase from Thermoproteus tenax has been identified, cloned, over-expressed and biochemically characterised. A molecular modelling approach has been used to predict the 3D structure allowing its comparison with other related enzymes. This enzyme has high similarity to a previously characterised aminotransferase from Thermoproteus uzoniensis however its substrate specificity shows key differences towards the substrate α-ketoglutarate. Examination of the active sites of the two related enzymes reveals a single amino acid substitution of a glycine residue to a serine residue which could be responsible for this difference. When Gly104 in T. tenax was mutated to a serine residue and the resultant enzyme characterised, this single amino acid change resulted in a dramatic reduction in activity towards α-ketoglutarate with an 18-fold reduction in Vmax and a 20-fold Km increase, resulting in a 370-fold lower catalytic efficiency. Structural comparisons between the two related Thermoproteus enzymes and another branched chain aminotransferase from Geoglobus acetivorans has revealed that the serine residue affects the flexibility of a key loop involved in catalysis. This subtle difference has provided further insight into our understanding of the substrate specificity of these industrially important enzymes.
Impact of early PCSK9 inhibitor treatment on heart after percutaneous coronary intervention in patients with STEMI: Design and rationale of the PERFECT II trial
Authors: Xia Jiachun , Wang Xinyue , Zhou Jun , Wang Dong , Pang Yanan , Xu Xin , Sang Zhenchi , Zhang Yi , Zhang Junfeng , Wu Sicheng , Xiao Zhengguang , Hou Lei
Published: September 2022

Background and aims

Primary percutaneous coronary intervention (PPCI) is the most effective treatment strategy for ST-segment elevation myocardial infarction (STEMI). Nevertheless, dysregulated inflammation induced by myocardial reperfusion injury may increase the final infarct size and induce maladaptive myocardial remodeling. Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, as a novel and potent lipid-lowering drug, plays an important role in inflammation. The aim of this study is to investigate whether the early application of PCSK9 inhibitor can increase the myocardial salvage index (MSI) and improve ventricular remodeling in patients with STEMI.

Design

The PERFECT II trial is a prospective, open-label, multicenter, randomized controlled study involving 160 patients with STEMI who are scheduled to undergo PPCI. The eligible patients will be divided into PCSK9 inhibitor group and control group via the interactive web response system, at a 1:1 ratio. In the PCSK9 inhibitor group, the PCSK9 inhibitor alirocumab at a dose of 75 mg will be subcutaneously injected immediately after PPCI and administered every 2 weeks thereafter for 3 months based on conventional treatment. In the control group, conventional treatment will be administered. The primary endpoint is MSI, as measured by cardiac magnetic resonance imaging (CMR) at 1 week after PPCI. The secondary endpoints are the peak time of creatine kinase (CK)-MB and troponin I (TnI)/TnT after PPCI; the postoperative fall time of the ST segment on electrocardiography (ECG); the rate of plasma low-density lipoprotein cholesterol (LDL-C) compliance (< 1.4 mmol/L and a reduction of >50% from baseline) at 1, 3, and 6 months after PPCI; infarct size and ejection fraction (EF) measured by CMR at 6 months after PPCI; the occurrence of major adverse cardiovascular event (MACE: a composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and heart failure needed to be hospitalized).

Conclusions

This is the first multicenter study to investigate the effect of early application of the PCSK9 inhibitor alirocumab on MSI in patients with STEMI undergoing PPCI. The findings will provide an opportunity to explore novel ideas and methods for the treatment of acute myocardial infarction.

Trial registration

ClinicalTrials.gov, identifier: NCT05292404.
Higher Blood Cadmium Concentration Is Associated With Increased Likelihood of Abdominal Aortic Calcification
Authors: Qin Zheng , Liu Qiang , Jiao Pengcheng , Geng Jiwen , Liao Ruoxi , Su Baihai
Published: September 2022

Aims

This study aimed to evaluate the association between blood cadmium concentration (BCC) and abdominal aortic calcification (AAC) in adults aged ≥40 years in the United States.

Methods

Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Participants without data about BCC and AAC scores were excluded. BCC was directly measured using inductively coupled plasma mass spectrometry (ICP–MS). AAC scores were quantified by the Kauppila scoring system, and severe AAC was defined as an AAC score >6. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between cadmium exposure with AAC scores and severe AAC.

Results

A total of 1,530 participants were included with an average BCC of 0.47 ± 0.02 μg/L and AAC score of 1.40 ± 0.10 [mean ± standard error (SE)]. The prevalence of severe AAC was 7.96% in the whole subjects and increased with the higher BCC tertiles (Tertile 1: 4.74%, Tertile 2: 9.83%, and Tertile 3: 10.17%; p = 0.0395). We observed a significant positive association between BCC and the AAC score (β = 0.16, 95% CI: 0.01~0.30) and an increased risk of severe AAC [odds ratio (OR) = 1.45; 95% CI: 1.03~2.04]. Subgroup analysis and interaction tests revealed that there was no dependence for the association between BCC and AAC.

Conclusion

Blood cadmium concentration was associated with a higher AAC score and an increased likelihood of severe AAC in adults in the United States. Cadmium exposure is a risk factor for AAC, and attention should be given to the management of blood cadmium.
Periprocedural Strategies for Stroke Prevention in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Linder Matthias , Seiffert Moritz
Published: September 2022

Cerebrovascular events remain a serious complication in patients undergoing transcatheter aortic valve implantation with an incidence of 2–3% at 30 days. While expanding TAVI to younger low-risk patients, prevention of periprocedural strokes becomes even more important. Different cerebral embolic protection devices have been tested but a clear clinical benefit has not been demonstrated in randomized trials. Due to the multifactorial aetiology with different predisposing factors, stroke prevention should include procedural and periprocedural strategies. This article aims to summarize different approaches and discuss open questions.
Which cardiac parameters best predict the cardiovascular outcomes among patients with anti-PD-1 immunotherapy-induced myocardial injury?
Authors: Peng Xiongjun , Zheng Yawen , Zhu Zhaowei , Liu Na , Zhou Shenghua , Long Junke
Published: September 2022

Aim

To explore the association of cardiac parameters with different clinical outcomes in patients with anti-PD-1 immunotherapy-induced myocardial injury.

Methods and results

We screened 3,848 patients who received anti-PD-1 immunotherapy from June 2018 to Oct 2021 at the Second Xiangya Hospital of Central South University. Among those patients, 134 patients were diagnosed with anti-PD-1 immunotherapy-induced myocardial injury. Twenty-four patients with cardiovascular symptoms were divided into the major adverse cardiac events (MACE) group, and 110 patients without cardiovascular symptoms were divided into the non-MACE group. We compared creatine kinase isozyme (CK-MB), high-sensitivity troponin T (hsTNT), N-terminal pro–B-type natriuretic peptide (NT-ProBNP), electrocardiography (ECG), and echocardiographic parameters between the two groups of patients. CK-MB, hsTNT, NT-proBNP [2,600.0 (1,317.00–7,950.00) vs. 472.9 (280.40–788.80), p ≤ 0.001], left ventricular end-diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF) and QRS interval were significantly different. The receiver operating characteristic (ROC) curve was used to compare the accuracy of various indicators to predict the occurrence of MACE events. NT-ProBNP (area under the curve [AUC] 97.1) was the best predictor, followed by CK-MB (AUC = 94.1), LVEF (AUC = 83.4), LVEDd (AUC = 81.5), and other indicators. In the MACE group, 11/24 patients had experienced cardiogenic death by the end of follow-up. There were significant differences in the CK-MB, hsTNT, NT-proBNP, LVEDd, LVEF, and QRS intervals between the deceased patients and the survivors. The ROC curve shows that hsTNT is the most accurate marker for predicting cardiogenic death in the MACE group (AUC = 91.6).

Conclusion

In patients with myocardial injury after PD-1 inhibitor treatment, NT-proBNP is the parameter of choice to predict the likelihood of developing cardiovascular symptoms, whereas, in symptomatic patients, hsTNT is the optimal parameter associated with the outcome of death compared with other cardiac parameters.
Mechanical circulatory support devices and treatment strategies for right heart failure
Authors: Kuroda Taiyo , Miyagi Chihiro , Fukamachi Kiyotaka , Karimov Jamshid H.
Published: September 2022

The importance of right heart failure (RHF) treatment is magnified over the years due to the increased risk of mortality. Additionally, the multifactorial origin and pathophysiological mechanisms of RHF render this clinical condition and the choices for appropriate therapeutic target strategies remain to be complex. The recent change in the United Network for Organ Sharing (UNOS) allocation criteria of heart transplant may have impacted for the number of left ventricular assist devices (LVADs), but LVADs still have been widely used to treat advanced heart failure, and 4.1 to 7.4% of LVAD patients require a right ventricular assist device (RVAD). In addition, patients admitted with primary left ventricular failure often need right ventricular support. Thus, there is unmet need for temporary or long-term support RVAD implantation exists. In RHF treatment with mechanical circulatory support (MCS) devices, the timing of the intervention and prediction of duration of the support play a major role in successful treatment and outcomes. In this review, we attempt to describe the prevalence and pathophysiological mechanisms of RHF origin, and provide an overview of existing treatment options, strategy and device choices for MCS treatment for RHF.