bluuebunny/crossref_metadata_2025 huggingface dataset:
Small-Signal Stability Analysis of the Power System Based on Active Support of Renewable Energy VSCs
Authors: Chu Tianfeng , Xu Miao , Xie Yu , Wang Shunjiang , Li Dianyang , Liu Gang
Published: May 2022

With the large-scale renewable energy access to the power system, the voltage source converters (VSCs) in the system are gradually increasing. The system inertia is weakened, which leads to the decrease in frequency supportability and affects the stability of the power system. After adopting active support control, VSC-based renewable energy units have inertia supportability similar to traditional synchronous generators (SGs), which can improve the frequency stability of the power system. This article is intended to the control strategy based on active support of renewable energy. Small-signal stability of a two-zone system with different control strategies for VSCs under different conditions is analyzed. At the same time, the dynamic adjustment effect of different parameters on active support control is considered, and frequency stability of a two-zone system with inertial flexible control is improved. In this article, the basic principle of active support control is expounded in detail. Compared with PQ-control and droop-control, it is verified that active support control has good frequency supportability. The small-signal model of VSCs for active support and two-machine system is established. Combined with the simulation system, the influence of virtual inertia and damping coefficient on system stability is verified.
Design and Validation of Reversing Assistant Based on Extreme Learning Machine
Authors: Di Huanyu , Yan Yipeng , Zhao Mingxin , Kang Mingxin
Published: May 2022

As an important function of the advanced driver assistance system (ADAS), the reversing assistant (RA) achieves trajectory retracing by applying accurate position estimation and tracking control. To overcome the problem of the modeling complexity in dead reckoning for the reversing assistant function, the heading angular rate is compensated by using the extreme learning machine (ELM) to improve the positioning accuracy. In addition, considering the time delay of the steering system, a tracking controller with a feed-forward of the recorded steering angle and a self-tuning PID feedback controller is designed based on the preview-and-following scheme. Vehicle experiments under various reversing scenarios prove that the proposed positioning method and tracking control scheme are effective, the overall lateral error is less than 10 cm, and the heading angle error is less than 1°, which meets the requirements of performance indicators.
Over-Voltage Regulation of Distribution Networks by Coordinated Operation of PV Inverters and Demand Side Management Program
Authors: Heidari Yazdi Seyed Saeid , Rahimi Tohid , Khadem Haghighian Saeideh , Gharehpetian Gevork B. , Bagheri Mehdi
Published: May 2022

The increase of Photovoltaics (PV) units’ penetration factor in the power grids might create overvoltage over the network buses. The active power curtailment (APC) and the reactive power provision methods use inverters to regulate their output active and reactive powers for high PV-penetrated grids. However, the mentioned solutions would reduce the maximum injectable active solar power to the grid, not financially acceptable. Continuous employment of the maximum apparent power capacity of the inverters will practically decrease the inverters’ lifetime, require special design considerations, and make the control system complex. To overcome those issues, a feasible solution would be increasing the load consumption within the time intervals in which the grid faces the over-voltage problem. In this research, the demand response (DR) program is employed. Load shifting techniques are exerted to move a portion of loads from the peak hours to when further power consumption is expected for voltage level reduction purposes. A new long-term strategy based on the coordinated operation of the PV inverters and load shifting techniques is proposed to resolve the over-voltage issue in the network. Consequently, the PV inverter’s contribution to voltage control is reduced; a new sight of DR potential is implemented, and also the under-voltage level in peak times is decreased significantly.
Influence of Dust Aerosols on Snow Cover Over the Tibetan Plateau
Authors: Zhao Dan , Chen Siyu , Chen Yu , Gong Yongqi , Lou Gaotong , Cheng Shanling , Bi Hongru
Published: May 2022

Dust in the atmosphere and snow on the Tibetan Plateau (TP) remarkably influence the Asian climate, which can influence snow cover by changing radiative forcing. In this study, we investigated the spatial and temporal distributions of dust and snow cover over the TP from 2009 to 2018 and estimated the relative contributions of atmospheric dust and dust-on-snow to the change in snow cover over the northern TP through the use of reanalysis datasets and satellite retrievals. The results show that the high and low centers of aerosol and dust aerosol optical depth (AOD) are roughly similar. Dust concentrations over the TP generally decrease from north to south and from west to east, showing decreasing trends in the winter half-year (December to May). The correlation coefficients between the dust concentration and snow cover over the northern TP are −0.6 in spring. Dust in the atmosphere and on snow over the TP could significantly influence snow cover by changing the radiative forcing, and the influence of dust deposited on snow is greater than that in the atmosphere. Atmospheric dust reduces the surface net solar radiation by −3.84 W m−2 by absorbing shortwave radiation, decreasing the surface temperature by −2.27°C, and finally increasing the snow cover by 1.04%. However, dust deposited on snow can decrease the surface albedo by −0.004 by reducing the surface optical properties, induce surface warming at 0.42°C, and reduce snow cover by −2.00% by rapid snowmelt in the northern TP.
Re-Visiting the Role of Education on Poverty Through the Channel of Financial Inclusion: Evidence From Lower-Income and Lower-Middle-Income Countries
Authors: Shi Zheng , Qamruzzaman Md.
Published: May 2022

For attaining sustainable economic development in the lower and lower-middle-income nations, the role of poverty reduction has been critically addressed along with the economic determents that manage poverty level which has accelerated the economic progress by ensuring the higher performance of other macrovariables including FDI inflows, financial development, trade openness, and human capital accumulation. The purpose of this study was to evaluate the role of education and financial inclusion in poverty reduction in lower and lower-middle-income countries for the period 1995–2018, with a panel of 68 nations. The study applied several econometrical tools, including a cross-sectional dependency test (CDS), panel unit root test, panel cointegration test, generalized methods of moment (GMM), and system-GMM. The CDS results confirmed the sharing of typical dynamics in research units. The test of stationarity detected variables was integrated after the first difference. A panel cointegration test documented the long-run association between education, financial inclusion, and poverty. The study documented that government investment in education positively assists poverty reduction, implying a negative association between them. Furthermore, the inclusion of the population into the formal financial system expedited the poverty reduction process that has access to formal financial benefits allowing earning opportunities and higher purchasing power, eventually supporting an increased standard of living. Directional causality tests revealed feedback hypothesis holds in explaining the nexus between education, financial inclusion, and poverty, i.e., [ED←→Poverty; FI←→Poverty]. For policy reform and restructuring, it is essential to pay considerable attention to development in education and access to the formal financial system because progress in education and finance has positive spillover effects on the aggregated economy.
Importance of Diagnostic Accuracy in Big Data: False-Positive Diagnoses of Type 2 Diabetes in Health Insurance Claims Data of 70 Million Germans
Authors: Brinks Ralph , Tönnies Thaddäus , Hoyer Annika
Published: May 2022

Large data sets comprising diagnoses of chronic conditions are becoming increasingly available for research purposes. In Germany, it is planned that aggregated claims data – including medical diagnoses from the statutory health insurance – with roughly 70 million insurants will be published regularly. The validity of the diagnoses in such big datasets can hardly be assessed. In case the dataset comprises prevalence, incidence, and mortality, it is possible to estimate the proportion of false-positive diagnoses using mathematical relations from the illness-death model. We apply the method to age-specific aggregated claims data from 70 million Germans about type 2 diabetes in Germany stratified by sex and report the findings in terms of the age-specific ratio of false-positive diagnoses of type 2 diabetes (FPR) in the dataset. The FPR for men and women changes with age. In men, the FPR increases linearly from 1 to 3 per 1,000 in the age group of 30–50 years. For age between 50 and 80 years, FPR remains below 4 per 1,000. After 80 years of age, we have an increase to approximately 5 per 1,000. In women, we find a steep increase from age 30 to 60 years, the peak FPR is reached at approximately 12 per 1,000 between 60 and 70 years of age. After age 70 years, the FPR of women drops tremendously. In all age groups, the FPR is higher in women than in men. In terms of absolute numbers, we find that there are 217,000 people with a false-positive diagnosis in the dataset (95% confidence interval, CI: 204–229), the vast majority being women (172,000, 95% CI: 162–180). Our work indicates that possible false-positive (and negative) diagnoses should appropriately be dealt with in claims data, for example, by the inclusion of age- and sex-specific error terms in statistical models, to avoid potentially biased or wrong conclusions.
Fertilization Rapidly Alters the Feeding Activity of Grassland Soil Mesofauna Independent of Management History
Authors: Birkhofer Klaus , Baulechner Dennis , Diekötter Tim , Zaitsev Andrey , Wolters Volkmar
Published: May 2022

Nitrogen fertilization of permanent grasslands affects soil fauna communities by modifying their taxonomic composition, population dynamics and feeding activity. However, it is not well understood if the edaphic fauna adapts to these external inputs so that the immediate response to fertilizer application depends on the long-term nutrient management strategy. We performed a field experiment in permanent grasslands under agricultural management in three regions across Germany. We used experimental fertilization with an organic plant-sourced fertilizer along a long-term nutrient management gradient to study the immediate and long-term effects of fertilization and their interdependence on the taxonomic composition and feeding activity of the soil mesofauna (Nematoda, Oribatida, and Collembola). Sampling season, soil properties, vegetation structure, and geographic location were considered as additional predictor variables to reflect heterogeneity in environmental conditions. The taxonomic composition, richness and total abundance of soil mesofauna communities were significantly affected by long-term nutrient management, but not by experimental fertilization. However, N pulses rapidly (within days) reduced the feeding activity estimated with bait-lamina strips independent of long-term nutrient management strategies. Experimental addition of organic plant-sourced fertilizer may have led to a rapid build-up of microbial biomass, providing alternative food sources for the soil mesofauna and causing a shift away from the bait-lamina substrate. Our study indicates that community changes associated with the long-term nutrient management regime in permanent grasslands do not alter the strong functional response of the soil mesofauna to N pulses. There is an urgent need to develop nutrient management strategies for permanent grasslands that take into account both the conservation of the edaphic faunal community and changes of ecosystem functions caused by rapid responses of the soil mesofauna to fertilizer inputs.
Multistage Combination Classifier Augmented Model for Protein Secondary Structure Prediction
Authors: Zhang Xu , Liu Yiwei , Wang Yaming , Zhang Liang , Feng Lin , Jin Bo , Zhang Hongzhe
Published: May 2022

In the field of bioinformatics, understanding protein secondary structure is very important for exploring diseases and finding new treatments. Considering that the physical experiment-based protein secondary structure prediction methods are time-consuming and expensive, some pattern recognition and machine learning methods are proposed. However, most of the methods achieve quite similar performance, which seems to reach a model capacity bottleneck. As both model design and learning process can affect the model learning capacity, we pay attention to the latter part. To this end, a framework called Multistage Combination Classifier Augmented Model (MCCM) is proposed to solve the protein secondary structure prediction task. Specifically, first, a feature extraction module is introduced to extract features with different levels of learning difficulties. Second, multistage combination classifiers are proposed to learn decision boundaries for easy and hard samples, respectively, with the latter penalizing the loss value of the hard samples and finally improving the prediction performance of hard samples. Third, based on the Dirichlet distribution and information entropy measurement, a sample difficulty discrimination module is designed to assign samples with different learning difficulty levels to the aforementioned classifiers. The experimental results on the publicly available benchmark CB513 dataset show that our method outperforms most state-of-the-art models.
De Novo Assembly of Plasmodium knowlesi Genomes From Clinical Samples Explains the Counterintuitive Intrachromosomal Organization of Variant SICAvar and kir Multiple Gene Family Members
Authors: Oresegun Damilola R. , Thorpe Peter , Benavente Ernest Diez , Campino Susana , Muh Fauzi , Moon Robert William , Clark Taane Gregory , Cox-Singh Janet
Published: May 2022

Plasmodium knowlesi, a malaria parasite of Old World macaque monkeys, is used extensively to model Plasmodium biology. Recently, P. knowlesi was found in the human population of Southeast Asia, particularly Malaysia. P. knowlesi causes uncomplicated to severe and fatal malaria in the human host with features in common with the more prevalent and virulent malaria caused by Plasmodium falciparum. As such, P. knowlesi presents a unique opportunity to develop experimental translational model systems for malaria pathophysiology informed by clinical data from same-species human infections. Experimental lines of P. knowlesi represent well-characterized genetically stable parasites, and to maximize their utility as a backdrop for understanding malaria pathophysiology, genetically diverse contemporary clinical isolates, essentially wild-type, require comparable characterization. The Oxford Nanopore PCR-free long-read sequencing platform was used to sequence and de novo assemble P. knowlesi genomes from frozen clinical samples. The sequencing platform and assembly pipelines were designed to facilitate capturing data and describing, for the first time, P. knowlesi schizont-infected cell agglutination (SICA) var and Knowlesi-Interspersed Repeats (kir) multiple gene families in parasites acquired from nature. The SICAvar gene family members code for antigenically variant proteins analogous to the virulence-associated P. falciparum erythrocyte membrane protein (PfEMP1) multiple var gene family. Evidence presented here suggests that the SICAvar family members have arisen through a process of gene duplication, selection pressure, and variation. Highly evolving genes including PfEMP1family members tend to be restricted to relatively unstable sub-telomeric regions that drive change with core genes protected in genetically stable intrachromosomal locations. The comparable SICAvar and kir gene family members are counter-intuitively located across chromosomes. Here, we demonstrate that, in contrast to conserved core genes, SICAvar and kir genes occupy otherwise gene-sparse chromosomal locations that accommodate rapid evolution and change. The novel methods presented here offer the malaria research community not only new tools to generate comprehensive genome sequence data from small clinical samples but also new insight into the complexity of clinically important real-world parasites.
Characterization of the Immune Cell Infiltration Landscape Uncovers Prognostic and Immunogenic Characteristics in Lung Adenocarcinoma
Authors: Wang Xin , Xu Zhenyi , Liu Zhilin , Lin Weihao , Cao Zheng , Feng Xiaoli , Gao Yibo , He Jie
Published: May 2022

The immune cell infiltration in TME has been reported to be associated with prognosis and immunotherapy efficiency of lung cancers. However, to date, the immune infiltrative landscape of lung adenocarcinoma (LUAD) has not been elucidated yet. Therefore, this study aimed to identify a new transcriptomic-based TME classification and develop a risk scoring system to predict the clinical outcomes of patients with LUAD. We applied “CIBERSORT” algorithm to analyze the transcriptomic data of LUAD samples and classified LUAD into four discrete subtypes according to the distinct immune cell infiltration patterns. Furthermore, we established a novel predictive tool (TMEscore) to quantify the immune infiltration patterns for each LUAD patient by principal component analysis. The TMEscore displayed as a reliable and independent prognostic biomarker for LUAD, with worse survival in TMEscrore-high patients and better survival in TMEscrore-low patients in both TCGA and other five GEO cohorts. In addition, enriched pathways and genomic alterations were also analyzed and compared in different TMEscore subgroups, and we observed that high TMEscore was significantly correlated with more aggressive molecular changes, while the low TMEscore subgroup enriched in immune active-related pathways. The TMEscore-low subtype showed overexpression of PD-1, CTLA4, and associations of other markers of sensitivity to immunotherapy, including TMB, immunophenoscore (IPS) analysis, and tumor immune dysfunction and exclusion (TIDE) algorithm. Conclusively, TMEscore is a promising and reliable biomarker to distinguish the prognosis, the molecular and immune characteristics, and the benefit from ICIs treatments in LUAD.
An Immune-Related Prognostic Signature Predicts Overall Survival in Stomach Adenocarcinomas
Authors: Zhou Kangjie , Hu Nan , Hong Yidong , Wu Xueyu , Zhang Jingzhou , Lai Huan , Zhang Yang , Wu Fenglei
Published: May 2022

This study aimed to explore an immune response-related gene signature to predict the clinical prognosis and tumor immunity of stomach adenocarcinomas (STAD). Based on the expression and clinical data of STAD in the TCGA database, the immune cell infiltration status was evaluated using CIBERSORT and ESTIMATE methods. Samples were grouped into “hot” and “cold” tumors based on immune cell infiltration status and consensus clustering. The infiltration abundance of activated memory CD4 T cells and CD8 T cells had a significant effect on the overall survival of STAD patients. Among the three clusters, cluster 2 had a higher immune score and a significantly higher abundance of CD8 T cells and activated memory CD4 T cells were assigned as a hot tumor, while cluster 1 and 3 were assigned as a cold tumor. DEGs between hot and cold tumors were mainly enriched in immune-related biological processes and pathways. Total of 13 DEGs were related to the overall survival (OS). After the univariate and multivariable Cox regression analysis, three signature genes (PEG10, DKK1, and RGS1) was identified to establish a prognostic model. Patients with the high-risk score were associated with worse survival, and the risk score had an independent prognostic value. Based on TIMER online tool, the infiltration levels of six immune cell types showed significant differences among different copy number statuses of PEG10, DKK1, and RGS1. In this study, an immune-related prognostic model containing three genes was established to predict survival for STAD patients.
Systemic Immune Dysregulation in Early Breast Cancer Is Associated With Decreased Plasma Levels of Both Soluble Co-Inhibitory and Co-Stimulatory Immune Checkpoint Molecules
Authors: Rapoport Bernardo L. , Steel Helen C. , Hlatshwayo Nomsa , Theron Annette J. , Meyer Pieter W. A. , Nayler Simon , Benn Carol-Ann , Smit Teresa , Kwofie Luyanda L. I. , Heyman Liezl , Anderson Ronald
Published: May 2022

Breast cancer cells exploit the up-regulation or down-regulation of immune checkpoint proteins to evade anti-tumor immune responses. To explore the possible involvement of this mechanism in promoting systemic immunosuppression, the pre-treatment levels of soluble co-inhibitory and co-stimulatory immune checkpoint molecules, as well as those of cytokines, chemokines, and growth factors were measured in 98 newly diagnosed breast cancer patients and compared with those of 45 healthy controls using multiplex bead array and ELISA technologies. Plasma concentrations of the co-stimulatory immune checkpoints, GITR, GITRL, CD27, CD28, CD40, CD80, CD86 and ICOS, as well as the co-inhibitory molecules, PD-L1, CTLA-4 and TIM-3, were all significantly lower in early breast cancer patients compared to healthy controls, as were those of HVEM and sTLR-2, whereas the plasma concentrations of CX3CL1 (fractalkine), CCL5 (RANTES) and those of the growth factors, M-CSF, FGF-21 and GDF-15 were significantly increased. However, when analyzed according to the patients’ breast cancer characteristics, these being triple negative breast cancer (TNBC) vs. non-TNBC, tumor size, stage, nodal status and age, no significant differences were detected between the plasma levels of the various immune checkpoint molecules, cytokines, chemokines and growth factors. Additionally, none of these biomarkers correlated with pathological complete response. This study has identified low plasma levels of soluble co-stimulatory and co-inhibitory immune checkpoint molecules in newly diagnosed, non-metastatic breast cancer patients compared to healthy controls, which is a novel finding seemingly consistent with a state of systemic immune dysregulation. Plausible mechanisms include an association with elevated levels of M-CSF and CCL5, implicating the involvement of immune suppressor cells of the M2-macrophage/monocyte phenotype as possible drivers of this state of systemic immune quiescence/dysregulation.
Integrative Analysis of the Genomic and Immune Microenvironment Characteristics Associated With Clear Cell Renal Cell Carcinoma Progression: Implications for Prognosis and Immunotherapy
Authors: Lin Enyu , Zhu Ping , Ye Chujin , Huang ManLi , Liu Xuechao , Tian Kaiwen , Tang Yanlin , Zeng Jiayi , Cheng Shouyu , Liu Jiumin , Liu Yanjun , Yu Yuming
Published: May 2022

Unlike early clear cell renal cell carcinoma (ccRCC), locally advanced and metastatic ccRCC present poor treatment outcomes and prognosis. As immune checkpoint inhibitors have achieved favorable results in the adjuvant treatment of metastatic ccRCC, we aimed to investigate the immunogenomic landscape during ccRCC progression and its potential impact on immunotherapy and prognosis. Using multi-omics and immunotherapy ccRCC datasets, an integrated analysis was performed to identify genomic alterations, immune microenvironment features, and related biological processes during ccRCC progression and evaluate their relevance to immunotherapy response and prognosis. We found that aggressive and metastatic ccRCC had higher proportions of genomic alterations, including SETD2 mutations, Del(14q), Del(9p), and higher immunosuppressive cellular and molecular infiltration levels. Of these, the Del(14q) might mediate immune escape in ccRCC via the VEGFA-VEGFR2 signaling pathway. Furthermore, immune-related pathways associated with ccRCC progression did not affect the immunotherapeutic response to ccRCC. Conversely, cell cycle pathways not only affected ccRCC progression and prognosis, but also were related to ccRCC immunotherapeutic response resistance. Overall, we described the immunogenomic characteristics of ccRCC progression and their correlations with immunotherapeutic response and prognosis, providing new insights into their prediction and the development of novel therapeutic strategies.
Prognostic Features of the Tumor Immune Microenvironment in Glioma and Their Clinical Applications: Analysis of Multiple Cohorts
Authors: Zhang Chunlong , Zhang Yuxi , Tan Guiyuan , Mi Wanqi , Zhong Xiaoling , Zhang Yu , Zhao Ziyan , Li Feng , Xu Yanjun , Zhang Yunpeng
Published: May 2022

Glioma is the most common malignant tumor of the central nervous system. Tumor purity is a source of important prognostic factor for glioma patients, showing the key roles of the microenvironment in glioma prognosis. In this study, we systematically screened functional characterization related to the tumor immune microenvironment and constructed a risk model named Glioma MicroEnvironment Functional Signature (GMEFS) based on eight cohorts. The prognostic value of the GMEFS model was also verified in another two glioma cohorts, glioblastoma (GBM) and low-grade glioma (LGG) cohorts, from The Cancer Genome Atlas (TCGA). Nomograms were established in the training and testing cohorts to validate the clinical use of this model. Furthermore, the relationships between the risk score, intrinsic molecular subtypes, tumor purity, and tumor-infiltrating immune cell abundance were also evaluated. Meanwhile, the performance of the GMEFS model in glioma formation and glioma recurrence was systematically analyzed based on 16 glioma cohorts from the Gene Expression Omnibus (GEO) database. Based on multiple-cohort integrated analysis, risk subpathway signatures were identified, and a drug–subpathway association network was further constructed to explore candidate therapy target regions. Three subpathways derived from Focal adhesion (path: 04510) were identified and contained known targets including platelet derived growth factor receptor alpha (PDGFRA), epidermal growth factor receptor (EGFR), and erb-b2 receptor tyrosine kinase 2 (ERBB2). In conclusion, the novel functional signatures identified in this study could serve as a robust prognostic biomarker, and this study provided a framework to identify candidate therapeutic target regions, which further guide glioma patients’ clinical decision.
Paired Donor and Recipient Immunophenotyping in Allogeneic Hematopoietic Stem Cell Transplantation: A Cellular Network Approach
Authors: Wittenbecher Friedrich , Lesch Stella , Kolling Stefan , Blau Igor-Wolfgang , Vuong Lam , Borchert Franziska , Movasshagi Kamran , Tietze-Bürger Carola , Penack Olaf , Ahn Johann , Bullinger Lars , Frentsch Marco , Na Il-Kang
Published: May 2022

Success and complications of allogeneic hematopoietic stem cell transplantation (alloHSCT) are closely connected to the transferred graft and immune reconstitution post alloHSCT. Due to the variety of immune cells and their distinct roles, a broad evaluation of the immune cellular network is warranted in mobilization and reconstitution studies in alloHSCT. Here, we propose a comprehensive phenotypic analysis of 26 immune cell subsets with multicolor flow cytometry from only 100µl whole blood per time point. Using this approach, we provide an extensive longitudinal analysis of almost 200 time points from 21 donor-recipient pairs. We observe a broad mobilization of innate and adaptive immune cell subsets after granulocyte-colony stimulating factor (G-CSF) treatment of healthy donors. Our data suggest that the relative quantitative immune cell subset composition in recipients approaches that of healthy donors from day +180 post alloHSCT onwards. Correlation of donor and recipient cell counts reveals distinct association patterns for different immune cell subsets and hierarchical clustering of recipient cell counts identifies distinct reconstitution groups in the first month after transplantation. We suggest our comprehensive immune subset analysis as a feasible and time efficient approach for a broad immune assessment for future clinical studies in the context of alloHSCT. This comprehensive cell composition assessment can be a critical step towards personalized graft composition strategies and individualized therapy management in areas such as GvHD prophylaxis in the highly complex immunological setting of alloHSCT.
Effects of Estrogens on Osteoimmunology: A Role in Bone Metastasis
Authors: Marie Julien C. , Bonnelye Edith
Published: May 2022

Bone loss associated with estrogen deficiency indicates a fundamental role of these hormones in skeletal growth and bone remodeling. In the last decades, growing recent evidence demonstrated that estrogens can also affect the immune compartment of the bone. In this review, we summarize the impacts of estrogens on bone immune cells and their consequences on bone homeostasis, metastasis settlement into the bone and tumor progression. We also addressed the role of an orphan nuclear receptor ERRalpha (“Estrogen-receptor Related Receptor alpha”) on macrophages and T lymphocytes, and as an immunomodulator in bone metastases. Hence, this review links estrogens to bone immune cells in osteo-oncology.
Bat Employs a Conserved MDA5 Gene to Trigger Antiviral Innate Immune Responses
Authors: Wang Jie , Lin Zhenyu , Liu Qiuju , Fu Feiyu , Wang Zhaofei , Ma Jingjiao , Wang Hengan , Yan Yaxian , Cheng Yuqiang , Sun Jianhe
Published: May 2022

Bats are important hosts for various zoonotic viral diseases. However, they rarely show signs of disease infection with such viruses. As the first line for virus control, the innate immune system of bats attracted our full attention. In this study, the Tadarida brasiliensis MDA5 gene (batMDA5), a major sensor for anti-RNA viral infection, was first cloned, and its biological functions in antiviral innate immunity were identified. Bioinformatics analysis shows that the amino acid sequence of batMDA5 is poorly conserved among species, and it is evolutionarily closer to humans. The mRNA of batMDA5 was significantly upregulated in Newcastle disease virus (NDV), avian influenza virus (AIV), and vesicular stomatitis virus (VSV)-infected bat TB 1 Lu cells. Overexpression of batMDA5 could activate IFNβ and inhibit vesicular stomatitis virus (VSV-GFP) replication in TB 1 Lu cells, while knockdown of batMDA5 yielded the opposite result. In addition, we found that the CARD domain was essential for MDA5 to activate IFNβ by constructing MDA5 domain mutant plasmids. These results indicated that bat employs a conserved MDA5 gene to trigger anti-RNA virus innate immune response. This study helps understand the biological role of MDA5 in innate immunity during evolution.
6-Valent Virus-Like Particle-Based Vaccine Induced Potent and Sustained Immunity Against Noroviruses in Mice
Authors: Hou Wenli , Lv Lihui , Wang Yihan , Xing Man , Guo Yingying , Xie Di , Wei Xin , Zhang Xiuyue , Liu Hui , Ren Jiling , Zhou Dongming
Published: May 2022

Norovirus is a major cause of acute gastroenteritis worldwide, and no vaccine is currently available. The genetic and antigenic diversity of Norovirus presents challenges for providing broad immune protection, which calls for a multivalent vaccine application. In this study, we investigated the possibility of developing a virus-like particle (VLP)-based 6-valent Norovirus vaccine candidate (Hexa-VLPs) that covers GI.1, GII.2, GII.3, GII.4, GII.6, and GII.17 genotypes. Hexa-VLPs (30 µg) adjuvanted with 500 µg of aluminum hydroxide (alum) were selected as the optimal immunization dose after a dose-escalation study. Potent and long-lasting blockade antibody responses were induced by 2-or 3-shot Hexa-VLPs, especially for the emerging GII.P16-GII.2 and GII.17 (Kawasaki 2014) genotypes. Hexa-VLPs plus alum elicited Th1/Th2 mixed yet Th2-skewed immune responses, characterized by an IgG1-biased subclass profile and significant IL-4+ T-cell activation. Notably, simultaneous immunization with a mixture of six VLPs revealed no immunological interference among the component antigens. These results demonstrate that Hexa-VLPs are promising broad-spectrum vaccines to provide immunoprotection against major GI/GII epidemic strains in the future.
The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review
Authors: Ke Qiao , Xin Fuli , Fang Huipeng , Zeng Yongyi , Wang Lei , Liu Jingfeng
Published: May 2022

Background and Aims

Regardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC.

Methods

PubMed, MedLine, Embase, the Cochrane Library, and Web of Knowledge were used to screen the eligible studies evaluating the clinical efficacy and safety of triple therapy for patients with uHCC up to April 25th 2022, as well as Chinese databases. The endpoints were the complete response (CR), objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS) rate, overall survival (OS) rate, and the incidence of adverse events (AEs).

Results

A total of 15 studies were eligible with 741 patients receiving transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with TKIs and ICIs. The pooled rate and 95% confidence interval (CI) for CR, ORR, and DCR were 0.124 (0.069–0.190), 0.606 (0.528–0.682), and 0.885 (0.835–0.927). The pooled rates for PFS at 0.5 years and 1 year were 0.781 (0.688–0.862) and 0.387 (0.293–0.486), respectively. The pooled rates for OS at 1, 2, and 3 years were 0.690 (0.585–0.786), 0.212 (0.117–0.324), and 0.056 (0.028–0.091), respectively. In addition, the pooled rate and 95%CI for the conversion surgery was 0.359 (0.153–0.595). The subgroup analysis of control studies showed that triple therapy was superior to TACE+TKIs, TKIs+ICIs, and TKIs in CR, ORR, and DCR, conversion rate; PFS; and OS. No fatal AEs were reported, and the top three most common AEs were elevated ALT, elevated AST, and hypertension, as well as severe AEs (grading ≥3).

Conclusion

With the current data, we concluded that the triple therapy of TACE/HAIC, TKIs, and ICIs would provide a clinical benefit for uHCC both in short- and long-term outcomes without increasing severe AEs, but the conclusion needs further validation.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970.
Coastal Marine Geochemical Provinces and Background Values in Sediments: A Methodological Approach
Authors: Romano Elena , Ausili Antonella , Bergamin Luisa
Published: May 2022

The Italian approach to determining background values (BGVs) of metals and trace elements in marine sediments according to the national legislation transposing the water framework directive (WFD) has been illustrated. This study may be helpful for all countries that need to establish local BGVs for the correct assessment of contamination in areas with wide geological and geochemical variability and, particularly, for those that need assessing the good chemical status according to the WFD. The first step was clearly defining the BGV as a concentration value that allows for discriminating between natural and anthropogenic contributions and establishing the concept of the marine geochemical province (MGP). Successively, criteria for delimiting the MGPs were provided, similar to those adopted for the geochemical mapping of the territory. Finally, an integrated method based on the constitution of a dataset from unpolluted sediments obtained from pre-industrial levels was chosen for determining the BGV.
Preparation and Photocatalytic and Antibacterial Activities of Micro/Nanostructured TiO2-Based Photocatalysts for Application in Orthopedic Implants
Authors: Qi Liang , Guo Binghua , Lu Qing , Gong Hanghui , Wang Min , He Jinlong , Jia Bin , Ren Jing , Zheng Shicheng , Lu Yufeng
Published: May 2022

Micro/nanostructured TiO2, ion-doped TiO2, and heterojunction TiO2 composite photocatalysts have low toxicity, high biocompatibility, and high photocatalytic and antibacterial activities and have broad applications in the fields of photocatalytic, antibacterial, and orthopedic implants. The photocatalytic and antibacterial activities of TiO2 and TiO2-based photocatalysts depend on their preparation methods. In this review, the preparation methods of TiO2, ion-doped TiO2, and heterojunction TiO2 composite photocatalysts and their effects on photocatalytic and antibacterial activities were reviewed. Based on the excellent physical and chemical properties of TiO2, ion-doped TiO2, and heterojunction TiO2-based photocatalysts, their applications in the field of orthopedic implants were reviewed. Meanwhile, the development trend of the photocatalyst in the fields of photocatalysis, bacteriostasis, and medicine was prospected. The purpose of this review was to point out the direction for further study on photocatalytic and antibacterial activities and related applications of TiO2 and TiO2-based photocatalysts.
Comparison of Global and Regional Compliance-Guided Positive End-Expiratory Pressure Titration on Regional Lung Ventilation in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome
Authors: Ren Hong , Xie Li , Wang Zhulin , Tang Xiaoliao , Ning Botao , Teng Teng , Qian Juan , Wang Ying , Fu Lijun , Zhao Zhanqi , Xiang Long
Published: May 2022

Purpose

To investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (Crs) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS).

Methods

Patients with moderate-to-severe pARDS (PaO2/FiO2 < 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEPC) and EIT-based regional compliance (PEEPEIT) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVDSD) were also calculated and compared.

Results

A total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEPC and PEEPEIT were identical in 6 patients. In others, the differences were only ± 2 cm H2O (one PEEP step). There were no statistical differences in global compliance at PEEPC and PEEPEIT [28.7 (2.84–33.15) vs. 29.74 (2.84–33.47) ml/cm H2O median (IQR), p = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions.

Conclusion

Although EIT provided information on ventilation distribution, PEEP selected with the best Crs might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.
Construction and Analysis of a Joint Diagnosis Model of Random Forest and Artificial Neural Network for Obesity
Authors: Yu Jian , Xie Xiaoyan , Zhang Yun , Jiang Feng , Wu Chuyan
Published: May 2022

Obesity is a significant global health concern since it is connected to a higher risk of several chronic diseases. As a consequence, obesity may be described as a condition that reduces human life expectancy and significantly impacts life quality. Because traditional obesity diagnosis procedures have several flaws, it is vital to design new diagnostic models to enhance current methods. More obesity-related markers have been discovered in recent years as a result of improvements and enhancements in gene sequencing technology. Using current gene expression profiles from the Gene Expression Omnibus (GEO) collection, we identified differentially expressed genes (DEGs) associated with obesity and found 12 important genes (CRLS1, ANG, ALPK3, ADSSL1, ABCC1, HLF, AZGP1, TSC22D3, F2R, FXN, PEMT, and SPTAN1) using a random forest classifier. ALPK3, HLF, FXN, and SPTAN1 are the only genes that have never been linked to obesity. We also used an artificial neural network to build a novel obesity diagnosis model and tested its diagnostic effectiveness using public datasets.
Emergence of a High-Risk Klebsiella michiganensis Clone Disseminating Carbapenemase Genes
Authors: Prah Isaac , Nukui Yoko , Yamaoka Shoji , Saito Ryoichi
Published: May 2022

Klebsiella michiganensis is emerging as an important human pathogen of concern especially strains with plasmid-mediated carbapenemase genes. The IncX3-blaNDM-5 plasmid has been described as the primary vector for blaNDM-5 dissemination. However, whether strains with this plasmid have any competitive edge remain largely unexplored. We characterized a blaNDM-5-producing Klebsiella michiganensis strain (KO_408) from Japan and sought to understand the driving force behind the recent dissemination of IncX3-blaNDM-5 plasmids in different bacterial hosts. Antibiotic susceptibility testing, conjugation, and whole-genome sequencing were performed for KO_408, a clinical isolate recovered from a respiratory culture. Fitness, stability, and competitive assays were performed using the IncX3-blaNDM-5 plasmid, pKO_4-NDM-5. KO_408 was ascribed to a novel sequence type, ST256, and harbored resistance genes conforming to its MDR phenotype. The blaNDM-5 gene was localized on the ~44.9 kb IncX3 plasmid (pKO_4-NDM-5), which was transferable in the conjugal assay. The acquisition of pKO_4-NDM-5 did not impose any fitness burden and showed high stability in the host cells. However, transformants with pKO_4-NDM-5 were outcompeted by their host cells and transconjugants with the IncX3-blaOXA-181 plasmid. The genetic environment of blaNDM-5 in pKO_4-NDM-5 has been previously described. pKO_4-NDM-5 showed a close phylogenetic distance with seven similar plasmids from China. KO_408 clustered with strains within the KoI phylogroup, which is closely associated with carbapenemase genes. This study highlights the emergence of a high-risk Klebsiella michiganensis clone harboring carbapenemase genes and affirms that the recent spread of IncX3-blaNDM-5 plasmids might be due to their low fitness cost and stability but not their competitive prowess.
One Cell at a Time: Advances in Single-Cell Methods and Instrumentation for Discovery in Aquatic Microbiology
Authors: Grujcic Vesna , Taylor Gordon T. , Foster Rachel A.
Published: May 2022

Studying microbes from a single-cell perspective has become a major theme and interest within the field of aquatic microbiology. One emerging trend is the unfailing observation of heterogeneity in activity levels within microbial populations. Wherever researchers have looked, intra-population variability in biochemical composition, growth rates, and responses to varying environmental conditions has been evident and probably reflect coexisting genetically distinct strains of the same species. Such observations of heterogeneity require a shift away from bulk analytical approaches and development of new methods or adaptation of existing techniques, many of which were first pioneered in other, unrelated fields, e.g., material, physical, and biomedical sciences. Many co-opted approaches were initially optimized using model organisms. In a field with so few cultivable models, method development has been challenging but has also contributed tremendous insights, breakthroughs, and stimulated curiosity. In this perspective, we present a subset of methods that have been effectively applied to study aquatic microbes at the single-cell level. Opportunities and challenges for innovation are also discussed. We suggest future directions for aquatic microbiological research that will benefit from open access to sophisticated instruments and highly interdisciplinary collaborations.
Proteomic Analysis Reveals Proteins Involved in the Mode of Action of β-Citronellol Identified From Citrus hystrix DC. Leaf Against Candida albicans
Authors: Buakaew Watunyoo , Pankla Sranujit Rungnapa , Noysang Chanai , Krobthong Sucheewin , Yingchutrakul Yodying , Thongsri Yordhathai , Potup Pachuen , Daowtak Krai , Usuwanthim Kanchana
Published: May 2022

Candida albicans is a fungus that lives primarily on the mucosal surfaces of healthy humans, such as the oral cavity, vagina, and gastrointestinal tract. This commensal organism can be controlled by other microbiota, while certain conditions can increase the risk of C. albicans outgrowth and cause disease. Prevalence of the drug-resistant phenotype, as well as the severity of C. albicans infection in immunocompromised patients, presents a challenge for scientists to develop novel, effective treatment, and prevention strategies. β-Citronellol is an intriguing active compound of several plants that has been linked to antifungal activity, but data on the mechanism of action in terms of proteomic profiling are lacking. Here, β-citronellol identified from Citrus hystrix DC. leaf against C. albicans were evaluated. A proteomic approach was used to identify potential target proteins involved in the mode of action of β-citronellol. This study identified and discussed three protein groups based on the 126 major proteins that were altered in response to β-citronellol treatment, 46 of which were downregulated and 80 of which were upregulated. Significant protein groups include cell wall proteins (e.g., Als2p, Rbt1p, and Pga4p), cellular stress response enzymes (e.g., Sod1p, Gst2p, and Ddr48p), and ATP synthesis-associated proteins (e.g., Atp3p, Atp7p, Cox1p, and Cobp). Results demonstrated the complexities of protein interactions influenced by β-citronellol treatment and highlighted the potential of antifungal activity for future clinical and drug development research.