bluuebunny/crossref_metadata_2025 huggingface dataset:
The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule
Authors: Cordeiro Jéssica F. C. , Fernandes Talita M. , Toro Diana M. , da Silva-Neto Pedro V. , Pimentel Vinícius E. , Pérez Malena M. , de Carvalho Jonatan C. S. , Fraga-Silva Thais F. C. , Oliveira Camilla N. S. , Argolo Jamille G. M. , Degiovani Augusto M. , Ostini Fátima M. , Puginna Enrico F. , da Silva João S. , Santos Isabel K. F. M. , Bonato Vânia L. D. , Cardoso Cristina R. B. , Dias-Baruffi Marcelo , Faccioli Lúcia H. , Donadi Eduardo A. , Sorgi Carlos A. , Fernandes Ana P. M. ,   on behalf of the IMMUNOCOVID Study Group
Published: August 2022

The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.
Integrated Analysis of Transcriptome and Metabolome Reveals the Regulation of Chitooligosaccharide on Drought Tolerance in Sugarcane (Saccharum spp. Hybrid) under Drought Stress
Authors: Yang Shan , Chu Na , Zhou Hongkai , Li Jiashuo , Feng Naijie , Su Junbo , Deng Zuhu , Shen Xuefeng , Zheng Dianfeng
Published: August 2022

Sugarcane (Saccharum spp. hybrid) is an important crop for sugar and biofuels, and often suffers from water shortages during growth. Currently, there is limited knowledge concerning the molecular mechanism involved in sugarcane response to drought stress (DS) and whether chitooligosaccharide could alleviate DS. Here, we carried out a combined transcriptome and metabolome of sugarcane in three different treatment groups: control group (CG), DS group, and DS + chitooligosaccharide group (COS). A total of 12,275 (6404 up-regulated and 5871 down-regulated) differentially expressed genes (DEGs) were identified when comparing the CG and DS transcriptomes (T_CG/DS), and 2525 (1261 up-regulated and 1264 down-regulated) DEGs were identified in comparing the DS and COS transcriptomes (T_DS/COS). GO and KEGG analysis showed that DEGs associated with photosynthesis were significantly enriched and had down-regulated expression. For T_DS/COS, photosynthesis DEGs were also significantly enriched but had up-regulated expression. Together, these results indicate that DS of sugarcane has a significantly negative influence on photosynthesis, and that COS can alleviate these negative effects. In metabolome analysis, lipids, others, amino acids and derivatives and alkaloids were the main significantly different metabolites (SDMs) observed in sugarcane response to DS, and COS treatment reduced the content of these metabolites. KEGG analysis of the metabolome showed that 2-oxocarboxylic acid metabolism, ABC transporters, biosynthesis of amino acids, glucosinolate biosynthesis and valine, leucine and isoleucine biosynthesis were the top-5 KEGG enriched pathways when comparing the CG and DS metabolome (M_CG/DS). Comparing DS with COS (M_DS/COS) showed that purine metabolism and phenylalanine metabolism were enriched. Combined transcriptome and metabolome analysis revealed that pyruvate and phenylalanine metabolism were KEGG-enriched pathways for CG/DS and DS/COS, respectively. For pyruvate metabolism, 87 DEGs (47 up-regulated and 40 down-regulated) and five SDMs (1 up-regulated and 4 down-regulated) were enriched. Pyruvate was closely related with 14 DEGs (|r| > 0.99) after Pearson’s correlation analysis, and only 1 DEG (Sspon.02G0043670-1B) was positively correlated. For phenylalanine metabolism, 13 DEGs (7 up-regulated and 6 down-regulated) and 6 SDMs (1 up-regulated and 5 down-regulated) were identified. Five PAL genes were closely related with 6 SDMs through Pearson’s correlation analysis, and the novel.31257 gene had significantly up-regulated expression. Collectively, our results showed that DS has significant adverse effects on the physiology, transcriptome, and metabolome of sugarcane, particularly genes involved in photosynthesis. We further show that COS treatment can alleviate these negative effects.
From Diabetes to Atherosclerosis: Potential of Metformin for Management of Cardiovascular Disease
Authors: Poznyak Anastasia V. , Litvinova Larisa , Poggio Paolo , Moschetta Donato , Sukhorukov Vasily Nikolaevich , Orekhov Alexander N.
Published: August 2022

Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal. Today, we know a lot about the pathogenesis of atherosclerosis. However, the main knowledge is that the disease is extremely complicated. The development of atherosclerosis is associated with more than one molecular mechanism, each making a significant contribution. These mechanisms include endothelial dysfunction, inflammation, mitochondrial dysfunction, oxidative stress, and lipid metabolism disorders. This complexity inevitably leads to difficulties in treatment and prevention. One of the possible therapeutic options for atherosclerosis and its consequences may be metformin, which has already proven itself in the treatment of diabetes. Both diabetes and atherosclerosis are complex metabolic diseases, the pathogenesis of which involves many different mechanisms, including those common to both diseases. This makes metformin a suitable candidate for investigating its efficacy in cardiovascular disease. In this review, we highlight aspects such as the mechanisms of action and targets of metformin, in addition to summarizing the available data from clinical trials on the effective reduction of cardiovascular risks.
Reorganization of the Landscape of Translated mRNAs in NSUN2-Deficient Cells and Specific Features of NSUN2 Target mRNAs
Authors: Kossinova Olga A. , Gopanenko Alexander V. , Babaylova Elena S. , Tupikin Alexey E. , Kabilov Marsel R. , Malygin Alexey A. , Karpova Galina G.
Published: August 2022

The RNA cytosine C5 methyltransferase NSUN2 has a variety of RNA substrates and plays an important role in mRNA metabolism. NSUN2 binds to specific sequences enriched in exosomal mRNAs, suggesting its possible involvement in the sorting of mRNAs into exosomes. We applied the photoactivatable.4-thiouridine-enhanced cross-linking and immunoprecipitation assay involving high-throughput RNA sequencing (RNA-seq) to HEK293T cells to determine NSUN2 mRNA targets. NSUN2 cross-linking sites were found in more than one hundred relatively abundant mRNAs with a high GC content and a pronounced secondary structure. Then, utilizing RNA-seq for the total and polysome-associated mRNA from HEK293T cells with and without the knockdown of NSUN2, we identified differentially expressed genes, as well as genes with altered translational efficiency (GATEs). It turned out that the up-regulated GATE mRNAs were much shorter on average than the down-regulated ones, and their GC content was higher; moreover, they contained motifs with C residues located in GC-rich environments. Our findings reveal the specific features of mRNAs that make them potential targets for NSUN2 and expand our understanding of the role of NSUN2 in controlling translation and, possibly, in mRNA sorting into exosomes implemented through the methylation of cytosine residues.
Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways
Authors: Xu Zhaokun , Hao Xiujing , Li Min , Luo Haixia
Published: August 2022

Rhodococcus equi (R. equi) is a Gram-positive coccobacillus that causes pneumonia in foals of less than 3 months, which have the ability of replication in macrophages. The ability of R. equi persist in macrophages is dependent on the virulence plasmid pVAPA. Gram-positive extracellular vesicles (EVs) carry a variety of virulence factors and play an important role in pathogenic infection. There are few studies on R. equi-derived EVs (R. equi-EVs), and little knowledge regarding the mechanisms of how R. equi-EVs communicate with the host cell. In this study, we examine the properties of EVs produced by the virulence strain R. equi 103+ (103+-EVs) and avirulenct strain R. equi 103− (103−-EVs). We observed that 103+-EVs and 103−-EVs are similar to other Gram-positive extracellular vesicles, which range from 40 to 260 nm in diameter. The 103+-EVs or 103−-EVs could be taken up by mouse macrophage J774A.1 and cause macrophage cytotoxicity. Incubation of 103+-EVs or 103−-EVs with J774A.1 cells would result in increased expression levels of IL-1β, IL-6, and TNF-α. Moreover, the expression of TLR2, p-NF-κB, p-p38, and p-ERK were significantly increased in J774A.1 cells stimulated with R. equi-EVs. In addition, we presented that the level of inflammatory factors and expression of TLR2, p-NF-κB, p-p38, and p-ERK in J774A.1 cells showed a significant decreased when incubation with proteinase K pretreated-R. equi-EVs. Overall, our data indicate that R. equi-derived EVs are capable of mediating inflammatory responses in macrophages via TLR2-NF-κB/MAPK pathways, and R. equi-EVs proteins were responsible for TLR2-NF-κB/MAPK mediated inflammatory responses in macrophage. Our study is the first to reveal potential roles for R. equi-EVs in immune response in R. equi-host interactions and to compare the differences in macrophage inflammatory responses mediated by EVs derived from virulent strain R. equi and avirulent strain R. equi. The results of this study have improved our knowledge of the pathogenicity of R. equi.
A Pan-RNase Inhibitor Enabling CRISPR-mRNA Platforms for Engineering of Primary Human Monocytes
Authors: Laoharawee Kanut , Johnson Matthew J. , Lahr Walker S. , Sipe Christopher J. , Kleinboehl Evan , Peterson Joseph J. , Lonetree Cara-lin , Bell Jason B. , Slipek Nicholas J. , Crane Andrew T. , Webber Beau R. , Moriarity Branden S.
Published: August 2022

Monocytes and their downstream effectors are critical components of the innate immune system. Monocytes are equipped with chemokine receptors, allowing them to migrate to various tissues, where they can differentiate into macrophage and dendritic cell subsets and participate in tissue homeostasis, infection, autoimmune disease, and cancer. Enabling genome engineering in monocytes and their effector cells will facilitate a myriad of applications for basic and translational research. Here, we demonstrate that CRISPR-Cas9 RNPs can be used for efficient gene knockout in primary human monocytes. In addition, we demonstrate that intracellular RNases are likely responsible for poor and heterogenous mRNA expression as incorporation of pan-RNase inhibitor allows efficient genome engineering following mRNA-based delivery of Cas9 and base editor enzymes. Moreover, we demonstrate that CRISPR-Cas9 combined with an rAAV vector DNA donor template mediates site-specific insertion and expression of a transgene in primary human monocytes. Finally, we demonstrate that SIRPa knock-out monocyte-derived macrophages have enhanced activity against cancer cells, highlighting the potential for application in cellular immunotherapies.
Exploring the Function of Quorum Sensing Regulated Biofilms in Biological Wastewater Treatment: A Review
Authors: Sahreen Sania , Mukhtar Hamid , Imre Kálmán , Morar Adriana , Herman Viorel , Sharif Sundas
Published: August 2022

Quorum sensing (QS), a type of bacterial cell–cell communication, produces autoinducers which help in biofilm formation in response to cell population density. In this review, biofilm formation, the role of QS in biofilm formation and development with reference to biological wastewater treatment are discussed. Autoinducers, for example, acyl-homoserine lactones (AHLs), auto-inducing oligo-peptides (AIPs) and autoinducer 2, present in both Gram-negative and Gram-positive bacteria, with their mechanism, are also explained. Over the years, wastewater treatment (WWT) by QS-regulated biofilms and their optimization for WWT have gained much attention. This article gives a comprehensive review of QS regulation methods, QS enrichment methods and QS inhibition methods in biological waste treatment systems. Typical QS enrichment methods comprise adding QS molecules, adding QS accelerants and cultivating QS bacteria, while typical QS inhibition methods consist of additions of quorum quenching (QQ) bacteria, QS-degrading enzymes, QS-degrading oxidants, and QS inhibitors. Potential applications of QS regulated biofilms for WWT have also been summarized. At last, the knowledge gaps present in current researches are analyzed, and future study requirements are proposed.
Inhibition of Class I Histone Deacetylase Activity Blocks the Induction of TNFAIP3 Both Directly and Indirectly via the Suppression of Endogenous TNF-α
Authors: Schioppa Tiziana , Nguyen Hoang Oanh , Tiberio Laura , Sozio Francesca , Gaudenzi Carolina , Passari Mauro , Del Prete Annalisa , Bosisio Daniela , Salvi Valentina
Published: August 2022

Histone deacetylase inhibitors (HDIs) are promising drugs for the treatment of inflammatory diseases. However, their therapeutical exploitation is slowed down by severe adverse manifestations that can hardly be foreseen, mainly due to incomplete knowledge of how HDIs impact the delicate balance of inflammatory mediators. In this work, we characterized the effects of the HDI trichostatin A (TSA) on the expression of TNFAIP3, which is a crucial inhibitor of the classical NF-kB pathway and an LPS-induced negative feedback regulator. The accumulation of TNFAIP3 mRNA after LPS stimulation showed biphasic behavior, with one wave within the first hour of stimulation and a second wave several hours later, which were both reduced by TSA. By using inhibition and knockdown approaches, we identified two temporally and mechanistically distinct modes of action. The first wave of TNAIP3 accumulation was directly blunted by the histone deacetylase (HDAC) blockade. By contrast, the second wave was decreased mainly because of the lack of endogenous TNF-α induction, which, in turn, depended on the intact HDAC activity. In both cases, class I HDACs appeared to play a nonredundant role, with HDAC3 required, but not sufficient, for TNF-α and TNFAIP3 induction. In addition to TNFAIP3, TNF-α is known to induce many response genes that orchestrate the inflammatory cascade. Thus, suppression of TNF-α may represent a general mechanism through which HDIs regulate a selected set of target genes.
A Combination of a Genome-Wide Association Study and a Transcriptome Analysis Reveals circRNAs as New Regulators Involved in the Response to Salt Stress in Maize
Authors: Liu Peng , Zhu Yuxiao , Liu Hao , Liang Zhenjuan , Zhang Minyan , Zou Chaoying , Yuan Guangsheng , Gao Shibin , Pan Guangtang , Shen Yaou , Ma Langlang
Published: August 2022

Salinization seriously threatens the normal growth of maize, especially at the seedling stage. Recent studies have demonstrated that circular RNAs (circRNAs) play vital roles in the regulation of plant stress resistance. Here, we performed a genome-wide association study (GWAS) on the survival rate of 300 maize accessions under a salt stress treatment. A total of 5 trait-associated SNPs and 86 candidate genes were obtained by the GWAS. We performed RNA sequencing for 28 transcriptome libraries derived from 2 maize lines with contrasting salt tolerance under normal and salt treatment conditions. A total of 1217 highly expressed circRNAs were identified, of which 371 were responsive to a salt treatment. Using PCR and Sanger sequencing, we verified the reliability of these differentially expressed circRNAs. An integration of the GWAS and RNA-Seq analyses uncovered two differentially expressed hub genes (Zm00001eb013650 and Zm00001eb198930), which were regulated by four circRNAs. Based on these results, we constructed a regulation model of circRNA/miRNA/mRNA that mediated salt stress tolerance in maize. By conducting hub gene-based association analyses, we detected a favorable haplotype in Zm00001eb198930, which was responsible for high salt tolerance. These results help to clarify the regulatory relationship between circRNAs and their target genes as well as to develop salt-tolerant lines for maize breeding.
Analysis of the Equilibrium Distribution of Ligands in Heterogeneous Media–Approaches and Pitfalls
Authors: Moreno Maria João , Loura Luís M. S. , Martins Jorge , Salvador Armindo , Velazquez-Campoy Adrian
Published: August 2022

The equilibrium distribution of small molecules (ligands) between binding agents in heterogeneous media is an important property that determines their activity. Heterogeneous systems containing proteins and lipid membranes are particularly relevant due to their prevalence in biological systems, and their importance to ligand distribution, which, in turn, is crucial to ligand’s availability and biological activity. In this work, we review several approaches and formalisms for the analysis of the equilibrium distribution of ligands in the presence of proteins, lipid membranes, or both. Special attention is given to common pitfalls in the analysis, with the establishment of the validity limits for the distinct approaches. Due to its widespread use, special attention is given to the characterization of ligand binding through the analysis of Stern–Volmer plots of protein fluorescence quenching. Systems of increasing complexity are considered, from proteins with single to multiple binding sites, from ligands interacting with proteins only to biomembranes containing lipid bilayers and membrane proteins. A new formalism is proposed, in which ligand binding is treated as a partition process, while considering the saturation of protein binding sites. This formalism is particularly useful for the characterization of interaction with membrane proteins.
High mRNA Expression Levels of Heat Shock Protein Family B Member 2 (HSPB2) Are Associated with Breast Cancer Patients’ Relapse and Poor Survival
Authors: Sklirou Aimilia D. , Gianniou Despoina D. , Karousi Paraskevi , Cheimonidi Christina , Papachristopoulou Georgia , Kontos Christos K. , Scorilas Andreas , Trougakos Ioannis P.
Published: August 2022

Small heat shock proteins (sHSPs) are ubiquitous ATP-independent chaperones that contribute to the maintenance of proteome integrity and functionality. Recent evidence suggests that sHSPs are ubiquitously expressed in numerous types of tumors and have been proposed to be implicated in oncogenesis and malignant progression. Heat shock protein family B member 2 (HSPB2) is a member of the sHSPs, which is found to be expressed, among others, in human breast cancer cell lines and constitutes an inhibitor of apical caspase activation in the extrinsic apoptotic pathway. In this study, we investigated the potential prognostic significance of HSPB2 mRNA expression levels in breast cancer, which represents the most frequent malignancy in females and one of the three most common cancer types worldwide. To this end, malignant breast tumors along with paired non-cancerous breast tissue specimens were used. HSPB2 expression levels were quantified in these two cohorts using a sensitive and accurate SYBR green-based quantitative real-time polymerase chain reaction (q-RT-PCR). Extensive biostatistical analyses were performed including Kaplan–Meier and Cox regression survival analyses for the assessment of the results. The significant downregulation of HSPB2 gene expression was revealed in breast tumors compared to their adjacent non-cancerous breast tissues. Notably, high HSPB2 mRNA expression predicts poor disease-free survival and overall survival of breast cancer patients. Multivariate Cox regression analysis revealed that HSPB2 mRNA overexpression is a significant predictor of poor prognosis in breast cancer, independent of other clinicopathological factors. In conclusion, high HSPB2 mRNA expression levels are associated with breast cancer patients’ relapse and poor survival.
Cross-Linked Hyaluronate and Corticosteroid Combination Ameliorate the Rat Experimental Tendinopathy through Anti-Senescent and -Apoptotic Effects
Authors: Ko Po-Yen , Hsu Che-Chia , Chen Shih-Yao , Kuo Li-Chieh , Su Wei-Ren , Jou I-Ming , Su Fong-Chin , Wu Po-Ting
Published: August 2022

The combination of cross-linked hyaluronate (cHA) and corticosteroid showed more rapid pain or functional improvement in knee osteoarthritis and adhesive capsulitis. However, rare evidence of this combination in treating tendinopathy has been reported. We hypothesized that the specific formulations of cHA and dexamethasone (DEX) conferred amelioration of tendinopathy via anti-apoptosis and anti-senescence. In this controlled laboratory study, primary tenocytes from the human tendinopathic long head of biceps were treated with three cHA formulations (cHA:linealized HA = 80:20, 50:50, and 20:80) + DEX with or without IL-1β stimulation. Cell viability, inflammatory cytokines, tendon-related proliferation markers, matrix metalloproteinases (MMPs), senescent markers, and apoptosis were examined. The in vivo therapeutic effects of the selected cHA + DEX combinations were evaluated in a collagenase-induced rat patellar tendinopathy model. The expression levels of inflammatory mediators, including IL-1β, IL-6, COX-2, MMP-1, and MMP-3 were significantly reduced in all cHA + DEX-treated tenocytes (p < 0.05, all). The cHA (50:50) + DEX and cHA (20:80) + DEX combinations protected tenocytes from cytotoxicity, senescence, and apoptosis induced by DEX in either IL-1β stimulation or none. Furthermore, the two combinations significantly improved the rat experimental tendinopathy by reducing ultrasound feature scores and histological scores as well as the levels of apoptosis, senescence, and senescence-associated secretory phenotypes (p < 0.05, all). We identified two specific cHA formulations (cHA (50:50) and cHA (20:80)) + DEX that could ameliorate tendinopathy through anti-senescence and -apoptosis without cytotoxicity. This study provides a possible approach to treating tendinopathy using the combination of two well-known agents.
Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies
Authors: Almagro Juan C. , Mellado-Sánchez Gabriela , Pedraza-Escalona Martha , Pérez-Tapia Sonia M.
Published: August 2022

Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.
Association between APOE Genotype with Body Composition and Cardiovascular Disease Risk Markers Is Modulated by BMI in Healthy Adults: Findings from the BODYCON Study
Authors: Ozen Ezgi , Mihaylova Rada G. , Lord Natalie J. , Lovegrove Julie A. , Jackson Kim G.
Published: August 2022

Body mass index (BMI) has been suggested to play an important role in the relationship between the APOLIPOPROTEIN (APO)E genotype and cardiovascular disease (CVD) risk. Using data from the BODYCON cross-sectional study (n = 360 adults) we assessed the association between body composition and CVD risk markers according to APOE genotype, with examination of the role of BMI. In this study cohort, the APOE2/E3 group had lower fasting blood lipids than APOE4 carriers and APOE3/E3 group (p ≤ 0.01). After stratifying the group according to BMI, APOE4 carriers in the normal BMI subgroup had a higher lean mass compared with the APOE3/E3 group (p = 0.02) whereas in the overweight/obese subgroup, the android to gynoid percentage fat ratio was lower in APOE4 carriers than APOE3/E3 group (p = 0.04). Fasting lipid concentrations were only different between the APOE2/E3 and other genotype groups within the normal weight BMI subgroup (p ≤ 0.04). This finding was associated with a lower dietary fibre and a higher trans-fat intake compared with APOE4 carriers, and a lower carbohydrate intake relative to the APOE3/E3 group. Our results confirm previous reports that BMI modulates the effect of APOE on CVD risk markers and suggest novel interactions on body composition, with diet a potential modulator of this relationship.
Early Empirical Antibiotic Therapy Modification in Sepsis Using Beta-Lacta Test Directly on Blood Cultures
Authors: Mizrahi Assaf , Jaureguy Françoise , Petit Héloise , Péan de Ponfilly Gauthier , Carbonnelle Etienne , Le Monnier Alban , Zahar Jean-Ralph , Pilmis Benoît
Published: August 2022

Background: Sepsis caused by multi-drug-resistant Gram-negative bacilli lead physicians to prescribe broad-spectrum antibiotic therapy, such as carbapenems. Rapid susceptibility testing can help with the rational use of antibiotics. The aim of this study was to measure the clinical impact associated with rapid reporting of Beta-Lacta test (BLT) directly on blood cultures positive with Gram-negative bacilli. Methods: In an observational, multicentric, prospective study, we included patients with sepsis caused by Enterobacterales observed on Gram staining of the positive blood cultures. BLT and antimicrobial susceptibility testing (AST) were performed directly on the blood cultures. Clinical impact was measured on the proportion of patients for whom the probabilistic antibiotic therapy was modified according to BLT, including patients receiving carbapenem. Results: 170 patients were included, of whom 44 (25.9%) were receiving inadequate empirical antibiotic therapy. Among them, 27 (15.9%) benefited from an early modification, according to the BLT results. Among 126 (74.1%) patients receiving appropriate probabilistic antibiotic therapy, we modified the antibiotic therapy for 28 (16.5%) of them, including 4/14 (28.5%) de-escalation from carbapenem to a third-generation cephalosporin. Conclusions: Implementation of BLT performed directly on blood cultures allowed us to rapidly modify the empirical antibiotic therapy for about one-third of patients with sepsis caused by Enterobacterales.
OptiNET—Automatic Network Topology Optimization
Authors: Maniatopoulos Andreas , Alvanaki Paraskevi , Mitianoudis Nikolaos
Published: August 2022

The recent boom of artificial Neural Networks (NN) has shown that NN can provide viable solutions to a variety of problems. However, their complexity and the lack of efficient interpretation of NN architectures (commonly considered black box techniques) has adverse effects on the optimization of each NN architecture. One cannot simply use a generic topology and have the best performance in every application field, since the network topology is commonly fine-tuned to the problem/dataset in question. In this paper, we introduce a novel method of computationally assessing the complexity of the dataset. The NN is treated as an information channel, and thus information theory is used to estimate the optimal number of neurons for each layer, reducing the memory and computational load, while achieving the same, if not greater, accuracy. Experiments using common datasets confirm the theoretical findings, and the derived algorithm seems to improve the performance of the original architecture.
China Data Cube (CDC) for Big Earth Observation Data: Practices and Lessons Learned
Authors: Cao Qianqian , Li Guoqing , Yao Xiaochuang , Ma Yue
Published: August 2022

In the face of tight natural resources and complex as well as volatile environments, and in order to meet the pressure brought by population growth, we need to overcome a series of challenges. As a new data management paradigm, the Earth Observation Data Cube simplifies the way that users manage and use earth observation data, and provides an analysis-ready form to access big spatiotemporal data, so as to realize the greater potential of earth observation data. Based on the Open Data Cube (ODC) framework, combined with analysis-ready data (ARD) generation technology, the design and implementation of CDC_DLTool, extending the support for data loading and the processing of international and Chinese imagery data covering China, this study eventually constructs the China Data Cube (CDC) framework. In the framework of this CDC grid, this study carried out case studies of water change monitoring based on international satellite imagery data of Landsat 8 in addition to vegetation change monitoring based on Chinese satellite imagery data of GF-1. The experimental results show that, compared with traditional scene-based data organization, the minimum management unit of this framework is a pixel, which makes the unified organization and management of multisource heterogeneous satellite imagery data more convenient and faster.
FMAA: A Flexible Signal Timing Method for An Isolated Intersection with Conflicting Traffic Flows
Authors: Nie Lei , Wang Qifeng , Zhang Mingxuan , Wu Libing
Published: August 2022

Optimizing traffic signal timing can effectively alleviate urban traffic congestion. However, most of the existing signal timing methods struggle to deal with conflicting traffic flows in heavy traffic; therefore, more effective methods are urgently required. In this paper, we propose a flexible signal timing method that combines all-red control and adaptive timing (FMAA) to deal with conflicting traffic flows at an isolated intersection. First, we consider a Vehicle-to-Infrastructure (V2I) communication-based vehicular network environment, in which fine-grained traffic information can be collected by Road Side Units (RSUs) and uploaded to a cloud server for designing signal timing methods. Second, the congestion degree of Conflict Area (CA) is defined and utilized to trigger all-red control in congested cases. Third, the tolerance degree of the Waiting Area (WA) is defined and utilized to perform adaptive timing in other cases. Finally, simulations were conducted using SUMO, and the proposed FMAA method performed better than the comparative methods in terms of average speed, waiting time, and congested vehicles, thus improving traffic efficiency at an isolated intersection with conflicting traffic flows.
MOF Derived Manganese Oxides Nanospheres Embedded in N-Doped Carbon for Oxygen Reduction Reaction
Authors: Zhang Zhibin , Huo Ge , Si Fengzhan , Fu Xian-Zhu , Liu Shao-Qing , Luo Jing-Li
Published: August 2022

Manganese oxides (MnOx) have been regarded as promising catalyst candidates for oxygen reduction reaction (ORR) due to their natural abundance and extremely low toxicity. However, the intrinsic low conductivity of MnOx limits their application. In this work, Mn oxide embedded in N doped porous carbon (MnOx@C-N) electrocatalysts were prepared through a facile zeolitic imidazolate framework (ZIF-8) template method for ORR. The structure, morphology, and composition of the prepared materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Electrocatalytic performances of the prepared materials were investigated by linear sweep voltammetry. Benefiting from the well-defined morphology, high surface area, and porous structure, the MnOx@C-N electrocatalyst showed the highest ORR activity among all investigated materials with the limiting current density of 5.38 mA/cm2 at a rotation speed of 1600 rpm, the positive half-wave potential of 0.645 V vs. RHE, and the electron transfer number of 3.90. This work showcases an effective strategy to enhance ORR activity of MnOx.
Comparative Efficacy of a Fungal Entomopathogen with a Broad Host Range against Two Human-Associated Pests
Authors: Ashbrook Aaron R. , Mikaelyan Aram , Schal Coby
Published: August 2022

The ability of a fungal entomopathogen to infect an insect depends on a variety of factors, including strain, host, and environmental conditions. Similarly, an insect’s ability to prevent fungal infection is dependent on its biology, environment, and evolutionary history. Synanthropic pests have adapted to thrive in the indoor environment, yet they arose from divergent evolutionary lineages and occupy different feeding guilds. The hematophagous bed bug (Cimex lectularius) and omnivorous German cockroach (Blattella germanica) are highly successful indoors, but have evolved different physiological and behavioral adaptations to cope with the human-built environment, some of which also reduce the efficacy of fungal biopesticides. In order to gain greater insight into the host barriers that prevent or constrain fungal infection in bed bugs and German cockroaches, we tested different doses of Beauveria bassiana GHA through surface contact, topical application, feeding, and injection. Bed bugs were generally more susceptible to infection by B. bassiana with the mode of delivery having a significant impact on infectivity. The German cockroach was highly resilient to infection, requiring high doses of fungal conidia (>8.8 × 104) delivered by injection into the hemocoel to cause mortality. Mortality occurred much faster in both insect species after exposure to surfaces dusted with dry conidia than surfaces treated with conidia suspended in water or oil. These findings highlight the importance of developing innovative delivery techniques to enhance fungal entomopathogens against bed bugs and cockroaches.
Moth Diversity Increases along a Continent-Wide Gradient of Environmental Productivity in South African Savannahs
Authors: Delabye Sylvain , Storch David , Sedláček Ondřej , Albrecht Tomáš , Hořák David , Maicher Vincent , Tószögyová Anna , Tropek Robert
Published: August 2022

Environmental productivity, i.e., the amount of biomass produced by primary producers, belongs among the key factors for the biodiversity patterns. Although the relationship of diversity to environmental productivity differs among studied taxa, detailed data are largely missing for most groups, including insects. Here, we present a study of moth diversity patterns at local and regional scales along a continent-wide gradient of environmental productivity in southern African savannah ecosystems. We sampled diversity of moths (Lepidoptera: Heterocera) at 120 local plots along a gradient of normalized difference vegetation index (NDVI) from the Namib Desert to woodland savannahs along the Zambezi River. By standardized light trapping, we collected 12,372 specimens belonging to 487 moth species. The relationship between species richness for most analyzed moth groups and environmental productivity was significantly positively linear at the local and regional scales. The absence of a significant relationship of most moth groups’ abundance to environmental productivity did not support the role of the number of individuals in the diversity–productivity relationship for south African moths. We hypothesize the effects of water availability, habitat complexity, and plant diversity drive the observed moth diversity patterns.
If You Know Them, You Avoid Them: The Imperative Need to Improve the Narrative Regarding Perioperative Adverse Events
Authors: Eppler Michael , Sayegh Aref , Goldenberg Mitchell , Sholklapper Tamir , Hemal Sij , Cacciamani Giovanni
Published: August 2022

There are few things in life as exciting as growing up in the countryside [...]
A Novel Muco-Gingival Approach for Immediate Implant Placement to Obtain Soft- and Hard-Tissue Augmentation
Authors: Stefanini Martina , Sangiorgi Matteo , Bianchelli Diego , Bellone Pietro , Gelpi Federico , De Santis Daniele , Zucchelli Giovanni
Published: August 2022

The aim of this article is to describe a novel approach combining muco-gingival, regenerative and prosthetics concepts for immediate implant insertion that overcomes the limits traditionally considered as contraindications for Type 1 flapless implant positioning, simultaneously obtaining soft- and hard-tissue augmentation. After pre-surgical CBCT evaluation, the surgical technique consisted in the execution of a lateral-approach coronally advanced envelope flap, with oblique submarginal interproximal incisions directed towards the flap’s center of rotation (the tooth to be extracted); after buccal-flap elevation, the atraumatic extraction of the tooth was performed. Following guided implant insertion, a mixture of biomaterial and autologous bone was placed, stabilized by a pericardium membrane and a connective-tissue graft sutured in the inner aspect of the buccal flap. The peri-implant soft tissues were conditioned with a provisional crown until the shape and position for the mucosal scallop to resemble the gingival margin of the adjacent corresponding tooth were obtained; then, the definitive screw-retained restoration was placed. Within the limitations of this case report, the proposed immediate implant placement approach combining CTG application and buccal bone regeneration showed the possibility of obtaining 1-year-follow-up implant success, stable bone level, good esthetic results and high patient satisfaction.
Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study
Authors: Gao Qian , Zhen Kaiyuan , Xia Lei , Wang Wei , Xu Yaping , Si Chaozeng , Zhang Zhu , Dong Fen , Lei Jieping , Yang Peiran , Liu Jixiang , Sun Ziyi , Zhang Tieshan , Wan Jun , Xie Wanmu , Liu Peng , Jia Cunbo , Zhai Zhenguo , Wang Chen
Published: August 2022

Background: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. Methods: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. Results: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). Conclusions: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.
Cardiac Magnetic Resonance Shows Improved Outcomes in Patients with an ST-Segment Elevation Myocardial Infarction and a High Thrombus Burden Treated with Adjuvant Aspiration Thrombectomy
Authors: Zajdel Wojciech , Miszalski-Jamka Tomasz , Zalewski Jarosław , Legutko Jacek , Żmudka Krzysztof , Paszek Elżbieta
Published: August 2022

There is a discrepancy between epicardial vessel patency and microcirculation perfusion in a third of patients treated with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Optimization with aspiration thrombectomy (AT) may reduce distal embolization and microvascular obstruction. The effect of AT in the treatment of STEMI is debatable. The purpose of this study was to use cardiac magnetic resonance (CMR) to determine whether AT influences microvascular obstruction (MVO), infarct size and left ventricular (LV) remodelling in STEMI patients. Sixty STEMI patients with a thrombus-occluded coronary artery were randomized in a 2:1 fashion to receive PCI proceeded by AT (AT + PCI group), or PCI only. MVO, myocardial infarct size and LV remodelling were assessed by CMR during the index hospitalization and 6 months thereafter. The majority of patients had a large thrombus burden (TIMI thrombus grade 5 in over 70% of patients). PCI and AT were effective in all cases. There were no periprocedural strokes. CMR showed that the addition of AT to standard PCI was associated with lesser MVO when indexed to the infarct size and larger infarct size reduction. There were less patients with left ventricle remodelling in the AT + PCI vs. the PCI only group. To conclude, in STEMI patients with a high thrombus burden, AT added to PCI is effective in reducing infarct size, MVO and LV remodelling.
Long-Term Outcomes after Non-Traumatic Out-of-Hospital Cardiac Arrest in Pediatric Patients: A Systematic Review
Authors: Ng Zi Hui Celeste , Ho Siyuan Joseph , Caleb Tan , Yaow Clyve Yu Leon , Teoh Seth En , Tham Lai Peng , Ong Marcus Eng Hock , Chong Shu-Ling , Ho Andrew Fu Wah
Published: August 2022

Long-term outcomes after non-traumatic pediatric out-of-hospital cardiac arrest (OHCA) are not well understood. This systematic review aimed to summarize long-term outcomes (1 year and beyond), including overall survival, survival with favorable neurological outcomes, and health-related quality of life (HRQoL) outcomes) amongst pediatric OHCA patients who survived to discharge. Embase, Medline, and The Cochrane Library were searched from inception to October 6, 2021. Studies were included if they reported outcomes at 1 year or beyond after pediatric OHCA. Data abstraction and quality assessment was conducted by three authors independently. Qualitative outcomes were reported systematically. Seven studies were included, and amongst patients that survived to hospital discharge or to 30 days, longer-term survival was at least 95% at 24 months of follow up. A highly variable proportion (range 10–71%) of patients had favorable neurological outcomes at 24 months of follow up. With regard to health-related quality of life outcomes, at a time point distal to 1 year, at least 60% of pediatric non-traumatic OHCA patients were reported to have good outcomes. Our study found that at least 95% of pediatric OHCA patients, who survived to discharge, survived to a time point distal to 1 year. There is a general paucity of data surrounding the pediatric OHCA population.
Pitfalls in the Serological Evaluation of Maternal Cytomegalovirus Infection as a Potential Cause of Fetal and Neonatal Involvements: A Narrative Literature Review
Authors: Iijima Shigeo
Published: August 2022

Cytomegalovirus (CMV) is the most common cause of intrauterine infection and serological assays are the primary tools for assessing CMV infections during pregnancy. CMV-specific immunoglobulin M (IgM) antibodies have been used as a diagnostic marker for primary CMV infection in pregnant women, although CMV-IgM has been detected in non-primary CMV infections. IgG avidity testing may aid the distinguishing of primary from non-primary CMV infection; however, there is no standardized assay for detecting this difference. Moreover, when maternal serology shows positive CMV-IgG with negative CMV-IgM findings, vertical transmission probability following primary CMV infection is often excluded. However, symptomatic congenital CMV infections in the context of negative findings for maternal CMV-IgM have been reported recently. The absence of CMV-IgM is recognized in both primary and non-primary CMV infections. Furthermore, maternal non-primary CMV infections during pregnancy may yield a greater proportion of symptomatic congenital CMV infections than previously thought. If universal prenatal screening is performed, ultrasonography for abnormal fetal findings should be conducted regardless of CMV-IgM antibody status. If not universally screened, CMV antibody screening should be performed whenever routine fetal ultrasound reveals abnormal findings. For suspected fetal CMV infection, amniotic fluid or postnatal infant urine CMV-DNA testing is required.
A Comparison of the Effect of a 4.4-MHz Radiofrequency Deep Heating Therapy and Ultrasound on Low Back Pain: A Randomized, Double-Blind, Multicenter Trial
Authors: Lee Jung Hwan , Do Jong Geol , Park Hee Jin , Lee Yong-Taek , Kim Sang Jun
Published: August 2022

Despite the increasing interest in RF (Radiofrequency) therapy, little is known about its effectiveness for low back pain (LBP). The aim of this study was to investigate the effectiveness of 4.4-MHz RF diathermy compared to ultrasound (US) in patients with LBP. One-hundred-and-eighteen patients with LBP were randomized with RF (n = 62) or US (n = 56). Investigator and subjects were blinded to the treatment group. Either RF (4.4 MHz, 45 W/cm2) or US (1 MHz, 2 W/cm2) was applied for 10 to 15 min, 3 times per week for 4 weeks. The primary outcome was the Oswestry Disability Index (ODI, %). Secondary outcomes were numeric rating scale (NRS), Biering–Sorensen test, up-and-go test, successful pain relief, and successful functional improvement. Clinical outcomes were evaluated prior to intervention (baseline), and at 4 and 12 weeks after treatment. There were no significant differences between the groups regarding baseline demographic and clinical characteristics. Both groups observed a significant improvement of ODI (%), NRS, Biering–Sorensen test, and up-and-go test at 4 and 12 weeks after treatment (p < 0.05); however, no significant differences were found between groups. The RF group showed a higher proportion of successful pain relief at 12 weeks after treatment than the US group (p = 0.048). The RF diathermy showed favorable results in pain reduction, improvement of function, mobility, and back muscle endurance. Compared with US, RF diathermy obtained slightly better perception of patients in pain relief at 12 weeks after treatment. The results from this study indicated that 4.4-MHz RF diathermy can effectively be used as a conservative treatment option for patients with LBP.