bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomy and Community in Learning Languages Online: A Critical Autoethnography of Teaching and Learning in COVID-19 Confinement During 2020
Authors: Dutton Jacqueline
Published: September 2021

During COVID-19 confinement in 2020, there has been a massive increase in learning languages online via a variety of apps, short courses, and as part of higher education on-campus degrees converted to online learning. This study argues that attention to the balance of autonomy and community is vital to successful language learning online. An initial exploration of recent scholarship on autonomy and community in learning languages online validates this approach to evaluating the situation. The specific phenomenon of online language teaching and learning during 2020 at the University of Melbourne is then presented as an autoethnographic case study and analyzed in the context of this research. In 2020, the author participated in online language learning experiences from several different perspectives. As Head of Languages, she led development of a new undergraduate certificate in languages in response to an Australian Federal Government initiative to offer significant subsidies for online language certificates in 2020. As a keen language learner, she enrolled in one of these certificates to study Italian. As a French lecturer, she converted Matters of Taste—French Eating Cultures, a highly interactive and sensory oriented on-campus subject for advanced French students, to online delivery. The autoethnographic work undertaken in this article aims to examine critically the author’s experiences of teaching and learning in 2020, assessing the advantages and disadvantages of learning languages online from positions of both teacher and learner. These experiences are triangulated with the academic and administrative leadership and coordination required to produce a schema that relates intentions to outcomes in this particularly challenging context. This study is intended to offer insights that may help language educators reflect on their various roles during COVID-19 confinement. In conclusion, this study demonstrates that negotiating the balance between autonomy and community is (still) the key to learning languages online during COVID-19 confinement in 2020.
Surgical Outcomes of Aldosterone-Producing Adenoma on the Basis of the Histopathological Findings
Authors: Wang Huiping , Wang Fen , Zhang Yushi , Wen Jin , Dong Dexin , Chang Xiaoyan , Sun Hao , Ma Xiaosen , Cui Yunying , Chen Shi , Lu Lin , Ren Weidong , Tong Anli , Li Yuxiu
Published: September 2021

Introduction

Previous studies on the surgical outcomes of aldosterone-producing adenoma (APA) patients were mainly based on the histopathological diagnosis of HE staining or adrenal venous sampling (AVS) instead of the functional pathology. The aim of the present study was to evaluate the surgical outcomes of APA patients based on the functional pathological diagnosis of APA according to HISTALDO (histopathology of primary aldosteronism) consensus.

Methods

Clinical data of 137 patients with suspected APA were analyzed retrospectively. All patients had hypertension and spontaneous hypokalemia. In all patients, CT showed a unilateral solitary hypodense adrenal lesion, and a contralateral adrenal gland of normal morphology. Tumors were removed and immunostained for CYP11B2, and their pathology were identified based on HISTALDO consensus. Patients were followed up 6 to 24 months after operation.

Results

Among 137 cases of presumptive APA diagnosed by CT, 130 (95%) cases were pathologically diagnosed with classical pathology, including 123 APA(90%) and 7 aldosterone-producing nodule (APN) (5%). 7 cases (5%) had non-functioning adenoma (NFA) with aldosterone-producing micronodule (APM) or multiple aldosterone-producing micronodule (MAPM) in the surrounding adrenal tissue. In all 137 patients, hypertension was complete or partial clinical success postoperatively. Complete clinical success was achieved in 73 (53%), and partial clinical success was achieved in 64 (47%) cases. Serum potassium level recovered to normal in all. In 123 patients with APA, complete clinical success was reached in 67 (54%), and partial clinical success was reached in 56 (46%) cases. Gender, duration of hypertension and the highest SBP were significant independent predictors for cure of APA after surgery. A multiple logistic regression model integrating the three predictors was constructed to predict the outcome, which achieved a sensitivity of 72.4% and a specificity of 73.1%.

Conclusion

The specificity of CT in the diagnosis of APA and APN patients with hypokalemia was 95%. All patients achieved complete or partial clinical success after surgery. Gender, duration of hypertension and the highest SBP were independent predictors for the postoperative cure of APA.
The Potential of Metabolomic Analyses as Predictive Biomarkers of Preterm Delivery: A Systematic Review
Authors: Ronde Emma , Reiss Irwin K. M. , Hankemeier Thomas , De Meij Tim G. , Frerichs Nina , Schoenmakers Sam
Published: September 2021

Scope

as the leading cause of perinatal mortality and morbidity worldwide, the impact of premature delivery is undisputable. Thus far, non-invasive, cost-efficient and accurate biochemical markers to predict preterm delivery are scarce. The aim of this systematic review is to investigate the potential of non-invasive metabolomic biomarkers for the prediction of preterm delivery.

Methods and Results

Databases were systematically searched from March 2019 up to May 2020 resulting in 4062 articles, of which 45 were retrieved for full-text assessment. The resulting metabolites used for further analyses, such as ferritin, prostaglandin and different vitamins were obtained from different human anatomical compartments or sources (vaginal fluid, serum, urine and umbilical cord) and compared between groups of women with preterm and term delivery. None of the reported metabolites showed uniform results, however, a combination of metabolomics biomarkers may have potential to predict preterm delivery and need to be evaluated in future studies.
Primary Cilia Mediate TSH-Regulated Thyroglobulin Endocytic Pathways
Authors: Lee Junguee , Sul Hae Joung , Kim Kun-Ho , Chang Joon Young , Shong Minho
Published: September 2021

Primary cilia are sensory organelles with a variety of receptors and channels on their membranes. Recently, primary cilia were proposed to be crucial sites for exocytosis and endocytosis of vesicles associated with endocytic control of various ciliary signaling pathways. Thyroglobulin (Tg) synthesis and Tg exocytosis/endocytosis are critical for the functions of thyroid follicular cells, where primary cilia are relatively well preserved. LRP2/megalin has been detected on the apical surface of absorptive epithelial cells, including thyrocytes. LRP2/megalin on thyrocytes serves as a Tg receptor and can mediate Tg endocytosis. In this study, we investigated the role of primary cilia in LRP2/megalin expression in thyroid gland stimulated with endogenous TSH using MMI-treated and Tg-Cre;Ift88flox/flox mice. LRP2/megalin expression in thyroid follicles was higher in MMI-treated mice than in untreated control mice. MMI-treated mice exhibited a significant increase in ciliogenesis in thyroid follicular cells relative to untreated controls. Furthermore, MMI-induced ciliogenesis accompanied increases in LRP2/megalin expression in thyroid follicular cells, in which LRP2/megalin was localized to the primary cilium. By contrast, in Tg-Cre;Ift88flox/flox mice, thyroid with defective primary cilia expressed markedly lower levels of LRP2/megalin. Serum Tg levels were elevated in MMI-treated mice and reduced in Tg-Cre;Ift88flox/flox mice. Taken together, these results indicate that defective ciliogenesis in murine thyroid follicular cells is associated with impaired LRP2/megalin expression and reduced serum Tg levels. Our results strongly suggest that primary cilia harbors LRP2/megalin, and are involved in TSH-mediated endocytosis of Tg in murine thyroid follicles.
Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery
Authors: Gonçalves Any Elisa de Souza Schmidt , Rocha Guilherme Zweig , Marin Rodrigo , Camargo Rafael Ludemann , Santos Andrey dos , Carmo Helison do , Guadagnini Dioze , Petrucci Orlando , Moysés Zenaide Providello , Salemi Vera Maria Cury , Oliveira Alexandre Gabarra , Saad Mario José Abdalla
Published: September 2021

Obesity and insulin resistance (IR) are well-studied risk factors for systemic cardiovascular disease, but their impact on pulmonary hypertension (PH) is not well clarified. This study aims to investigate if diet-induced obesity induces PH and if peroxisome-proliferator-activated receptor (PPAR-γ) and/or endoplasmic reticulum (ER) stress are involved in this process. Mice were maintained on a high-fat diet (HFD) for 4 months, and IR and PH were confirmed. In a separate group, after 4 months of HFD, mice were treated with pioglitazone (PIO) or 4-phenylbutyric acid for the last month. The results demonstrated that HFD for at least 4 months is able to increase pulmonary artery pressure, which is maintained, and this animal model can be used to investigate the link between IR and PH, without changes in ER stress in the pulmonary artery. There was also a reduction in circulating adiponectin and in perivascular adiponectin expression in the pulmonary artery, associated with a reduction in PPAR-γ expression. Treatment with PIO improved IR and PH and reversed the lower expression of adiponectin and PPAR-γ in the pulmonary artery, highlighting this drug as potential benefit for this poorly recognized complication of obesity.
Association of Pericardiac Adipose Tissue With Coronary Artery Disease
Authors: Li Mingxuan , Qi Lin , Li Yanglei , Zhang Shuyi , Lin Lei , Zhou Lijin , Han Wanlin , Qu Xinkai , Cai Junfeng , Ye Maoqing , Shi Kailei
Published: September 2021

Background and Aim

Coronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD.

Methods

We acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry.

Results

A total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively.

Conclusion

This study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD.
Prevalence of Pathogenic Germline DICER1 Variants in Young Individuals Thyroidectomised Due to Goitre – A National Danish Cohort
Authors: Altaraihi Mays , Hansen Thomas van Overeem , Santoni-Rugiu Eric , Rossing Maria , Rasmussen Åse Krogh , Gerdes Anne-Marie , Wadt Karin
Published: September 2021

Introduction

DICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre.

Methods

Danish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing.

Results

Six of 46 individuals, 13% (CI [3.3;22.7], p <0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1. They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1).

Conclusions

We recommend referral of patients thyroidectomised due to goitre aged <21 years and patients thyroidectomised due to goitre aged <25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling.
A Satellite-Based Model for Estimating Latent Heat Flux From Urban Vegetation
Authors: Smith Ian A. , Winbourne Joy B. , Tieskens Koen F. , Jones Taylor S. , Bromley Fern L. , Li Dan , Hutyra Lucy R.
Published: September 2021

The impacts of extreme heat events are amplified in cities due to unique urban thermal properties. Urban greenspace mitigates high temperatures through evapotranspiration and shading; however, quantification of vegetative cooling potential in cities is often limited to simple remote sensing greenness indices or sparse, in situ measurements. Here, we develop a spatially explicit, high-resolution model of urban latent heat flux from vegetation. The model iterates through three core equations that consider urban climatological and physiological characteristics, producing estimates of latent heat flux at 30-m spatial resolution and hourly temporal resolution. We find strong agreement between field observations and model estimates of latent heat flux across a range of ecosystem types, including cities. This model introduces a valuable tool to quantify the spatial heterogeneity of vegetation cooling benefits across the complex landscape of cities at an adequate resolution to inform policies addressing the effects of extreme heat events.
Identifying Protein Complexes With Clear Module Structure Using Pairwise Constraints in Protein Interaction Networks
Authors: Liu Guangming , Liu Bo , Li Aimin , Wang Xiaofan , Yu Jian , Zhou Xuezhong
Published: September 2021

The protein-protein interaction (PPI) networks can be regarded as powerful platforms to elucidate the principle and mechanism of cellular organization. Uncovering protein complexes from PPI networks will lead to a better understanding of the science of biological function in cellular systems. In recent decades, numerous computational algorithms have been developed to identify protein complexes. However, the majority of them primarily concern the topological structure of PPI networks and lack of the consideration for the native organized structure among protein complexes. The PPI networks generated by high-throughput technology include a fraction of false protein interactions which make it difficult to identify protein complexes efficiently. To tackle these challenges, we propose a novel semi-supervised protein complex detection model based on non-negative matrix tri-factorization, which not only considers topological structure of a PPI network but also makes full use of available high quality known protein pairs with must-link constraints. We propose non-overlapping (NSSNMTF) and overlapping (OSSNMTF) protein complex detection algorithms to identify the significant protein complexes with clear module structures from PPI networks. In addition, the proposed two protein complex detection algorithms outperform a diverse range of state-of-the-art protein complex identification algorithms on both synthetic networks and human related PPI networks.
Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model
Authors: Ma Chao , Zhang Xin , Zhao Xudong , Zhang Nan , Zhou Sixin , Zhang Yonghui , Li Peiyu
Published: September 2021

Background

Accumulating evidence has demonstrated that immune-related long non-coding ribonucleic acids (irlncRNAs) can be used as prognostic indicators of overall survival (OS) in patients with colorectal cancer (CRC). Our aim in this research, therefore, was to construct a risk model using irlncRNA pairs with no requirement for a specific expression level, in hope of reliably predicting the prognosis and immune landscape of CRC patients.

Methods

Clinical and transcriptome profiling data of CRC patients downloaded from the Cancer Genome Atlas (TCGA) database were analyzed to identify differentially expressed (DE) irlncRNAs. The irlncRNA pairs significantly correlated with the prognosis of patients were screened out by univariable Cox regression analysis and a prognostic model was constructed by Lasso and multivariate Cox regression analyses. A receiver operating characteristic (ROC) curve was then plotted, with the area under the curve calculated to confirm the reliability of the model. Based on the optimal cutoff value, CRC patients in the high- or low-risk groups were distinguished, laying the ground for evaluating the risk model from the following perspectives: survival, clinicopathological traits, tumor-infiltrating immune cells (TIICs), antitumor drug efficacy, kinase inhibitor efficacy, and molecules related to immune checkpoints.

Results

A prognostic model consisting of 15 irlncRNA pairs was constructed, which was found to have a high correlation with patient prognosis in a cohort from the TCGA (p < 0.001, HR = 1.089, 95% CI [1.067–1.112]). According to both univariate and multivariate Cox analyses, this model could be used as an independent prognostic indicator in the TCGA cohort (p < 0.001). Effective differentiation between high- and low-risk patients was also accomplished, on the basis of aggressive clinicopathological characteristics, sensitivity to antitumor drugs, and kinase inhibitors, the tumor immune infiltration status, and the expression levels of specific molecules related to immune checkpoints.

Conclusion

The prognostic model established with irlncRNA pairs is a promising indicator for prognosis prediction in CRC patients.
ACE2 Netlas: In silico Functional Characterization and Drug-Gene Interactions of ACE2 Gene Network to Understand Its Potential Involvement in COVID-19 Susceptibility
Authors: Pathak Gita A. , Wendt Frank R. , Goswami Aranyak , Koller Dora , De Angelis Flavio ,   COVID-19 Host Genetics Initiative, Polimanti Renato
Published: September 2021

Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed an integrative multi-level characterization of genes that interact with ACE2 (ACE2-gene network) for their statistically enriched biological properties in the context of COVID-19. The phenome-wide association of 51 genes including ACE2 with 4,756 traits categorized into 26 phenotype categories, showed enrichment of immunological, respiratory, environmental, skeletal, dermatological, and metabolic domains (p < 4e-4). Transcriptomic regulation of ACE2-gene network was enriched for tissue-specificity in kidney, small intestine, and colon (p < 4.7e-4). Leveraging the drug-gene interaction database we identified 47 drugs, including dexamethasone and spironolactone, among others. Considering genetic variants within ± 10 kb of ACE2-network genes we identified miRNAs whose binding sites may be altered as a consequence of genetic variation. The identified miRNAs revealed statistical over-representation of inflammation, aging, diabetes, and heart conditions. The genetic variant associations in RORA, SLC12A6, and SLC6A19 genes were observed in genome-wide association study (GWAS) of COVID-19 susceptibility. We also report the GWAS-identified variant in 3p21.31 locus, serves as trans-QTL for RORA and RORC genes. Overall, functional characterization of ACE2-gene network highlights several potential mechanisms in COVID-19 susceptibility. The data can also be accessed at https://gpwhiz.github.io/ACE2Netlas/.
COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration
Authors: Li Shushan , Wang Haitao , Zhang Yi , Qiao Renqiu , Xia Peige , Kong Zhiheng , Zhao Hongbo , Yin Li
Published: September 2021

Background

Osteoarthritis (OA) is one of the most common age-related degenerative diseases. In recent years, some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA. However, the molecular mechanism of synovitis in the pathological process of OA has not been elucidated. This study aimed to identify novel biomarkers associated with OA and to emphasize the role of immune cells in the pathogenesis of OA.

Methods

Microarray datasets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases and were then analyzed using R software. To determine differential immune cell subtype infiltration, the CIBERSORT deconvolution algorithm was used. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expressions of selected genes. Besides, Western blotting was used to assess the protein expression levels in osteoarthritic chondrocytes.

Results

After analyzing the database profiles, two potential biomarkers, collagen type 3 alpha 1 chain (COL3A1), and matrix metalloproteinase 9 (MMP9), associated with OA were discovered, which were confirmed by qRT-PCR and Western blotting. Specifically, the results revealed that, as the concentration of IL-1β increased, so did the gene and protein expression levels of COL3A1 and MMP9.

Conclusion

The findings provide valuable information and direction for future research into novel targets for OA immunotherapy and diagnosis and aids in the discovery of the underlying biological mechanisms of OA pathogenesis.
Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation
Authors: Shestak Anna G. , Makarov Leonid M. , Komoliatova Vera N. , Kolesnikova Irina V. , Skorodumova Liubov O. , Generozov Edward V. , Zaklyazminskaya Elena V.
Published: September 2021

Primary cardiac channelopathies are a group of diseases wherein the role of DNA testing in aiding diagnosis and treatment-based decision-making is gaining increasing attention. However, in some cases, evaluating the pathogenicity of new variants is still challenging. We report an accurate multistage assessment of a rare genetic variant in the SCN5A gene using next-generation sequencing (NGS) techniques and Sanger sequencing. Female sportsman (14 years old) underwent genetic counseling and DNA testing due to QT interval prolongation registered during ECG Holter monitoring. Genetic testing of the proband was performed in two independent laboratories. Primary DNA testing was performed by WES using the Ion ProtonTM System. Target panel sequencing of 11 genes was performed using PGM Ion Torrent. Search for variants in non-canonical and canonical exons 6 was performed by Sanger sequencing. The cascade familial screening and control re-sequencing were provided for proband with identified genetic variant p.S216L (g.38655290G>A, NM_198056.2:c.647C>T, and rs41276525) in the canonical exon 6 of the SCN5A gene after receiving data from another laboratory. Control Sanger and NGS sequencing revealed the absence p.S216L in the canonical exon 6 and confirmed the presence of p.S216L (g.38655522G>A, c.647C>T, and rs201002736) in the non-canonical exon 6 of the SCN5A gene. The identified variant was re-interpreted. The non-canonical transcripts of the exon 6 of the SCN5A gene is poorly represented in cardiac tissue (gnomAD). The detected variant was found in proband’s healthy mother. The correct interpretation of genetic data requires close cooperation between clinicians and researchers. It can help to avoid financial costs and stress for proband’s and families.
Updated Genome Assembly of Bighead Carp (Hypophthalmichthys nobilis) and Its Differences Between Male and Female on Genomic, Transcriptomic, and Methylation Level
Authors: Fu Beide , Zhou Ying , Liu Haiyang , Yu Xiaomu , Tong Jingou
Published: September 2021

Cyprinidae is one of the largest family in freshwater fishes, and it is most intensively cultured fish taxon of the world. However, studies about sex determination in this large family is still rear, and one of the reasons is lack of high quality and complete genome. Here, we used nanopore to sequence the genome of a male bighead carp, obtaining contig N50 = 24.25 Mb, which is one of the best assemblies in Cyprinidae. Five males and five females were re-sequenced, and a male-specific region on LG19 was confirmed. We find this region holds many male-specific markers in other Cyprinidae fishes, such as grass carp and silver carp. Transcriptome analyses of hypothalamus and pituitary tissues showed that several sex-specific differentially expressed genes were associated with steroid biosynthesis. The UCH64E gene, located in the male-specific region on LG19, showed higher expression levels in male than female tissues of bighead carp. The methyl-RAD of hypothalamus tissues between males and females indicated that the sexual methylation differences are significant in bighead carp. We also compared the methylation sites recognized using methyl-RAD and nanopore raw reads and found that approximately 73% of the methylation sites identified using methyl-RAD were within nanopore CpG sites.
SCDRHA: A scRNA-Seq Data Dimensionality Reduction Algorithm Based on Hierarchical Autoencoder
Authors: Zhao Jianping , Wang Na , Wang Haiyun , Zheng Chunhou , Su Yansen
Published: September 2021

Dimensionality reduction of high-dimensional data is crucial for single-cell RNA sequencing (scRNA-seq) visualization and clustering. One prominent challenge in scRNA-seq studies comes from the dropout events, which lead to zero-inflated data. To address this issue, in this paper, we propose a scRNA-seq data dimensionality reduction algorithm based on a hierarchical autoencoder, termed SCDRHA. The proposed SCDRHA consists of two core modules, where the first module is a deep count autoencoder (DCA) that is used to denoise data, and the second module is a graph autoencoder that projects the data into a low-dimensional space. Experimental results demonstrate that SCDRHA has better performance than existing state-of-the-art algorithms on dimension reduction and noise reduction in five real scRNA-seq datasets. Besides, SCDRHA can also dramatically improve the performance of data visualization and cell clustering.
Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics
Authors: Pan Jiahui , Zhang Xinyue , Fang Xuedong , Xin Zhuoyuan
Published: September 2021

Background

Gastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.

Methods

Ferroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).

Results

A ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.

Conclusion

Our prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.
Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases
Authors: Kretschmer Dorothee , Breitmeyer Ricarda , Gekeler Cordula , Lebtig Marco , Schlatterer Katja , Nega Mulugeta , Stahl Mark , Stapels Daphne , Rooijakkers Suzan , Peschel Andreas
Published: September 2021

Neutrophil granulocytes act as a first line of defense against pathogenic staphylococci. However, Staphylococcus aureus has a remarkable capacity to survive neutrophil killing, which distinguishes it from the less-pathogenic Staphylococcus epidermidis. Both species release phenol-soluble modulin (PSM) toxins, which activate the neutrophil formyl-peptide receptor 2 (FPR2) to promote neutrophil influx and phagocytosis, and which disrupt neutrophils or their phagosomal membranes at high concentrations. We show here that the neutrophil serine proteases (NSPs) neutrophil elastase, cathepsin G and proteinase 3, which are released into the extracellular space or the phagosome upon neutrophil FPR2 stimulation, effectively degrade PSMs thereby preventing their capacity to activate and destroy neutrophils. Notably, S. aureus, but not S. epidermidis, secretes potent NSP-inhibitory proteins, Eap, EapH1, EapH2, which prevented the degradation of PSMs by NSPs. Accordingly, a S. aureus mutant lacking all three NSP inhibitory proteins was less effective in activating and destroying neutrophils and it survived less well in the presence of neutrophils than the parental strain. We show that Eap proteins promote pathology via PSM-mediated FPR2 activation since murine intraperitoneal infection with the S. aureus parental but not with the NSP inhibitors mutant strain, led to a significantly higher bacterial load in the peritoneum and kidneys of mFpr2-/- compared to wild-type mice. These data demonstrate that NSPs can very effectively detoxify some of the most potent staphylococcal toxins and that the prominent human pathogen S. aureus has developed efficient inhibitors to preserve PSM functions. Preventing PSM degradation during infection represents an important survival strategy to ensure FPR2 activation.
Substance P and Alpha-Calcitonin Gene-Related Peptide Differentially Affect Human Osteoarthritic and Healthy Chondrocytes
Authors: Stöckl Sabine , Eitner Annett , Bauer Richard J. , König Matthias , Johnstone Brian , Grässel Susanne
Published: September 2021

Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.
SARS-CoV-2 Antibody Isotypes in Systemic Lupus Erythematosus Patients Prior to Vaccination: Associations With Disease Activity, Antinuclear Antibodies, and Immunomodulatory Drugs During the First Year of the Pandemic
Authors: Sjöwall Johanna , Azharuddin Mohammad , Frodlund Martina , Zhang Yuming , Sandner Laura , Dahle Charlotte , Hinkula Jorma , Sjöwall Christopher
Published: September 2021

Objectives

Impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels.

Methods

One hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology.

Results

During the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of ≥1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p= 0.04) and anti-dsDNA (p= 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, >38.5°C) did not associate with SARS-CoV-2 antibodies.

Conclusion

Our data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.
TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease
Authors: Jones Esther L. , Laidlaw Stephen M. , Dustin Lynn B.
Published: September 2021

TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody target in Sjögren’s syndrome, systemic lupus erythematosus, and other rheumatic autoimmune diseases. Here, we summarise the structure and function of this enzyme, its roles in innate immunity, adaptive immunity and cellular homeostasis, the pathogenesis of autoimmunity against TRIM21, and the potential impacts of autoantibodies to this intracellular protein.
Evaluation of Regional Surface Energy Budget Over Ocean Derived From Satellites
Authors: Kato Seiji , Rose Fred G. , Chang Fu-Lung , Painemal David , Smith William L.
Published: September 2021

The energy balance equation of an atmospheric column indicates that two approaches are possible to compute regional net surface energy flux. The first approach is to use the sum of surface energy flux components Fnet,c and the second approach is to use net top-of-atmosphere (TOA) irradiance and horizontal energy transport by the atmosphere Fnet,t. When regional net energy flux is averaged over the global ocean, Fnet,c and Fnet,t are, respectively, 16 and 2 Wm–2, both larger than the ocean heating rate derived from ocean temperature measurements. The difference is larger than the estimated uncertainty of Fnet,t of 11 Wm–2. Larger regional differences between Fnet,c and Fnet,t exist over tropical ocean. The seasonal variability of energy flux components averaged between 45°N and 45°S ocean reveals that the surface provides net energy to the atmosphere from May to July. These two examples demonstrates that the energy balance can be used to assess the quality of energy flux data products.
Ferries and Environmental DNA: Underway Sampling From Commercial Vessels Provides New Opportunities for Systematic Genetic Surveys of Marine Biodiversity
Authors: Valsecchi Elena , Arcangeli Antonella , Lombardi Roberto , Boyse Elizabeth , Carr Ian M. , Galli Paolo , Goodman Simon J.
Published: September 2021

Marine environmental DNA (eDNA) is an important tool for biodiversity research and monitoring but challenges remain in scaling surveys over large spatial areas, and increasing the frequency of sampling in remote locations at reasonable cost. Here we demonstrate the feasibility of sampling from commercial vessels (Mediterranean ferries) while underway, as a strategy to facilitate replicable, systematic marine eDNA surveys in locations that would normally be challenging and expensive for researchers to access. Sixteen eDNA samples were collected from four fixed sampling stations, and in response to four cetacean sightings, across three cruises undertaken along the 300 km ferry route between Livorno (Tuscany) and Golfo Aranci (Sardinia) in the Ligurian/Tyrrhenian Seas, June-July 2018. Using 12SrDNA and 16SrDNA metabarcoding markers, we recovered diverse marine vertebrate Molecular Operational Taxonomic Units (MOTUs) from teleost fish, elasmobranchs, and cetaceans. We detected sample heterogeneity consistent with previously known variation in species occurrences, including putative species spawning peaks associated with specific sea surface temperature ranges, and increased night time abundance of bathypelagic species known to undertake diel migrations through the water column. We suggest commercial vessel based marine eDNA sampling using the global shipping network has potential to facilitate broad-scale biodiversity monitoring in the world’s oceans.
Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus
Authors: Zhou Jing , Wang Fa-Da , Wang Meng-Lan , Tao Ya-Chao , Wu Dong-Bo , Sheng Yun-Jian , Xiao Gui-Bao , Chen Xue-Bin , Chen Xin , Chen En-Qiang
Published: September 2021

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state. A considerable number of patients will develop active hepatitis or occult progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, whether antiviral therapy should be recommended for chronic HBV infection with normal ALT level has been a hot topic in clinical practice. In this paper, the definition of immune tolerance, the relationship between ALT and liver inflammation, and the benefits of antiviral therapy were reviewed, and we hope it will be helpful for clinicians to have a deeper understanding of whether antiviral therapy should be considered for chronic HBV infection with normal ALT.
Clinical Significance and Integrative Analysis of the SMC Family in Hepatocellular Carcinoma
Authors: Nie Hui , Wang Yutong , Yang Xuejie , Liao Zhiming , He Xiaoyun , Zhou Jianhua , Ou Chunlin
Published: September 2021

Worldwide, hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor prognosis. The structural maintenance of chromosomes (SMC) gene family has been shown to play important roles in human cancers. Nevertheless, the role of SMC members in HCC is not well-understood. In this study, we comprehensively explored the role of the SMC family in HCC using a series of bioinformatic analysis tools. Studies have demonstrated that the mRNA expression levels of SMC1A, SMC1B, SMC2, SMC4, and SMC6 are significantly overexpressed in HCC, and the protein levels of SMC1A, SMC2, SMC3, SMC4, SMC5, and SMC6 are similarly elevated. Moreover, HCC patients with high SMC2 and SMC4 expression levels exhibit poor survival. Using KEGG and GO analyses, we analyzed the enrichment of gene expression in the biological functions and pathways of the SMC family in HCC. Immune infiltration analysis revealed that the expression of the SMC family is closely associated with B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and DCs. In conclusion, our findings will enhance a more thorough understanding of the SMC family in HCC progression and provide new directions for the diagnosis and treatment of HCC in the future.
Evasion of Antiviral Innate Immunity by Porcine Reproductive and Respiratory Syndrome Virus
Authors: Wang Tong-Yun , Sun Ming-Xia , Zhang Hong-Liang , Wang Gang , Zhan Guoqing , Tian Zhi-Jun , Cai Xue-Hui , Su Chenhe , Tang Yan-Dong
Published: September 2021

Innate immunity is the front line for antiviral immune responses and bridges adaptive immunity against viral infections. However, various viruses have evolved many strategies to evade host innate immunity. A typical virus is the porcine reproductive and respiratory syndrome virus (PRRSV), one of the most globally devastating viruses threatening the swine industry worldwide. PRRSV engages several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by PRRSV to evade pattern recognition receptors signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR)-JAK-STAT signaling pathway, and interferon-stimulated genes. Deciphering the antiviral immune evasion mechanisms by PRRSV will enhance our understanding of PRRSV’s pathogenesis and help us to develop more effective methods to control and eliminate PRRSV.
Heat Stress Alters the Intestinal Microbiota and Metabolomic Profiles in Mice
Authors: Wen Chaoyue , Li Siyu , Wang Jiaojiao , Zhu Yimin , Zong Xin , Wang Yizhen , Jin Mingliang
Published: September 2021

Background

Heat stress has negative effects on the intestinal health of humans and animals. However, the impact of heat stress on intestinal microbial and metabolic changes remains elusive. Here, we investigated the cecal microbial and metabolic profiles in mice in response to heat stress.

Methods

The mouse heat stress model was constructed by simulating a high-temperature environment. Twenty mice were randomly assigned to two groups, the control group (CON, 25°C) and the heat treatment group (HS, 40°C from 13:00 to 15:00 every day for 7 days). Serum and cecal contents were collected from the mice for serum biochemical analysis, 16S rRNA high-throughput sequencing, and non-targeted metabolomics.

Results

Both core body temperature and water intake were significantly increased in the HS group. Serum biochemical indicators were also affected, including significantly increased triglyceride and decreased low-density lipoprotein in the heat stress group. The composition and structure of intestinal microbiota were remarkably altered in the HS group. At the species level, the relative abundance of Candidatus Arthromitus sp. SFB-mouse-Japan and Lactobacillus murinus significantly reduced, while that of Lachnospiraceae bacterium 3-1 obviously increased after HS. Metabolomic analysis of the cecal contents clearly distinguished metabolite changes between the groups. The significantly different metabolites identified were mainly involved in the fatty acid synthesis, purine metabolism, fatty acid metabolism, cyanoamino acid metabolism, glyceride metabolism, and plasmalogen synthesis.

Conclusion

In summary, high temperature disrupted the homeostatic balance of the intestinal microbiota in mice and also induced significant alterations in intestinal metabolites. This study provides a basis for treating intestinal disorders caused by elevated temperature in humans and animals and can further formulate nutritional countermeasures to reduce heat stress-induced damage.
Identification of a Novel Quinvirus in the Family Betaflexiviridae That Infects Winter Wheat
Authors: Kondo Hideki , Yoshida Naoto , Fujita Miki , Maruyama Kazuyuki , Hyodo Kiwamu , Hisano Hiroshi , Tamada Tetsuo , Andika Ida Bagus , Suzuki Nobuhiro
Published: September 2021

Yellow mosaic disease in winter wheat is usually attributed to the infection by bymoviruses or furoviruses; however, there is still limited information on whether other viral agents are also associated with this disease. To investigate the wheat viromes associated with yellow mosaic disease, we carried out de novo RNA sequencing (RNA-seq) analyses of symptomatic and asymptomatic wheat-leaf samples obtained from a field in Hokkaido, Japan, in 2018 and 2019. The analyses revealed the infection by a novel betaflexivirus, which tentatively named wheat virus Q (WVQ), together with wheat yellow mosaic virus (WYMV, a bymovirus) and northern cereal mosaic virus (a cytorhabdovirus). Basic local alignment search tool (BLAST) analyses showed that the WVQ strains (of which there are at least three) were related to the members of the genus Foveavirus in the subfamily Quinvirinae (family Betaflexiviridae). In the phylogenetic tree, they form a clade distant from that of the foveaviruses, suggesting that WVQ is a member of a novel genus in the Quinvirinae. Laboratory tests confirmed that WVQ, like WYMV, is potentially transmitted through the soil to wheat plants. WVQ was also found to infect rye plants grown in the same field. Moreover, WVQ-derived small interfering RNAs accumulated in the infected wheat plants, indicating that WVQ infection induces antiviral RNA silencing responses. Given its common coexistence with WYMV, the impact of WVQ infection on yellow mosaic disease in the field warrants detailed investigation.