bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of the Risk Factors of Knee Injury During Drop-Jump Landing With Core-related Measurements in Amature Basketball Players
Authors: Guo Liang , Zhang Jing , Wu Ying , Li Li
Published: September 2021

Purpose: To evaluate the relationship between specific aspects of core stability and knee injury risk factors during drop-jump (DJ) landing.

Methods: Eighteen college-aged male amateur basketball players participated in the project. Kinetic and kinematic data for DJ tasks were collected with force plates and infrared cameras. Raw data were processed to calculate knee joint angles and joint moments during DJ landing. Different components of core stability were represented by the sit-ups in 20 s (SU), trunk extensor endurance, trunk flexion and extension range of motion, dominant extremity single-leg stance time (DLS), and dominant extremity single-leg hop distance, respectively.

Methods: Correlation and regression were used to determine the relationship between jumping-related biomechanical parameters and core stability components.

Results: SU shared significant variance with the peak moment of knee extension (PMKE, p < 0.05), the peak moment of knee abduction (PMKA, p < 0.05), and the angle of knee internal rotation at initial contact (AKRI, p < 0.05). DLS shared significant variance with the angular motion of knee internal rotation (AMKR, p < 0.05) and the AKRI (p < 0.01). SU and DLS together could explain 52% of the variance observed in the AKRI, and the result was significant.

Conclusion: Core stability’s strength and motor control aspects played an essential role in preventing knee injury during DJ landing. An integrative training program addressing core strength and motor control could be considered for coaches and athletes to prevent knee injury through core training and conditioning.
The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings
Authors: Merimi Makram , El-Majzoub Rania , Lagneaux Laurence , Moussa Agha Douâa , Bouhtit Fatima , Meuleman Nathalie , Fahmi Hassan , Lewalle Philippe , Fayyad-Kazan Mohammad , Najar Mehdi
Published: September 2021

Graphical Abstract

The road map of MSC review.
Genotype Distribution Change After Human Papillomavirus Vaccination in Two Autonomous Communities in Spain
Authors: Freire-Salinas Javier , Benito Rafael , Azueta Ainara , Gil Joaquina , Mendoza Claudia , Nicolás Montserrat , García-Berbel Pilar , Algarate Sonia , Gómez-Román Javier
Published: September 2021

Context

It has been more than 10 years since the human papillomavirus (HPV) vaccination program was initiated in most advanced countries. Thus, it seems necessary to change the uterine cervical cancer screening strategy. Molecular-based tests are considered essential in this scenario.

Objective

We aimed to review the distribution of the HPV genotypes after the introduction of the vaccination program with Cervarix® and Gardasil 4® in two autonomous communities in Spain, looking for possible changes in distribution and the occurrence of a herd effect.

Design

A cross-sectional study was performed in 45,362 samples that were processed in the Cantabria and Aragon communities during the period from 2002 to 2016. We compared the genotype distribution before and after the vaccination program was initiated.

Results

Genotypes HPV6 and HPV11 have decreased significantly after the introduction of the vaccine. HPV16 has had a decrease, but not a significant one in the statistical analysis. However, HPV31, HPV52, and HPV45 have increased in percentage. A replacement phenomenon with other genotypes not included in the vaccine has been observed in our population.

Conclusions

Continued surveillance is needed to provide further indication of any changes over time in the genotypes in circulation. This will be facilitated by monitoring the genotyping results from the new model of cervical screening using primary HPV DNA testing.
Potential Roles of the Free Salivary Microbiome Dysbiosis in Periodontal Diseases
Authors: Diao Jing , Yuan Chao , Tong Peiyuan , Ma Zhangke , Sun Xiangyu , Zheng Shuguo
Published: September 2021

Saliva is a vital mediator in the oral cavity. The dysbiosis of free bacteria in saliva might be related to the onset, development, prognosis, and recurrence of periodontal diseases, but this potential relationship is still unclear. The objective of this study was to investigate the potential roles of the free salivary microbiome in different periodontal statuses, their reaction to nonsurgical periodontal therapy, and differences between diseased individuals after treatment and healthy persons. We recruited 15 healthy individuals, 15 individuals with gingivitis, and 15 individuals with stage I/II generalized periodontitis. A total of 90 unstimulated whole saliva samples were collected and sequenced using full-length bacterial 16S rRNA gene sequencing. We found that as the severity of disease increased, from healthy to gingivitis and periodontitis, the degree of dysbiosis also increased. A higher abundance of Prevotella intermedia and Catonella morbi and a lower abundance of Porphyromonas pasteri, Prevotella nanceiensis, and Haemophilus parainfluenzae might be biomarkers of periodontitis, with an area under curve (AUC) reaching 0.9733. When patients received supragingival scaling, there were more pathogens related to recolonization in the saliva of periodontitis patients than in healthy persons. Even after effective nonsurgical periodontal therapy, individuals with periodontitis displayed a more dysbiotic and pathogenic microbial community in their saliva than healthy individuals. Therefore, the gradual transition in the entire salivary microbial community from healthy to diseased includes a gradual shift to dysbiosis. Free salivary pathogens might play an important role in the recolonization of bacteria as well as the prognosis and recurrence of periodontal diseases.
Comparison of the Ocular Microbiomes of Dry Eye Patients With and Without Autoimmune Disease
Authors: Qi Yun , Wan Yong , Li Tianhui , Zhang Ming , Song Yu , Hu Yaguang , Sun Yining , Li Li
Published: September 2021

Purpose

The pathogenesis of dry eye concomitant with autoimmune disease is different from that of dry eye without autoimmune disease. The aim of this study was to explore differences in the microbiota diversity and composition in dry eye with and without autoimmune disease.

Methods

Swab samples from the inferior fornix of the conjunctival sac were obtained from dry eye patients without autoimmune disease (n = 49, dry eye group) and from those with autoimmune disease (n = 38, immdry eye group). Isolated bacterial DNAs from swabs were analyzed with 16S rRNA amplicon sequencing.

Results

Analysis of the alpha diversity revealed no significant differences between subjects in the dry eye and immdry eye groups. Those in the immdry eye group had a distinct microbial composition compared with those in the dry eye group. The combination of the genera Corynebacterium and Pelomonas distinguished subjects in the immdry eye group from those in the dry eye group, with an area under the curve of 0.73 (95% CI = 0.62–0.84). For the same bacteria, the correlations between microbe abundance and the ocular surface parameters were different in the two groups. In addition, the functions of the microbial communities were altered in the two groups.

Conclusions

Our study demonstrates changes in the composition and function of the ocular microbiome between subjects in the immdry eye and dry eye groups, which suggests that the potential pathogenesis is different.
The Integrative Analysis of Competitive Endogenous RNA Regulatory Networks in Coronary Artery Disease
Authors: Ji Yuyao , Yan Tao , Zhu Shijie , Wu Runda , Zhu Miao , Zhang Yangyang , Guo Changfa , Yao Kang
Published: September 2021

Background: Coronary artery disease (CAD) is the leading cause of cardiovascular death. The competitive endogenous RNAs (ceRNAs) hypothesis is a new theory that explains the relationship between lncRNAs and miRNAs. The mechanism of ceRNAs in the pathological process of CAD has not been fully elucidated. The objective of this study was to explore the ceRNA mechanism in CAD using the integrative bioinformatics analysis and provide new research ideas for the occurrence and development of CAD.

Methods: The GSE113079 dataset was downloaded, and differentially expressed lncRNAs (DElncRNAs) and genes (DEGs) were identified using the limma package in the R language. Weighted gene correlation network analysis (WGCNA) was performed on DElncRNAs and DEGs to explore lncRNAs and genes associated with CAD. Functional enrichment analysis was performed on hub genes in the significant module identified via WGCNA. Four online databases, including TargetScan, miRDB, miRTarBase, and Starbase, combined with an online tool, miRWalk, were used to construct ceRNA regulatory networks.

Results: DEGs were clustered into ten co-expression modules with different colors using WGCNA. The brown module was identified as the key module with the highest correlation coefficient. 188 hub genes were identified in the brown module for functional enrichment analysis. DElncRNAs were clustered into sixteen modules, including seven modules related to CAD with the correlation coefficient more than 0.5. Three ceRNA networks were identified, including OIP5-AS1-miR-204-5p/miR-211-5p-SMOC1, OIP5-AS1-miR-92b-3p-DKK3, and OIP5-AS1-miR-25-3p-TMEM184B.

Conclusion: Three ceRNA regulatory networks identified in this study may play crucial roles in the occurrence and development of CAD, which provide novel insights into the ceRNA mechanism in CAD.
Lingua Franca of Cardiogenic Shock: Speaking the Same Language
Authors: Long Ashleigh , Baran David A.
Published: September 2021

Cardiogenic shock has remained a vexing clinical problem over the last 20 years despite progressive development of increasingly capable percutaneous mechanical circulatory support devices. It is increasingly clear that the published trials of various percutaneous mechanical circulatory support devices have compared heterogenous populations of cardiogenic shock patients, and therefore have not yielded a single result where one approach improved survival. To classify patients, various risk scores such as the CARDSHOCK and IABP-Shock-II scores have been developed and validated but they have not been broadly applied. The Society for Cardiac Angiography and Intervention Expert Consensus on Classification of Cardiogenic Shock has been widely studied since its publication in 2019, and is reviewed at length. In particular, there have been numerous validation studies done and these are reviewed. Finally, the directions for future research are reviewed.
Adeno-Associated Virus-Mediated Gain-of-Function mPCSK9 Expression in the Mouse Induces Hypercholesterolemia, Monocytosis, Neutrophilia, and a Hypercoagulative State
Authors: Louloudis Georgios , Ambrosini Samuele , Paneni Francesco , Camici Giovanni G. , Benke Dietmar , Klohs Jan
Published: September 2021

Hypercholesterolemia has previously been induced in the mouse by a single intravenous injection of adeno-associated virus (AAV)-based vector harboring gain-of-function pro-protein convertase subtilisin/kexin type 9. Despite the recent emergence of the PCSK9-AAV model, the profile of hematological and coagulation parameters associated with it has yet to be characterized. We injected 1.0 × 1011 viral particles of mPCSK9-AAV or control AAV into juvenile male C57BL/6N mice and fed them with either a Western-type high-fat diet (HFD) or standard diet over the course of 3 weeks. mPCSK9-AAV mice on HFD exhibited greater plasma PCSK9 concentration and lower low-density lipoprotein levels, concomitant with increased total cholesterol and non-high-density lipoprotein (non-HDL)-cholesterol concentrations, and lower HDL-cholesterol concentrations than control mice. Furthermore, mPCSK9-AAV-injected mice on HFD exhibited no signs of atherosclerosis at 3 weeks after the AAV injection. Hypercholesterolemia was associated with a thromboinflammatory phenotype, as neutrophil levels, monocyte levels, and neutrophil-to-lymphocyte ratios were higher and activated partial thromboplastin times (aPTTs) was lower in HFD-fed mPCSK9-AAV mice. Therefore, the mPCSK9-AAV is a suitable model of hypercholesterolemia to examine the role of thromboinflammatory processes in the pathogenesis of cardiovascular and cerebrovascular diseases.
Artificial Intelligence Based Multimodality Imaging: A New Frontier in Coronary Artery Disease Management
Authors: Maragna Riccardo , Giacari Carlo Maria , Guglielmo Marco , Baggiano Andrea , Fusini Laura , Guaricci Andrea Igoren , Rossi Alexia , Rabbat Mark , Pontone Gianluca
Published: September 2021

Coronary artery disease (CAD) represents one of the most important causes of death around the world. Multimodality imaging plays a fundamental role in both diagnosis and risk stratification of acute and chronic CAD. For example, the role of Coronary Computed Tomography Angiography (CCTA) has become increasingly important to rule out CAD according to the latest guidelines. These changes and others will likely increase the request for appropriate imaging tests in the future. In this setting, artificial intelligence (AI) will play a pivotal role in echocardiography, CCTA, cardiac magnetic resonance and nuclear imaging, making multimodality imaging more efficient and reliable for clinicians, as well as more sustainable for healthcare systems. Furthermore, AI can assist clinicians in identifying early predictors of adverse outcome that human eyes cannot see in the fog of “big data.” AI algorithms applied to multimodality imaging will play a fundamental role in the management of patients with suspected or established CAD. This study aims to provide a comprehensive overview of current and future AI applications to the field of multimodality imaging of ischemic heart disease.
Intravascular Lithotripsy-Assisted Transfemoral TAVI: The Copenhagen Experience and Literature Review
Authors: Sawaya Fadi J. , Bajoras Vilhelmas , Vanhaverbeke Maarten , Wang Christina , Bieliauskas Gintautas , Søndergaard Lars , De Backer Ole
Published: September 2021

Transcatheter aortic valve implantation (TAVI) is currently an established therapy for elderly patients with symptomatic severe aortic valve stenosis across all surgical risk categories. Access is an important aspect when planning for and performing TAVI. The superiority of a transfemoral (TF) approach compared to a transthoracic (transapical, direct aortic) approach has been demonstrated in several studies. Recently, the introduction of intravascular lithotripsy (IVL) has made it possible to treat patients with calcified iliofemoral disease by TF approach. This article aimed to provide a comprehensive overview on the following aspects: (1) preprocedural planning for IVL-assisted TF-TAVI; (2) procedural aspects in IVL-assisted TF-TAVI; (3) outcomes of IVL-assisted TF-TAVI in an experienced TAVI center; and (4) literature review and discussion of this new emerging approach.
How to Design a Relevant Corpus for Sleepiness Detection Through Voice?
Authors: Martin Vincent P. , Rouas Jean-Luc , Micoulaud-Franchi Jean-Arthur , Philip Pierre , Krajewski Jarek
Published: September 2021

This article presents research on the detection of pathologies affecting speech through automatic analysis. Voice processing has indeed been used for evaluating several diseases such as Parkinson, Alzheimer, or depression. If some studies present results that seem sufficient for clinical applications, this is not the case for the detection of sleepiness. Even two international challenges and the recent advent of deep learning techniques have still not managed to change this situation. This article explores the hypothesis that the observed average performances of automatic processing find their cause in the design of the corpora. To this aim, we first discuss and refine the concept ofsleepinessrelated to the ground-truth labels. Second, we present an in-depth study of four corpora, bringing to light the methodological choices that have been made and the underlying biases they may have induced. Finally, in light of this information, we propose guidelines for the design of new corpora.
Why Web-Conferencing Matters: Rescuing Education in the Time of COVID-19 Pandemic Crisis
Authors: Adipat Surattana
Published: September 2021

Physical interaction between humans has steadily decreased over the past year as a result of the COVID-19 pandemic. As a result, the adoption of e-conferencing has seen a huge increase in conducting business globally and technologically mediated interactions are now the order of the day—the new normal. The virtualization of meetings promotes collaboration among colleagues, target markets, associates, teachers, and students working towards the organization’s objectives. Using web conferencing in learning meets the primary goal of both educators and students. It facilitates the creation of the best learning environment for students and aids in the realization of a balance between life and teaching duties for educators. Through web conferencing, higher learning institutions have the ability to capitalize on the available technologies to expand access to instructors online while also creating new experiences in the teaching and learning environment. The elimination of the need to travel for students’ field trips has also been realized due to technological advances, and virtual tours have replaced these trips. A descriptive approach is adopted for the study, and it relies on information from peer-reviewed journals. Drawing from the literature review, the study first identifies web-conferencing in various facets of education. Secondly, it discusses web-conferencing adoption and its influence on teaching and learning. Third, a discussion on the importance and benefits as well as disadvantages of web-conferencing is outlined. Fourth, the study exemplifies two web-conferencing platforms: Zoom and Google Meet. The study further discusses the future of adopting web-conferencing in education.
Kalman Filter Photovoltaic Power Prediction Model Based on Forecasting Experience
Authors: Yang Ying , Yu Tianyang , Zhao Weiguang , Zhu Xianhui
Published: September 2021

A Kalman filter photovoltaic (PV) power prediction model based on forecasting experience is proposed to solve the problem that the accuracy of the prediction method based on historical experience is reduced under anomalous situations. This study uses the hourly solar irradiance forecasting model, numerical weather prediction (NWP) data, and the photoelectric conversion model to calculate the ground irradiance and PV power generation, which are used as the forecasting experience data. The dynamic equation of the Kalman filter model is obtained by fitting the forecasting data to make the prediction model with the future situation information properties while solving the modeling difficulties caused by the transcendental equation characteristic of the photoelectric conversion model. In the iterative process of the Kalman filter algorithm, the measured power is used to correct the prediction error and significantly limit the error variability so as to realize the ultra-short-term accurate prediction of PV power and ultimately improve the management of PV energy storage power stations. The comparative analysis through DKASC data simulation verifies that the results show that the proposed model is effective and can achieve better results in predictive accuracy.
Mungbean DIRIGENT Gene Subfamilies and Their Expression Profiles Under Salt and Drought Stresses
Authors: Xu Wenying , Liu Tong , Zhang Huiying , Zhu Hong
Published: September 2021

DIRIGENT (DIR) genes are key players in environmental stress responses that have been identified in many vascular plant species. However, few studies have examined the VrDIR genes in mungbean. In this study, we characterized 37 VrDIR genes in mungbean using a genome-wide identification method. VrDIRs were distributed on seven of the 11 mungbean chromosomes, and chromosome three contained the most VrDIR genes, with seven members. Thirty-two of the 37 VrDIRs contained a typical DIR gene structure, with one exon; the conserved DIR domain (i.e., Pfam domain) occupied most of the protein in 33 of the 37 VrDIRs. The gene structures of VrDIR genes were analyzed, and a total of 19 distinct motifs were detected. VrDIR genes were classified into five groups based on their phylogenetic relationships, and 13 duplicated gene pairs were identified. In addition, a total of 92 cis-acting elements were detected in all 37 VrDIR promoter regions, and VrDIR genes contained different numbers and types of cis-acting elements. As a result, VrDIR genes showed distinct expression patterns in different tissues and in response to salt and drought stress.
Genomic Prediction of Two Complex Orthopedic Traits Across Multiple Pure and Mixed Breed Dogs
Authors: Jiang Liping , Li Zhuo , Hayward Jessica J. , Hayashi Kei , Krotscheck Ursula , Todhunter Rory J. , Tang You , Huang Meng
Published: September 2021

Canine hip dysplasia (CHD) and rupture of the cranial cruciate ligament (RCCL) are two complex inherited orthopedic traits of dogs. These two traits may occur concurrently in the same dog. Genomic prediction of these two diseases would benefit veterinary medicine, the dog’s owner, and dog breeders because of their high prevalence, and because both traits result in painful debilitating osteoarthritis in affected joints. In this study, 842 unique dogs from 6 breeds with hip and stifle phenotypes were genotyped on a customized Illumina high density 183 k single nucleotide polymorphism (SNP) array and also analyzed using an imputed dataset of 20,487,155 SNPs. To implement genomic prediction, two different statistical methods were employed: Genomic Best Linear Unbiased Prediction (GBLUP) and a Bayesian method called BayesC. The cross-validation results showed that the two methods gave similar prediction accuracy (r = 0.3–0.4) for CHD (measured as Norberg angle) and RCCL in the multi-breed population. For CHD, the average correlation of the AUC was 0.71 (BayesC) and 0.70 (GBLUP), which is a medium level of prediction accuracy and consistent with Pearson correlation results. For RCCL, the correlation of the AUC was slightly higher. The prediction accuracy of GBLUP from the imputed genotype data was similar to the accuracy from DNA array data. We demonstrated that the genomic prediction of CHD and RCCL with DNA array genotype data is feasible in a multiple breed population if there is a genetic connection, such as breed, between the reference population and the validation population. Albeit these traits have heritability of about one-third, higher accuracy is needed to implement in a natural population and predicting a complex phenotype will require much larger number of dogs within a breed and across breeds. It is possible that with higher accuracy, genomic prediction of these orthopedic traits could be implemented in a clinical setting for early diagnosis and treatment, and the selection of dogs for breeding. These results need continuous improvement in model prediction through ongoing genotyping and data sharing. When genomic prediction indicates that a dog is susceptible to one of these orthopedic traits, it should be accompanied by clinical and radiographic screening at an acceptable age with appropriate follow-up.
Regulation of Long Non-coding RNA KCNQ1OT1 Network in Colorectal Cancer Immunity
Authors: Liu Junjie , Lv Wei , Li Shuling , Deng Jingwen
Published: September 2021

Over the past few decades, researchers have become aware of the importance of non-coding RNA, which makes up the vast majority of the transcriptome. Long non-coding RNAs (lncRNAs) in turn constitute the largest fraction of non-coding transcripts. Increasing evidence has been found for the crucial roles of lncRNAs in both tissue homeostasis and development, and for their functional contributions to and regulation of the development and progression of various human diseases such as cancers. However, so far, only few findings with regards to functional lncRNAs in cancers have been translated into clinical applications. Based on multiple factors such as binding affinity of miRNAs to their lncRNA sponges, we analyzed the competitive endogenous RNA (ceRNA) network for the colorectal cancer RNA-seq datasets from The Cancer Genome Atlas (TCGA). After performing the ceRNA network construction and survival analysis, the lncRNA KCNQ1OT1 was found to be significantly upregulated in colorectal cancer tissues and associated with the survival of patients. A KCNQ1OT1-related lncRNA-miRNA-mRNA ceRNA network was constructed. A gene set variation analysis (GSVA) indicated that the expression of the KCNQ1OT1 ceRNA network in colorectal cancer tissues and normal tissues were significantly different, not only in the TCGA-COAD dataset but also in three other GEO datasets used as validation. By predicting comprehensive immune cell subsets from gene expression data, in samples grouped by differential expression levels of the KCNQ1OT1 ceRNA network in a cohort of patients, we found that CD4+, CD8+, and cytotoxic T cells and 14 other immune cell subsets were at different levels in the high- and low-KCNQ1OT1 ceRNA network score groups. These results indicated that the KCNQ1OT1 ceRNA network could be involved in the regulation of the tumor microenvironment, which would provide the rationale to further exploit KCNQ1OT1 as a possible functional contributor to and therapeutic target for colorectal cancer.
Deep Learning Methods in Predicting Gene Expression Levels for the Malaria Parasite
Authors: Tran Tuan , Rekabdar Banafsheh , Ekenna Chinwe
Published: September 2021

Malaria is a mosquito-borne disease caused by single-celled blood parasites of the genus Plasmodium. The most severe cases of this disease are caused by the Plasmodium species, Falciparum. Once infected, a human host experiences symptoms of recurrent and intermittent fevers occurring over a time-frame of 48 hours, attributed to the synchronized developmental cycle of the parasite during the blood stage. To understand the regulated periodicity of Plasmodium falciparum transcription, this paper forecast and predict the P. falciparum gene transcription during its blood stage life cycle implementing a well-tuned recurrent neural network with gated recurrent units. Additionally, we also employ a spiking neural network to predict the expression levels of the P. falciparum gene. We provide results of this prediction on multiple genes including potential genes that express possible drug target enzymes. Our results show a high level of accuracy in being able to predict and forecast the expression levels of the different genes.
Assessment of Imputation Quality: Comparison of Phasing and Imputation Algorithms in Real Data
Authors: Stahl Katharina , Gola Damian , König Inke R.
Published: September 2021

Despite the widespread use of genotype imputation tools and the availability of different approaches, late developments of currently used programs have not been compared comprehensively. We therefore assessed the performance of 35 combinations of phasing and imputation programs, including versions of SHAPEIT, Eagle, Beagle, minimac, PBWT, and IMPUTE, for genetic imputation of completely missing SNPs with a HRC reference panel regarding quality and speed. We used a data set comprising 1,149 fully sequenced individuals from the German population, subsetting the SNPs to approximate the Illumina Infinium-Omni5 array. Five hundred fifty-three thousand two hundred and thirty-four SNPs across two selected chromosomes were utilized for comparison between imputed and sequenced genotypes. We found that all tested programs with the exception of PBWT impute genotypes with very high accuracy (mean error rate < 0.005). PBTW hardly ever imputes the less frequent allele correctly (mean concordance for genotypes including the minor allele <0.0002). For all programs, imputation accuracy drops for rare alleles with a frequency <0.05. Even though overall concordance is high, concordance drops with genotype probability, indicating that low genotype probabilities are rare. The mean concordance of SNPs with a genotype probability <95% drops below 0.9, at which point disregarding imputed genotypes might prove favorable. For fast and accurate imputation, a combination of Eagle2.4.1 using a reference panel for phasing and Beagle5.1 for imputation performs best. Replacing Beagle5.1 with minimac3, minimac4, Beagle4.1, or IMPUTE4 results in a small gain in accuracy at a high cost of speed.
FnCas12a/crRNA-Mediated Genome Editing in Eimeria tenella
Authors: Cheng Peipei , Zhang Zhihao , Yang Fayu , Cai Shuo , Wang Lina , Wang Chunmei , Wang Mi , Liu Yingchun , Fei Chenzhong , Zhang Lifang , Xue Feiqun , Gu Feng
Published: September 2021

Eimeria species are intracellular parasites residing inside the intestinal epithelial cell, which cause poultry coccidiosis and result in significant financial losses in the poultry industry. Genome editing of Eimeria is of immense importance for the development of vaccines and drugs. CRISPR/Cas9 has been utilized for manipulating the genome of Eimeria tenella (E. tenella). Ectopic expression of Cas9, i.e., via plasmids, would introduce transgene, which substantially limits its application, especially for vaccine development. In this study, we initially optimized the condition of the transfection protocol. We demonstrated that with the optimized condition, the transfection of FnCas12a (also known as “FnCpf1”) protein and crRNA targeting EtHistone H4 triggered DNA double-strand breaks in vivo. We then used this strategy to knock-in a coding cassette for an enhanced yellow fluorescent protein (EYFP) and dihydrofolate reductase–thymidylate synthase gene (DHFR) as a selection marker to tag endogenous EtActin. The engineered E. tenella parasite possesses EYFP expression in its entire life cycle. Our results demonstrated that FnCas12a could trigger genome editing in E. tenella, which augments the applicability of the dissection of gene function and the development of anticoccidial drugs and vaccines for Eimeria species.
Comparative Analysis of Unsupervised Protein Similarity Prediction Based on Graph Embedding
Authors: Zhang Yuanyuan , Wang Ziqi , Wang Shudong , Shang Junliang
Published: September 2021

The study of protein–protein interaction and the determination of protein functions are important parts of proteomics. Computational methods are used to study the similarity between proteins based on Gene Ontology (GO) to explore their functions and possible interactions. GO is a series of standardized terms that describe gene products from molecular functions, biological processes, and cell components. Previous studies on assessing the similarity of GO terms were primarily based on Information Content (IC) between GO terms to measure the similarity of proteins. However, these methods tend to ignore the structural information between GO terms. Therefore, considering the structural information of GO terms, we systematically analyze the performance of the GO graph and GO Annotation (GOA) graph in calculating the similarity of proteins using different graph embedding methods. When applied to the actual Human and Yeast datasets, the feature vectors of GO terms and proteins are learned based on different graph embedding methods. To measure the similarity of the proteins annotated by different GO numbers, we used Dynamic Time Warping (DTW) and cosine to calculate protein similarity in GO graph and GOA graph, respectively. Link prediction experiments were then performed to evaluate the reliability of protein similarity networks constructed by different methods. It is shown that graph embedding methods have obvious advantages over the traditional IC-based methods. We found that random walk graph embedding methods, in particular, showed excellent performance in calculating the similarity of proteins. By comparing link prediction experiment results from GO(DTW) and GOA(cosine) methods, it is shown that GO(DTW) features provide highly effective information for analyzing the similarity among proteins.
Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues
Authors: Atcha Hamza , Meli Vijaykumar S. , Davis Chase T. , Brumm Kyle T. , Anis Sara , Chin Jessica , Jiang Kevin , Pathak Medha M. , Liu Wendy F.
Published: September 2021

Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While the effects of soluble cues, including cytokines and chemokines, have been widely studied, the effects of physical cues, including mechanical stimuli, in regulating macrophage form and function are less well understood. In this study, we examined the effects of static and cyclic uniaxial stretch on macrophage inflammatory and healing activation. We found that cyclic stretch altered macrophage morphology and responses to IFNγ/LPS and IL4/IL13. Interestingly, we found that both static and cyclic stretch suppressed IFNγ/LPS induced inflammation. In contrast, IL4/IL13 mediated healing responses were suppressed with cyclic but enhanced with static stretch conditions. Mechanistically, both static and cyclic stretch increased expression of the integrin CD11b (αM integrin), decreased expression of the mechanosensitive ion channel Piezo1, and knock down of either CD11b or Piezo1 through siRNA abrogated stretch-mediated changes in inflammatory responses. Moreover, we found that knock down of CD11b enhanced the expression of Piezo1, and conversely knock down of Piezo1 enhanced CD11b expression, suggesting the potential for crosstalk between integrins and ion channels. Finally, stretch-mediated differences in macrophage activation were also dependent on actin, since pharmacological inhibition of actin polymerization abrogated the changes in activation with stretch. Together, this study demonstrates that the physical environment synergizes with biochemical cues to regulate macrophage morphology and function, and suggests a role for CD11b and Piezo1 crosstalk in mechanotransduction in macrophages.
Aquaculture Reuse Water, Genetic Line, and Vaccination Affect Rainbow Trout (Oncorhynchus mykiss) Disease Susceptibility and Infection Dynamics
Authors: Everson Jeremy L. , Jones Darbi R. , Taylor Amy K. , Rutan Barb J. , Leeds Timothy D. , Langwig Kate E. , Wargo Andrew R. , Wiens Gregory D.
Published: September 2021

Infectious hematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum are major pathogens of farmed rainbow trout. Improved control strategies are desired but the influence of on-farm environmental factors that lead to disease outbreaks remain poorly understood. Water reuse is an important environmental factor affecting disease. Prior studies have established a replicated outdoor-tank system capable of varying the exposure to reuse water by controlling water flow from commercial trout production raceways. The goal of this research was to evaluate the effect of constant or pulsed reuse water exposure on survival, pathogen prevalence, and pathogen load. Herein, we compared two commercial lines of rainbow trout, Clear Springs Food (CSF) and Troutex (Tx) that were either vaccinated against IHNV with a DNA vaccine or sham vaccinated. Over a 27-day experimental period in constant reuse water, all fish from both lines and treatments, died while mortality in control fish in spring water was <1%. Water reuse exposure, genetic line, vaccination, and the interaction between genetic line and water exposure affected survival (P<0.05). Compared to all other water sources, fish exposed to constant reuse water had 46- to 710-fold greater risk of death (P<0.0001). Tx fish had a 2.7-fold greater risk of death compared to CSF fish in constant reuse water (P ≤ 0.001), while risk of death did not differ in spring water (P=0.98). Sham-vaccinated fish had 2.1-fold greater risk of death compared to vaccinated fish (P=0.02). Both IHNV prevalence and load were lower in vaccinated fish compared to sham-vaccinated fish, and unexpectedly, F. psychrophilum load associated with fin/gill tissues from live-sampled fish was lower in vaccinated fish compared to sham-vaccinated fish. As a result, up to forty-five percent of unvaccinated fish were naturally co-infected with F. psychrophilum and IHNV and the coinfected fish exhibited the highest IHNV loads. Under laboratory challenge conditions, co-infection with F. psychrophilum and IHNV overwhelmed IHNV vaccine-induced protection. In summary, we demonstrate that exposure to reuse water or multi-pathogen challenge can initiate complex disease dynamics that can overwhelm both vaccination and host genetic resistance.
Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis
Authors: Wang Chuqiao , Liang Guorui , Shen Jieni , Kong Haifan , Wu Donghong , Huang Jinxiang , Li Xuefeng
Published: September 2021

Sepsis, an infection-induced systemic inflammatory disorder, is often accompanied by multiple organ dysfunction syndromes with high incidence and mortality rates, and those who survive are often left with long-term sequelae, bringing great burden to social economy. Therefore, novel approaches to solve this puzzle are urgently needed. Previous studies revealed that long non-coding RNAs (lncRNAs) have exerted significant influences on the process of sepsis. The aim of this review is to summarize our understanding of lncRNAs as potential sepsis-related diagnostic markers and therapeutic targets, and provide new insights into the diagnosis and treatment for sepsis. In this study, we also introduced the current diagnostic markers of sepsis and discussed their limitations, while review the research advances in lncRNAs as promising biomarkers for diagnosis and prognosis of sepsis. Furthermore, the roles of lncRNAs in sepsis-induced organ dysfunction were illustrated in terms of different organ systems. Nevertheless, further studies should be carried out to elucidate underlying molecular mechanisms and pathological process of sepsis.
γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends
Authors: Barros Mateus de Souza , de Araújo Nilberto Dias , Magalhães-Gama Fábio , Pereira Ribeiro Thaís Lohana , Alves Hanna Fabíola Silva , Tarragô Andréa Monteiro , Malheiro Adriana , Costa Allyson Guimarães
Published: September 2021

Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.
A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis
Authors: Fischinger Stephanie , Cizmeci Deniz , Shin Sally , Davies Leela , Grace Patricia S. , Sivro Aida , Yende-Zuma Nonhlanhla , Streeck Hendrik , Fortune Sarah M. , Lauffenburger Douglas A. , Naidoo Kogieleum , Alter Galit
Published: September 2021

South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a leading cause of death for HIV infected individuals, and correlates of TB recurrence protection/risk have yet to be defined, here we sought to understand the antibody associated mechanisms of recurrent TB by investigating the humoral response in a longitudinal cohort of HIV co-infected individuals previously treated for TB with and without recurrent disease during follow-up, in order to identify antibody correlates of protection between individuals who do not have recurrent TB and individuals who do. We used a high-throughput, “systems serology” approach to profile biophysical and functional characteristics of antibodies targeting antigens from Mycobacterium tuberculosis (Mtb). Differences in antibody profiles were noted between individuals with and without recurrent TB, albeit these differences were largely observed close to the time of re-diagnosis. Individuals with recurrent TB had decreased Mtb-antigen specific IgG3 titers, but not other IgG subclasses or IgA, compared to control individuals. These data point to a potential role for Mtb-specific IgG3 responses as biomarkers or direct mediators of protective immunity against Mtb recurrence.
Delta Opioid Receptor Agonists Ameliorate Colonic Inflammation by Modulating Immune Responses
Authors: Nagata Kazuki , Nagase Hiroshi , Okuzumi Ayumi , Nishiyama Chiharu
Published: September 2021

The opioid receptors play important roles in the regulation of sense and emotions. Although it is recently revealed that opioid receptors are also expressed in various cells, but not restricted in the central nervous system, the effects of opioids on peripheral immune cells are largely unknown. In the current study, we evaluated the effect of opioids on immune system by using selective agonists for δ opioid receptor. Systemic administration of KNT-127 or intraperitoneal injection of YNT-2715 (a KNT-127-related compound that cannot pass through the blood-brain barrier) significantly alleviated the pathology of dextran sodium sulfate-induced colitis. In KNT-127-treated mice, the levels of an inflammatory cytokine IL-6 in the serum, and macrophages in the mesenteric lymph nodes (MLNs) were decreased in the progression stage, and those of regulatory T cells (Tregs) in the MLN were increased in the recovery stage. In vitro experiments revealed that KNT-127 inhibited the release of IL-6 and another inflammatory cytokine TNF-α from macrophages and accelerated the development of Tregs. Our study suggests that δ opioid agonists act directly on immune cells to improve the pathology of the colitis and can be candidates of immunomodulatory drugs.
The Role of Innate Lymphoid Cells in Chronic Respiratory Diseases
Authors: Hsu Amy T. , Gottschalk Timothy A. , Tsantikos Evelyn , Hibbs Margaret L.
Published: September 2021

The lung is a vital mucosal organ that is constantly exposed to the external environment, and as such, its defenses are continuously under threat. The pulmonary immune system has evolved to sense and respond to these danger signals while remaining silent to innocuous aeroantigens. The origin of the defense system is the respiratory epithelium, which responds rapidly to insults by the production of an array of mediators that initiate protection by directly killing microbes, activating tissue-resident immune cells and recruiting leukocytes from the blood. At the steady-state, the lung comprises a large collection of leukocytes, amongst which are specialized cells of lymphoid origin known as innate lymphoid cells (ILCs). ILCs are divided into three major helper-like subsets, ILC1, ILC2 and ILC3, which are considered the innate counterparts of type 1, 2 and 17 T helper cells, respectively, in addition to natural killer cells and lymphoid tissue inducer cells. Although ILCs represent a small fraction of the pulmonary immune system, they play an important role in early responses to pathogens and facilitate the acquisition of adaptive immunity. However, it is now also emerging that these cells are active participants in the development of chronic lung diseases. In this mini-review, we provide an update on our current understanding of the role of ILCs and their regulation in the lung. We summarise how these cells and their mediators initiate, sustain and potentially control pulmonary inflammation, and their contribution to the respiratory diseases chronic obstructive pulmonary disease (COPD) and asthma.
A Comprehensive Prognostic and Immunological Analysis of a Six-Gene Signature Associated With Glycolysis and Immune Response in Uveal Melanoma
Authors: Liu Jun , Lu Jianjun , Li Wenli
Published: September 2021

Uveal melanoma (UM) is a subtype of melanoma with poor prognosis. This study aimed to construct a new prognostic gene signature that can be used for survival prediction and risk stratification of UM patients. In this work, transcriptome data from the Molecular Signatures Database were used to identify the cancer hallmarks most relevant to the prognosis of UM patients. Weighted gene co-expression network, univariate least absolute contraction and selection operator (LASSO), and multivariate Cox regression analyses were used to construct the prognostic gene characteristics. Kaplan–Meier and receiver operating characteristic (ROC) curves were used to evaluate the survival predictive ability of the gene signature. The results showed that glycolysis and immune response were the main risk factors for overall survival (OS) in UM patients. Using univariate Cox regression analysis, 238 candidates related to the prognosis of UM patients were identified (p < 0.05). Using LASSO and multivariate Cox regression analyses, a six-gene signature including ARPC1B, BTBD6, GUSB, KRTCAP2, RHBDD3, and SLC39A4 was constructed. Kaplan–Meier analysis of the UM cohort in the training set showed that patients with higher risk scores had worse OS (HR = 2.61, p < 0.001). The time-dependent ROC (t-ROC) curve showed that the risk score had good predictive efficiency for UM patients in the training set (AUC > 0.9). Besides, t-ROC analysis showed that the predictive ability of risk scores was significantly higher than that of other clinicopathological characteristics. Univariate and multivariate Cox regression analyses showed that risk score was an independent risk factor for OS in UM patients. The prognostic value of risk scores was further verified in two external UM cohorts (GSE22138 and GSE84976). Two-factor survival analysis showed that UM patients with high hypoxia or immune response scores and high risk scores had the worst prognosis. Moreover, a nomogram based on the six-gene signature was established for clinical practice. In addition, risk scores were related to the immune infiltration profiles. Taken together, this study identified a new prognostic six-gene signature related to glycolysis and immune response. This six-gene signature can not only be used for survival prediction and risk stratification but also may be a potential therapeutic target for UM patients.