bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in Detecting Low Prevalence Somatic TERT Promoter Mutations in Papillary Thyroid Carcinoma
Authors: da Costa Vitor Rodrigues , Bim Larissa Valdemarin , Pacheco e Silva Luiza Dornelles Penteado , Colloza-Gama Gabriel Avelar , Bastos André Uchimura , Delcelo Rosana , Oler Gisele , Cerutti Janete Maria
Published: March 2021

Background

Two recurrent TERT (telomerase reverse transcriptase) promoter mutations, C228T and C250T, have been reported in thyroid carcinomas and were correlated with high-risk clinicopathological features and a worse prognosis. Although far more frequent in the poorly differentiated and undifferentiated thyroid cancer, the TERT promoter mutations play a significant role on PTC recurrence and disease-specific mortality. However, the prevalence varies considerably through studies and it is uncertain if these differences are due to population variation or the methodology used to detect TERT mutations. In this study we aim to compare three different strategies to detect TERT promoter mutations in PTC.

Methods

DNA was isolated from formalin-fixed paraffin-embedded (FFPE) specimens from 89 PTC and 40 paired lymph node metastases. The prevalence of the hot spot TERT C228T and C250T mutations was assessed in FFPE samples using TaqMan SNP genotyping assays. Random samples were tested by Sanger Sequencing and droplet digital PCR (ddPCR).

Results

In general, 16 out of 89 (18%) PTC samples and 14 out of 40 (35%) lymph node metastases harbored TERT promoter mutations by TaqMan assay. Sanger sequencing, performed in random selected samples, failed to detect TERT mutations in four samples that were positive by TaqMan SNP genotyping assay. Remarkably, ddPCR assay allowed detection of TERT promoter mutations in six samples that harbor very low mutant allele frequency (≤ 2%) and were negative by both genotype assay and Sanger Sequencing.

Conclusion

This study observed a good concordance among the methodologies used to detect TERT promoter mutations when a high percentage of mutated alleles was present. Sanger analysis demonstrated a limit of detection for mutated alleles. Therefore, the prevalence of TERT promoter mutations in PTC may be higher than previously reported, since most studies have conventionally used Sanger sequencing. The efficient characterization of genetic alterations that are used as preoperative or postoperative diagnostic, risk stratification of the patient and individualized treatment decisions, mainly in highly heterogeneous tumors, require highly sensitive and specific approaches.
Storage-Transmission Joint Planning Method to Deal with Insufficient Flexibility and Transmission Congestion
Authors: Yang Xiuyu , Chai Guofeng , Liu Xueyuan , Xu Minghong , Guo Qi
Published: March 2021

The insufficient power system flexibility and transmission congestion are two fundamental reasons for wind power curtailment. As the scale of the wind power in the power system is growing rapidly, the two factors of wind power curtailment events coexist and have a certain coupling relationship. The configuration of the energy storage system can not only increase the flexibility of the system but also alleviate transmission congestion. Therefore, the joint planning of energy storage and transmission grid that takes into account the flexibility of the system and the transmission congestion is of great significance to solve the wind curtailment. Hence, this paper first decouples the insufficient flexibility and transmission congestion wind power curtailment, and quantitatively analyzes the impact of transmission capacity on the coupling relationship between the two; second, reveals the principle of joint planning of energy storage system and transmission congestion, and constructs an optimization model, and proposes to set up the capacity of the wind power which connects the power network. The solution procedure, which deals with grid planning and the energy storage system optimization in turn, not only ensures the accuracy of the model, but also significantly reduces the calculation cost. Finally, a case study of a wind power base in Northeast China and an improved Garver-6 system are carried out to verify the effectiveness of the proposed method.
Genome-Wide Association Study-Based Identification of SNPs and Haplotypes Associated With Goose Reproductive Performance and Egg Quality
Authors: Gao Guangliang , Gao Dengfeng , Zhao Xianzhi , Xu Songsong , Zhang Keshan , Wu Rui , Yin Chunhui , Li Jing , Xie Youhui , Hu Silu , Wang Qigui
Published: March 2021

Geese are one of the most economically important waterfowl. However, the low reproductive performance and egg quality of geese hinder the development of the goose industry. The identification and application of genetic markers may improve the accuracy of beneficial trait selection. To identify the genetic markers associated with goose reproductive performance and egg quality traits, we performed a genome-wide association study (GWAS) for body weight at birth (BBW), the number of eggs at 48 weeks of age (EN48), the number of eggs at 60 weeks of age (EN60) and egg yolk color (EYC). The GWAS acquired 2.896 Tb of raw sequencing data with an average depth of 12.44× and identified 9,279,339 SNPs. The results of GWAS showed that 26 SNPs were significantly associated with BBW, EN48, EN60, and EYC. Moreover, five of these SNPs significantly associated with EN48 and EN60 were in a haplotype block on chromosome 35 from 4,512,855 to 4,541,709 bp, oriented to TMEM161A and another five SNPs significantly correlated to EYC were constructed in haplotype block on chromosome 5 from 21,069,009 to 21,363,580, which annotated by TMEM161A, CALCR, TFPI2, and GLP1R. Those genes were enriched in epidermal growth factor-activated receptor activity, regulation of epidermal growth factor receptor signaling pathway. The SNPs, haplotype markers, and candidate genes identified in this study can be used to improve the accuracy of marker-assisted selection for the reproductive performance and egg quality traits of geese. In addition, the candidate genes significantly associated with these traits may provide a foundation for better understanding the mechanisms underlying reproduction and egg quality in geese.
An in vitro Study on the Role of Hepatitis B Virus X Protein C-Terminal Truncation in Liver Disease Development
Authors: Siddiqui Zaheenul Islam , Azam Syed Ali , Khan Wajihul Hasan , Afroz Masarrat , Farooqui Sabihur Rahman , Amir Fatima , Azmi Md Iqbal , Anwer Ayesha , Khan Saniya , Mehmankhah Mahboubeh , Parveen Shama , Kazim Syed Naqui
Published: March 2021

Hepatitis B virus X protein C-terminal 127 amino acid truncation is often found expressed in hepatocellular carcinoma (HCC) tissue samples. The presentin vitrostudy tried to determine the role of this truncation mutant in the hepatitis B–related liver diseases such as fibrosis, cirrhosis, HCC, and metastasis. HBx gene and its 127 amino acid truncation mutant were cloned in mammalian expression vectors and transfected in human hepatoma cell line. Changes in cell growth/proliferation, cell cycle phase distribution, expression of cell cycle regulatory genes, mitochondrial depolarization, and intracellular reactive oxygen species (ROS) level were analyzed. Green fluorescent protein (GFP)–tagged version of HBx and the truncation mutant were also created and the effects of truncation on HBx intracellular expression pattern and localization were studied. Effect of time lapse on protein expression pattern was also analyzed. The truncation mutant of HBx is more efficient in inducing cell proliferation, and causes more ROS production and less mitochondrial depolarization as compared with wild type (wt) HBx. In addition, gene expression is altered in favor of carcinogenesis in the presence of the truncation mutant. Furthermore, mitochondrial perinuclear aggregation is achieved earlier in the presence of the truncation mutant. Therefore, HBx C-terminal 127 amino acid truncation might be playing important roles in the development of hepatitis B–related liver diseases by inducing cell proliferation, altering gene expression, altering mitochondrial potential, inducing mitochondrial clustering and oxidative stress, and changing HBx expression pattern.
Cytokines and Soluble HLA-G Levels in the Acute and Recovery Phases of Arbovirus-Infected Brazilian Patients Exhibiting Neurological Complications
Authors: Almeida Renata Santos , Ferreira Maria Lúcia Brito , Sonon Paulin , Cordeiro Marli Tenório , Sadissou Ibrahim , Diniz George Tadeu Nunes , Militão-Albuquerque Maria de Fátima Pessoa , Franca Rafael Freitas De Oliveira , Donadi Eduardo Antonio , Lucena-Silva Norma
Published: March 2021

Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1β, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.
The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy
Authors: Lee Jongdae , Lozano-Ruiz Beatriz , Yang Fengyuan Mandy , Fan Dengxia Denise , Shen Liya , González-Navajas Jose M.
Published: March 2021

During the last decade, immune checkpoint inhibition (ICI) has become a pillar of cancer therapy. Antibodies targeting CTLA-4 or PD-1/PD-L1 have been approved in several malignancies, with thousands of clinical trials currently underway. While the majority of cancer immunotherapies have traditionally focused on enhancing cytotoxic responses by CD8+ or NK cells, there are clear evidences that CD4+ T cell responses can modulate the immune response against tumors and influence the efficacy of ICI therapy. CD4+ T cells can differentiate into several subsets of helper T cells (Th) or regulatory T cells (Treg), with a wide range of effector and/or regulatory functions. Importantly, different Th subsets may have different and sometimes contrasting roles in the clinical response to ICI therapy, which in addition may vary depending on the organ and tumor niche. In this review, we discuss recent evidence that highlights how ICI therapy impacts Th1, Th9, and Th17 cells and vice versa. These data might be important designing better interventions that unleash the full potential of immune response against cancer.
Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice
Authors: Jash Arijita , Usaneerungrueng Chomkan , Howie Heather L. , Qiu Annie , Luckey Chance John , Zimring James C. , Hudson Krystalyn E.
Published: March 2021

Red blood cells expressing alloantigens are well known to be capable of inducing robust humoral alloantibody responses both in transfusion and pregnancy. However, the majority of transfusion recipients and pregnant women never make alloantibodies, even after repeat exposure to foreign RBCs. More recently, RBCs have been used as a cellular therapeutic—very much like transfusion, engineered RBCs are highly immunogenic in some cases but not others. In animal models of both transfusion and RBC based therapeutics, RBCs that do not induce an immune response also cause tolerance. Despite a robust phenomenology, the mechanisms of what regulates immunity vs. tolerance to RBCs remains unclear. However, it has been reported that copy number of alloantigens on the RBCs is a critical factor, with a very low copy number causing non-responsiveness (in both humans and mice) and also leading to tolerance in mice. Recently, we reported that an IgG2c specific for an RBC antigen can substantially enhance the humoral immune response upon transfusion of RBCs expressing that antigen. Herein, we report that an IgG2c converts RBCs with low antigen copy number from a tolerogenic to an immunogenic stimulus. These findings report the first known stimulus that induces humoral alloimmunization to a low copy number RBC alloantigen and identify a previously undescribed molecular switch that has the ability to affect responder vs. non-responder phenotypes of transfusion recipients.
Developing Antimicrobial Synergy With AMPs
Authors: Duong Leora , Gross Steven P. , Siryaporn Albert
Published: March 2021

Antimicrobial peptides (AMPs) have been extensively studied due to their vast natural abundance and ability to kill microbes. In an era critically lacking in new antibiotics, manipulating AMPs for therapeutic application is a promising option. However, bacterial pathogens resistant to AMPs remain problematic. To improve AMPs antimicrobial efficacy, their use in conjunction with other antimicrobials has been proposed. How might this work? AMPs kill bacteria by forming pores in bacterial membranes or by inhibiting bacterial macromolecular functions. What remains unknown is the duration for which AMPs keep bacterial pores open, and the extent to which bacteria can recover by repairing these pores. In this mini-review, we discuss various antimicrobial synergies with AMPs. Such synergies might arise if the antimicrobial agents helped to keep bacterial pores open for longer periods of time, prevented pore repair, perturbed bacterial intracellular functions at greater levels, or performed other independent bacterial killing mechanisms. We first discuss combinations of AMPs, and then focus on histones, which have antimicrobial activity and co-localize with AMPs on lipid droplets and in neutrophil extracellular traps (NETs). Recent work has demonstrated that histones can enhance AMP-induced membrane permeation. It is possible that histones, histone fragments, and histone-like peptides could amplify the antimicrobial effects of AMPs, giving rise to antimicrobial synergy. If so, clarifying these mechanisms will thus improve our overall understanding of the antimicrobial processes and potentially contribute to improved drug design.
Genotypic Diversity and Pathogenic Potential of Clinical and Environmental Vibrio parahaemolyticus Isolates From Brazil
Authors: Santos Leandro de O. , de Lanna Cristóvão A. , Arcanjo Anna Carolina da C. , Bisch Paulo M. , von Krüger Wanda M. A.
Published: March 2021

Vibrio parahaemolyticus strains recovered from human diarrheal stools (one in 1975 and two in 2001) and environmental sources (four, between 2008 and 2010) were investigated for the presence of virulence genes (trh, tdh, and vpadF), pandemic markers (orf8, toxRSnew), and with respect to their pathogenic potential in two systemic infection models. Based only on the presence or absence of these genetic markers, they were classified as follows: the environmental strains were non-pathogenic, whereas among the clinical strains, the one isolated in 1975 was pathogenic (non-pandemic), and the other two were pathogenic (pandemic). The pathogenic potential of the strains was evaluated in mice and Galleria mellonella larvae infection models, and except for the clinical (pathogenic, non-pandemic) isolate, the others produced lethal infection in both organisms, regardless of their source, serotype, and genotype (tdh, orf8, toxRSnew, and vpadF). Based on mice and larval mortality rates, the strains were then grouped according to virulence (high, intermediate, and avirulent), and remarkably similar results were obtained by using these models: The clinical strain (pathogenic and non-pandemic) was classified as avirulent, and other strains (four non-pathogenic and two pandemic) were considered of high or intermediate virulence. In summary, these findings demonstrate that G. mellonella larvae can indeed be used as an alternative model to study the pathogenicity of V. parahaemolyticus. Moreover, they raise doubts about the use of traditional virulence markers to predict pathogenesis of the species and show that reliable models are indispensable to determine the pathogenic potential of environmental isolates considered non-pathogenic, based on the absence of the long-standing virulence indicators.
A Mini-Review on Lichen-Based Nanoparticles and Their Applications as Antimicrobial Agents
Authors: Rattan Rohit , Shukla Sudeep , Sharma Bharti , Bhat Mamta
Published: March 2021

Biological entities such as green plants, fungi, and lichens are now a days persistently explored for the synthesis of nanoparticles. Lichen-based nanoparticles are also becoming increasingly popular owing to their biocompatibility, eco-friendliness, and cost-effectiveness. The lichen-based metal nanomaterials, particularly synthesized using green chemistry approaches, have turned out to be great substitutes to conventional antimicrobial therapies. Many scientific reports established the significant antimicrobial properties exhibited by the lichen nanoparticles. Therefore, the present mini-review summarizes an overview of lichen-based nanomaterials, their synthesis, their applications, and the molecular mechanism of their potential as broad spectrum antimicrobial agents for biomedical applications.
Conservation of Archaeal C/D Box sRNA-Guided RNA Modifications
Authors: Breuer Ruth , Gomes-Filho Jose-Vicente , Randau Lennart
Published: March 2021

Post-transcriptional modifications fulfill many important roles during ribosomal RNA maturation in all three domains of life. Ribose 2'-O-methylations constitute the most abundant chemical rRNA modification and are, for example, involved in RNA folding and stabilization. In archaea, these modification sites are determined by variable sets of C/D box sRNAs that guide the activity of the rRNA 2'-O-methyltransferase fibrillarin. Each C/D box sRNA contains two guide sequences that can act in coordination to bridge rRNA sequences. Here, we will review the landscape of archaeal C/D box sRNA genes and their target sites. One focus is placed on the apparent accelerated evolution of guide sequences and the varied pairing of the two individual guides, which results in different rRNA modification patterns and RNA chaperone activities.
Ictal and Interictal Cardiac Manifestations in Epilepsy. A Review of Their Relation With an Altered Central Control of Autonomic Functions and With the Risk of SUDEP
Authors: Mazzola Laure , Rheims Sylvain
Published: March 2021

There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.
Blur Detection Sensitivity Increases in Children Using Orthokeratology
Authors: Xu Jingjing , Tao Chunwen , Mao Xinjie , Lu Xin , Bao Jinhua , Drobe Björn , Chen Hao
Published: March 2021

Purpose

To investigate changes in blur detection sensitivity in children using orthokeratology (Ortho-K) and explore the relationships between blur detection thresholds (BDTs) and aberrations and accommodative function.

Methods

Thirty-two children aged 8–14 years old who underwent Ortho-K treatment participated in and completed this study. Their BDTs, aberrations, and accommodative responses (ARs) were measured before and after a month of Ortho-K treatment. A two forced-choice double-staircase procedure with varying extents of blur in three images (Tumbling Es, Lena, and Street View) was used to measure the BDTs. The participants were required to judge whether the images looked blurry. The BDT of each of the images (BDT_Es, BDT_Lena, and BDT_Street) was the average value of the last three reversals. The accommodative lag was quantified by the difference between the AR and the accommodative demand (AD). Changes in the BDTs, aberrations, and accommodative lags and their relationships were analyzed.

Results

After a month of wearing Ortho-K lenses, the children’s BDT_Es and BDT_Lena values decreased, the aberrations increased significantly (for all, P ≤0.050), and the accommodative lag decreased to a certain extent [T(31) = 2.029, P = 0.051]. Before Ortho-K treatment, higher-order aberrations (HOAs) were related to BDT_Lena (r = 0.463, P = 0.008) and the accommodative lag was related to BDT_Es (r = −0.356, P = −0.046). After one month, no significant correlations were found between the BDTs and aberrations or accommodative lags, as well as between the variations of them (for all, P ≥ 0.069).

Conclusion

Ortho-K treatment increased the children’s level of blur detection sensitivity, which may have contributed to their good visual acuity.
Biological Timing and Neurodevelopmental Disorders: A Role for Circadian Dysfunction in Autism Spectrum Disorders
Authors: Lorsung Ethan , Karthikeyan Ramanujam , Cao Ruifeng
Published: March 2021

Autism spectrum disorders (ASDs) are a spectrum of neurodevelopmental disorders characterized by impaired social interaction and communication, as well as stereotyped and repetitive behaviors. ASDs affect nearly 2% of the United States child population and the worldwide prevalence has dramatically increased in recent years. The etiology is not clear but ASD is thought to be caused by a combination of intrinsic and extrinsic factors. Circadian rhythms are the ∼24 h rhythms driven by the endogenous biological clock, and they are found in a variety of physiological processes. Growing evidence from basic and clinical studies suggest that the dysfunction of the circadian timing system may be associated with ASD and its pathogenesis. Here we review the findings that link circadian dysfunctions to ASD in both experimental and clinical studies. We first introduce the organization of the circadian system and ASD. Next, we review physiological indicators of circadian rhythms that are found disrupted in ASD individuals, including sleep–wake cycles, melatonin, cortisol, and serotonin. Finally, we review evidence in epidemiology, human genetics, and biochemistry that indicates underlying associations between circadian regulation and the pathogenesis of ASD. In conclusion, we propose that understanding the functional importance of the circadian clock in normal and aberrant neurodevelopmental processes may provide a novel perspective to tackle ASD, and clinical treatments for ASD individuals should comprise an integrative approach considering the dynamics of daily rhythms in physical, mental, and social processes.
Circulating Serum Exosomal Long Non-Coding RNAs FOXD2-AS1, NRIR, and XLOC_009459 as Diagnostic Biomarkers for Colorectal Cancer
Authors: Yu Miao , Song Xing-guo , Zhao Ya-jing , Dong Xiao-han , Niu Li-min , Zhang Zhi-jun , Shang Xiao-ling , Tang You-yong , Song Xian-rang , Xie Li
Published: March 2021

Background

Exosomes derived from cancer cells encapsulate various kinds of tumor-specific molecules and thus can interact with adjacent or distant cells to mediate information exchange. Long non-coding RNAs (lncRNAs) in exosomes have the potential as diagnostic and prognostic biomarkers in different types of cancers. The current study was aimed to identify circulating exosomal lncRNAs for the diagnosis of colorectal cancer (CRC).

Methods

Exosomes were isolated from the serum by ultracentrifugation and verified by transmission electron microscope (TEM), qNano, and immunoblotting. Exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 were selected by lncRNA microarray and validated by qPCR in 203 CRC patients and 201 healthy donors. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficiency of serum exosomal lncRNAs.

Results

Exosomal FOXD2-AS1, NRIR, and XLOC_009459 (TCONS_00020073) levels were significantly upregulated in 203 CRC patients and 80 early-stage CRC patients compared to 201 healthy donors, possessing the area under the curve (AUC) of 0.728, 0.660, and 0.682 for CRC, as well as 0.743, 0.660, and 0.689 for early-stage CRC, respectively. Notably, their combination demonstrated the markedly elevated AUC of 0.736 for CRC and 0.758 for early-stage CRC, indicating their potential as diagnostic biomarkers for CRC.

Conclusions

Our data suggested that exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 act as the promising biomarkers for the diagnostics of CRC and early-stage CRC.
Identification of a Novel Four-Gene Signature Correlated With the Prognosis of Patients With Hepatocellular Carcinoma: A Comprehensive Analysis
Authors: Zhu Weihua , Ru Lixin , Ma Zhenchao
Published: March 2021

Purpose

Hepatocellular carcinoma (HCC) is a common solid-tumor malignancy with high heterogeneity, and accurate prognostic prediction in HCC remains difficult. This analysis was performed to find a novel prognostic multigene signature.

Methods

The TCGA-LIHC dataset was analyzed for differentially coexpressed genes through weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. A protein-protein interaction (PPI) network and univariate Cox regression analysis of overall survival (OS) were utilized to identify their prognostic value. Next, we used least absolute shrinkage and selection operator (LASSO) Cox regression to establish a prognostic module. Subsequently, the ICGC-LIRI-JP dataset was applied for further validation. Based on this module, HCC cases were stratified into high-risk and low-risk groups, and differentially expressed genes (DEGs) were identified. Functional enrichment analyses of these DEGs were conducted. Finally, single-sample gene set enrichment analysis (ssGSEA) was performed to explore the correlation between the prognostic signature and immune status.

Results

A total of 393 differentially coexpressed genes were obtained. Forty differentially coexpressed hub genes were identified using the CytoHubba plugin, and 38 of them were closely correlated with OS. Afterward, we established the four-gene prognostic signature with an acceptable accuracy (area under the curve [AUC] of 1-year survival: 0.739). The ICGC-LIRI-JP dataset also supported the acceptable accuracy (AUC of 1-year survival:0.752). Compared with low-risk cohort, HCC cases in the high-risk cohort had shorter OS, higher tumor grades, and higher T stages. The risk scores of this signature still act as independent predictors of OS (P<0.001). Functional enrichment analyses suggest that it was mainly organelle fission and nuclear division that were enriched. Finally, ssGSEA revealed that this signature is strongly associated with the immune status of HCC patients.

Conclusions

The proposed prognostic signature of four differentially coexpressed hub genes has satisfactory prognostic ability, providing important insight into the prediction of HCC prognosis.
Oncoproteins of High-Risk HPV and EBV Cooperate to Enhance Cell Motility and Invasion of Human Breast Cancer Cells via Erk1/Erk2 and β-Catenin Signaling Pathways
Authors: Gupta Ishita , Jabeen Ayesha , Vranic Semir , Al Moustafa Ala-Eddin , Al-Thawadi Hamda
Published: March 2021

Breast cancer is a leading cause of death in women around the world. Most breast cancer-related deaths are a result of complications from the metastatic spread. Several recent studies reported that high-risk human papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are co-presented in different types of human carcinomas including breast; however, the cooperative effects between high-risk HPVs and EBV oncoproteins in human breast cancer have not been investigated yet. Thus, we herein explored the cooperation outcome between E6/E7 and latent membrane protein 1 (LMP1) oncoproteins of high-risk HPV type 16 and EBV, respectively, in two human breast cancer cell lines, MCF7 and MDA-MB-231. Our data revealed that the cooperation of E6/E7 and LMP1 oncoproteins stimulates cell proliferation and deregulates cell cycle progression of human breast cancer and normal mammary cells; in parallel, we noted that E6/E7/LMP1 incite colony formation of both breast cancer cell lines but not normal cells. More significantly, our results point out that the co-expression of E6/E7 and LMP1 oncoproteins enhances cell motility and invasion of MCF7 and MDA-MB-231 cell lines; this is accompanied by deregulation of epithelial–mesenchymal transition biomarkers including E-cadherin, β-catenin, fascin, and vimentin. The molecular pathway analysis of HPV and EBV oncoproteins cooperation shows that it can enhance the phosphorylation of extracellular signal-regulated kinases (Erk1/Erk2) in addition to β-catenin, which could be behind the effect of this cooperation in our cell models. The study clearly suggests that high-risk HPV and EBV coinfection can play an important role in breast cancer progressionviaErk1/Erk2 and β-catenin signaling pathways.
Aberrations of Genomic Imprinting in Glioblastoma Formation
Authors: Lozano-Ureña Anna , Jiménez-Villalba Esteban , Pinedo-Serrano Alejandro , Jordán-Pla Antonio , Kirstein Martina , Ferrón Sacri R.
Published: March 2021

In human glioblastoma (GBM), the presence of a small population of cells with stem cell characteristics, the glioma stem cells (GSCs), has been described. These cells have GBM potential and are responsible for the origin of the tumors. However, whether GSCs originate from normal neural stem cells (NSCs) as a consequence of genetic and epigenetic changes and/or dedifferentiation from somatic cells remains to be investigated. Genomic imprinting is an epigenetic marking process that causes genes to be expressed depending on their parental origin. The dysregulation of the imprinting pattern or the loss of genomic imprinting (LOI) have been described in different tumors including GBM, being one of the earliest and most common events that occurs in human cancers. Here we have gathered the current knowledge of the role of imprinted genes in normal NSCs function and how the imprinting process is altered in human GBM. We also review the changes at particular imprinted loci that might be involved in the development of the tumor. Understanding the mechanistic similarities in the regulation of genomic imprinting between normal NSCs and GBM cells will be helpful to identify molecular players that might be involved in the development of human GBM.
Auto-Regulation Method vs. Fixed-Loading Method in Maximum Strength Training for Athletes: A Systematic Review and Meta-Analysis
Authors: Zhang Xing , Li Hansen , Bi Shilin , Luo Yong , Cao Yang , Zhang Guodong
Published: March 2021

The auto-regulation method is a rising training strategy to improve strength and motor performance, and the Autoregulatory Progressive Resistance Exercise (APRE), Rating of Perceived Exertion program (RPE), and Velocity-Based Training (VBT) are the three common auto-regulation programs. However, whether the auto-regulation method is more effective than the traditional strength training (the fixed-loading method) in maximum strength training is still unclear. The present study searched the Pubmed, SPORTDiscus, Web of Science, Embase, EBSCO, Cochrane, CNKI, and CQVIP databases, and included eight related studies published between 2010 and 2020, with a total of 166 subjects including division 1 college players and athletes with at least 1-year training history, and interventions ranging from 5 to 10 weeks. A meta-analysis was performed to check the difference between the two training methods, and analyzed the differences in the existing auto-regulation programs' effectiveness. The overall results showed that the auto-regulation method was more effective than the fixed-loading method in maximum strength training (effect size = 0.64; P < 0.001; I2 = 0%). In specific, the pooled results in subgroup analysis indicated that the auto-regulation method may effectively improve the strength performance in squat (effect size = 4.64; P < 0.05; I2 = 54%) and bench press (effect size = 3.21; P < 0.05; I2 = 62%). Greater benefits of the auto-regulation method on strength improvement could be achieved in an 8-week or even shorter training (effect size = 0.87; P < 0.001; I2 = 0%) compared with those of 8–10 weeks (effect size = 0.32; P < 0.001; I2 = 0%). The APRE is the most effective training program among the three auto-regulation programs (effect size = 0.78; P < 0.001; I2 = 0%). In conclusion, the auto-regulation method could be more effective than the fixed-loading method in maximum strength training. The APRE is a convenient and effective training program that may be considered a practical training program to replace traditional training in athletes.
Lipidomics Revealed Alteration of Sphingolipid Metabolism During the Reparative Phase After Myocardial Infarction Injury
Authors: Hua Tong , Bao Qiankun , He Xue , Cai Wenbin , He Jinlong
Published: March 2021

Aberrant sphingolipid metabolism contributes to cardiac pathophysiology. Emerging evidence found that an increased level of ceramide during the inflammatory phase of post-myocardial infarction (MI) served as a biomarker and was associated with cardiac dysfunction. However, the alternation of the sphingolipid profile during the reparative phase after MI is still not fully understood. Using a mouse model of the left anterior descending ligation that leads to MI, we performed metabolomics studies to assess the alternations of both plasma and myocardial sphingolipid profiles during the reparative phase post-MI. A total number of 193 sphingolipid metabolites were detected. Myocardial sphingolipids but not plasma sphingolipids showed marked change after MI injury. Ceramide-1-phosphates, which were accumulated after MI, contributed highly to the difference in sphingolipid profiles between groups. Consistently, the expression of ceramide kinase, which phosphorylates ceramides to generate ceramide-1-phosphates, was upregulated in heart tissue after MI injury. Our findings revealed the altering sphingolipid metabolism during the reparative phase post-MI and highlighted the potential role of ceramide kinase/ceramide-1-phosphate in ischemic heart disease.
Molecular Analysis of the E2F/DP Gene Family of Daucus carota and Involvement of the DcE2F1 Factor in Cell Proliferation
Authors: Perrotta Lara , Giordo Roberta , Francis Dennis , Rogers Hilary J. , Albani Diego
Published: March 2021

E2F transcription factors are key components of the RB/E2F pathway that, through the action of cyclin-dependent kinases, regulates cell cycle progression in both plants and animals. Moreover, plant and animal E2Fs have also been shown to regulate other cellular functions in addition to cell proliferation. Based on structural and functional features, they can be divided into different classes that have been shown to act as activators or repressors of E2F-dependent genes. Among the first plant E2F factors to be reported, we previously described DcE2F1, an activating E2F which is expressed in cycling carrot (Daucus carota) cells. In this study, we describe the identification of the additional members of the E2F/DP family of D. carota, which includes four typical E2Fs, three atypical E2F/DEL genes, and three related DP genes. Expression analyses of the carrot E2F and DP genes reveal distinctive patterns and suggest that the functions of some of them are not necessarily linked to cell proliferation. DcE2F1 was previously shown to transactivate an E2F-responsive promoter in transient assays but the functional role of this protein in planta was not defined. Sequence comparisons indicate that DcE2F1 could be an ortholog of the AtE2FA factor of Arabidopsis thaliana. Moreover, ectopic expression of the DcE2F1 cDNA in transgenic Arabidopsis plants is able to upregulate AtE2FB and promotes cell proliferation, giving rise to polycotyly with low frequency, effects that are highly similar to those observed when over-expressing AtE2FA. These results indicate that DcE2F1 is involved in the control of cell proliferation and plays important roles in the regulation of embryo and plant development.
Breathing Biofeedback for Police Officers in a Stressful Virtual Environment: Challenges and Opportunities
Authors: Brammer Jan C. , van Peer Jacobien M. , Michela Abele , van Rooij Marieke M. J. W. , Oostenveld Robert , Klumpers Floris , Dorrestijn Wendy , Granic Isabela , Roelofs Karin
Published: March 2021

As part of the Dutch national science program “Professional Games for Professional Skills” we developed a stress-exposure biofeedback training in virtual reality (VR) for the Dutch police. We aim to reduce the acute negative impact of stress on performance, as well as long-term consequences for mental health by facilitating physiological stress regulation during a demanding decision task. Conventional biofeedback applications mainly train physiological regulation at rest. This might limit the transfer of the regulation skills to stressful situations. In contrast, we provide the user with the opportunity to practice breathing regulation while they carry out a complex task in VR. This setting poses challenges from a technical – (real-time processing of noisy biosignals) as well as from a user-experience perspective (multi-tasking). We illustrate how we approach these challenges in our training and hope to contribute a useful reference for researchers and developers in academia or industry who are interested in using biosignals to control elements in a dynamic virtual environment.
What Stimuli Are Necessary for Anchoring Effects to Occur?
Authors: Onuki Yutaro , Honda Hidehito , Ueda Kazuhiro
Published: March 2021

The anchoring effect is a form of cognitive bias in which exposure to some piece of information affects its subsequent numerical estimation. Previous studies have discussed which stimuli, such as numbers or semantic priming stimuli, are most likely to induce anchoring effects. However, it has not been determined whether anchoring effects will occur when a number is presented alone or when the semantic priming stimuli have an equivalent dimension between a target and the stimuli without a number. We conducted five experimental studies (N= 493) using stimuli to induce anchoring effects. We found that anchoring effects did not occur when a number was presented alone or when phrases to induce semantic priming were used without presenting a number. These results indicate that both numerical and semantic priming stimuli must be presented for anchoring effects to occur. Our findings represent a substantial contribution to the literature on anchoring effects by offering insights into how these effects are generated.
The Digital Stressors Scale: Development and Validation of a New Survey Instrument to Measure Digital Stress Perceptions in the Workplace Context
Authors: Fischer Thomas , Reuter Martin , Riedl René
Published: March 2021

This article reports on the development of an instrument to measure the perceived stress that results from the use and ubiquity of digital technology in the workplace. Based upon a contemporary understanding of stress and a set of stressors that is a substantial update to existing scales, the Digital Stressors Scale (DSS) advances the measurement of digital stress. Initially, 138 items were constructed for the instrument and grouped into a set of 15 digital stressors. Based on a sample ofN= 1,998 online questionnaires completed by individuals representative of the US employed population, the scale was refined using exploratory factor analyses (EFA) and PLS-SEM. The resulting and final scale consists of ten stressor categories reflective of one higher-order construct and a total of 50 items. Through a nomological network that includes important outcome variables of digital stress (emotional exhaustion, innovation climate, job satisfaction, user satisfaction) it was then demonstrated that the DSS provides substantial explanatory power, particularly related to emotional exhaustion and user satisfaction. Thus, the DSS constitutes a state-of-the-art self-report instrument to measure the extent of distress appraisal related to digital technologies in the workplace and helps to explain further how and why information and communication technologies can lead to adverse outcomes in individuals, thereby providing the starting point for job related organizational interventions.
Art Therapy Alleviates the Levels of Depression and Blood Glucose in Diabetic Patients: A Systematic Review and Meta-Analysis
Authors: Yang Qingqi , Shao Qunhui , Xu Qiang , Shi Hui , Li Lin
Published: March 2021

Objective: To systematically analyze the effects of art therapy on the levels of depression, anxiety, blood glucose, and glycated hemoglobin in diabetic patients.

Methods: We searched Cochrane Library, PubMed, Embase, and ClinicalTrials.gov databases from inception to January 24, 2021. The language of publication was limited to English. Randomized controlled trials (RCTs) that used art therapy to improve mental disorders in diabetic patients were involved. After selection of eligible studies, data were extracted, including the first author's full-name, year of publication, the first author's country of residence, number of intervention and control groups, the mean age of participants, method of intervention, duration of follow-up, and outcome measures. Assessment of quality of the included studies and data extraction were independently carried out by two researchers. RevMan 5.3 software was used to perform statistical analysis.

Results: A total of 396 samples from five studies were included, and the eligible studies were RCTs with a parallel design. Methods of art therapy included music therapy and painting therapy. The results showed that compared with the control group, art therapy could positively affect the levels of depression [standardized mean difference (SMD), −1.36; 95% confidence interval (CI), (−1.63, −1.09); P < 0.00001] and blood glucose in diabetic patients [mean difference (MD), −0.90; 95% CI, (−1.03, −0.77); P < 0.0001], while it had no influence on the levels of anxiety [SMD, −0.31; 95% CI, (−0.93, 0.31); P = 0.32] and glycated hemoglobin [MD, 0.22; 95% CI, (−0.02, 0.46); P = 0.07].

Conclusion: Art therapy may have significant effects on the levels of depression and blood glucose for diabetic patients.
Prospects for the Use of Cannabinoids in Psychiatric Disorders
Authors: Graczyk Michał , Łukowicz Małgorzata , Dzierzanowski Tomasz
Published: March 2021

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.
Effects of Pandemic Outbreak on Economies: Evidence From Business History Context
Authors: Shang Yunfeng , Li Haiwei , Zhang Ren
Published: March 2021

The coronavirus pandemic has highlighted the capitalist dysfunction showing that considering profit over people can be deadly. The study reveals the LME economies were more responsive toward the impact of the disease outbreaks as compared to the CME economies wherein the impact of the disease was moderated by the government involvement. This allows us to draw that the impact of the disease outbreaks can be moderated by increasing the involvement of the government authorities.