bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-mediated YTHDF2 expression and activation of the mTOR/AKT axis in lung squamous cell carcinoma
Authors: Xu Peng , Hu Kang , Sun Zhi-Gang , Zhang Nan 
Published: August 2021

Abstract
Background

N6-methyladenosine (m6A) is a dynamic and reversible internal RNA structure of eukaryotic mRNA. YTH domain family 2 (YTHDF2), an m6A-specific reader YTH domain family, plays fundamental roles in several types of cancer. However, the function of YTHDF2 in lung squamous cell carcinoma (LUSC) remains elusive.
Methods

Functionally, NCI-H226 and SK-MES-1 cells were exposed to hypoxia to detect the protein levels of hypoxia-inducible factor-1α (HIF-1α), endogenous YTHDF2, and phospho-AKT (Ser473) analyzed by western blotting and then the association of these proteins with LUSC was analyzed with a bioinformatics database. Next, we established stable YTHDF2 upregulation models in NCI-H226 and SK-MES-1 cells to explore the function of YTHDF2 in LUSC cells by performing in vitro and in vivo assays. Finally, we affirmed that YTHDF2 overexpression was involved in activating the mTOR/AKT signaling and inducing the EMT process in LUSC using western blotting. Clinically, immunohistochemical staining revealed the relationship between YTHDF2 expression levels and the clinicopathological characteristics of lung squamous cell carcinoma patients.
Results

The results showed that hypoxia-mediated YTHDF2, a tumor promoter, promoted cell proliferation and invasion by activating the mTOR/AKT axis and inducing the EMT process in LUSC. Moreover, YTHDF2 was closely associated with pN (pN– 37.0%, pN + 73.9%; P = 0.002) and pTNM stage (pI 50.0%, PII 43.3%, pIIIa 80.6%; P = 0.007), ultimately resulting in poor survival for LUSC patients.
Conclusion

In brief, the results highlight the critical role of YTHDF2 in both hypoxia exposure and the pathogenesis of LUSC.
Performance Analysis and Optimization of RIS-Assisted Networks in Nakagami-m Environment
Authors: Samuh Monjed H. ,   Anas Salhab1, El-Malek Ahmed H. Abd 
Published: August 2021

Abstract

This work studies and optimizes the performance of reconfigurable intelligent surface (RIS)-aided networks in Nakagami- m fading environment. First, accurate closed-form approximations for the channel distributions are derived. Then, closed-form formulas for the system outage probability, average symbol error probability (ASEP), and the channel capacity are obtained. Furthermore, we provide three different optimization approaches for finding the optimum number of reflecting elements to achieve a target outage probability. At the high signal-to-noise ratio (SNR) regime, a closed-form expression for the asymptotic outage probability is obtained to give more insights into the system performance. Results show that the considered system can achieve a diversity order of, where a is a function of the Nakagami- m fading parameter m and the number of reflecting elements N . Moreover, findings show that m is more influential on the diversity order than N . Finally, the achieved expressions are applicable to non-integer values of m and any number of meta-surface elements N .
LncRNA RHPN1-AS1 Inhibition Induces Autophagy and Apoptosis in Prostate Cancer Cells via the miR-7-5p/EGFR/PI3K/AKT/mTOR Signaling Pathway
Authors: Ma Xiu-Long , Ren Hong-Tao , Zhang Yang , Wang Bao-Feng , Ma Hong-Bing 
Published: August 2021

Abstract
lncRNA RHPN1-AS1 (RHPN1-AS1) has been confirmed to promote tumor progression in multiple cancers and is upregulated in prostate cancer (PCa), but whether it has an effect on PCa progression remains unclear. In this study, we found that PCa patients with high RHPN1-AS1 expression had a shorter survival time, and RHPN1-AS1 was significantly upregulated in PCa tissues and cells. Based on informatics analysis we predicted that miR-7-5p binds to 3’UTR of RHPN1-AS1 and epidermal growth factor receptor (EGFR) and verified it by luciferase reporter gene assay. Subsequently, we transfected PCa cells with RHPN1-AS1 overexpression vector (RHPN1-AS1), knockdown plasmids (sh-RHPN1-AS1) and/or miR-7-5p mimics or inhibitor and/or overexpression vector (EGFR) or small interfering RNA of EGFR (si-EGFR) or its control, and found that overexpression of RHPN1-AS1 inhibited miR-7-5p expression and promoted EGFR expression, silencing RHPN1-AS1 inhibited proliferation and invasion and induced G2/M arrest, apoptosis and autophagy in PCa cells. 3MA (an inhibitor of autophagy)-mediated autophagy inhibition attenuated RHPN1-AS1 inhibition-induced apoptosis. Overexpression miR-7-5p or silencing EGFR promoted LC3-I to LC3-II conversion, enhanced autophagy activity, induced cleaved-caspase-3 expression and apoptosis in PCa cells. Furthermore, we found that overexpression of RHPN1-AS1 promoted phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR, inhibited LC3-I to LC3-II conversion and reduced apoptosis in PCa cells, while GSK2126458 (an inhibitor of PI3K) reversed the effect of RHPN1-AS1 on PCa cells. In summary, RHPN1-AS1 acted as a ceRNA of miR-7-5p to upregulate EGFR expression, silencing RHPN1-AS1 suppressed PCa tumor progression by inducing autophagy and apoptosis in PCa cells through the miR-7-5p/EGFR/PI3K/AKT/mTOR pathway.
Symmetry Breaking of PT-symmetric Solitons in Self-defocusing Saturable Nonlinear Schrödinger Equation
Authors: WenBo Bo , Dai Chao-Qing , Wang Yue-Yue , Li Peng-Fei 
Published: August 2021

Abstract
The symmetry breaking phenomenon of the parity-time (PT) symmetric solitons in self-defocusing saturable nonlinear Schrödinger equation is studied. As the soliton power increases, branches of asymmetric solitons are separated from antisymmetric solitons, and they coexist with both symmetric and antisymmetric solitons. The anti-symmetric solitons require different power thresholds when they are under different saturable nonlinear strength. The stronger the saturable nonlinearity is, the larger the power threshold is. The saturable nonlinear strength has obvious modulation effect on the symmetry breaking of antisymmetric solitons and the bifurcation of the power curve. However, when the modulation strength of PT- symmetric potential increases, the effect of this modulation effect weakens. The antisymmetric solitons are only stable in the low power region, and the stability of symmetric and asymmetric solitons is less affected by the soliton power. The increase of the saturable nonlinear strength leads to the increase of the critical power of the symmetry breaking. When a beam propagates in a PT-symmetric optical waveguide, the symmetry breaking of antisymmetric solitons can be controlled by changing the saturable nonlinear strength.
miR-200a-3p Facilitates Bladder Cancer Cell Proliferation by Targeting A20
Authors: wan pei , Chen Zhilin , Huang Minzhi , Jiang Huiming , Wu Huajun , Zhong Kaihua , Ding Guodong , Wang Bing 
Published: August 2021

Abstract
BackgroundMicroRNAs (miRs) are endogenous, single-stranded, non-coding RNAs that are involved in various physiological processes, development and the progression of various types of cancer. The role of miR-200a-3p in various types of cancer has been previously reported. The present study aimed to investigate the expression levels of miR-200a-3p in human bladder cancer, as well as its potential role in disease pathogenesis.MethodsIn vitro: Agilent miRNA microarray and QPCR analysis of miR-200a-3p expression in bladder cancer. Gene overexpression and interference technology analysis of the effects of miR-200a-3p and de-ubiquituination enzyme TNFα induced protein 3 (A20) on the function of bladder cancer cells; dual luciferase technology for promoter efficiency analysis; Animal experiments: Nude mice are used for tumor formation experiments, and the effects of genes on tumors are directly analyzed on animals;ResultsCompared with adjacent non-tumor tissues, miR-200a-3p expression levels were significantly upregulated in bladder cancer tissues. Moreover, increased miR-200a-3p expression was significantly associated with distant metastasis and advanced stage. In addition, compared with the miR-Negative control (NC) group, miR-200a-3p overexpression promoted bladder cancer cell proliferation, migration, invasion, cell cycle and release of inflammatory cytokines, but inhibited cell apoptosis. Mechanistically, de-ubiquituination enzyme TNFα induced protein 3 (A20) was identified as a target gene of miR-200a-3p in bladder cancer cell lines. An inverse association between miR-200a-3p expression and A20 expression in bladder cancer tissues and cell lines was also identified. A20 overexpression in miR-200a-3p-overexpression bladder cancer cells attenuated miR-200a-3p overexpression-mediated effects on cell proliferation, migration, apoptosis and cytokine production. Moreover, compared with the miR-NC group, miR-200a-3p overexpression significantly promoted tumor growth in vivo, and A20 overexpression blocked the promoting effect of miR-200a-3p on bladder cancer. ConclusionsThe results of the present study indicated that miR-200a-3p might serve as an oncogene in human bladder cancer by targeting a novel gene A20; therefore, miR-200a-3p and A20 might serve as novel therapeutic targets for bladder cancer.
Dichotomous role of Shp2 for naïve and primed pluripotency maintenance in embryonic stem cells
Authors: Kim Seong Min , Kwon Eun-Ji , Kim Yun-Jeong , Go Young-Hyun , Oh Ji-Young , Park Seokwoo , Do Jeong-Tae , Kim Keuntae , Cha Hyuk-Jin 
Published: August 2021

Abstract
The requirement of the Mek1 inhibitor (iMek1) during naïve pluripotency maintenance results from the activation of the Mek1-Erk1/2 (Mek/Erk) signaling pathway upon leukemia inhibitory factor (LIF) stimulation. Through a meta-analysis of previous genome-wide screening for negative regulators of naïve pluripotency, Ptpn11 (encoding the Shp2 protein, which serves both as a tyrosine phosphatase and putative adapter), was predicted as one of the key factors for the negative modulation of naïve pluripotency through LIF-dependent Jak/Stat3 signaling. Using an isogenic pair of naïve and primed mouse embryonic stem cells (mESCs), we demonstrated the differential role of Shp2 in naïve and primed pluripotency. Loss of Shp2 increased naive pluripotency by promoting Jak/Stat3 signaling and disturbed in vivo differentiation potential. In sharp contrast, Shp2 depletion significantly impeded the self-renewal of ESCs under primed culture conditions, which was concurrent with a reduction in Mek/Erk signaling. Similarly, upon treatment with an allosteric Shp2 inhibitor (iShp2), the cells sustained Stat3 phosphorylation and decoupled Mek/Erk signaling, thus replacing the use of iMek1 not only for maintenance but also for the establishment of naïve ESCs through reprogramming. Taken together, our findings highlight the differential roles of Shp2 in naïve and primed pluripotency and propose the usage of iShp2 instead of iMek1 for the efficient maintenance and establishment of naïve pluripotency.
In-hospital Mortality in SARS-CoV-2 stratified by Gender: A Retrospective Study
Authors: Jarallah Mohammed Al , Rajan Rajesh , Dashti Raja , Alsabar Ahmad R , Pan Jiazhu , Kobalava Zhanna D , Abdelnaby Hassan , Aboelhassan Wael , Almutairi Farah , Alotaibi Naser , Saleh Mohammad Al , AlNasrallah Noor , Al-Bader Bader , Malhas Haya , Ramadhan Maryam , Hamza Mahdy , Brady Peter A , Al-Zakwani Ibrahim , Abdullah Mohammed , Alroomi Moudhi 
Published: August 2021

Abstract
Background: The aim of this study was to determine in-hospital mortality in patients presenting with acute respiratory syndrome corona virus 2 (SARS-CoV-2) and to evaluate for any differences in outcome according to gender. Methods: Patients with SRS-CoV-2 infection were recruited into this retrospective cohort study between February 26 and September 8, 2020 and strаtified ассоrding tо the gender. Results: In tоtаl оf 3360 раtients (meаn аge 44 ± 17 years) were included, of whom 2221 (66%) were mаle. The average length of hospitalization was 13 days (range: 2–31 days). During hospitalization and follow-up 176 patients (5.24%) died. Mortality rates were significantly different according to gender (p=<0.001). Specifically, male gender was associated with significantly greater mortality when compared to female gender with results significant at an alpha of 0.05, LL = 28.67, df = 1, p = 0.001, suggesting that gender could reliably determine mortality rates. The coefficient for the males was significant, B = 1.02, SE = 0.21, HR = 2.78, p< .001, indicating that an observation in the male category will have a hazard 2.78 times greater than that in the female category. Multivariate logistic regression confirmed male patients admitted with SARS-CoV-2had higher сumulаtive аll-саuse in-hоsрitаl mоrtаlity (6.8% vs. 2.3%; аdjusted оdds rаtiо (аОR), 2.80; 95% (СI): [1.61 - 5.03]; р < 0.001). Conclusions: Male gender was an independent predictor of in-hospital death in this study. The mortality rate among male SARS-CoV-2 patients was 2.8 times higher when compared with females.
Association between Serum Zinc and hs-CRP Concentrations in Different Metabolic Syndrome Phenotypes
Authors: Darroudi Susan , Tayefi Batool , Esmaily Habibollah , Sadabadi Fatemeh , Haghighi Hamideh Moalemzadeh , Mohammadpour Amir Hooshang , Ferns Gordon A , Mouhebati Mohsen , Ghayour-Mobarhan Majid 
Published: August 2021

Abstract
Background: Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease and all-cause mortality. Zinc (Zn) is an essential trace element for the synthesis, storage, and release of insulin. The relationship between serum Zn and MetS is controversial. In this study we have evaluated whether serum Zn levels are associated with hsCRP level according to MetS phenotypes. Method: A total of 9493 individuals (3768 men and 5635 women) were recruited as part of the Mashhad Stroke and Heart Association Disorder (MASHAD) study. We measured the concentration of serum Zn by flame atomic absorption (Varian AA240FS) and we divided the subjects into quartile of serum Zn. We used SPSS version 18 statistical analyses for all. GraphPad Prism 6 for figures was used.Results: In this study there were significant differences between quartiles of Zn according to sex. The results showed that the level of serum hs-CRP were higher in subjects with metabolic syndrome who also had a serum Zn >95 µg/dl. In subjects with serum Zn <70 µg/dl, an increase in serum hs-CRP was associated with an increased risk of MetS by 2.2%, 1.022(CI: 1.01-1.034). Moreover, among subjects in the first, second and third quartiles of serum Zn, some phenotypes of metabolic syndrome (WHB, WHT, WTG, WTB, WHBG, WHTG, and WTBG) were associated with a risk of increasing hs-CRP level (p< 0.05). Conclusion: Serum hs-CRP concentrations were related to MetS phenotypes. This relationship was modified by serum Zn level. According to the number of MetS components serum Zn levels decreased as the number of MetS component increased, and low serum zinc levels (Q1) showed an overall greater prevalence of MetS.
Risk Factors Affect Accurate Prognosis in ASXL1-mutated Acute Myeloid Leukemia
Authors: Fan Yi , Liao Linxiao , Liu Yajun , Wu Zhenzhen , Wang Chong , Jiang Zhongxing , Wang Shujuan , Liu Yanfang 
Published: August 2021

Abstract
Background: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML.Methods: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Results: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥60 years, WBC count ≥50×109/L、FLT3-ITD mutations、RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to be double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P=0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P=0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients.Conclusion: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.
A Novel Prognostic Model for Clear Cell Renal Cell Carcinoma with Differentially Expressed Immune-related lncRNA Pairs Based on the Cancer Genome Atlas
Authors: Zhao Chen , Xiong Kewei , Liu Fengming , Li Xiangpan 
Published: August 2021

Abstract
Objective: To construct a novel prognostic model of immune-related lncRNA (irlncRNA) pairs in clear cell renal cell carcinoma (ccRCC). Methods: RNA-seq and clinical data were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed irlncRNAs (DEirlncRNAs) were obtained by co-expression strategy with immune genes. A 0-1 matrix was constructed according to DEirlncRNAs relevant expression levels. Univariate cox regression was used to select potential target pairs. Lasso regression with cross validation and multivariate cox regression were carried out to extract the final biomarker pairs for risk score calculation. Through calculating the optimal cutoff of AUCs, patients were divided into high and low risk group. Model validation was conducted by independent prognostic analysis, survival analysis, tumor-infiltrating and chemosensitivity analysis. Results: A total of 42 DEirlncRNAs were identified and 12 target pairs were included to construct the final model. The risk score were both significantly different according to univariate (p<0.001, HR=1.391, 95%CI [1.313–1.475]) and multivariate cox regression (p<0.001, HR=1.3104, 95%CI [1.227-1.399]). The AUC reached 0.765 at 1-year, 0.724 at 3-year and 0.785 at 5-year. Patients in the high-risk group had significantly poor survival, higher level of CD8+T infiltration, lower drug sensitivity of sunitinib and temsirolimus but higher sensitivity of lapatinib and pazopanib.Conclusion: The novel prognostic model constructed by paring irlncRNAs showed an effective clinical prediction in ccRCC patients.
Sequence-Order Frequency Matrix - Sampling and Machine learning with Smith-Waterman (SOFM-SMSW) for Protein Remote Homology Detection
Authors: Nakshathram Sajithra , Duraisamy Ramyachitra , Pandurangan Manikandan 
Published: August 2021

Abstract

Background: Protein Remote Homology Detection (PRHD) is used to find the homologous proteins which are similar in function and structure but sharing low sequence identity. In general, the Sequence-Order Frequency Matrix (SOFM) was used for protein remote homology detection. In the SOFM Top-n-gram (SOFM-Top) algorithm, the probability of substrings was calculated based on the highest probability value of substrings. Moreover, SOFM-Smith Waterman (SOFM-SW) algorithm combines the SOFM with local alignment for protein remote homology detection. However, the computation complexity of SOFM based PRHD is high since it processes all protein sequences in SOFM.Objective: Sequence-Order Frequency Matrix - Sampling and Machine learning with Smith-Waterman (SOFM-SMSW) algorithm is proposed for predicting the protein remote homology. The SOFM-SMSW algorithm used the PVS method to select the optimum target sequences based on the uniform distribution measure.Method: This research work considers the most important sequences for PRHD by introducing Proportional Volume Sampling (PVS). After sampling the protein sequences, a feature vector is constructed and labeling is performed based on the concatenation between two protein sequences. Then, a substitution score which represents the structural alignment is learned using k-Nearest Neighbor (k-NN). Based on the learned substitution score and alignment score, the protein homology is detected using Smith-Waterman algorithm and Support Vector Machine (SVM). By selecting the most important sequences, the accuracy of PRHD is improved and the computational complexity for PRHD is reduced by using structural alignment along with the local alignment.Results: The performance of the proposed SOFM-SMSW algorithm is tested with SCOP database and it has been compared with various existing algorithms such as SVM Top-N-gram, SVM pairwise, GPkernal, Long Short-Term Memory (LSTM), SOFM Top-N-gram and SOFM-SW. Conclusion: The experimental results illustrate that the proposed SOFM-SMSW algorithm has better accuracy, precision, recall, ROC and ROC 50 for PRHD than the other existing algorithms.
The Consequences of COVID-19-Related Anxiety on Children’s Health: A Cross-Sectional Study
Authors: Nejad Farhad Nosrati , Adelinejad Fateme , ziapour arash , Golzarpour Majid , Azizi Seyyed Amar , Mehedi Nafiul , Khosravi Masoume Mousavi 
Published: August 2021

Abstract
Background: The emergence of the COVID-19 pandemic has triggered a worldwide health catastrophe. Anxiety caused by COVID-19 has had a negative impact on people's physical and mental health. According to the findings of the research, significant emphasis has been devoted to measures linked to the identification of persons with coronavirus infection, but the identification of the affected individuals' mental health issues has been overlooked. Despite study data indicating an increase in fear and anxiety in patients with coronavirus and others, little research on COVID-19-related cardiac disease has been conducted so far.Methods: This cross-sectional study used a survey method with a chosen self-reported questionnaire for data collection from Mashhad residents. The research sample included 435 households with children aged 5 to 18. The data was analyzed using SPSS software version 25 and comprised two measures, (1) the Coronary Disease Anxiety Scale (CDAS) and (2) the Child Health Questionnaire (CHQ) developed by Landgraf and Abets. The findings indicated that COVID-19-related anxiety has a detrimental influence on children's health. According to the data, 19% of the children’s variance showed negative effects on health ( β= -0.625, Sig = 0.001, Adj.R2 = 0.193).Results: The findings revealed a significant difference in children's health mean scores related to forms of insurance coverage, parents' education level, housing status, and COVID-19-associated anxiety. Children's anxiety levels have increased, causing harm to their health and a reduction in their health status.Conclusion: The outcomes of the study will help health professionals and governments establish appropriate protective measures to address this worldwide health problem.