bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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

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

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.
Beta-Diketone–Cobalt Complexes Sensitize Glioma Stem Cells to Temozolomide Partly Through the ERK-MGMT Pathway
Authors: Zhang Kaizhi , Lang Fang , Mang Jing
Published: August 2021

Glioblastoma multiforme is characterized by high invasiveness, multidrug resistance, and inevitable recurrence, and current standard treatment regimens are not curative. Even if most glioma cells are eliminated by chemotherapy and radiotherapy, glioma stem cells can survive and differentiate into new tumor cells, thereby triggering tumor recurrence and drug resistance. Therefore, inhibiting tumor invasiveness, reversing drug resistance, and effectively ablating glioma stem cells are critical for improving the prognosis of glioblastoma multiforme. Previous studies reported that the combination of β-diketone–cobalt complexes (CoAc2) and temozolomide (TMZ) has synergistic inhibitory effects on glioma cells. Therefore, we compared cell proliferation, colony-forming capacity, cell migration, and invasion of TMZ-resistant glioma cells and corresponding glioma stem cells after treatment with CoAc2 and/or TMZ. We also explored the underlying mechanism by which CoAc2 sensitizes cells to TMZ through transcriptome sequencing and related signal pathway blockade. We found that CoAc2 significantly increased the inhibitory effect of TMZ on the proliferation, colony formation, migration, invasion, and survival of drug-resistant stem cells. By downregulating ERK pathway activity, CoAc2 inhibited the expression of O6-methylguanine-DNA methyltransferase and eventually sensitized drug-resistant glioma cells to TMZ. In conclusion, the combined use of CoAc2 and TMZ can reverse TMZ resistance and significantly enhance its inhibitory effect on the malignant phenotype of glioma cells and glioma stem cells.
Construction and Validation of a Prognostic Model Based on 11 Lymph Node Metastasis Related Genes for Overall Survival in Endometrial Cancer
Authors: Wu Hong , Feng haiqin , Miao Xiaoli , Ma jiancai , Liu Cairu , Zhang Lina , Yang Liping
Published: August 2021

Background: Endometrial cancer (EC) is one of the most common malignant tumor in the female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic model and effective biomarkers for early diagnosis is important to reduce the mortality rate. Methods: We downloaded the RNA-sequencing data and clinical information from the TCGA database. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed genes (DEGs). A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related LNM related genes signature. Subsequently, a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic significance of the risk model and key gene was validated in vitro. Results: In total, 89 LRGs were identified. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan–Meier curve indicated that patients in the low-risk group had considerably better OS (P = 3.583e−08). The area under the curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival verification performed in three subgroups from the nomogram demonstrated the validity of the model. The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively. Conclusions: Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients. By detecting the mutation of the risk signature, clinicians can accurately treat patients with targeted therapy, thereby improving their survival rate.
ERAS Improves Postoperative Recovery in Children
Authors: Wu Tingmei , Li Haiwen , Zhou Huixia , Hao Xuemei , Wang Xiaojun , Lu Yan , Ge Wenchao , Li Xiangpeng , Li Dongming , Li Wei , Ma Lifei , Tao Tian , Zhou Xiaoguang , Ma Yaqun , Guo Hang
Published: August 2021

Objective: Enhanced recovery after surgery (ERAS) protocols are established in adults but not fully evaluated in children. This study investigated whether an ERAS protocol improved recovery and influenced postoperative inflammatory cytokine levels in children undergoing surgery for hydronephrosis. Methods: This randomized controlled study included patients who underwent robot-assisted laparoscopic surgery for hydronephrosis at Bayi Children's Hospital (Beijing, China) between October 2018 and September 2019. Patients were randomized to an ERAS group (perioperative ERAS protocol) or control group (standard perioperative management). Outcomes related to postoperative recovery and inflammatory cytokine levels were evaluated. Results: The final analysis included 18 patients in each group. Five patients (27.78%) in each group experienced postoperative complications (abdominal pain, nausea and vomiting, subcutaneous emphysema or fever). The ERAS group had a shorter time to first postoperative flatus than the control group (25 vs. 49 hours; P =0.009), although the time for abdominal drainage flow to reach ≤20 mL/day, time to urinary catheter removal and length of hospital stay did not differ significantly between groups. Preoperative plasma cytokine levels were comparable between groups. Compared with the control group, the ERAS group had a higher IL-6 level on postoperative day 2 ( P <0.05) and a lower concentration of IL-1β on postoperative days 1 and 2 ( P <0.05). Postoperative levels of CRP, TNFα and IL-10 did not differ significantly between groups. Conclusions: ERAS may accelerate postoperative recovery and modulate the postoperative inflammatory response in pediatric patients undergoing robot-assisted laparoscopic pyeloplasty for hydronephrosis.
The Influece of The Laser on Acoustic Phonon Amplification in Parabolic Potential Well
Authors: Tien Dung Nguyen , Thanh Thuy Do , Canh Trung Le
Published: August 2021

We present a theoretical study of the kinetic equation for acoustic phonons in semiconductor quantum well with parabolic potential well under intense laser field. Using this method, we find the expression for the phonon rate coefficient for the general case, the condition of the acoustic phonon rate and the influence of the parameters of laser on this rate coefficient. We numerically calculate the rate of acoustic phonon excitation by the absorption of laser field energy at different temperature.
Circular RNA Hsa_Circ_0002483 Promotes Growth and Invasion of Lung Adenocarcinoma by Sponging miR-125a-3p
Authors: Wan Jun , Ding Guanggui , Zhou Min , Ling Xiean , Rao ZhanPeng
Published: August 2021

Background: Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. Methods: The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as MTT, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis.Results: We found that circ_0002483 was upregulated in LUAC tissue samples and associated with TNM stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively modulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. Conclusions: Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.
Unidentified Persons With Disabilities in India- A Study Based on 76th Round of NSS (2018-19) Data
Authors: Mishra Radhe Shyam , Mohanty Sanjay K , Chanda Srei
Published: August 2021

Background: Identification of the disabled and providing them a disability certificate is the first step for provisioning educational, employment, and other social benefits in a welfare state. Deprivation from disability certificate deprives persons with disability (PwDs) from government policy and programme. Though studies examined the extent, variation, and pattern of disability, no attempt has been made in understanding the extent and variation of unidentified PwDs in India. The study aims to examine the variation in unidentified PwDs by type of disability, state and socio-economic correlates.Data and methods: The unit data from the 76th round (schedule 26) of Nation Sample Survey, 2018 is used in analyses. A total of 1,06,894 disabled across seven types of disabilities; any disability, locomotor, visual, hearing, speech, mental retardation, mental illness, and other disability have been analysed. Descriptive statistics and logistic regression analyses are used.Results: 7 in 10 disabled person in India don’t have a disability certificate. The percentage share of PwDs with a disability certificate varies 12% among those with hearing disability to 47% with mental retardation. Unadjusted odds ratio shows that person with hearing disability (OR=0.30 CI 0.303-0.304) are less likely to hold a disability certificate compare to locomotor disability followed by mental illness (OR=0.52 CI 0.519 0520), and visual disability (OR= 0.74 CI 0.736 0.738). Person with mental retardation are two times more likely to hold the disability certificate (OR 2.05 CI 2.046 2.047) than the visual disabled. States variation in percent share of disability certificate is found to be large. The result depicts that there remains a high variation in the access of disability certificates across states in India. Conclusion: A nationwide drive to include the unidentified disabled is recommended with documentation and inclusion in the administrative processes.
Comprehensive Analysis of Prognostic Significance and Immune Infiltration for FAM83 Family in Cervical Cancer
Authors: Qi Yue , Wang Yue
Published: August 2021

Background: This study aimed to explore the expression of Family with sequence similarity 83 (FAM83) members in cervical cancer, its prognostic value, related signaling pathways, regulatory mechanisms, and immune infiltration. It’s of great value to explore the potential role of FAM83 family in cervical cancer and provide a new scientific basis for targeted therapy.Methods: The expression, gene mutations and prognostic value of FAM83 family members in cervical cancer were analyzed by various bioinformatics tools and databases. We further explored the interaction regulation network and immune infiltration between FAM83 family members and their closely related genes through a series of databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted.Results: This study showed that the expression levels of FAM83A/B/C/D/E/F/G/H gene were upregulated in cervical cancer, the expression of FAM83B/C/D/E/F/G/H were related to tumor stages of cervical cancer, and the promoter methylation of FAM83A/D/E/F/G genes in cervical cancer were lower than those in normal tissues. What’s more, high expression of FAM83A, FAM83B, and FAM83H mRNA was associated with shortened overall survival. GO results showed that FAM83A, FAM83B, and FAM83H and their closely related genes can play an important role in cell-cell junction, calcium-dependent protein binding, regulation of peptidase activity, inflammatory response. KEGG analysis results showed that FAM83A, FAM83B, and FAM83H and their closely related genes were significantly enriched in cancer pathways, estrogen signaling pathway, MAPK signaling pathway. Furthermore, FAM83A, FAM83B, and FAM83H are all closely related to lymphocytes (Tcm_CD4, Tcm_CD8, and neutrophils) and immunomodulators (TGFBR1, TGFB1, and TNFSF9).Conclusions: With multiple databases, we found that the high expression of FAM83A, FAM83B, and FAM83H were associated with the shortened survival time and poor prognosis in patients with cervical cancer, and also closely correlated with lymphocytes and immune infiltration, suggesting that FAM83A, FAM83B, and FAM83H played an important role in the occurrence, development, malignant biological behavior, and immune infilatration of cervical cancer, which provides an important theoretical basis for early diagnosis and targeted therapy for cervical cancer.
Red Blood Cells Pathology in Patients with Coronavirus Disease 2019 (COVID-19)
Authors: Karalyan Zaven , Hakobyan Lina , Abroyan Liana , Avetisyan Aida , Avagyan Hranush , Hakobyan Sona , Bayramyan Nane , Voskanyan Henrik , Niazyan Lyudmila , Davidyants Mher , Sargsyan Knarik , Ghalechyan Tehmine , Semerjyan Anna , Karalova Elena
Published: August 2021

Introduction The severe acute respiratory syndrome-related coronavirus 2 (SARS-Cov-2) infection may cause hematological disorders. This pathology has been studied to a lesser extent compared to the respiratory system pathology. The main purpose of this article is to investigate the general pathology of red blood cells in coronavirus infection.MethodsIn current study 74 patients suffering from SARS-Cov-2 treated at the National Center of Infectious Diseases, Ministry of Health Armenia were included. Investigated patients were classified as: 1. Regular group (fever, respiratory symptoms and radiographic evidence of pneumonia). 2. Severe group – patients manifesting shortness of breath (over 30 breaths per minute); peripheral blood oxygen saturation below 92% in rest; pneumonia affecting over 50% of tissue; and/or respiratory failure and indicated mechanical ventilation support and/or organ failure requiring intensive care unit treatment. 3. Low saturation group with peripheral blood oxygen saturation below 85% in rest. 4. Erythroblastosis group with count of erythroblasts over 0.5% among total of nucleated blood cells. Clinical laboratory investigation included all main routine studies.Microspectrophotometry was performed on SMP-05 Opton scanning microspectrophotometer to measure the spectra of hemoglobin (Hb) in unstained erythrocytes. ResultsErythroblasts were common (present in about 30%) finding among SARS-Cov-2 patients but predominating mainly in the severe group. Serum ferritin and C-reactive protein (CRP) levels as well as anisocytosis highly correlate with the severity of the disease. Microspectrophotometric studies showed significant changes of hemoglobin adsorption spectra in individual erythrocytes. However, in severe form of SARS-CoV-2, increase of hemoglobin absorbance occurred in within 420 nm wavelength spectrum compared with regular group.ConclusionOur findings suggest that the increased levels of ferritin, CRP, anisocytosis and partially increase in Hb adsorption on 420 nm wavelength may positively correlate with adverse outcomes in SARS-Cov-2 infection.
Autism and Inner Speech: A Computational Model of Language Functions in Autistic Flexible Behaviour
Authors: Granato Giovanni , Borghi Anna M. , Mattera Andrea , Baldassarre Gianluca
Published: August 2021

Experimental and computational studies propose that inner speech boosts categorisation skills and executive functions, making human behaviour more focused and flexible. In addition, many clinical studies highlight a relationship between poor inner-speech and an executive impairment in autism spectrum condition (ASC), but contrasting findings are reported. Here we investigate the latter issue through a previously implemented and validated computational model of the Wisconsin Cards Sorting Tests.In particular, the model was applied to detect the individual differences in cognitive flexibility and inner speech contribution in ASC and neurotypical participants. Our results suggest that the use of inner-speech increases along the life-span of neurotypical participants but is absent in ASC ones. Although we found more attentional failures in autistic children/teenagers and more perseverative behaviours in autistic young/older adults, only ASC children and ASC older adults exhibited a lower performance than matched control groups. Overall, our results corroborate the idea that the lower use of inner speech in ASC teenagers and young adults is compensated by alternative cognitive strategies (e.g., visual thinking), but it could represent a disadvantage for children (for the missing support of development) and older adults (for the missing compensation of cognitive decline). Moreover, the results suggest that cognitive-behavioural therapies should focus on developing inner speech skills in ASC children as this could provide cognitive support along their whole life span.
Characteristics and Recovery Methods of Studies Falsely Excluded During Literature Screening –A Systematic Review
Authors: Affengruber Lisa , Dobrescu Andreea , Persad Emma , Klerings Irma , Wagner Gernot , Sommer Isolde , Gartlehner Gerald
Published: August 2021

Background: Due to the growing need to provide evidence syntheses under time constraints, researchers have begun focusing on the exploration of rapid review methods, which often employ single-reviewer literature screening. However, single-reviewer screening misses, on average, 13% of relevant studies, compared to 3% with dual-reviewer screening. Little guidance exists regarding methods to recover studies falsely excluded during literature screening. Likewise, it is unclear whether specific study characteristics can predict an increased risk of false exclusion. This systematic review aimed to identify supplementary search methods that can be used to recover studies falsely excluded during literature screening. Moreover, it strove to identify study-level predictors that indicate an elevated risk of false exclusions of studies during literature screening. Methods: We performed literature searches for eligible studies in Medline, Science Citation Index Expanded, Social Sciences Citation Index, Current Contents Connect, Embase, Epistemonikos.org, and Information Science & Technology Abstracts from 1999 to June 23, 2020. We searched for grey literature, checked reference lists, and conducted hand searches in two relevant journals and similar articles searches current to January 28, 2021. Two investigators independently screened the literature; one investigator performed the data extraction, a second investigator checked for correctness and completeness. Two reviewers assessed the risk of bias of eligible studies. We synthesized the results narratively. Results: Three methods studies, two with a case study design and one with a case series design, met the inclusion criteria. One study reported that all falsely excluded publications (8%) could be recovered through reference list checking compared to other supplementary search methods. No included methods study analyzed the impact of recovered studies on conclusions or meta-analyses. Two studies reported that up to 8% of studies were falsely excluded due to uninformative titles and abstracts, and one study showed that 11% of non-English studies were falsely excluded. Conclusions: Due to the limited evidence based on two case studies and one case series, we can draw no firm conclusion about the most reliable and most valid method to recover studies falsely excluded during literature screening or about the characteristics that might predict a higher risk of false exclusion. Systematic review registration: https://osf.io/v2pjr/
AHSA1 is a Prognostic Biomarker that Correlates with Macrophage Infiltration in Pan-Cancer
Authors: Li Fulei , Liu Chengdong , Chen Yanling , Li Shasha , Bai Lu
Published: August 2021

Background: Activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) is differentially expressed in several tumor types. However, its association with immune cell infiltration remains elusive. Methods: AHSA1 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data and normal tissue expression data from Genotype-Tissue Expression (GTEx). The clinical prognostic role of AHSA1 in pan-cancer was investigated, and an enrichment analysis of AHSA1 was performed using the R package “clusterProfiler.” We downloaded data regarding the immune cell infiltration level of TCGA pan-cancer tissues and analyzed the association between immune cell infiltration and AHSA1 expression. Results: The results of TCGA pan-cancer data analysis revealed that AHSA1 was overexpressed and associated with poor survival in patients with cancer. Furthermore, the infiltration levels of tumor-associated macrophages (TAMs) were higher, while those of CD8+ T cells were lower, in the high AHSA1 expression group. Conclusions: Our study suggests that AHSA1 is an oncogene and a risk factor for patient survival in cancer. AHSA1 may contribute to high infiltration levels of TAMs and low infiltration levels of CD8+ T cells, thus indicating that high AHSA1 expression may be associated with the tumor immunosuppressive microenvironment.
Biological Nitrogen Fixation, Carbon assimilation and plant performance of Lotus tenuis, contribute to define a strategic role in the lowlands in the Salado River Basin (Argentina)
Authors: CAMPESTRE MARIA PAULA , ANTONELLI CRISTIAN JAVIER , BAILLERES MATIAS ANDRES , MAGUIRE VANINA GISELLE , TABOADA MIGUEL ANGEL , RUIZ OSCAR ADOLFO
Published: August 2021

Background and AimsForage production constitutes a great challenge for the Salado River Basin (Argentina), the major area devoted to livestock in the country. The successful naturalization of the European legume Lotus tenuis has been a productive and environmental relevance for the region. This study aims to evaluate its strategic contribution, reporting for the first time the B value for this species in these marginal environments for agriculture.MethodsThe 15N natural abundance method was used to evaluate the BNF of L. tenuis at soil plots and non-leguminous weed species in the same plots were utilized as reference plants. The assays included determinations of the 13C isotope, as well. Simultaneously, evaluations were carried out in the greenhouse for the determination of the B value of L. tenuis and the relative reproducibility of the field experiments.ResultsThe results obtained demonstrated that the L. tenuis promotion is accompanied by an increase in forage quality, due to the predominance of this C3 legume species, over C4 species. Moreover, its contribution to N inputs to the system, through the BNF with native rhizobia demonstrated to be about 80%, a highly relevant percentage for these constrained agroecosystems.ConclusionsThis work supports the hypothesis that L. tenuis promotion plays a strategic role in the sustainability of the ecosystem, especially in soil constrained areas. Joined with data previously published, the results obtained contribute to support the criteria that define the naturalized legume playing a strategic role in the sustainability of agriculture marginal soils.
Factual Demonstration of Blockchain Routing in Delay Tolerant Network
Authors: Dalal Renu , Khari Manju
Published: August 2021

Frequent disconnection, high end-to-end latency, dynamic topology, sparse node density, lack of pre-existing infrastructure, and opportunistic message transmission on wireless link, makes routing difficult in Opportunistic network (Oppnet). In present scenario, Oppnet allows the people to interact with contrasting ways like with diverse mobility, groups, and etc. During transmission of messages in such network security and trust performs major role. Delay Tolerant Network (DTN) are much prone of having inherent risk of attack. Malicious node, selfish node, and attacks are major impact on deteriorating network performance. To prevent the network from such deteriorating factors, this paper introduces the new platform to provide reliable and authentic transmission of message in opportunistic network. Blockchain-based Routing in Opportunistic Network (BRON) uses the concept of Blockchain through which each node work as an authentic node and transmit the secure messages in Oppnet. Opportunistic Network Environment (ONE) tool is used to implement BRON. This protocol generates 36% reduced packet drops ratio, 57% enhanced delivery ratio, 55% lesser overhead ratio, 35.2% reduced average latency, and 65% lesser average buffer time as compared to direct delivery ratio with respect to number of nodes.
Examination of Apoptotic and Autophagic Effects of Chronic Roflumilast Use on Rat Testicular Tissue by Immunohistochemical and Immunofluorescence Methods
Authors: gezer arzu , SARI Ebru KARADAĞ
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
Building Resilience Through Cross Industry Team Collaboration
Authors: Mandal Susanta
Published: August 2021

This paper addresses the key issues that go into the making of a heavy truck wherein steel made parts are used in the making of a chassis , so here the challenge for both for the bodyframe designer of the automobile industry and the sheet metal designer of the steel industry to come up with solutions that not only addresses problems relating to the lowering of the weight but also making it strong enough to bear enough loads taking into account changes in materials used , kinematics – differences in body angles that affects the velocity of the actions directed , how parts connected not only in the truck but also in the processes followed including changes in design and thereafter the prototypes to be tried out in the face of oncoming changes . A pentagonal framework that includes open cost modelling as well a business model that talks of creating a value streams in consonance with the changes for the uncertain future has been included.
The SARS-CoV-2 arginine dimers
Authors: Romeu Antonio R. , Ollé Enric
Published: August 2021

Arginine is present, even as a dimer, in the viral polybasic furin cleavage sites, including that of SARS-CoV-2 in its protein S, whose acquisition is one of its characteristics that distinguishes it from the rest of the sarbecoviruses. The CGGCGG sequence encodes the SARS-CoV-2 furin site RR dimer. The aim of this work is to report the other SARS-CoV-2 arginine pairs, with particular emphasis in their codon usage. Here we show the presence of RR dimers in the orf1ab related non structural proteins nsp3, nsp4, nsp6, nsp13 and nsp14A2. Also, with a higher proportion in the structural protein nucleocapsid. All these RR dimers were strictly conserved in the sarbecovirus strains closest to SARS-CoV-2, and none of them was encoded by the CGGCGG sequence.
Application of Ultrasonography to Neuro-COVID-19
Authors: Ruggiero Marco
Published: August 2021

Neurological and psychiatric symptoms are frequently observed in COVID-19, the disease caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), and the term "Neuro-COVID-19" has been coined to indicate the plethora of short- and long-term neurologic and psychiatric manifestations. In a significant percentage of cases, neuro-psychiatric symptoms persist after recovery and long-term sequelae have been reported. SARS-CoV-2 can infect the brain through different routes and the damage can be direct, that is due to the virus itself, or indirect, that is associated with abnormal immune responses, inflammation, and hypoxia. Studies of brain specimens obtained from autopsy demonstrated the presence of the virus in a minority of cases and this leads to hypothesize that SARS-CoV-2 may hide in sanctuary sites in the central nervous system in analogy with what observed for HIV. The existence of sanctuary sites for SARS-CoV-2 has the potential to decrease the efficacy of antiviral therapies or vaccination and may even prevent complete eradication of SARS-CoV-2 from the infected organism. In 2017, a diagnostic and therapeutic procedure was proposed with the goal of identifying and treating pathogens hiding in sanctuaries that elude diagnosis and therapy. This procedure is based on clinical evaluation, diagnostic ultrasonography, therapeutic ultrasounds, and laboratory analyses. Here, it is demonstrated that application of ultrasonography to Neuro-COVID-19 requires a specific adaptation that takes into account brain movements synchronous with breathing as well as the sensitivity of SARS-CoV-2 to ultrasounds.