bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological dislocations for plasmonic mode localization
Authors: Epstein Eliav , Singh Leeju , Fox Maayan , Sternklar Shmuel , Gorodetski Yuri
Published: October 2020

We study the localization of plasmonic modes on topological dislocations obtained by an abrupt change in the geometry of unit-cells in a plasmonic metasurface. We experimentally demonstrate mode localization in line defects and point singularities in the topology. These results are confirmed by numerical simulations of the near field distributions along the topology boundaries. We present structures with line dislocations supporting dark and bright modes. Moreover, we show that in structures with point dislocations the localization strength can be further manipulated by modifying the topological order of the structure.
PPM1D is Associated With Prognosis of Bladder Cancer in the Chinese Population
Authors: Cao Shuangqing , Zheng Lei
Published: October 2020

Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.
What is the Impact of Infrapopliteal Endovascular Intervention on Free Flap Survival in Diabetic Foot Reconstruction?
Authors: Thai Duy Quang , Lee Dong Hwan , Lee Woo Beom , Hahn Hyung Min , Lee Il Jae
Published: October 2020

Background The combination of endovascular intervention and microvascular free flap transfer has been effectively used for the chronic ischemic wounds of lower limb. This study aimed to indicate the influence of angioplasty on the free flap survival in diabetic foot ulcer reconstruction.Methods A retrospective research was conducted of 46 diabetic patients with chronic ulcer of the foot. All the patients underwent the free flap reconstruction because of their non-healing wound with tendon or bone exposure. Patient’s demography, clinical data related to vascular status, vascular intervention, free flap transfer procedure were collected. Flap survival rate was compared between the group of severe arterial stenosis and non-severe group and between the different revascularization result groups as well. Results The average was 56.2 ± 10.8 years with 14 men (30.4%) and 32 women (69.6%). All of 23 patients (50%) who had severe infrapopliteal arterial stenosis underwent endovascular intervention. The final result of the pedal arch was type 1 in 13/23 patients (56.5%), type 2A and 2B in 7/23 and 2/23 patients respectively and type 3 in only one patient. Total flap necrosis was in 5 cases (10.9%), marginal necrosis in 4 cases (8.7%) and wound dehiscence in 4 cases (8.7%). There was no significant difference of flap loss between the severe arterial stenosis patients and non-severe arterial stenosis patients. In severe arterial stenosis group, after endovascular intervention, patients with type 1 of pedal arch had a significantly lower rate of total flap necrosis compared to the others. There was also no association between using of revascularized recipient artery and flap survival.Conclusions Our study revealed the crucial of quality of pedal arch on free flap survival. The PTA should aim to re-establish the complete pedal arch to increase the rate of wound healing as well as the flap success.
Somatic mutations in single human cardiomyocytes demonstrate accelerated age-related DNA damage and cell fusion
Authors: Walsh Christopher , Choudhury Sangita , Huang August , Kim Junho Junho , Morillo Katherine , Maury Eduardo , Zhou Zinan Zinan , Kenny Connor , Lee Eunjung , Chen Ming
Published: October 2020

The accumulation of somatic DNA mutations is a hallmark of aging in many dividing cells and contributes to carcinogenesis. Here we survey the landscape of somatic single-nucleotide variants (sSNVs) in heart muscle cells (cardiomyocytes) which normally do not proliferate but often become polyploid with age. Using single-cell whole-genome sequencing we analyzed sSNVs from 48 single cardiomyocytes from 10 healthy individuals (ages 0.4 - 82 yrs.). Cardiomyocyte sSNVs increased strikingly with age, at rates faster than reported in many dividing cells, or in non-dividing neurons. Analysis of nucleotide substitution patterns revealed age-related “clock-like” mutational signatures resembling those previously described. However, cardiomyocytes showed distinct mutational signatures that are rare or absent in other cells, implicating failed nucleotide excision repair of oxidative damage and defective mismatch repair (MMR) during aging. A lineage tree of cardiomyocytes, constructed using clonal sSNVs, revealed that some tetraploid (10%) and most cardiomyocytes with higher ploidy (>60%) derive from distinct clonal origins, implicating cell fusion as a mechanism contributing to many polyploid cardiomyocytes. Since age-accumulated sSNVs create dozens of damaging exonic mutations, cell fusion to form multiploid cardiomyocytes may represent an evolutionary mechanism of cellular genetic compensation that minimizes complete knockout of essential genes during aging. The rates and patterns of accumulation of cardiac mutations provide a paradigm to understand the influence of genomic aging on age-related heart disease.
Aberrant Wnt signalling induces comedo-like changes in the upper hair follicle
Authors: Shang Wei , Tan Alvin , Steensel Maurice , Lim Xinhong
Published: October 2020

Comedonal acne is a common skin disease characterized by cystic dilation of the hair follicle junctional zone. While the molecular mechanisms of acne pathogenesis are not well understood, an emerging hypothesis holds that imbalances in key signalling pathways may lead to abnormal fate determination of sebaceous progenitor cells. The subsequent accumulation of cells could then cause cyst formation in the hair follicle junctional zone and lower infundibulum, forming blackheads. This notion is supported by the observation that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes severe comedonic acne and seboatrophy by inducing fate changes in Lrig1-expressing stem cells, as well as recent human GWAS studies implicating the Wnt signalling pathway in acne. To test the possible involvement of Wnt signals in blackhead formation, we used an Lrig1-CreERT2 mouse line to modulate Wnt signalling in stem cells of the junctional zone, which are known to contribute to the junctional zone, infundibulum, and sebaceous glands. We find that persistent activation of Wnt signalling in the junctional zone leads to formation of comedone-like cysts with associated atrophic sebaceous glands. The cysts strongly express stem cell markers and can be partially reduced by treatment with all-trans retinoic acid, a well-established acne treatment, as well as by inhibition of Hedgehog signalling. In contrast, loss of Wnt signalling leads to enlargement of the junctional zone, infundibulum and sebaceous glands. These data lead us to suggest that abnormal Wnt signalling could be involved in acne pathogenesis by inhibiting differentiation and retaining junctional zone cells in a proliferative progenitor state, leading to their accumulation into comedones.
Variable expressed methylation sites of aging-related genes in asthma
Authors: Yang Yu , Yuan Lin , Yang Ming , Du Xizi , Qin Ling , Wang Leyuan , Zhou Kai , Wu Mengping , He Ruoxi , Feng Juntao , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi
Published: October 2020

Background: Asthma is a complex pulmonary inflammatory disease which is common in the elderly. Aging-related alterations have also been found in the structural cells and immune cells of asthma patients although the pathological mechanism of the differential aging-related gene in the development of asthma is still obscure. Of note, DNA methylation (DNAm) have been proven to play an important role in the regulation of aging-related genes. However, the methylation levels of aging-related genes in asthma patients are largely unclear.Methods: First, the mRNA levels and DNAm level of the previous screened 9 aging-related genes in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients were detected by multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR. Secondly, the correlation between the DNAm level of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Lastly, the Receiver Operator Characteristic (ROC) curve and Principal Component Analysis (PCA) were used to identify the feasibility of the candidate CpG sites as asthma markers.Results: The mRNA expression of the 9 aging-related gene in peripheral blood of asthma patients was significantly different from those of HCs. Besides, the methylation level of the 9 aging-related genes also altered in asthma patients, and a total of 68 CpG sites were related to the severity of asthma. Notably, 10 of the 68 CpG sites had a significant relationship with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma.Conclusions: In summary, this study confirmed the changes in the mRNA expression and DNAm level of aging-related genes in asthma patients. The differential DMSs are associated with the clinical evaluation indicators of asthma, which may indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarker of asthma.
Landscape of Lipidomic Metabolites in Gut-liver Axis of Sprague-Dawley Rats after Oral Exposure to Titanium Dioxide Nanoparticles
Authors: Chen Zhangjian , Han Shuo , Zheng Pai , Zhang Jiahe , Zhou Shupei , Jia Guang
Published: October 2020

Background: The application of titanium dioxide nanoparticles (TiO2 NPs) as food additives poses a risk of oral exposure that may lead to adverse health effects. Even though the substantial evidence supported liver as the target organ of TiO2 NPs via oral exposure, the mechanism of liver toxicity remains largely unknown. Since the liver is a key organ for lipid metabolism, this study focused on the landscape of lipidomic metabolites in gut-liver axis of Sprague Dawley (SD) rats exposed to TiO2 NPs at 0, 2, 10, 50 mg/kg body weight per day for 90 days.Results: TiO2 NPs (50 mg/kg) caused slight hepatotoxicity and changed lipidomic signatures of main organs or systems in the gut-liver axis including liver, serum and gut. The cluster profile from the above biological samples all pointed to the same key metabolic pathway and metabolites, which was glycerophospholipid metabolism and Phosphatidylcholines (PCs), respectively. In addition, absolute quantitative lipidomics verified the changes of three PCs concentrations, including PC(16:0/20:1), PC(18:0/18:0) and PC(18:2/20:2) in the serum samples after treatment of TiO2 NPs (50 mg/kg). The contents of malondialdehyde (MDA) in serum and liver increased significantly, which were positively correlated with most differential lipophilic metabolites.Conclusions: The gut was presumed to be the original site of oxidative stress and disorder of lipid metabolism, which resulted in hepatotoxicity through the gut-liver axis. Lipid peroxidation may be the initial step of lipid metabolism disorder induced by TiO2 NPs. Most nanomaterials (NMs) have oxidation induction and antibacterial properties, so the toxic pathway revealed in the present study may be primary and universal.
Estimating Unreported COVID-19 Cases in the United States Based on the tvSIRu Model
Authors: Liu Lingbo , Hu Tao , Bao Shuming , Wu Hao , Peng Zhenghong , Wang Ru
Published: October 2020

BackgroundThe potential unreported infection may impair and mislead policymaking for COVID-19，and the contemporary spread of COVID-19 varies in different counties of the United States. It is necessary to estimate the cases that may be underestimated based on county-level data to take better countermeasures against COVID-19. We suggested taking time-varying SIR models with unreported infection rates (UIR)to estimate the factual COVID-19 cases in the United States.MethodsSIR integrated with unreported infection rates (SIRu) of fixed time effect and SIR with time-varying parameters (tvSIRu)were applied to estimate and compare the value of transmission rate(TR), UIR, and infection fatality rate (IFR) based on US county-level COVID-19 data. ResultsBased on US county-level COVID-19 data from January 22 (T1) to August 20 (T212) in 2020, SIRu was first tested and verified by a general OLS regression. The further regression of SIRu at the country-level showed that the average values of TR, UIR, and IFR were 0.034,19.5, 0.51% respectively. The range of TR, UIR, IFR of all states ranged were 0.007-0.157 (mean=0.048) ,7.31-185.6 (mean=38.89), and 0.04%-2.22% (mean=0.22%). Among time-varying transmission rate equations, the power function showed better fitness, which indicated a decline in TR decreasing from 227.58 (T1) to 0.022 (T212). The general equation of tvSIRu showed that both the UIR and IFR were gradually increasing, wherein, the UIR has an estimate of 9.1(95%CI = 5.7-14.0), and IFR was 0.70% (0.52%-0.95%) at T212.InterpretationDespite the decline in TR and IFR, the UIR of the United States is still on the rise, which had been supposed to decrease with sufficient tests or improved countersues. The US medical system may be largely affected by severe cases in the rapid spread of COVDI-19.
WITHDRAWN: Elementary Quadrature for the Riccati equation
Authors: Zhao Ji-Xiang
Published: October 2020

Using suitable transformation in combination with a specific Riccati-type equation solvable, the problem of solving Riccati equation can be transformed into that of a quasi-Abel equation of the second kind. By the extended Julia’s integrability condition, the general solutions of Riccati equation in the form of elementary quadrature are obtained, which contains numerous. This method opens up a new prospect for the study of nonlinear differential equations by analytical method.
Floristics and Structure of Arboreal Components in a Restored Atlantic Forest Area
Authors: Silva Wiane Meloni , Martins Sebastião Venâncio , Cruz Ricardo Alcántara de la , Torres Carlos Moreira Miquelino Eleto , Cosimo Luiz Henrique Elias , Zanuncio José Cola
Published: October 2020

Background: Coffee and livestock degrade Seasonal Semideciduous Forests in the Zona da Mata region of the Atlantic Forest biome in Brazil. The floristic composition must be studied to preserve and conserve forest remnants. The objective was to evaluate the arboreal structure, characterize the seed dispersal syndrome and the ecological group of forest species of a 45-year-old restored area in Viçosa, Minas Gerais state, Brazil. The phytosociological parameters density, frequency, dominance and importance value, Shannon's diversity and Pielou's equability were evaluated considering individuals with DBH (diameter at breast height) ≥ 5 cm in sixteen contiguous plots (25 x 25 m). Results: A total of 1,323 individuals from 109 species and 35 botanical families were registered, of which 90 were native and 15 exotic species. The importance value (VI= 11.9%) was highest for Guarea guidonia (Fabaceae). The Shannon's diversity (H') was 3.46 and the equability (J') was 0.74. The number of species (33%) was largest for the initial secondary successional class and the number of individuals with zoochoric dispersion syndrome for the late secondary class (38.3%). The basal area was 44.1 m² ha-1 and the average height was 13 m (ranging from 2 to 32 m). Conclusion: The restored Semideciduous Seasonal Forest is in an advanced successional stage with zoochoric species and a great number of late secondary species.
High concordance between next generation sequencing and single-nucleotide polymorphism array in preimplantation genetic testing for aneuploid
Authors: Ou Zhanhui , Chen Zhiheng , Deng Yu , Yin Minna , Sun Ling
Published: October 2020

Background: Single-nucleotide polymorphism array (SNP array) and next generation sequencing (NGS) in detecting chromosome aneuploidy are widely used in clinical work. Aims: To compare the concordance between NGS and SNP array in 67 embryos (from 23 couples). Methods: In the first part of the study, 28 blastocysts with unknown ploidy were both analyzed with NGS and SNP array. While in the second part, 39 with normal ploidy detected by NGS were re-analyzed with SNP array. Results: In the first part of the study, the concordance rate between NGS and SNP array was 92.9% (26/28). Among the 28 blastocysts, 18 were abnormal and 10 blastocysts were with normal ploidy status when analyzed by NGS. Among the 18 abnormal blastocysts, two blastocysts were with low level of mosaicism as analyzed by NGS, but euploid with SNP array. In the second part, concordance rate between NGS and SNP array was 100% (39/39). At last, one couple had no blastocyst to transfer. The other 22 couples were transferred with single blastocyst. Among them, two couples suffered abortions before 12 weeks, and the karyotype of villus was normal. One couple with only 1 normal blastocyst failed to conceive after the transfer. In total nineteen couples had healthy babies born. Conclusions: There was a high concordance rate between NGS and SNP array. But NGS was also able to detect mosaicism sensitively. Hence, using NGS for PGT-A may increase the chances of having a healthy and live newborn child.
Factors Related to ICU-Acquired Infections Incidence in Iran: Analysis of National Nosocomial Infections Registry Data
Authors: Izadi Neda , Eshrati Babak , Mehrabi Yadollah , Etemad Korosh , Hashemi-Nazari Seyed-Saeed
Published: October 2020

Background: Patients admitted to intensive care units (ICUs) are particularly susceptible to hospital-acquired infections (HAIs) and the HAIs are higher in the ICUs than other wards of the hospital. This study aimed at investigating factors associated with ICU-acquired infections incidence in Iran. Methods: In this multi-center study, Iranian nosocomial infections surveillance (INIS) and hospital statistics and information system (AVAB) were used to collect data on patients with HAIs in 2018. The data was expanded based on 12 months of the year (13,632 records in terms of "hospital-ward-month") and then, the last observation carried forward method was used to replace the missing data. The generalized negative binomial regression with “patient-days” as an offset variable was used to identify the factors affecting ICU-acquired infections incidence.Results: The median age of patients was 57.5 (IQR=55.09) years. Of the 22.92%, 5.76%, 13.62%, 43.41%, and 14.29% of patients were in NICU, PICU, internal ICU, general ICU, and surgical ICU, respectively. Only 13.73% of hospitals were in efficient zone (zone III). Based on multivariable regression, the number of death (IRR=1.02), the number of infections due to the device (catheters and ventilators) (IRR=1.1), ward type (PICU (IRR=1.58), internal ICU (IRR=1.63), general ICU (IRR=1.53) and surgical ICU (IRR=1.47)), hospital's expertise, hospital's accreditation, bed occupancy rate indicator (IRR=1.17 for moderate conditions) were associated with an increase of ICU-acquired infections incidence. Infection due to ventilator, infection due to catheter, and the number of surgery in hospitals reduced 5%, 7%, and 1% incidence of infections, respectively. Conclusions: Based on the results, the most common ICU-acquired infections were VAE and UTI. Therefore due to the high sensitivity of intensive care units, full hygiene should be taught to the medical staff, especially the ICU wards. Ventilators and catheters should be used in special circumstances and minimum duration.
Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer
Authors: Zhou Ye , Zang Mingde , Hou Junyi , Wang Jiangli , Huang Yakai , Ding Xusheng , Wang Yanong
Published: October 2020

BackgroundCrocetin is an active component of saffron stigma, which has important therapeutic effects on various diseases including tumors, arthritis, hemorrhages, etc. However, the effects of crocetin on gastric cancer (GC) cells and their underlying mechanisms remain unclear.MethodsCell counting kit‑8 (CCK‑8), transwell assays, F-actin staining, tube formation and vasculogenic mimicry (VM) assays were used to examine the effects of crocetin on cell proliferation, migration and angiogenesis in GC. Enzyme linked immunosorbent assay (ELISA) and Western blot assay were performed to evaluate expression level of Sonic hedgehog (Shh) signaling and activation of epithelial‑mesenchymal transition (EMT) in GC cells treated with or without crocetin. Proliferation of xenograft tumors was detected by immunohistochemistry. ResultsCrocetin significantly inhibited tube formation of human umbilical vein endothelial (HUVEC) cells and VM formation of GC cells, as well as its proliferation, invasion and migration. Crocetin destroyed cytoskeleton and mosaic vessels formed by HUVEC and GC cells. Furthermore, we found that crocetin suppressed cell proliferation, migration, EMT, tube and VM formation through inhibiting Shh signaling pathway. Utilization of recombinant Shh reversed the suppressing effects of crocetin on cell proliferation, migration, angiogenesis and EMT. In addition, anti-tumor effect of crocetin was confirmed in xenograft tumors.ConclusionsCrocetin suppressed GC progression by inhibiting cell proliferation, migration and angiogenesis including tubes formed by HUVEC cells and VM vessels formed by GC cells, which were mediated by suppressing Shh signaling pathway. These results indicated that crocetin may function as an effective therapeutic drug against GC.
RDH10 and ATRA sensitize triple-negative breast cancer to taxane-based chemotherapy through regulation of PIN1
Authors: Grainger Jordan , Zhang Lingxin , Yu Jia , Vedell Peter T , Thompson Kevin , Kalari Krishna R , Suman Vera J , Boughey Judy C , Goetz Matthew P , Wang Liewei
Published: October 2020

Background: With few targeted therapies available for triple-negative breast cancer (TNBC), there is a critical need to identify biomarkers that can predict chemotherapy-response. Copy number amplifications (CNAmps) have been implicated in tumorigenesis, progression, and treatment response. Previously, we performed a prospective neoadjuvant chemotherapy study (BEAUTY) and identified a 5 Mb CNAmp in TNBC patients associated with pathological complete response rates to taxane- and anthracycline-based chemotherapy. Here we further interrogated this amplicon and its role in chemotherapy response. Methods: Using siRNA screening of genes identified in the 5 Mb CNAmp, followed by cytotoxicity assays, we identified RDH10 significantly associated with chemo-sensitivity in TNBC cell lines. Functional studies were performed using RDH10 knockdown or overexpression followed by cytotoxicity, cell proliferation, luciferase reporter assays, HPLC or western blot.Results: RDH10 is a rate-limiting step involved in the synthesis of all-trans retinoic acid (ATRA) - the active metabolite of retinoid metabolism that is frequently aberrant in cancer. Previous studies demonstrated ATRA to be a potent inhibitor of PIN1, a key regulator of several oncogenic signaling pathways often amplified in TNBC. We discovered that genetic manipulation of RDH10 affected ATRA intracellular concentrations, contributing to PIN1 degradation and taxane-response. Furthermore, co-treatment of TNBC cells with ATRA significantly increased taxane-sensitivity.Conclusion: RDH10 amplification increases endogenous levels of ATRA and degrades PIN1 in TNBC. ATRA-mediated degradation of PIN1 sensitizes TNBC to chemotherapy, suggesting that RDH10 may be a novel biomarker of taxane response and the addition of ATRA to standard chemotherapy may improve chemo-sensitivity.
Ice XIX: The second hydrogen-ordered polymorph related to ice VI
Authors: Gasser Tobias , Thoeny Alexander , Fortes Andrew , Loerting Thomas
Published: October 2020

We here report ex situ calorimetry and high-resolution neutron powder diffraction data of a novel ice polymorph produced at 1.8 GPa and recovered to ambient pressure at 80 K. Ice XIX, previously called ice β-XV by us, is shown to be partially hydrogen-ordered and crystallising in a √2 x √2 × 1 supercell with respect to the parent ice VI phase. Our powder data match two nearly degenerate structural models in space-groups \(P\stackrel{-}{4}\) and Pcc2, in which the water molecules are partially antiferroelectrically ordered. Key to the synthesis of deuterated ice XIX is the use of DCl as dopant and the use of a D2O/H2O mixture, where the small H2O fraction nucleates ice XIX. This provides the basis to study the first order-order transition known in ice physics, from ice XIX to its sibling ice XV at ambient pressure. It proceeds via a transition state, ice VI‡, which contains a disordered H-sublattice, whereas both ice XIX and ice XV are fully crystalline.
Prognostic nomogram for patients with invasive endocervical adenocarcinoma incorporating HPV E6/E7 mRNA in situ hybridization and clinical characteristics
Authors: Liu Li-Li , Chen Shu-Lin , Yan Shu-Mei , Li Yue , Yang Xia , Zhang Shi-Wen , Yang Hai-Xia , Wan Ting , Luo Rong-Zhen
Published: October 2020

Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific method. We aimed to examine the diagnostic and prognostic utility of this technique in endocervical adenocarcinoma (ECA) and build a useful prognostic nomogram model using this approach. Methods: The model was constructed from a retrospective study of 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center between 2010 and 2014. The model's predictive efficiency and discriminative capability were defined by a concordance index (C-index) and calibration curve. Results: The overall sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively, compared to 60.2% and 90.0% for p16 immunohistochemistry, 80.5% and 80.0% for HPV DNA, and 63.3% and 50% for HPV genotype. The independent factors derived from multivariable analysis of the whole cohort to predict overall survival (OS) were age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope, which were all incorporated into the nomogram with (nomogram B) or without (nomogram A) FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825 (p = 0.002 and p < 0.001), which was significantly higher than the C-index for FIGO stage (0.653) and treatment (0.578). No significant difference occurred between nomograms A (0.825) and B (0.836). Furthermore, a risk stratification system was established to accurately stratify patients with ECA into two subgroups with significantly different prognosis. Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the proposed nomogram using HPV E6/E7 RNAscope showed more accurate outcome in terms of prognosis in patients with ECA.
Integrated weighted gene co-expression network analysis identified that TLR2 and CD40 are related to coronary artery disease
Authors: Qi Bin , Chen Jian-Hong , Tao Lin , Zhu Chuan-Meng , Wang Yong , Deng Guo-Xiong , Miao Liu
Published: October 2020

Background: The current research attempted to identify possible hub genes and pathways of coronary artery disease (CAD) and to detect the possible mechanisms.Methods: Array data from GSE90074 were downloaded from the Gene Expression Omnibus (GEO) database. Integrated weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene module and clinical characteristics. Gene Ontology annotation, Disease Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by clusterProfiler and the DOSE package in R. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection to identify hub genes. Then, further functional validation of hub genes in other microarrays and population samples was performed, and survival analysis was performed to investigate the prognosis.Results: A total of 660 genes were located in three modules and associated with CAD. GO functions identified 484 biological processes, 39 cellular components, and 22 molecular functions with an adjusted P < 0.05. Approximately 38 pathways were enriched in KEGG pathway analysis, and 147 DO items were identified with an adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). There were a total of four modules with a score > 10 after PPI network analysis using the MCODE app, and two hub genes (TLR2 and CD14) were identified. Then, we validated the information from the GSE60993 dataset using the GSE59867 dataset and population samples, and we found that these two genes were associated with plaque vulnerability. These two genes varied at different time points after myocardial infarction, and both of them had the lowest prognosis of heart failure when they were expressed at low levels.Conclusion: We performed an integrated WGCNA and validated that TLR2 and CD14 were closely associated with the severity of coronary artery disease, plaque instability and the prognosis of heart failure after myocardial infarction.
Transposable Element Subfamily Annotation is Unreliable in Biological Replicates
Authors: Carey Kaitlin , Patterson Gilia , Wheeler Travis J
Published: October 2020

Background: Transposable element (TE) sequences are classified into families based on the reconstructed history of replication, and into subfamilies based on more fine-grained features that in some cases capture family history, and in other cases are simply intended to improve annotation sensitivity. We evaluate the reliability of annotation with common subfamilies by assessing the extent to which subfamily annotation is reproducible in replicate copies created by segmental duplications in the human genome, and in homologous copies shared by human and chimpanzee.Results: We find that standard methods annotate over 10% of replicates as belonging to different subfamilies, despite the fact that they are expected to be annotated as belonging to the same subfamily. Point mutations and homologous recombiniation appear to be responsible for some of this discordant annotation (particularly in the young Alu family), but are unlikely to fully explain the annotation unreliability.Conclusions: The surprisingly high level of disagreement in subfamily annotation of homologous sequence highlights a need for further research into definition of TE subfamilies, methods for representing subfamily annotation confidence of TE instances, and approaches to better utilizing such nuanced annotation data in downstream analysis.
Identification of novel inhibitors of Angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19)
Authors: Upreti Shobha , Prusty Jyoti Sankar , Pandey Satish Chandra , Kumar Awanish , Samant Mukesh
Published: October 2020

The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 16 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, β-sitosterol was found with the highest binding affinity -12.2 Kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, Luteoxanthin and Violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target specific therapeutic drugs against COVID-19.
Rapid Electrochemical Detection of Coronavirus SARS-CoV-2.
Authors: Chaibun Thanyarat , Puenpa Jiratchaya , Ngamdee Tatchanun , Boonapatcharoen Nimaradee , Athamanolap Pornpat , O’Mullane Anthony Peter , Vongpunsawad Sompong , Poovorawan Yong , Yin Lee Su , Lertanantawong Benchaporn
Published: October 2020

COVID-19 is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis of COVID-19 depends on quantitative reverse transcription PCR (qRT-PCR), which is time-consuming and requires expensive instrumentation. Here, we report an ultrasensitive electrochemical biosensor based on isothermal rolling circle amplification (RCA) for rapid detection of SARS-CoV-2. The assay involves the hybridization of the RCA amplicons with probes that were functionalized with redox active labels that are detectable by an electrochemical biosensor. The one-step sandwich hybridization assay could detect as low as 1 copy/mL of N and S genes, in less than 2 hours. Sensor evaluation with 105 clinical samples, including 40 SARS-CoV-2 positive and 9 samples positive for other respiratory viruses, gave a 100% concordance result with qRT-PCR, with complete correlation between the biosensor current signals and quantitation cycle (Cq) values. In summary, this biosensor could be used as an on-site, real-time diagnostic test for COVID-19.
Clinical and molecular characteristics of COVID-19 patients with persistent SARS-CoV-2 infection
Authors: Sun Chaoyang , Fan Junpeng , Huang Jia , Guo Ensong , Fu Yu , Liu Si , Xiao Rourou , Liu Chen , Lu Funian , Qin Tianyu , He Chao , Wang Zizhuo , Qin Xu , Hu Dianxing , You Lixin , Li Xi , Wang Tian , Wu Peng , Chen Gang , Zhou Jianfeng , Li Kezhen
Published: October 2020

The clinical features, molecular characteristics, and immune responses of COVID-19 patients with persistent SARS-CoV-2 infection are not yet well described. In this study, we investigated the differences in clinical parameters, laboratory indexes, plasma cytokines, and peripheral blood mononuclear cell responses, which were assessed using single-cell RNA-sequencing in patients with non-critical COVID-19 with long durations (LDs) and short durations (SDs) of viral shedding. Our results revealed that clinical parameters and laboratory indexes, such as c-reactive protein (CRP) and D-dimer, were comparable between SDs and LDs. Most inflammatory cytokines/chemokines, such as IL-2, IL2R, TNFα/β, IL1β, and CCL5 were present at low levels in LDs. Our single-cell RNA-sequencing revealed a reconfiguration of the peripheral immune cell phenotype in LDs, including decreases in natural killer (NK) cells and CD14+ monocytes and an increase in regulatory T cells (Tregs). Furthermore, most cell subsets in LDs consistently exhibited reduced expression of ribosomal protein (RP) genes, indicating dysfunctions in cytokine/chemokine synthesis, folding, modification, and assembly. Accordingly, the negative correlation between the RP levels and viral shedding duration was validated in an independent cohort of bulk-RNA-sequencing data from 103 non-critical patients, which may help guide clinical management and resource allocation. Moreover, peripheral T and NK cells and memory B cells in LDs likely failed to activate, which contributed to the persistence of viral shedding.
Knowledge, attitude and practices associated with COVID-19 among health care workers: A cross-sectional study in India.
Authors: Gopalakrishnan Shivkumar , Kandasamy Sangeetha , Almohammed Omar A. , Abraham Bobby , Senthilkumar Monika
Published: October 2020

Background: In India, SARS-CoV-2 pandemic has caused phenomenal loss of lives and overburdened the health system. Low morale, fatigue and inadequate knowledge among health personnel are perceived threats to pandemic control. Knowledge, Attitude and Practice (KAP) studies among HCWs can identify crucial knowledge gaps and gauge psychological impact. We aimed to assess the COVID-19 related current level of knowledge, attitude and practices among our HCWs.Methods: A cross-sectional, electronically distributed, questionnaire-based study was conducted among HCWs. The questionnaire identified participants’ demographics and the current KAP related to COVID-19. Descriptive statistics were used to present the participants’ demographics and Chi-square test to assess differences among the participants’ demographics based KAP. α < 0.05 was used for statistical significance. The association between the knowledge, attitude and practices was assessed using Pearson correlation coefficient (r).Results: Of 1,429 total participants, 71.9% belonged to age group 21-40 years. Female workers constituted 61.5%. Only 40.2% received any infection control training and 62.7% relied upon single source of information update. However, 82.9% of participants had adequate knowledge. Being married, urban dwelling and higher qualification were associated with knowledge adequacy (p<0.001). Interestingly, senior HCWs (age 41-50 years) were least likely to have adequate knowledge (74.1%). 84.2% had positive attitude towards COVID. Notably, 83.8% feared providing care to COVID patient. 93% practised safety precautions correctly most of the times and training had no influence on practise. Positive correlation was recognized between adequate knowledge and positive attitude (r=0.26).Conclusion: More than 80% of HCWs in India had adequate knowledge, positive attitude and practiced safely most of the time. However pitfalls like poor training, knowledge uncertainties and fear of disease acquisition among HCWs need to be addressed. Adverse outcomes can be averted by structured training sessions and psychological support programs for HCWs.
The therapeutic effect and safety of the drugs for COVID-19: a systematic review and meta-analysis
Authors: Qiu Rong , Li Jingwei , Xiao Yuxuan , Gao Ziyi , Weng Yihang , Zhang Qiran , Wang Chengdi , Gong Hanlin , Li Weimin
Published: October 2020

Background: Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial. Objective: This study aimed to evaluate the efficiency and safety of the COVID-19 medicine. Methods: Studies were determined through searching PubMed, Embase, Cochrane Library and Medline. The clinical trials of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement and rate of serious adverse events. The risk ratio (RR) was adopted for variables as effect magnitude with 95% confidence intervals (CI), and the random‐effects model was adopted for analysis. Results: A total of eleven RCTs and eleven Non-RCTs involving 12,796 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 medicine has the obvious advantage in reducing discharge rate (RR, 1.18; 95% CI, 1.07-1.29, p<0. 05) and clinical improvement rate (RR, 1.15; 95% CI, 1.05-1.26, p<0. 05), no distinct effect on mortality (RR, 0.79; 95% CI, 0.53-1.17, p=0. 24). In addition, the serious adverse events rate (RR, 0.74; 95% CI, 0.62-0.88, p<0. 05) of COVID-19 medicine is lower than control group. Among different types of medicine, significant benefits in lowering the mortality seem to only occur in antiviral medicine. Conclusion: The results indicated antiviral medicine was potential drug of first choice recommended for COVID-19 treatment. Chloroquine/hydroxychloroquine therapy was not recommended for COVID-19 patients. Additionally, the ACEI/ARB could be adopted for COVID-19 treatment when combined with standard treatment.
COVID-19 associated histoplasmosis in an AIDS patient
Authors: Basso Rossana Patricia , Poester Vanice Rodrigues , Benelli Jéssica Louise , Stevens David A. , Zogbi Heruza Einsfeld , Vasconcellos Izadora Clezar da S. , Pasqualotto Alessandro Comarú , Xavier Melissa Orzechowski
Published: October 2020

Most reports associating fungal infections with Covid-19 have been cases of invasive aspergillosis. Here we report a case of severe histoplasmosis and Covid-19 infections in an HIV patient in Rio Grande, Southern Brazil. Histoplasmosis must be included on the list of opportunist fungal co-infections in Covid-19 patients with AIDS, mainly in endemic areas.
Linking Authentic Leadership and Employee Creative Behavior: The Mediating Role of Autonomous Motivation and Job Complexity
Authors: Fateh Adnan , Mustamil Norizah , Aslam Muhammad Zia
Published: October 2020

The main purpose of this study is to determine the relationship between authentic leadership and employee creative behaviour and to reveal two different mediating mechanisms (i.e., job complexity and autonomous motivation) through which authentic leadership influences employee creative behaviour. This study is based on self-determination theory. A total of (N = 354) respondents were asked to rate themselves on creative behaviour and their leader on authentic leadership style. The research used the internet-based survey tools in a cross-sectional. The study population was employees (mainly Software Developers) of software houses (software companies) working in Pakistan. Methodological tools of the research were partial least square structural equation modelling (PLS-SEM) for measuring the relationship between the variables. The results of the study show that authentic leadership positively influences employee creative behaviour directly as well as through two competing mechanisms of job complexity and autonomous motivation. Job complexity and autonomous motivation were tested as mediators between authentic leadership and employee creative behaviour independently and comparatively. Both the mediators successfully mediated the relationship between authentic leadership and employee creative behaviour with variable strength. The mediation path of job complexity was stronger in comparison with the mediation path of autonomous motivation. Further examination revealed that job complexity and autonomous motivation both mediate the relationship between authentic leadership and employee creative behaviour in a sequential manner. The results of the study are useful for both practitioners and researchers equally. For practitioners, the authors laid out the process through which managers can foster the creative behaviour of their employees using an authentic leadership style (i.e., by giving increased opportunities to indulge in complex work). Furthermore, for researchers, this study revealed the mechanisms through which authentic leadership influences and predicts creative behaviour. The findings of the study would benefit the authentic leadership theory for further development as a predictor of positive employee outcomes as this study confirmed a relatively complex mechanism through which it influences the creative behaviour of his followers.

Keywords
authentic leadership, autonomous motivation, creativity, employee creative behaviour, job complexity, self-determination theory, software houses of Pakistan, software developers.
Effects of Brand Hate on Brand Equity: The Role of Corporate Social Irresponsibility and Similar Competitor Offer
Authors: Husnain Mudassir , Syed Fauzia , Akhtar Waheed , Usman Muhammad
Published: October 2020

This paper summarises the arguments and counterarguments based on the assumptions of the theory of hate. The study is aimed at testing the mediating role of brand hate elicited in the relationship among the similar competitor offer, corporate social irresponsibility and brand equity. The study sample consisted of 550 participants from the education sector in Pakistan. The methodological tool of the research was structural equation modelling. Purposive sampling technique was used to reach the appropriate respondents for the study. This study was time-lagged conducted in three times data periods: in Time 1 a total of 800 surveys were distributed, out of which 722 were returned from respondents; in Time 2 722 surveys were distributed to same respondents, out of which 600 were returned; in Time 3 600 surveys were again distributed to the same respondents, out of which 550 were returned. The obtained results confirmed the mediating role of brand hate. Herewith, findings revealed that due to similar offers individual feelings such as loss of self-individuality usually developed and be negatively perceived. Thus, it yields to decline in product value. Likewise, corporate social irresponsibility found to have a more negative relationship with brand equity. Results of the current study revealed that negative feelings due to the similarity in competitor offer could stem from diverse sources. Therefore, it could result in an undesired personality self-loss, if a brand represented a similar brand as its competitors ultimately perceived negative and yielded a decline in value of product/service. The current study also unveiled that corporate social irresponsibility is a strong predictor of negative feelings. Corporate social irresponsibility motivates consumers towards brand hate, thus hampering brand equity. According to the mentioned above, there must be careful management of corporate social responsibility to avoid the negative effect on brand equity. In turn, brand hate mediating the relationship between similarity to competitor offer and brand equity alters consumer perception towards a brand. Thus, companies must fulfil consumers’ expectations to minimise brand hate which eventually increases brand equity. This study stands novel and considered as the first attempt to empirically explore the role of similarity to competitor offer and corporate social irresponsibility in eliciting brand hate that could adversely affect on brand equity. The study provided the limitations for future researchers, implications for managers and future directions.

Keywords
duplex theory of hate, tetra-Pak consumer, similar competitor offer, brand hate, brand equity, corporate social irresponsibility.