bluuebunny/crossref_metadata_2025 huggingface dataset:
An Optimized and Hybrid Energy Aware Routing Model for Effective Detection Of Flooding Attacks in a Manet Environment
Authors: Nandi Mallikarjuna , Kannan Anusha
Published: June 2021

Ad Hoc networks for communication have completely replaced the existing communication technologies which are dependant on infrastructure. An attractive and widely utilized field in communication systems is Mobile Ad Hoc Networks or the MANETs which are a derivative of the conventional Ad Hoc Networks. Security of information communicated through MANETs as well as the robust nature of the network is a prime issue of concern and research in recent times. Amongst various attacks prevalent on MANET environment, packet flooding is a common attack and causes a devastating effect on MANET nodes which if left undetected may lead to consequent crashing of the entire network. Floodding attacks also tend to consume enormous energy well above the prescribed energy consumption limits per node resulting in lifetime reduction. Hence, detection of these malicious nodes and their differentiation from trustworthy nodes is taken as the research objective in this paper. This paper presents feature extraction anda classification model based on ANFIS (Adaptive Neuro-Fuzzy Inference System). By using ANFIS classifier, the extracted featureis trained and then classified.Further to counter the flooding cum energy preserving routing, this paper proposes a SMA integration with AODVprotocol called SMA2AODV to detect flooding attacks for MANETs. After detecting, the hybrid model ACO combined with FDR PSO for optimizing energy. ACO-FDR PSO identifies the energy-efficient routeand minimizes energy consumption in the network, toincrease node lifetime that ensures energy-efficient routing. The performance metrics like throughput, packet delivery ratio, attack detection ratio, and energy consumption areanalyzedby using the NS-2 simulator with existing benchmark methods.
Soluble Programmed Death Molecule 1 (sPD-1) As Predictor of Interstitial Lung Disease in Rheumatoid Arthritis
Authors: Xu Li , Jiang Lichun , Nie Liuyan , Zhang Songzhao , Liu Lie , Du Yan , Xue Jing
Published: June 2021

Objective

To determine the relationship between serum soluble programmed death molecule-1 (sPD-1) levels and the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).
Methods

Blood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by enzyme-linked immunosorbent assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.
Results

Serum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = − 0.354), total lung capacity % (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.
Conclusion

Serum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.
Second Harmonic Generation Induced by Surface Plasma Wave on Metallic Surface in the Presence of Wiggler Magnetic Field
Authors: Dua Harleen Kaur , Kant Niti , Thakur Vishal
Published: June 2021

Under the influence of wiggler magnetic field, the phenomenon of second harmonic generation at the metal-semiconductor interface, induced by surface plasma wave (SPW) has been investigated. Metals like Cu, Ag and Al, each with a thin layer of n-InSb over it, are considered for our study. Laser light is incident on metal layered on glass prism in attenuated total reflection Kretschmann configuration (ATR) which generates SPW. The SPW further interacts nonlinearly with the electrons of n-type semiconductor layered over the metal, leading to second harmonic generation (SHG). The presence of an external wiggler magnetic field makes the process resonant and helps in phase matching. Relatively more enhancement in the amplitude of the second harmonic is observed for Cu-InSb as compared to Ag-InSb and Al-InSb. Numerical analysis shows that the enhancement in the amplitude of SHG increases with the wiggler magnetic field.
Intraarticular Bone Grafting in Atlantoaxial Facet Joints Via a Posterior Approach: Nonstructural or Structural —A Minimum 24-month Follow-up
Authors: Zhu Jun , Wu Jian , Luo Keyu , Wang Zhong , Jin Huaijian , Jin Yufei , Wang Yingbo , Liu Mingyong , Liu Peng
Published: June 2021

Objective. To investigate the necessity of nonstructural or structural intraarticular bone grafting in atlantoaxial facet joints via a posterior approach and the influence by presence of basilar invagination (BI).Methods. From November 2016 to October 2018, patients who underwent posterior atlantoaxial or occipitocervical arthrodesis surgery at one institute were retrospectively reviewed. Operation records, preoperative and postoperative clinical status and radiological films were analyzed. Results. 33 patients (19 without BI, 14 with BI) underwent posterior facet joint release followed by intraarticular bone grafting were enrolled finally. 24 nonstructural (15 without BI, 9 with BI) and 9 structural (4 without BI, 5 with BI) grafting were performed. The average follow-up was 32.15±6.73 months (24-47 months). Among them, 1 (3.03%) implant failure occurred, 32 (96.97%) achieved satisfactory neurological outcomes, including 28 (84.85%) complete and 4 (12.12%) acceptable reductions with complete fusion within 6 months. For patients without BI, structural and nonstructural grafting showed no significant difference in terms of reduction maintenance (100% vs 73.33%, p = 0.530), while for those with BI, structural grafting significantly increased the postoperative height of the joint space (5.67±1.22 mm vs 3.43±1.78 mm, p = 0.002) and maintained it much better than nonstructural grafting (88.89% vs 20.00%, p = 0.023), contributing notably to BI correction. Conclusion. Intraarticular structural bone grafting in atlantoaxial facet joints has the advantage of maintaining anterior column height in the case of lateral mass collapse or when BI correction is needed, otherwise, nonstructural bone grafting is enough.
Design and Simulation of Pottery Kiln
Authors: Govind Kiran , PU Keerthidas , R Karthik , R Kishore
Published: June 2021

Pottery industry is one of the small-scale industries in India. Most rural potters depend upontraditional pottery kilns for burning process by firewood or coconut husk. In order to producehigh quality pottery products better burning process is needed. The purpose of the project isto thermal analysis of burning process in a traditional furnace in order to achieve uniformtemperature inside the kiln and decrease the fuel consumption through better distribution of input heat. The traditional kilns are bonfire kilns, which involve open firing inshallow pit. These kilns suffer higher fuel consumption, poor ware strength andextensive breakage. Smokes produced during firing will serious health problems topottery workers and their family. There is lack of thermal studies on bonfire kilns. Accounting the demerits of traditional one is led to development of downdraught kiln. The thermal studies in performance of downdraught kiln by varying different parameters practically expensive and almost impossible. For this reason, the downdraught kiln is modeled and simulated on the computer by using the numerical method. By changing different parameter of the kiln like change in firewall height, Chimney height and roof geometry in simulation, substantial improvement in the performance of the kiln was detected. This modification is suggesting for the new design of improved pottery kiln.
Clinical Characteristics and Outcomes of Chronic Nonbacterial Osteomyelitis in Children: A Multicenter Case Series
Authors: Ma Le , Liu Haimei , Tang Hanyun , Zhang Zhiyong , Zou Lixia , Yu Haiguo , Sun Li , Li Xiaozhong , Tang Xuemei , Lu Meiping
Published: June 2021

Objective The study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). Methods Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. Results Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7-13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0-72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1-7). Most frequently affected bones were tibiofibula(88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and Hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate(MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. Conclusions The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.
Identification and Validation of a Hypoxia-Immune-Based Prognostic mRNA Signature for Oral Squamous Cell Carcinoma
Authors: Lv Shaohua , Li Jianhao , Piao Songlin , Li jichen
Published: June 2021

Background: Oral squamous cell carcinoma (OSCC) is a frequently encountered head and neck malignancy. Increasing evidence points towards an aberrant immune response and chronic cell hypoxia in the development of OSCC. However, there is a lack of a reliable hypoxia-immune-based gene signature that may serve to accurately prognosticate OSCC. Methods: The mRNA expression data of OSCC patients was extracted from the TCGA database. Hypoxia status was identified using the t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm. Both ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) was used for further evaluation of immune status. The DEGs in different hypoxia and immune status were determined. A Machine learning method-Least Absolute Shrinkage and Selection operator (LASSO) Cox regression analysis allowed us to select prognostically significant hypoxia- and immune-related mRNAs in order to construct prognostic gene signature to predict the overall survival (OS) of OSCC patients. Results: A total of 773 DEGs were classified into either Hypoxia_High and Hypoxia_Low groups. Immune-associated DEG expressions were used to divide individuals into Immune_High, Immune_ Medium and Immune_Low groups. A total of 193 mRNAs which were significant in both immune function and hypoxia status were identified. With the Lasso Cox regression model, 8 signature mRNAs (FAM122C, RNF157, RANBP17, SOWAHA, KIAA1211, RIPPLY2, INSL3, and DNAH1) associated with OS were selected for further calculation of their respective risk scores. The risk score showed a significant association with age, perineural and lymphovascular invasion. In the GEO validation cohort, a better OS was observed in patients from the low-risk group in comparison to those in the high-risk group. High-risk patients also demonstrated different immune infiltration characteristics from the low-risk group. All individuals from the TCGA OSCC cohort showed similar trends in all 6 immune checkpoints, with those of the low-risk group yielding higher immune indicator scores in contrast to their high-risk counterparts. Conclusion: The hypoxia-immune-based gene signature has prognostic potential in OSCC.
Gender and Age at Enrolment: the Predictor of Advanced Heart failure in Gene-negative Patients with Hypertrophic Cardiomyopathy
Authors: Qi Lin , Shan Zhengyi , Wei Ying , Wang Qing Yao , Zhao Peng
Published: June 2021

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) may develop concomitant advanced heart failure (HF). However, there is a paucity of data on the clinical outcomes of HCM patients without mutations who have advanced HF. Methods: A total of 1529 unrelated patients with HCM were enrolled and followed up. All patients were genotyped by whole exome or panel sequencing. Patients without mutations were studied to assess the impact of family history, clinical findings and echocardiographic parameters on advanced HF. Results: A total of 735unrelated patients with HCM were included in the study. The mean follow up duration was 3.2±2.3years. During follow-up,97 patients had advanced HF. Multivariable analysis revealed that risk factors significantly associated with advanced HF were gender [adjusted hazard ratio (HR)2.499, 95% confidence interval (CI) 1.531-4.081, P<0.001]and age at enrolment (adjusted HR 1.298,95% CI 1.00-1.682, P= 0.049) during the follow-up period. Conclusion: Female and older at enrolment can increase risk of advanced HF in gene-negative patients with HCM . Early detection and treatment have an important role to play in management and prevention of disease-related complications for gene-negative patients.
Uncovering CAZyme Induction in the Thermophilic Fungus Thermoascus Aurantiacus
Authors: Gabriel Raphael , Mueller Rebecca , Floerl Lena , Hopson Cynthia , Harth Simon , Schuerg Timo , Fleissner Andre , Singer Steven W.
Published: June 2021

Background: Filamentous fungi are excellent lignocellulose degraders, which they achieve through producing carbohydrate active enzymes (CAZymes). CAZyme production is highly orchestrated and the application of –omics methods such as RNA-Seq has greatly expanded understanding of this important biotechnological process. The thermophilic fungus Thermoascus aurantiacus secretes high amounts of highly active thermostable enzymes that enable saccharifications at higher temperatures; however, the genome-wide response to CAZyme induction is not understood. Results: A fed-batch system with plant biomass-derived sugars D-xylose, L-arabinose and cellobiose established that these sugars induce CAZyme expression in T. aurantiacus. The C5 sugars induced both cellulases and hemicellulases, while cellobiose specifically induced cellulases. A minimal medium formulation was developed to enable RNA-seq studies of T. aurantiacus with these inducers. It was found that D-xylose and L-arabinose strongly induced a wide variety of CAZymes, auxiliary activity (AA) enzymes and carbohydrate esterases (CEs), while cellobiose facilitated lower expression of mostly cellulase genes. Furthermore, putative orthologues of different unfolded protein response genes were up-regulated during the C5 sugar feeding together with genes in the C5 sugar assimilation pathways. Conclusion: This work has identified two additional CAZyme inducers for T. aurantiacus, L-arabinose and cellobiose, along with D-xylose. A combination of biochemical assays and RNA-seq measurements established that C5 sugars induce a suite of cellulases and hemicellulases, providing a path to produce a broad spectrum thermotolerant enzymatic mixture for deconstruction of plant biomass.
Preventing Healthcare-Associated Infections by Avoiding Unnecessary Hospitalization: Cohort Study
Authors: Porto Ercília Evangelista , Guimarães Thais , Dias João Ítalo , Padoveze Maria Clara
Published: June 2021

Background

Healthcare-associated infections (HAI) are major public health problem. The primary care is a key component of health systems, integrating the care across the care levels. Preventing unnecessary hospitalizations is one of objectives of primary care, thus avoiding exposing the patient to iatrogenic risks, such as HAI. The so-called Primary Care Sensitive Conditions (PCSC) have been used as an indicator that measures the effectiveness of primary care. This study aims at to identify whether there is an association between PCSC and HAI.
Methods

Prospective cohort with a nested case-control study. Sampling included 605 adult patients with more than 48 hours of hospitalization in public tertiary-care hospital in São Paulo, Brazil. We used structured questionnaire to characterize sociodemographic and clinical profile of participants. The information about hospitalization due to PCSC was collected from the patients’ medical record. The infection control team identified HAI cases in the routine surveillance using standard criteria. Multilevel regression model and the propensity score for case matching were used for data analysis.
Results

In our cohort, 55 (9.1%) patients were admitted due to PCSC. Overall, 32 (5.3%) of the cohort patients developed HAI. The Human Development Index of cities of patients’ origin was high, varying from 0.72 to 0.81, and the Gini index varied from 0.41 to 0.67. The average family income was around 2.5 Brazilian minimum wages (equivalent to USD 691.24 at the time of the study). We observed no relevant differences among patients with HAI or regarding individual or social indicators. The multilevel regression showed an odds ratio of 2.877 (95% CI: 0.960–8.262; p = 0.05) for potential association of HAI and PCSC, but not significant. In the analysis of the case-control study based on propensity balance, the group with PCSC had an odds ratio of 1.795 (95% CI 0.390–8.270) for the presence of HAI, but without statistical significance (p = 0.707).
Conclusion

This study did not demonstrated statistical association between HAI acquisition and PCSC. However, it is still unclear how much HAI rates are influenced by vulnerability conditions of patients that could be prevented by efficient primary care.
Enhanced RNAi stability through imperfect inverted repeats: nucleotide mismatches prevent intrinsic self-silencing of hpRNA transgenes in plants
Authors: Zhang Daai , Zhong Chengcheng , Smith Neil , Defeyter Rob , Greaves Ian , Swain Steve , Zhang Ren , Wang Ming-Bo
Published: June 2021

Hairpin RNA (hpRNA) transgenes, with a perfect inverted-repeat (IR) DNA, have been the most successful RNA interference (RNAi) method in plants. Here we show that hpRNA transgenes were invariably methylated in the IR DNA and the adjacent promoter, causing transcriptional self-silencing and preventing the full potential of RNAi. Nucleotide substitutions in the sense sequence, which disrupts the perfect IR DNA structure, were sufficient to prevent the intrinsic DNA methylation resulting in more uniform and persistent RNAi. Substituting all cytosine (C) with thymine (T) nucleotides, in a G:U hpRNA design, prevented DNA methylation and self-silencing but still allowed for the formation of perfect hpRNA due to G:U wobble base-pairing. The G:U design induces effective RNAi in 90–96% of transgenic lines, compared to 57–65% for the traditional hpRNA design. Furthermore, while a traditional hpRNA transgene showed increasing DNA methylation and self-silencing from cotyledons to true leaves, the G:U transgenes avoided this developmental progression of self-silencing and induced RNAi throughout plant growth. The G:U and traditional hpRNA transgenes generated small interfering RNA (siRNA) with different 5’ phosphorylation, which resembled the endogenous tasiRNA and miRNA, respectively. Furthermore, our results suggest that siRNAs from the two transgene designs function differently to induce target DNA methylation, one (from traditional hpRNA) through the canonical RdDM pathway and the other (G:U hpRNA) a non-canonical pathway. Our study not only revealed a methylation-resistant RNAi transgene design but also provided new mechanistic insights into small RNA biogenesis and function in plants.
The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms
Authors: Zhang Yuanyuan , Hutterer Evelyn , Hultin Sara , Bergman Otto , Forteza Maria , Andonovic Zorana , Ketelhuth Daniel , Roy Joy , Eriksson Per , Holmgren Lars
Published: June 2021

Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic and arterial ECs. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provokes a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and aneurysm diameters, as well as a positive correlation between AmotL2 and YAP expression. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular disease.
Appropriate sites for the active surveillance of carbapenemase-producing Enterobacteriaceae
Authors: Park Joung Ha , Choi Hye-Suk , Yang Hyejin , Lee Hyun-Ju , Kwak Sun Hee , Kim Eun Ok , Chong Yong Pil , Choi Sang-Ho , Lee Sang-Oh , Kim Yang Soo , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Jung Jiwon
Published: June 2021

Background: Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study.Methods: Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. Patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results: Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95).Conclusions: The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Thus, combining surveillance of the stool with other sites may be needed for detecting CPE.
PET Microplastics Affect Human Gut Microbiota Communities During Simulated Gastrointestinal Digestion. First Evidence of Plausible Polymer Biodegradation During Human Digestion
Authors: Tamargo Alba , Molinero Natalia , Reinosa Julián J. , Alcolea-Rodríguez Victor , Portela Raquel , Bañares Miguel A. , Fernández Jose F. , Moreno-Arribas M.Victoria
Published: June 2021

Microplastics are a widely recognized global problem due to their prevalence in natural environments and the food chain. However, the impacts of microplastics on human microbiota and their possible biotransformations during the gastrointestinal tract have not been well reported. To evaluate the potential risks of microplastics at the digestive level, completely passing a single dose of polyethylene terephthalate (PET) through the gastrointestinal tract was simulated by combining a harmonised static model and the dynamic gastrointestinal simgi® model, which recreates the different regions of the digestive tract in physiological conditions. PET MPs started several biotransformations in the gastrointestinal tract and appeared to expose the colon in ways that were structurally different from the original forms. We report that the feeding with microplastics alters human microbial colonic community composition, and hypothesize that some members of the colonic microbiota could adhere to MPs surface promoting the formation of biofilms. The work presented here indicates that microplastics are indeed capable of digestive-level health effects. Considering this evidence and the increasing exposure to microplastics in consumer foods and beverages, the impact of plastics on the functionality of the gut microbiome and their potential biodegradation through digestion and intestinal bacteria merits critical investigation.
Constructing MRNA, miRNA, circRNA and lncRNA Regulatory Network by Analysis of Microarray Data in Breast Cancer
Authors: Hassani Bita , Mollanoori Hasan , Pouresmaeili Farkhondeh , Asgari Yazdan , Ghafouri-Fard Soudeh
Published: June 2021

Background. Luminal tumors are the utmost frequent subtype of breast cancer (BC). Despite luminal BC has relatively good prognosis, in a subset of patients, disease relapse occurs to endocrine therapy ;hence, there is a critical need to identify new strategies to promote the early detection and more effective therapies. Noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) can interact with and modulate each other via diverse molecular mechanisms and make a complicated regulatory network. ncRNAs participate in diverse biological processes and disorders such as breast tumors. Therefore, understanding their regulatory mechanisms allow to develop new field of research and therapeutic options for BC patients. Methods. In this study, BC-specific RNA expression profiles including mRNAs, miRNAs, lncRNAs, and circRNAs were retrieved from Gene Expression Omnibus (GEO) microarray datasets, and differentially expressed (DE) items were obtained. Disease ontology, functional and pathway enrichment analyses were executed. The protein-protein interaction network was constructed, and hub mRNAs were extracted. The prognostic value of hub mRNAs in patients of BC were performed using GEPIA. Subsequently, a ceRNA network was established by Cytoscape.Results. In total, 691 DE genes, 122 DE lncRNAs, 60 DE miRNAs, and 38 DE circRNAs in breast tumor samples were compared with normal samples. Subsequently, 12 hub-genes including FOXO3, RHOA, EZH2, KIT, HSP90B1, NCOA3, RAC1, IGF1, CAV1, CXCR4, CCNB1, and ITGB1 were screened from the network. Kaplan-Meier Plotter results revealed that FOXO3 and RHOA were a suitable prognostic marker for patients with breast cancer. Finally, we determined possible ncRNAs (circ0007535, circ0002727, circ0005240, circ0014130, circ0044927, circ0007001, circ0089153, NORAD, MALAT1, TUG1, ZFAS1, OPI5-AS1, miR183, miR182, miR101, miR200c, miR200b, miR149, miR342, and miR1207) which could crosstalk with each other to regulate FOXO3 and RHOA through different regulatory patterns. Conclusion. These data might improve our perception of the breast tumorigenesis and could develop new field of research and therapeutic options for BC patients.
Identification of Immunodominant Epitopes in Allelic Variants VK210 and VK247 of Pakistani based Plasmodium Vivax Circumsporozoite Immunogen
Authors: Naz Shumaila , Ahmad Sajjad , Abbasi Sumra Wajid , Ismail Saba , Waseem Shahid , Qamar Muhammad Tahir ul , Ali Zain
Published: June 2021

Plasmodium vivax-induced malaria is one of the leading causes of morbidity and mortality in sub-tropical and tropical regions and known to infect 2.85 billion people globally. The continual rise and propagation of resistance against anti-malarial drugs is a prerequisite to identify a possible vaccine candidate for Plasmodium vivax (P. vivax). Circumsporozoite protein (CSP) is an important immunogen of malaria parasite that has conserved the CSP structure as an immune dominant B-cell epitope. In the current study, we focused on designing multi-epitope vaccines (MEVs) using various immunoinformatics tools against Pakistani based allelic variants VK210 and VK247 of P. vivax CSP (PvCSP) gene. Antigenicity, allergic potential and physicochemical parameters of both PvCSP variants were assessed for the designed MEVs and are within acceptable range suitable for post experimental investigations. The three-dimensional structures of both MEV shave been predicted ab initio, optimized, and validated by using different online servers. Structure and from residues perspectives, the MEVs are stable and are free from aggregation-prone regions. The stability of both MEVs has been improved by a disulfide engineering approach. To estimate the binding energy and stability of the MEVs, molecular docking simulation and binding free energy calculations with TLR-4 immune receptor have been conducted. The expression of both MEVs produced in Escherichia coli K12 expression system by in silico cloning was significant. Immune simulation revealed that the proposed MEVs induce strong humoral and cellular immunological responses, in addition to significant production of interleukins and cytokines. In conclusions, we believed that the MEVs proposed in current research, using combine approach of immunoinformatics, structural biology and biophysical approaches, could induce protective and effective immune responses against P. vivax and the experimental validation of our findings could contribute to the development of potential malaria vaccine.
A Novel Determination of the Relationship Between Exposure to Industrial Toxicant HFPO-DA and pqm-1-related Aging in C. elegans
Authors: Nagam Vishruth
Published: June 2021

Hexafluoropropylene oxide dimer acid (HFPO-DA, ammonium salt with trade name “GenX”) is an industrial toxicant that has recently been detected in the environment [1]. However, HFPO-DA’s potential aging-related effects on organisms of higher trophic levels, including worms and humans, have not been extensively explored. The purpose of this study is to quantify influences on C. elegans (free-living nematode) lifespan by HFPO-DA exposure, specifically via ingestion of food to simulate the mechanisms of toxicant exposure, through lower trophic-level organisms, commonly found in nature. C. elegans N2 (wild-type) samples were prepared with a uracil-based medium and E. coli OP50 (food source) at room temperature; C. elegans in the experimental, treated sample was fed E. coli OP50 incubated with 280 ng/L HFPO-DA. The target gene pqm-1 was selected due to its role in an evolutionarily conserved insulin signaling pathway and in promoting development. Molecular biology laboratory techniques (RNA extraction, qRT-PCR, fluorescence tagging, etc.) were used to quantify pqm-1 expression to yield four technical replicates for each sample. The data was analyzed through null hypothesis t-tests, heatmaps, protein interactions, and gene homology tools. HFPO-DA exposure through E. coli caused a statistically insignificant (0.811-fold) change in pqm-1-related aging in C. elegans. Future work includes investigating the effects of different levels of HFPO-DA exposure on C. elegans aging.
Do clinical practice guidelines consider evidence about test consequences? A critical document analysis
Authors: Tuut Mariska , Burgers Jako , Weijden Trudy van der , Langendam Miranda
Published: June 2021

Background

Supporting evidence for medical test recommendations in clinical practice guidelines (CPGs) should not only include diagnostic accuracy, but also the downstream consequences of the test result on patient relevant outcomes. The aim of this study is to assess the methodology of developing of evidence-based CPGs about medical tests, and to explore determinants of best CPGs.
Methods

We performed a systematic document analysis and quality assessment of publicly accessible CPGs about three common diagnostic topics: C-reactive protein (CRP), colonoscopy and fractional exhaled nitric oxide (FeNO). Evaluation of the complete test-treatment pathway (diagnostic accuracy as well as downstream consequences on patient relevant outcomes (i.e. burden of the test, natural course, treatment effectiveness, and link between test result and administration of treatment)) was considered best practice for developing medical test recommendations.
Results

We retrieved 15 recommendations in 15 CPGs. The methodological quality of the CPGs varied from poor to excellent. Seven CPGs reported the use of the GRADE approach. In three CPGs, however, we could not find elements of that approach in the guideline documents. Ten recommendations considered diagnostic accuracy. Four of these were supported with a systematic review of the literature and rating of the certainty in the evidence. None of the CPGs evaluated all steps of the test-treatment pathway. Burden of the test was considered in three CPGs, but not with a systematic review of the evidence. Natural course was considered in two CPGs, and also not with a systematic review of the evidence. In three recommendations, treatment effectiveness was considered, which was supported with a systematic review and rating of the certainty in the evidence in one CPG. The link between test result and administration of treatment was not considered in any CPG.
Conclusions

CPGs with recommendations about medical tests do not seem to consider evidence about test consequences on patient relevant outcomes. This might be explained by reporting issues and challenging methodology. Future research is needed to investigate how to facilitate guideline developers in explicitly and reliably considering all steps of a test-treatment pathway when developing medical test recommendations.
Mediation role of alexithymia, sensory processing sensitivity and emotional-mental processes between childhood trauma and adult psychopathology: a self-report study
Authors: DİNÇ Pelin KARACA , OKTAY Seda , BATIGÜN Ayşegül DURAK
Published: June 2021

Background
There is overwhelming evidence for a strong association between childhood trauma and adult psychopathology. This study aims to investigate the mediation roles of alexithymia, sensory processing sensitivity, and emotional-mental processes in the relationship between childhood traumas and adult psychopathology.
Methods
337 people (78.9% female, 21.1% male) between the ages of 20–64 participated in this study. Participants filled the scales online via google form. Reading Mind in the Eyes (EYES), Sensory Processing Sensitivity Scale (SPS), Toronto Alexithymia Scale (TAS-26), Childhood Trauma Questionnaire (CTQ), and the Brief Symptom Inventory (BSI) were used. SPSS Process (Model 4) was used to examine the mediating role of sensory processing sensitivity, alexithymia and the eyes test results in the relationship between childhood trauma and psychopathology.
Results
Sensory processing sensitivity and alexithymia have been found to mediate the relationship between childhood trauma and adult psychopathology. The eyes test (mentalization) was not found to have a mediating effect on this relationship.
Conclusion
This study shows that childhood traumas may relate more psychopathology in individuals with high sensory processing sensitivity and alexithymia. Our study may contribute to the understanding of what may lead to a person's vulnerability to experiencing psychopathology after childhood trauma. It may be important that future treatment and intervention programs should include sensory sensitivity and alexithymia. Sensory processing sensitivity and alexithymic characteristics of individuals can be examined in the treatment of psychological problems of individuals who have experienced childhood trauma.
Inhibitory Effects of Redroot Pigweed and Crabgrass on Germination and Growth----From Lab To Field
Authors: Hou Xincun , Hu Xu , Yue Yuesen , Guo Qiang , Zhao Chunqiao , Fan Xifeng , Wu Juying
Published: June 2021

Interactions between weeds and crops often occur by resource competition or allelopathy. However, it is still unknown how local weed species influence artificially introduced switchgrass. In this study, four experiments were conducted to evaluate the inhibitory effects of redroot pigweed (Amaranthus retroflexus) and crabgrass (Digitaria sanguinalis) on germination and growth of switchgrass, the lowland tetraploid cultivar ‘Alamo’ (Panicum virgatum cv. Alamo). Switchgrass germination was inhibited significantly in Petri dishes, with 48.1% and 33.9% inhibition on germination rate by redroot pigweed and crabgrass root aqueous extracts at 0.1 g·mL− 1 concentration, respectively. Significant inhibitory effects on switchgrass seedling biomass were observed at 5:5 proportion with redroot pigweed and crabgrass in glass jars, with 61.6% and 53.4% inhibition on plant biomass, respectively. Under the same root segregation, redroot pigweed had a stronger inhibitory effect on switchgrass seedling growth than crabgrass. Growth of transplanted switchgrass seedlings was inhibited significantly by local weeds in the field, with 46.2% and 11.7% inhibition on shoot biomass during the first and second growing seasons, respectively. However, no significant growth reduction in switchgrass was detected in the third growing season.
Integrated High-Throughput Small RNA and Transcriptome Sequencing Unveil The Shape-Dependent Toxicity of Nano-Alumina in Rat Astrocytes
Authors: Chen Yuanyuan , Dong Li , Deng Fuchang , Cao Yaqiang , Fu Yuanzheng , Zhu Mu , Qin Guangqiu , Schultz Dayna , Shekh Kamran , Tang Song
Published: June 2021

Background
The large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, is causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNAs and mRNAs profiles of astrocytes in rat cerebral cortex, ex vivo.
Results
Totals of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways.
Conclusions
In this study, we demonstrate that the toxicity of nanorods might be stronger than that of nanoflakes. And this study also demonstrates the critical role of morphology in nanotoxicity of nano-alumina and reveals its potential biomolecular mechanisms.
Titania Nanosheets Generates Peroxynitrite for S-Nitrosylation and Enhanced p53 Function in Lung Cancer Cells
Authors: Soonnarong Rapeepun , Tungsukruthai Sucharat , Nutho Bodee , Rungrotmongkol Thanyada , Vinayanuwattikun Chanida , Maluangnont Tosapol , chanvorachote pithi
Published: June 2021

Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated.Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics.Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization.Conclusions: Taking all the evidence together, we provided information on the apoptosis induction effect of the nanosheets through a molecular mechanism involving reactive nitrogen species, which affects the protein stability; thus emphasizing the novel mechanism of action of nanomaterials for cancer therapy.
An Exceptional Dark Matter from Cayley–Dickson Algebras
Authors: Masi Nicolo'
Published: June 2021

In this article I propose a new criterion to individuate the origin and the properties of the dark matter particle sector. The emerging candidates come from a straightforward algebraic conjecture: the symmetries of physical microscopic forces originate from the automorphism groups of main Cayley–Dickson algebras, from complex numbers to octonions and sedenions. This correspondence leads to a natural enlargement of the Standard Model color sector, from a SU(3) gauge group to an exceptional Higgs-broken G(2) group, following the octonionic automorphism relation guideline. In this picture, dark matter is a relic heavy G(2)-gluons ensemble, separated from the particle dynamics of the Standard Model due to the high mass scale of its constituents.
Optimization of Medium for Bioconversion Extruded Apple Pomace into Microbial Protein
Authors: Yang Zhe , Zhang Min , Jiang Lijun , Suo Wenjing , Deng Yuxin , Zhang Haijing , Guo Peng , Li Hongjun
Published: June 2021

The medium compositions such as carbon and nitrogen sources, moisture content and inorganic salt affected the microbial protein (MP) production. Imbalance of carbon-nitrogen ratio in apple pomace (AP) limited the microbial utilization. Hence, those conditions must be optimized to achieve maximum MP. In this work, AP was pretreated by extrusion technology to obtain extruded apple pomace (EAP). Subsequently, the medium compositions were optimized using Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD determined four significant factors (bran, glucose, packing quantity (PQ), water to material ratio (W/M)) out of the eight variables. The BBD results showed that optimal true protein content (10.42%), effective viable count (1.94×109 CFU/g) and crude protein content (18.73%) were achieved at bran 16.22%, glucose 8.09%, PQ 9.88 g and W/M 1.56. Compared with AP, the true protein and crude protein content of optimal fermented EAP (FEAP) were increased by 152% and 216%, respectively. According to fluorescence microscopy, the cellulose of AP was little effected by extrusion technology while was mostly degraded by mixed strains (Aspergillus niger, Candida utilis, Geotrichum candidum and Lactic acid bacteria). Combination of extrusion and fermentation, the medium compositions were optimized to promote the bioconversion of AP into MP feed.
Identifying The Most Important Workplace Factors in Predicting Mental Health Among British Columbia Nurses Using Machine Learning Techniques
Authors: Havaei Farinaz , Ji Xuejun , MacPhee Maura , Straight Heather
Published: June 2021

Objectives

Nurses are at a high risk of developing mental health problems due to exposure to work environment risk factors. Previous research in this area has only examined a few factors within nurses’ work environments, and those factors were not conceptualized with the goal of improving workplace mental health. The purpose of this study is to identify the most important work environment predictors of nurse mental health using a comprehensive and theoretically grounded measure based on the National Standard of Psychological Health and Safety in the Workplace.
Methods

This is an exploratory cross-sectional survey study of nurses in British Columbia, Canada. For this study, responses from a convenience sample of 4,029 actively working direct care nurses were analyzed using random forest regression methods. Key predictors include 13 work environment factors. Study outcomes include depression, anxiety, post-traumatic stress disorder (PTSD), burnout and life satisfaction.
Results

Overall, healthier reports of work environment conditions were associated with better nurse mental health. More specifically balance, psychological protection and workload management were the most important predictors of depression, anxiety, PTSD and emotional exhaustion. While engagement, workload management, psychological protection and balance were the most important predictors of depersonalization, engagement was the most important predictor of personal accomplishment. Balance, psychological protection and engagement were the most important predictors of life satisfaction.
Conclusions

Routine assessment with standardized tools of nurses’ work environment conditions and mental health is an important, evidence-based organizational intervention. This study suggests nurses’ mental health is particularly influenced by worklife balance, psychological protection and workload management.