bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of RNA Binding Protein Signature to Predict Overall Survival for Bladder Cancer
Authors: Li Danxia , Han Wenkai , Che Kai , niu haitao
Published: July 2021

Background: Bladder urothelial cancer (BLCA) is the 10th most common and 13th most deadly cancer globally. RNA binding proteins (RBPs) were reported to participate in the occurrence and progression of varieties of diseases, including malignant tumors. However, the role of RBPs in BLCA is rarely reported. Methods: We downloaded the transcriptome sequence gene expression data and the related clinical data from the cancer genome atlas (TCGA) database, and identified the differently expressed RBPs between BLCA and normal tissues. We explored the biological function by gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes database (KEGG) enrichment analysis. 388 key RBPs were obtained by protein-protein interaction (PPI). We constructed a prognostic risk model, explored the risk score related to BLCA, and validated the results both in the test group and HPA database. Results: In total, 388 differently expressed RBPs were discovered. Five prognostically relevant hub RBPs (YARS, EFTUD2, OAS1, DARS2, TRIM71) were used to construct a prognostic model based on multiple Cox analysis. We found that the overexpression of YARS, EFTUD2, DARS2, and TRIM71 were unfavorable prognostic factors for BLCA patients. Furthermore, we validated the results by the TCGA cohort and the Human Protein Atlas (HPA) database. Conclusion: We identified five RNA binding protein signatures to predict the overall survival for BLCA patients, which provide new insights for the pathogenesis and treatment of BLCA.
Optimal Surgical Margin to Avoid Locoregional Recurrence for Non-small Cell Lung Cancer Larger than 2.0 cm: A Retrospective Study
Authors: Suzuki Shigeki , Kazama Akio , Shigenobu Takao , Sakamaki Hiroyuki , Masugi Yohei , Tajima Atsushi
Published: July 2021

Background. A parenchymal surgical margin of“the clinical tumor size or more” or “2.0 cm or more” has been widely recognized as the optimal margin distance to avoid locoregional recurrence after sublobar resection for non-small cell lung cancer (NSCLC) of 2.0 cm or less. However, the safe margin distance to avoid locoregional recurrence for NSCLC larger than 2.0 cm remains unclear. Patients and Methods. Among 1,338 patients with resected primary lung cancers at two institutions between 2007 and 2016, 85 clinical N0M0 patients with NSCLCs larger than 2.0 cm who underwent sublobar resection were extracted. We classified these 85 NSCLCs as ground glass opacity (GGO)-dominant type or solid-dominant type according to computed tomography (CT) findings. Clinicopathological characteristics and the association between locoregional recurrence and margin distance were evaluated. Results. The median clinical tumor size was 2.5 (2.1-4.9) cm. Based on CT findings, 14 tumors (16%) were considered GGO-dominant type and 71 (84%) were solid-dominant type. No lymph node metastasis, lymphatic permeation or vascular invasion was pathologically confirmed in GGO-dominant type. All GGO-dominant tumors were resected with a margin distance the size of the solid part on CT or more, resulting in no local recurrence, whereas, solid-dominant tumors recurred locally even if they were resected with a margin distance of “the clinical tumor size or more”. Conclusions. The optimal surgical margin for NSCLC larger than 2.0 cm was “the size of the solid part on CT or more” for GGO-dominant type, but undefinable for solid-dominant type.
ADH7 Polymorphism and Alcohol Consumption on Risk of Head and Neck Squamous Cell Carcinoma in The Korean Population
Authors: Lee Dong Won , Ji Yong Bae , Song Chang Myeon , Kim Jeong Kyu , Lee Seung Hwan , Tae Kyung
Published: July 2021

Purpose
The development of head and neck squamous cell carcinoma (HNSCC) is closely associated with alcohol consumption. Also, it is related to individual genetic susceptibility, such as single nucleotide polymorphism (SNP) of alcohol dehydrogenase (ADH). This study aimed to investigate the association of ADH7 SNPs with the risk of HNSCC.
Methods and Patients:
We analyzed ADH7 rs1573496C > G, rs3737482T > C, rs1154460G > A, and rs284787T > C SNPs in 250 patients with HNSCC and 322 controls in the Korean populations. Genomic DNA was extracted from peripheral blood, and genotyping was done using the TaqMan assay. Linkage disequilibrium (LD) and haplotypes were analyzed.
Results
The odds ratios (OR) and 95% confidence intervals (CI) of the CT and CC genotypes of ADH7 rs3737482T > C were 0.48 (0.29–0.78) and 0.69 (0.49–0.96), indicating a significantly decreased risk. In SNP of rs1154460G > A, the OR and 95% CI of the AA genotype was 1.63 (1.11–2.40), showing a significant increase in the risk. Furthermore, SNPs of ADH7 rs3737482T > C and ADH7 rs1154460G > A exhibit synergistic interactions with alcohol composition on the risk of HNSCC. None of the haplotypes were associated with the risk of HNSCC.
Conclusions
ADH7 rs3737482T > C and rs1154460G > A SNPs are associated with the risk of development of HNSCC in Koreans. It could serve as a molecular biological marker to screen the high-risk groups for HNSCC.
Effects of the cefazolin shortage on the sales, cost, and appropriate use of other antimicrobials
Authors: KOIZUMI Ryuji , KUSAMA Yoshiki , ASAI Yusuke , GU Yoshiaki , MURAKI Yuichi , OHMAGARI Norio
Published: July 2021

Background

Shortages of antimicrobials lead to treatment failures, increase medical costs, and accelerate the development of antimicrobial resistance. We evaluated the effects of the serious cefazolin shortage in 2019 in Japan on the sales, costs, and appropriate use of other antimicrobials.
Methods

We evaluated monthly defined daily doses/1,000 inhabitants/day (DID) values of antimicrobial sales from January 2016 to December 2019 using wholesaler’s sales databases. Using 2016–2018 sales data, we generated a prediction model of DID in 2019 under the assumption that the cefazolin shortage did not occur. We then compared the predicted DID and actual DID. Cefazolin, government-recommended alternatives, and non-government-recommended broad-spectrum alternatives were assessed. Antimicrobial groups according to the AWaRe classification were also assessed to evaluate the effect on appropriate antimicrobial use. In addition, we evaluated changes in costs between 9 months before and after the cefazolin shortage.
Results

DID values of total antimicrobials increased sharply 1 month before the decrease in cefazolin. Actual DIDs were higher than predicted DIDs for ceftriaxone, flomoxef, clindamycin, cefotiam, piperacillin/tazobactam, and meropenem. Actual DID values were higher than the predicted DID values in the Watch group. The costs of antimicrobials between pre- and post- cefazolin shortage were unchanged.
Conclusion

The cefazolin shortage brought confusion to the antimicrobial market and led to a setback in the appropriate use of antimicrobials. Early recognition and structures for prompt reactions to antimicrobial shortages are needed. Moreover, development of a system to secure the supply of essential antimicrobials is required.
Integrated Strategies for Enhancing the Expression of Chitosanase AqCoA in the Pichia Pastoris by A Novel High-Copy Plasmid PMC-GAP
Authors: Wang Yanxin , Zhao Yuqiang , Luo Xue , Li Zhoukun , Ye Xianfeng , Huang Yan , Li Ding , Cui Zhongli
Published: July 2021

In our previous study, the chitosanase AqCoA and its products chitooligosaccharides exhibited significant application in fungal disease protection. In this study, to enhance the expression of AqCoA, we obtained various strains with multi-copy by a novel plasmid pMC-GAP with stable transformation ability in Pichia pastoris and built an integrated model combining the gene copy number, the chaperones and protein production of AqCoA. In terms of gene dosage, the highest enzyme activity was 0.32 U/ml in the strain with four copies, which was 1.78-fold higher than that in strain with only one copy (0.18 U/ml). In addition, we found the chaperone like PDI, ERO1, HAC1, YDJ1, SSE1, SSA4 and SSO2 improved protein expression. Furthermore, the PDI/ERO1, SSA4/SSE1 and YDJ1/SSO2 pairs synergistically increased by 61%, 31% and 42% in expression levels of the strain GAP-1AqCoA. Finally, we investigated the effect co-expression of gene copy and chaperones on protein expression. The maximum activity reached 2.319 U/ml by the strain with six chaperones intergrant plus sixteen copies, which was 13-fold higher than that by the control strain with only one copy (GAP-1AqCoA). Co-expression of gene dosage and chaperones significantly enhanced expression levels of AqCoA, which presented a powerful tool to improve foreign protein expression.
Metabolism Balance, Pyroptosis Regulation and Microenvironmental Protection by Exosomes Functioned as an Injectable Extracellular Matrix Hydrogel for Nucleus Pulposus Regeneration
Authors: Xing Hongyuan , Zhang Zengjie , Mao Qijiang , Wang Chenggui , Zhou Youlong , Zhou Xiaopeng , Ying Liwei , Xu Haibin , Hu Shaojun , Zhang Ning
Published: July 2021

Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) through regulating metabolic disorders, the microenvironment and cell homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for its application in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes that inherited the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can not only provide in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also provide an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@Exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD.
MS2 Virus-like Particle as an Efficient Drug Delivery Tool: Optimizing the Synthesis and Purification Protocol
Authors: Hashemi Khadijeh , Seno Mohammad Mahdi Ghahramani , Ahmadian Mohammad Reza , Malaekeh-Nikouei Bizhan , Bassami Mohammad Reza , Dehghani Hesam , Afkhami-Goli Amir
Published: July 2021

Introducing bacteriophage MS2 virus-like particles (VLPs) as gene and drug delivery tools increases the demand for optimizing their production and purification procedure. PEG precipitation method is used efficiently to purify VLPs, while the effects of pH and different electrolytes on the stability, size, and homogeneity of purified MS2 VLPs, and the encapsulated RNA sequences remained to be elucidated.In this regard, a vector, capable of producing VLP with an shRNA packed inside was prepared. The resulting VLPs in different buffers/solutions were assessed for their size, polydispersity index, and ability to protect the enclosed shRNA. We report that among Tris, HEPES, and PBS, with or without NaNO3, and also NaNO3 alone in different pH and ionic concentrations, the 100mM NaNO3-Tris buffer with pH:8 can be used as a new and optimal MS2 VLP production buffer, capable of inhibiting the VLPs aggregation. These VLPs show a size range of 27-30nm and suitable homogeneity with minimum 12-month stability at 4◦C. Moreover, the resulting MS2 VLPs were highly efficient and stable for at least 48 hours in conditions similar to in vivo. These features of MS2 VLPs produced in the newly introduced buffer make them an appropriate candidate for therapeutic agents’ delivery.
Shifts in Help-seeking Patterns During COVID-19: Should Social Distancing be Rebranded?
Authors: Junus Alvin , Kwan Ching , Wong Clifford , Chen Zhansheng , Yip Paul
Published: July 2021

Much focus has been placed on mental health symptoms brought forth by the COVID-19 pandemic, yet limited discourse & evidence have evaluated how the closure of multiple venues under social distancing measures impacted people's patterns of help-seeking, which had traditionally been the very coping mechanism that buffered individuals from the consequences of those studied symptoms.
Using a two-wave (June-July 2019 and June-September 2020) panel data on youths aged 11-35 years old, the present study shows that under social distancing, a significant proportion of individuals who used to rely on their strong ties for support no longer sought help even after controlling for stress level changes & sociodemographic factors, and only those who were facing heavier distress ended up seeking their strong ties for support.
By simply closing off social contexts that had traditionally facilitated social support provision among strong ties and not providing people with alternative contexts, current social distancing measures appeared to have effectively increased the difficulty for many to receive social support, thereby leaving them vulnerable to mental health impacts of the pandemic. To prevent the current pandemic from turning into a mental health pandemic, the mantra "social distancing" should be revised to encourage society to remain socially close even while physically distant.
Development and Psychometric Evaluation of an Instrument to Assess Knowledge, Attitude and Practice of Family Caregivers at Preventing Pressure Injuries (KAP-PI) in Indonesian Community-Dwelling Older Adults
Authors: Sari Sheizi Prista , Everink Irma , Lohrmann Christa , Amir Yufitriana , Sari Eka Afrima , Halfens Ruud JG , Beeckman Dimitri , Schols Jos MGA
Published: July 2021

Background: The prevalence of pressure injuries among community-dwelling older adults in countries worldwide is still a serious problem. In Indonesia, older adults mostly rely on family members for (medical) care. Therefore, involving family members in the prevention and treatment of PIs could potentially decrease its prevalence rates. However, family members are usually not trained for such tasks. Hence, it is essential to first get more insight into the current state of affairs on family members’ knowledge, attitude and actual practice of preventing PIs. Due to the lack of an existing instrument to measure knowledge, attitude and practice of family caregivers in preventing PIs, this study focuses on the development and evaluation of psychometric properties of such an instrument. Methods: Three phases of instrument development and evaluation were used, including item generation, instrument construction and psychometric testing of the instrument. A total of 372 family caregivers of community-dwelling older adults who randomly selected participated in this study. Statistical analysis of exploratory analysis, confirmatory factor analysis and Cronbach’s alpha were used for the evaluation.Results: The final version of the KAP-PI-instruments consists of a 12-item knowledge domain, a 9-item attitude domain, and a 12-item practice domain with Cronbach’s Alpha values of 0.83, 0.93 and 0.89, respectively. The instrument appeared to be both reliable and valid.Conclusion: The KAP-PI instrument can be used in family nursing or community nursing practice, education, and research to assess knowledge, attitude and practice of pressure injury prevention of family caregivers.
River Mangrove Maintains Certain Level Na+ and Cl- in Leaves to Adapt Seasonal Freshwater
Authors: Xu Li , Liu Chao , Xin Changpeng , Wang Wenqing
Published: July 2021

Background: Mangrove environments are often characterized by large fluctuations in salinity, ranging from freshwater to hypersaline conditions. Most reports have focused on the mechanisms by which mangroves adapt to high salinity. However, how mangroves cope with seasonal freshwater habitats has seldom been studied. To address this question, we surveyed the river salinity and leaf traits (chlorophyll fluorescence, ion concentrations, carbon isotope ratios and osmolality) of Aegiceras corniculatum (L.) Blanco (river mangrove) along a freshwater-dominated river.Results: Aegiceras corniculatum at the upstream site was subjected to low salinity, being in fresh water for a long period (up to 310 h) in the wet season and experiencing a short term of low salinity in the dry season. The actual photosystem II efficiency (ФPSII) and electron transport rates (ETR) of the leaves at the upstream site decreased in the wet season, and recovered substantially in the dry season. Quenching analysis indicated that there was only a down-regulation of photoprotection, but no photoinhibition at the upstream site in the wet season. An explanation for this is that high levels of Na+ and Cl- were maintained in the leaves in the wet season.Conclusions: Long-term freshwater is a stressful environment for A. corniculatum. Aegiceras corniculatum maintains certain level Na+ and Cl- to adapt the seasonal freshwater.
Orientation Kinetics of Chiral-Nematic N* Domains in Suspensions of Charged DNA Rods
Authors: Kang Kyongok
Published: July 2021

Many biological systems exhibit natural regulation mechanisms as necessary functions. Proteins, peptides, charged receptors, RNAs, and DNAs clearly demonstrate such varieties of structural dynamics in their biocomplexity. To understand the proper structural functionality of biomolecules, this requires integrated information from initiation, regulation, transfer and transport to desirable sustainable processes. Here, we demonstrate the orientation kinetics of stable chiral-nematic (N*) domains that are consistently formed in the suspensions of charged DNA rods at low ionic strengths. This is enhanced by large access of released dissociated condensed ions and the mobile diffusive ions of DNA rods, acting onto the perpendicular motions of the DNA rods in bulk. The quantification of collective orientations for these interacting charged DNA rods is extracted by image-time correlation (ITC) performed in Fourier transforms (FTs) for overall spectral density distributions. Three distinguishable length scales are clearly shown corresponding to the relevant motion of the N* domain in parallel, perpendicular and the optical pitch within the domains as well as the kinetics of local distributions in FTs. Particularly strong concentration transitions are confirmed by replica symmetry breaking of elastic deformations in N* domains in terms of the average twist angle and the order parameter. This work can be interesting for sufficient cooling of the given concentration of charged DNA rods, at low ionic strengths (below the critical value), mimicking super-cooled liquid and orientation glass in other biomacromolecules.
Proteomics of Restenosis Model in LDLR-deficient Hamster Coupled With the Proliferative Vascular Smooth Muscle Cells Reveal New Mechanism of Vascular Remodeling Diseases
Authors: Hu Zhao-Kun , Niu Jiang-Ling , Lin Jia-Jie , Dong Li-Hua
Published: July 2021

BackgroundVascular remodeling diseases is a global health problem, and the proliferation and migration of vascular smooth muscle cells (VSMCs) is an important pathological mechanism. Golden hamsters have potential value in the study of the pathogenesis and molecular characteristics of vascular remodeling diseases, due to their lipid distribution similar to that of humans. MethodsWe detected a large number of differential proteins in vascular remodeling disease using proteomic methods, and verified the proteins (PFKL and LDHA) of concern by immunofluorescence and Western Blot.ResultsIn this study, the molecular characteristics of vascular remodeling diseases were studied by golden hamster carotid artery proteomics and in vitro cultured rat VSMCs proteomics, and 1,246 and 1,070 differentially abundant proteins were detected, respectively. According to bioinformatics analysis, differentially abundant proteins are mainly related to carbohydrate metabolism, amino acid metabolism, acute inflammatory response, complement activation and cytoskeleton. ConclusionsAmong the numerous differentially abundant proteins, we found two proteins (PFKL and LDHA) of interest and verified them. Maybe they will become new biomarkers or drug targets for vascular remodeling diseases. Therefore, we not only provide a better animal model for the study of vascular remodeling diseases, but also provide new perspective for the pathological mechanism and treatment of vascular remodeling diseases.
Facile Synthesis of Cu2+ doped ZnO via Thermal Spreading method: A Dual Role to Photocatalyst for Organic Dye Amaranth and Photoluminescence for Blue-Green Emission
Authors: Chitra S. R. , Kannan S. Karthik , Arputhavalli G. Johnsy , Shkir Mohd , AlFaify S.
Published: July 2021

In this work “solve two problems with one single action” strategy was implemented for degradation of industrial dye Amaranth and enhanced blue-green emission for opto-electronics applications in Cu2+ doped ZnO materials. The different concentrations (weight (wt) %) of Cu2+ doped ZnO materials have been synthesized by the thermal spreading method. The as-prepared ZnO and Cu2+ doped ZnO materials have effectively confirmed by various spectroscopic methods. The crystalline phase, surface morphology, compositions of elements and energy bandgap were studied systematically enquired by PXRD, SEM, EDS and UV-vis spectroscopic analysis, respectively. With the dopant concentration, 18 wt% of Cu2+ doped ZnO revealed outstanding photocatalytic performance to the degradation of Amaranth under visible light irradiation with an efficacy of about 97%. Likewise, 18 wt% of Cu2+ doped ZnO shows an strong blue-green emission at around 495 nm owing to the internal oxygen vacancies. The present work gives some clue; it may be used as a proficient photocatalyst for degradation of dyes and luminescent material for optoelectronics applications.
Dexras1 Induces Dysdifferentiation of Oligodendrocytes by Inhibiting the cAMP-CREB Pathway in White Matter Injury After Subarachnoid Hemorrhage
Authors: Xin Yuanjun , Zhang Hongxia , Chen Jie , Liang Yidan , Zhao Jun , Xiang Xiang , Liang Fu Ming , Fu Wenqiao , Huang Hao , Wu Xintong , Deng Jiewen , He Zhaohui
Published: July 2021

BackgroundWhite matter damage (WMD), different from the widely studied neuronal death, is also involved in neurological dysfunction after subarachnoid hemorrhage (SAH) although the specific mechanism is not yet known. Dexras1 (RASD1) has been reported to be involved in nervous system damage in autoimmune encephalitis and multiple sclerosis; however, there is no information on whether Dexras1 participates in WMD after SAH. We hypothesized that Dexras1 participates in oligodendrocyte precursor cell (OPC) differentiation in WMD after SAH.MethodsIntracerebroventricular lentiviral administration was used to modulate Dexras1 levels to determine its functional influence on neurological injuries after SAH. Immunofluorescence, transmission electron microscopy, and Western blotting were used to investigate the effects of Dexras1 on demyelination, glial cell activation and differentiation of OPCs after SAH. Primary rat brain neurons were treated with oxyhemoglobin to elucidate the association between Dexras1 and cAMP-CREB.ResultsDexras1 levels were significantly increased after SAH, accompanied by clear neurological deficits, glial cell activation, OPC differentiation disorders, and myelin injury. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury after SAH, which were accompanied by increased glial cell activation and levels of inflammatory factors. In contrast, Dexras1 knockdown ameliorated demyelination, oligodendrocyte differentiation disorders, and glial cell activation. cAMP acted as an upstream agonist of CREB, with decreased TNF-α and IL-1β levels after SAH. However, the cAMP-CREB pathway was inhibited after Dexras1 overexpression.Conclusion﻿Dexras1 induced oligodendrocyte dysdifferentiation after SAH and regulated glial cell activation through suppression of the cAMP-CREB pathway. This research highlights a novel direction for the improvement of neurological dysfunction after SAH.
Evaluation of the Therapeutic Effect of Pulmonary Embolism by CT Pulmonary Angiography Combined With Clinical Indexes
Authors: Yuan Meng , Cui XinYuan , Yang ChunXue , Zhang XinYang , Zhao DeLi , Zhang JinLing
Published: July 2021

BackgroundTo evaluate the value of CT pulmonary angiography (CTPA) in evaluating the therapeutic efficacy of pulmonary embolism (PE) through the study of CT pulmonary artery obstruction index (PAOI), right ventricular function parameters and some clinical indexes related to coagulation function and cardiac function injury.Materials and methodsSelect 30 patients with pulmonary embolism who underwent CTPA examination before and after treatment in our hospital, sort out their CTPA images before and after treatment, and obtain PAOI and right heart function parameters, including ascending aorta diameter (AAd), main pulmonary artery diameter (MPAd), ratio of main pulmonary artery diameter to ascending aorta diameter (MPAd/AAd), right pulmonary artery trunk diameter (RPAd), left pulmonary artery trunk diameter (LPAd), the ratio of the maximum short axis diameter of the right ventricle to the maximum short axis diameter of the left ventricle (RVd/LVd), and calculate the pulmonary artery obstruction index (PAOI).At the same time obtain the required clinical indicators, including serum D-dimer, N-terminal B-type natriuretic peptide precursor (NT-proBNP), cardiac troponin I (cTnI), myocardial enzyme profile (aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK)).ResultsMPAd, RPAd,LPAd,RVd / LVd, PAOI, D-dimer, cTnI, CK, LDH, AST had significant changes after treatment (P < 0.05), while the other parameters and indexes had no significant differences before and after treatment (P > 0.05). PAOI is positively correlated with RVd/LVd, MPAd, D-dimer. The correlation coefficient ranges from 0.281 to 0.423, among which, the correlation with D-dimer is the closest, with a correlation coefficient of 0.423. There was no significant correlation between other parameters and PAOI (P < 0.05).Conclusion﻿CTPA is of great significance in evaluating the severity of pulmonary embolism, right heart function and therapeutic efficacy.
"Petal-like" Size-Tunable Gold Wrapped Immunoliposome to Enhance Tumor Deep Penetration for Multimodal Guided Two-step Strategy
Authors: Li Yanan , Song Wenting , Hu Yumin , Xia Yun , Li Zhen , Lu Yang , Shen Yan
Published: July 2021

BackgroundBreast cancer is the fastest-growing cancer among females and the second leading cause of female death. At present, targeted antibodies combined with hyperthermia locally in tumor has been identified as a potential combination therapy to combat tumors. But in fact, the uniformly deep distribution of photosensitizer in tumor sites is still an urgent problem, which limited the clinical application. We reported an HER2-modified thermosensitive liposome (immunoliposome)-assisted complex by reducing gold nanocluster on the surface (GTSL-CYC-HER2) to obtain a new type of bioplasma resonance structured carrier. The HER2 decoration on the surface enhanced targeting to the breast cancer tumor site and forming irregular, dense, "petal-like" shells of gold nanoclusters. Due to the good photothermal conversion ability under near-infrared light (NIR) irradiation, the thermosensitive liposome released the antitumor Chinese traditional medicine, cyclopamine, accompanied with the degradation of gold clusters into 3-5nm nanoparticles which can accelerate renal metabolism of the gold clusters. With the help of cyclopamine to degrade the tumor associated matrix, this size-tunable gold wrapped immunoliposome was more likely to penetrate the deeper layers of the tumor, while the presence of gold nanoparticles makes GTSL-CYC-HER2 multimodal imaging feasible.ResultsThe prepared GTSL-CYC-HER2 had a size of 113.5 nm and displayed excellent colloidal stability, photo-thermal conversion ability and NIR-sensitive drug release. These GTSL-CYC-HER2 were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. As for the in vivo experiments, compared to the other groups, under near-infrared laser irradiation, the temperature of GTSL-CYC-HER2 rises rapidly to the phase transition temperature, and released the cyclopamine locally in the tumor. Then, the released cyclopamine destroyed the stroma of the tumor tissue while killing the tumor cells, which in turn increased the penetration of the liposomes in deep tumor tissues. Moreover, the GTSL-CYC-HER2 enhanced the performance of multimodal computed tomography (CT) and photothermal (PT) imaging and enabled chemo-thermal combination therapy.ConclusionsThis optically controlled biodegradable plasmonic resonance structures not only improves the safety of the inorganic carrier application in vivo, but also greatly improves the anti-tumor efficiency through the visibility of in vivo CT and PT imaging, as well as chemotherapy combined with hyperthermia, and provides a synergistic treatment strategy that can broaden the conventional treatment alone.
Protective Effect of Ginsenoside Rd on Military Aviation Noise-Induced Cochlear Hair Cell Damage
Authors: Chen Xuemin , LIU Yu-hui , JI Shuai-fei , XUE Xin-miao , LIU Peng , LI Cong-cong , ZHANG Min , CHANG Yao-ming , WANG Xiao-cheng
Published: July 2021

Background Soldiers are often exposed to high-intensity noise produced by military weapons and equipment during activities, and the incidence of noise-induced hearing loss (NIHL) in many arms is high. Oxidative stress has a significant role in the pathogenesis of NIHL, and research has confirmed that ginsenoside Rd (GSRd) suppresses oxidative stress. Therefore, we hypothesized that GSRd may attenuate NIHL and cochlear hair cell loss, induced by military aviation noise stimulation, through the Sirtuin1/proliferator-activated receptor-gamma coactivator 1α (SIRT1/PGC-1α) signaling pathway.Methods Forty-eight male guinea pigs were randomly divided into four groups: control, noise stimulation, GSRd, and glycerol. The experimental groups received military helicopter noise stimulation at 115 dB (A) for 4 h daily for five consecutive days. Hair cell damage was evaluated by using inner ear basilar membrane preparation and scanning electron microscopy. Terminal dUTP nick end labeling and immunofluorescence staining were conducted. Changes in the SIRT1/PGC-1α signaling pathway and other apoptosis-related markers in the cochleae, as well as oxidative stress parameters were used as readouts.Results Loss of outer hair cells, more disordered cilia, prominent apoptosis, and elevated free radical levels were observed in the experimental groups. GSRd treatment markedly improved morphological changes and apoptosis through decreasing Bcl-2 associated X protein (Bax) expression and increasing Bcl-2 expression. In addition, GSRd upregulated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, decreased malondialdehyde (MDA) levels, and enhanced the activity of SIRT1 and PGC-1α messenger ribonucleic acid and protein expression.Conclusion GSRd can improve structural and functional damage to the cochleae caused by noise. The underlying mechanisms may be associated with the SIRT1/PGC-1α signaling pathway.
Emergence of OXA-10 and OXA-48 like carbapenemases among Enterobacter isolates from inpatients in southern Iran
Authors: Moradi Melika , Khashei Reza , Malekzadegan Yalda , Sarvari Jamal
Published: July 2021

Background

The global spread of carbapenemase-producing Enterobacteriaceae represents a public health concern. The aim of this study was to investigate prevalence of carbapenem resistance, oxacillinase types and the presence of class 1–3 integrons among Enterobacter clinical isolates from an Iranian inpatients’ population.
Methods

Ninety Enterobacter isolates recovered from hospitalized patients were diagnosed by the standard microbiological methods. Antibiogram pattern was also determined. The presence of class 1–3 integrons and four types of oxacillinase genes were assessed using PCR.
Results

Of the 90 Enterobacter isolates, the most common species was identified as E. aerogenes, (45.6%), followed by E. cloacae (30%). The highest resistance rate was against to ampicillin (96.7%). Multi-drug resistance (MDR) was substantial (93%). Carbapenemase producers were detected in 96% of carbapenem resistant isolates by mCIM test. The frequency of evaluated genes was as follows: intI1 = 50 (55.6%), intI2 = 12 (13.3%), blaoxa−1 =6 (6.7%), blaoxa−2 =5 (5.6%), blaoxa−10 =18 (20%), and blaoxa−48 =18 (20%).
Conclusion

The determinants of class 1 integron with OXA-10 and OXA-48 like carbapememases have been responsible of relatively considerable of carbapenem resistance among isolates. This is the first OXA-10 and OXA-48-producing Enterobacter spp. in Iran, indicating that the prevalence of oxacillinases might be on the rise in country.
Mathematical Modeling and Optimization Of Flexible Job Shop Problem with Sequence-Dependent Setup and Transportation Energy Consumptions
Authors: Meng Leilei
Published: July 2021

As environmental awareness grows, energy-aware scheduling is attracting increasing attention. This paper investigates the flexible job shop scheduling problem with sequence-dependent setup times and transportation times (FJSP-SDST-T) and the objective is to minimize total energy consumption. To begin with, the total energy consumption of the workshop is analyzed and a novel mixed integer linear programming (MILP) model is formulated. Due to that FJSP-SDST-T is NP-hard, an effective hybrid algorithm (HGA) that hybridizes the genetic algorithm (GA) and variable neighborhood search (VNS) algorithm is proposed to solve the problem specifically for that with large size. HGA takes advantage of the good global searching ability of GA and the powerful local searching ability of VNS, and it can have a good balance of intensification and diversification. Then, four energy-conscious decoding methods are designed, in which two energy-saving strategies namely postponing strategy and Turn Off/On strategy are specially designed according to the characteristics of FJSP-SDST-T. Finally, experiments are carried out and the results show the effectiveness of the MILP model, the energy-conscious decoding methods and HGA.
Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data
Authors: Smith Clare , Odd David , Harwood Rachel , Ward Joseph , Linney Michael , Clark Matthew , Hargreaves Dougal , Ladhani Shamez , Draper Elizabeth , Davis Peter , Kenny Simon , Whittaker Elizabeth , Luyt Karen , Viner Russell , Fraser Lorna
Published: July 2021

BackgroundDeaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive.MethodsDuring the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99·995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children.InterpretationSARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination.
Changing patterns of bloodstream infections in the community and in acute care across two COVID-19 epidemic waves: a retrospective analysis
Authors: Zhu Nina J , Rawson Timothy M , Mookerjee Siddharth , Price James R , Davies Frances , Otter Jonathan , Aylin Paul , Hope Russell , Gilchrist Mark , Shersing Yeeshika , Holmes Alison
Published: July 2021

Introduction We examined the epidemiology of community- and hospital-acquired bloodstream infections (BSIs) in COVID-19 and non-COVID-19 patients across two epidemic waves. Methods We analysed blood cultures, SARS-CoV-2 tests, and hospital episodes of patients presenting and admitted to a London hospital group between January 2020 and February 2021. We reported BSI incidence, as well as changes in sampling, case mix, bed and staff capacity, and COVID-19 variants. Results 34,044 blood cultures were taken. We identified 1,047 BSIs; 653 (62.4%) defined epidemiologically as community-acquired and 394 (37.6%) as hospital-acquired. BSI rates and community / hospital ratio were similar to those pre-pandemic. However, important changes in patterns were seen. Among community-acquired BSIs, Escherichia coli BSIs remained lower than pre-pandemic level during the two COVID-19 waves, however peaked following lockdown easing in May 2020, deviating from the historical trend of peaking in August. The hospital-acquired BSI rate was 100.4 per 100,000 patient-days across the pandemic, increasing to 132.3 during the first COVID-19 wave and 190.9 during the second, with significant increase seen in elective non-COVID-19 inpatients. Patients who developed a hospital-acquired BSI, including those without COVID-19, experienced 20.2 excess days of hospital stay and 26.7% higher mortality, higher than reported in pre-pandemic literature. In intensive care units (ICUs), the overall BSI rate was 311.8 per 100,000 patient-ICU days, increasing to 421.0 during the second wave, compared to 101.3 pre-COVID. The BSI incidence in those infected with the SARS-CoV-2 Alpha variant was similar to that seen with earlier variants. Conclusion The pandemic and national responses have had an impact on patterns of community- and hospital-acquired BSIs, in both COVID-19 and non-COVID-19 patients. Factors driving the observed BSI patterns are complex, including changed patient mix, deferred access to health care, and sub-optimal practice. Infection surveillance needs to consider key aspects of pandemic response and changes in healthcare access and practice.
Consumer behavior in digital era: impact of COVID 19
Authors: Rahmanov Farhad , Mursalov Muslum , Rosokhata Anna
Published: July 2021

The main goal of this paper is to research differences that start to change consumer behavior in the digital era since the advent of COVID 19. The events associated with the pandemic that led to increased social distance and complete lockdown undoubtedly affect not only the economic situation territories and countries in general, but also on the behavior of each individual. The situation that has arisen has forced more and more consumers to meet their needs with the help of digital tools, and this process has some special characteristics. The article shows the results of analytical and comparative analysis of the changes in consumer behavior in the digital space since the onset of the pandemic. It was researched trends change consumer demand in the study categories via Google Trends. The practical study was conducted on the basis of the analysis of changes in consumer behavior and their preferences in the direction of recreation and tourism, where the data of a sociological survey of Azerbaijani citizens to study the potential impact of COVID-19 on the tourism industry was used. The survey was conducted on April 13-21, 2020 by a team of researchers from the University of Northampton (UK), the National Institute of Geophysics, Geodesy and Geography – Bulgarian Academy of Sciences, University of National and World Economy (Bulgaria). According to the results of the study, conclusions were drawn that give new challenges to the development of marketing in the digital environment, namely: digital tools have had rapid unpredictable development since the COVID-19 pandemic, and remain as high level in demand after easing restrictive measures; entrepreneurship was not ready for such quick transformation; after the first interactions in digital space, the consumer has a stable experience of interaction with specific brands, but they disappoint the expectations of consumers in a personalized contact. Based on the conclusions, an algorithm for building relationships with consumers and increasing their level of loyalty in the digital environment is proposed. The results of this study could be used in the implementation of marketing goals of representatives of different levels of business structures, governments.
Study of thermophysics during diamond drilling of fibreglass and carbon fibre-reinforced polymer composites
Authors: Dudarev A. S. , Gumarov E. Kh.
Published: July 2021

This paper examines thermophysics of the drilling process of polymeric composite materials, such as carbon-fibre-reinforced plastics (CFRP) and fibreglass by tubular diamond drill bits. Features of the COMSOL Multiphysics engineering software package were used. We employed Fourier heat equations, which express the intensity of heat gain by a mobile source in a moving coordinate system. The research was performed using the proprietary method of modelling spatial thermal action upon drilling polymer composite materials (fibreglass and carbon-fibre-reinforced plastics) in the COMSOL Multiphysics software environment. A tubular diamond drill bit with a diameter of 10 mm with two slots was chosen as a model cutting tool. Solid plates with a thickness of 5.5 mm made of layered fibrous polymer composite materials (fibreglass, carbon-fibre-reinforced plastic) were used as a preform. As a result of computer calculations, we obtained temperature fields of fibreglass and carbon-fibre-reinforced plastic during diamond drilling with a tubular tool. When studying the thermal behaviour of fibreglass and carbon-fibre-reinforced plastics, maximum temperature fields were located. The study revealed that the temperature reaches 413.6 and 448.7 K during CFRP and fibreglass drilling, respectively. It was shown that the distance of heat transfer from the edge of the hole into the preform was 6.42 and 6.40 mm for CFRP and fibreglass, respectively. A method of modelling the thermal effects when cutting polymer composite materials developed in the COMSOL Multiphysics environment allows complex analytical calculations of temperatures induced by drilling to be simplified. In addition, its use prevents overheating of a preform during drilling, allows assessing the depth of heat distribution inside the preform from the edge of the formed hole in different polymer composite materials. These measures increase the machining quality of polymer composite materials.
Improving stripping efficiency of double curvature surface on a setup with turret head
Authors: Le Tri Vinh , Koltsov V. P. , Starodubtseva D. A. , Rakitskaya V. B.
Published: July 2021

The study was performed to develop a method for selecting a rational profile of a profiled flap wheel for a turret stripping head for cleaning parts with different radius of the transverse curvature. Researchers from the Irkutsk National Research Technical University and Irkutsk Aviation Plant designed and fabricated a special PFS-4 (peen forming setup) unit to implement manufacturing technology of large-scale contour-forming components. The unit is equipped with a CNC system, two movable operating elements, a shot blaster and a turret stripping head with four flap wheels. The paper offers methods and criteria for selecting the profiled flap wheel for stripping the contour-forming surfaces of the components, depending on the curvature radius of the latter. A flap wheel with an optimal curvature radius of 40 m was chosen for analysis, which allows a sufficiently large range of profile curvature of the processed components (from 8 to 40 m) to be covered. Profiled flap wheels 100 and 200 m wide with a flap profile radius of 40 m provided uniform material removal when cleaning the surface with a curvature radius from 8 to 40 m without further overlapping with a finished strip. It was shown that wider profiled flap wheels are necessary to increase stripping efficiency. In this case, a 300 mm wide flap wheel can be used for a component surface area with a transverse curvature radius over 14 m and a 400 mm wheel for surface areas with a curvature radius of over 20 m. Thus, comparing the stripping process of a curved surface by the straight flap wheel revealed that profiled flap wheels significantly expand the workability of the PFS-4 unit turret stripping head.
Influence of humic acids in lowland peat on the remediation properties of wheat plants against heavy metal contamination
Authors: Kirdey T. A.
Published: July 2021

Phytoremediation is a promising technology for removing heavy metals from soil and water. Despite the pronounced increase in heavy metal accumulation by cultivated plants under the influence of naturally occurring complexing agents, such as humic acids, their efficiency in phytoremediation has been poorly studied. In this regard, the aim of this work is to elucidate the effect of peat humic acid formulations on the remediation potential of wheat plants (Triticum aestivum L.) against heavy metal contamination. The influence of polymetallic pollution on the remediation properties of wheat was studied in model vegetation experiments using a culture solution. Plants were grown in a Hoagland nutrient solution. A complex exposure to heavy metals was simulated using 10 pmol/L CdSO4, 25 and 50 pmol/L CuSO4, 500 and 1000 pmol/L Pb(NO3)2 in various combinations with or without the addition of a peat humic acid formulation (0.005%).

The phytoremediation efficiency of the humic acid formulation was determined by the removal of heavy metals during the heading stage of wheat growth. The research results showed that the phytoremediation efficiency of the humic acid formulation is defined by both an increase in the absorption of heavy metals and a decrease in their toxic action on the plants. In the case of mixed contamination of the solution with highly toxic heavy metals, the samples with humic acids showed a 1.2-2.5-fold increase in the accumulation of copper and cadmium by wheat plants. The data demonstrates the possibility of using the formulation of peat humic acids in phytoremediation technologies as an effector of heavy metal phytoextraction.