bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Epitope Map of the Reported Protein Sequences of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Guevarra Leonardo A. , Ulanday Gianne Eduard L.
Published: March 2020

Identifying immunogenic sequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins is important in developing epitope-based vaccine and diagnostics. This step is critical in designing potent vaccines and highly specific diagnostic tools which can help prevent the spread of this disease. In this study, we identified, using in silico analysis tools, immunogenic epitopes of the reported sequences of SARS-CoV-2 proteins and determined similar sequences with known viral proteins. The amino acid sequences of the SARS-CoV-2 proteins were acquired from the National Center for Biotechnology Information (NCBI) database. B-cell epitope prediction was done using in silico analysis tools available at the Immune Epitope Database and Analysis Resources (IEDB). Blastp was performed on the identified immunogenic sequences to determine similarities with known viral proteins and deduce possible locations in the coronavirus. We were able to identify B-cell epitopes of the SARS-CoV-2 polyprotein, surface glycoprotein, envelop, membrane glycoprotein, nucleocapsid phosphoprotein, orf3, orf7a and orf8. No epitope was identified in orf6 and orf10. High similarities of the predicted immunogenic epitopes of the SARS-CoV-2 were observed with the 2003 SARS-CoV. However, unique epitopes were identified in non-structural proteins (NSP) 1 and 3 and surface glycoprotein of the SARS-CoV-2.
WITHDRAWN: The effect of crystallization level of silica nanoparticles on cell proliferation of MRC-5 cell line and its prediction using artificial neural network
Authors: Abbasi Fariba , Samaei Mohammad Reza , Hashemi Hassan , Savardashtaki Amir , Azhdarpoor Abolfazl , Fallahi Mohammad Javad , jalili mahrokh , Billet Sylvain
Published: March 2020

Background: This study investigated the effect of the level of silica nanoparticles (SiO2NPs) crystallization on the cell proliferation of MRC-5 cells and its prediction using an artificial neural network (ANN).Methods: Variables studied included temperature (70-1000°C), calcination time (2, 12 and 24 hours), and catalyst feed rate (0.01, 0.05 and 0.1mL/min). Cell proliferation was determined by the MTT test after 24 hours of exposure, and results were analyzed using the t-test in MATLAB.Results: the synthesized particles size was less than 50nm, and the XRD peak varied from 30 to 21° during the increase in calcination temperature. The maximum level of crystallization was at 800°C (58% relative to amorphous) with the lowest cell viability. Cell proliferation decreased with increasing concentration of nanoparticles (p<0.05) and increasing feed rate. There was also a positive relationship between increased crystallization and decreased cell proliferation (R2=0.78), but no such association was observed for calcination time. Cell proliferation of MRC-5 was slightly correlated with the linear regression model (MSE>0.12), while ANN was well predicted by the Levenberg–Marquardt algorithm. The suggested structure in this study was 4:10:1 with R2all=0.97, R2test=0.97, RMSE=0.25 and MSE=0.003. The correlation between laboratory results and ANN prediction was 0.94, and the minimum and maximum OD level in the laboratory data and predicted ANN were attributed to 20 and 13 runs.Conclusion: changes in the degree of crystallization of SiO2NPs, an increase in concentration, and the rate of catalyst feed during crystallization of SiO2NPs were practical factors in increasing cytotoxicity.
Multi-omics study of keystone species in the cystic fibrosis lung microbiome
Authors: Silveira Cynthia , Cobian-Guemes Ana Georgina , Uranga Carla , Baker Jonathon , Edlund Anna , Rohwer Forest , Conrad Douglas
Published: March 2020

Background: Ecological networking and in vitro studies have predicted that anaerobic, mucus-degrading bacteria are keystone species in cystic fibrosis (CF) microbiomes by sustaining the growth of canonical CF pathogens. Here, a multi-omics approach was deployed to test this hypothesis in vivo and in real time during a transition in antibiotic therapy of a CF patient with a hypervariable lung function phenotype . Results: Quantitative meta-omics and community culturing demonstrated that the use of a non-traditional clindamycin therapy targeting gram-positives and gram-negative anaerobes re-structured the entire CF microbial community. During rapid lung function loss, when the patient was off antibiotics, the microbial community was dominated by anaerobic mucus-degrading Streptococcus sp., Veilonella sp., and Prevotella sp. that produced fermentation gas and led to the accumulation of fermentation products in sputum. The rise of anaerobes was followed within 6 days by an increase in Pseudomonas aeruginosa transcripts encoding the acquisition of fermentation products from anaerobes and the production of virulence factors. The initiation of clindamycin treatment reduced the fermentation and the abundance of anaerobes. Clindamycin also lowered the abundance and transcription of P. aeruginosa, which is resistant to this antibiotic. The treatment stabilized the patient’s lung function and improved respiratory health for two months, lengthening by a factor of four the between-hospitalization time for this patient. Conclusions: The results presented here show that killing anaerobes, the weakest link in the community in terms of antibiotic resistance, effectively limited the growth of classic CF pathogen by disrupting community cross-feeding. The role that anaerobic, mucus-degrading bacteria played in structuring the CF microbiome corroborates in vivo their position as keystone bacteria, with high impact on community function despite lower relative abundances.
The host cellular protein Ndufaf4 interacts with the vesicular stomatitis virus M protein and affects viral propagation
Authors: Pan Wei , Wang Hongmei , He Hongbin
Published: March 2020

Background: Vesicular stomatitis virus (VSV) is an archetypal member of Mononegavirales which causes important diseases in cattle, horses and pigs. The matrix protein (M) of VSV plays critical roles in the replication, assembly/budding and pathogenesis of VSV. To further investigate the role of M during viral growth, we used a two-hybrid system to screen for host factors that interact with the M protein.Results: Here, NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4) was identified as an M-binding partner, and this interaction was confirmed by yeast cotransformation and GST pulldown assays. The globular domain of M was mapped and shown to be critical for the M-Ndufaf4 interaction. Two double mutations (E156A/H157A, D180A/E181A) in M impaired the M-Ndufaf4 interaction. Overexpression of Ndufaf4 inhibited VSV propagation, and knockdown of Ndufaf4 by short hairpin RNA (shRNA) markedly promoted VSV replication. Finally, we also demonstrate that the anti-VSV effect of Ndufaf4 is independent of activation of the type I IFN response. These results indicated that Ndufaf4 might exploit other mechanisms to affect VSV replication.Conclusions: In summary, we identify Ndufaf4 as a potential target for the inhibition of VSV replication. These results provided further insight into the study of VSVpathogenesis.
Genetic and epigenetic modifications of HPDL and SOX17 associated with breast cancer prognosis: a study based on The Cancer Genome Atlas
Authors: Gao Chundi , Li Huayao , Liu Cun , Wu Jibiao , Zhou Chao , Liu Lijuan , Zhuang Jing , sun Changgang
Published: March 2020

Background：The high heterogeneity of breast cancer (BRCA) makes it more challenging to interpret the genetic variation mechanisms involved in BRCA pathogenesis and prognosis. Areas with high DNA methylation (such as CpG islands) were accompanied by copy number variation (CNV), and these genomic variations affected the level of DNA methylation. Methods: In this study, we characterized inter-tumor heterogeneity and analyzed the effects of CNV on DNA methylation and gene expression. In addition, we performed a Genetic Set Enrichment Analysis (GSEA) to identify key pathways for changes between patients with low and high expression of genes. Results: Our analysis found that the CNV of HPDL and SOX17 is not only related to the patient's prognosis, but also related to gene methylation and expression levels affecting the patient's survival time. Conclusion: This study provided an effective bioinformatics basis for further exploration of molecular mechanisms related to BRCA and assessment of patient prognosis, but the development of biomarkers for diagnosis and treatment still requires further clinical data validation.
Supraphysiological estradiol levels on the hCG trigger day are associated with SGA for singletons born from fresh embryo transfer
Authors: Zhang Junwei , Du Mingze , Wu Yanli , Xiong Yiwen , Wang Yunxia , Li Zhe , Wang Lulu , Hu Jijun , Sun Lijun
Published: March 2020

The effects of supraphysiological estradiol (E2) on neonatal outcomes and the significance of specific E2 concentrations remain unclear. The purpose of this study was investigate whether supraphysiological E2 levels on the hCG trigger day are associated with small size for gestational age (SGA) in singletons born from fresh embryo transfer (ET) cycles. Patients with singleton pregnancies with delivered after transfer of fresh embryos, during the period of July 2012 to December 2017 at our center were included. We excluded cycles involving a vanishing twin, maternal age >35 years, basal FSH ≥10 mIU/ml, AMH ≤1 ng/ml or incomplete records. We then divided all cycles into 5 groups by E2 level on the day of hCG trigger: group A, <2000 pg/ml (reference group); group B, 2000 pg/ml≤E2<2999 pg/ml; group C, 3000 pg/ml≤E2<3999 pg/ml; group D, 4000 pg/ml≤E2<4999 pg/ml; and group E, ≥5000 pg/ml. The prevalence of SGA among singletons from fresh ET was the primary outcome. The SGA rate significantly increased when the E2 level was ≥4000 pg/ml, as observed by comparing groups D (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.16–2.76, P=0.01) and E (OR: 1.68, 95% CI: 1.10–2.56, P=0.02) with the reference group. Multivariate logistic regression indicated that a serum E2 level of at least 4000 pg/ml on the hCG trigger day was associated with increased SGA and with significant differences for groups D (adjusted OR [AOR]: 1.65, 95% CI: 1.05–2.59, P=0.03) and E (AOR: 1.60, 95% CI: 1.03–2.53, P=0.04) relative to the reference group. In conclusion，for fresh ET cycles, supraphysiological E2 ≥4000 pg/ml on the hCG trigger day increases the risk of singleton SGA.
Providing calves different feed source early in life would not affect feed sorting and rumen fermentation for a long term
Authors: Xiao Jianxin , Khan Muhammad Zahoor , Alugongo Gibson Maswayi , Wang Wei , Wang Yajing , Cao Zhijun , Li Shengli
Published: March 2020

This study aimed to investigate the short and long-term effect of early in life exposure to different feed sources on feed sorting and rumen fermentation of calves. Forty newborn female Holstein calves were randomly divided based on supplementation of concentrate (CON) or hay (HAY) only during the milk-feeding stage (d 1 to 56). After that, all calves were offered a total mixed ration (TMR) containing 43 % of forage and 57 % of concentrate until the end of the experiment (d 57 to 196). Rectal temperature, feed intake, body weight, body structural measurement, fecal and cough score were recorded ranges from day 1 to 196. Fresh and orts feed were sampled daily at the first two weeks (d 57-70) once TMR was offered and at the last week of the experiment (d 190 to 196) for analysis of feed sorting. Rumen fluid samples were collected at ranges from d 14-190 for detecting rumen pH and volatile fatty acids (VFA) concentrations. Our findings showed that early feed exposure did not influence calf health and growth performance but affected feed sorting in a short period. Upon transition to the same mixed diet, differences were found between treatments in the sorting of the different particle fractions. At week 9 and 10, calves early exposed to concentrates began to sort for fine particle fraction, and against the long particle fraction, whereas calves early fed hay sorted for the long particle fraction, and against the fine particle fraction. However, no carryover effect was found, the differences between treatments fade away when detecting feed sorting at the last week, all calves sorted for short and fine particle fractions, and sort against long and medium particle fractions. Although the pattern of feed sorting initially differed between treatments, the rumen pH and VFA concentration were not altered once all calves transitioned to a TMR. These results suggested that the feed familiarity established early in life would not affect diet selection and rumen fermentation in heifer later in life, the dietary experience after transition to same TMR would eventually override the effect of early feed experience.
Investigation of Potential therapeutic value of Shuanghuanglian Chinese medicine based on network pharmacology for coronavirus pneumonia
Authors: XU JIASHENG , LIAO KAILI , Zhang Guanyu , LI YIRAN , Zhou Weimin , Qiu Jiehua
Published: March 2020

Objective: The interaction network between coronavirus pneumonia and Shuanghuanglian was established to explore the potential therapeutic effect of the active ingredients of Shuanghuanglian on coronary virus pneumonia.Methods: Using the TCMSP database, the effective components of Shuanghuanglian were obtained by screening consistent with oral utilization，drug similarity and blood-brain barrier permeability thresholds, and the drug target prediction was performed.The SARS treatment target mining was performed through the GeneCards database, and the two data sets of therapeutic target and drug target were analyzed and the intersection was screened, and the wayne map was drawn.The intersection genes were used as potential therapeutic targets. Cytoscape 3.6 software was used to build a drug active ingredient-therapeutic target interaction network and analyze the active ingredient-therapeutic target point network Degree parameters to find important active ingredients and targets. Using DAVID and String databases to perform GO,KEGG enrichment analysis and protein interaction analysis on the intersection genes to find out the potential signal pathway of Shuanghuanglian against SARS.Results: 43 effective components against SARS were screened, includingcoptisine、Mandenol、Ethyl linolenate、phytofluene、wogonin、FORSYTHINOL、baicalein、Moslosooflavone、Panicolin, etc.A total of 115 intersection genes with coronavirus pneumonia were screened as important treatment targets: based on the protein interaction network, Shuanghuanglian's therapeutic targets for diseases were significantly enriched in 1763 GO and 133 KEGG signaling pathways; The main action pathways are: responses to steroid hormones and ketones, and development of the reproductive system, responses to lipopolysaccharides, Toxins, responses to bacteria and aging, and effects on epithelial cell proliferation.Conclusion: The active ingredients in Shuanghuanglian Chinese medicine compound can act on the disease-related target of coronavirus pneumonia and have potential therapeutic effects on coronavirus pneumonia.
Is reluctance to share Alzheimer’s disease biomarker status with a study partner a barrier to preclinical trial recruitment?
Authors: Cox Chelsea G , Ryan Mary M , Gillen Daniel L , Grill Joshua D
Published: March 2020

Background: Preclinical Alzheimer’s disease (AD) clinical trials test candidate treatments in individuals with biomarker evidence of AD but no cognitive impairment. Participants are required to co-enroll with a knowledgeable study partner, to whom AD biomarker information will be disclosed.Methods: We performed in-person mixed-methods interviews with 200 cognitively unimpaired older adults to investigate whether reluctance to share biomarker results is associated with viewing the study partner requirement to be a barrier to preclinical AD trial recruitment.Results: Eighteen percent of participants reported strong agreement that the study partner requirement was a barrier to enrollment. Ten participants (5%) agreed at any level that they would be reluctant to share their biomarker result with a study partner. The estimated odds of viewing the study partner requirement as a barrier to enrollment were 26 times higher for these participants (OR=26.3, 95% CI 4.0, 172.3), compared to those who strongly disagreed that they would be reluctant to share their biomarker result. Overall, participants more frequently agreed with positive statements than negative statements about the study partner requirement, including 76% indicating they would want their study partner with them if they learned AD biomarker results.Conclusions: This is one of the first studies to explore how potential preclinical AD trial participants feel about sharing their personal biomarker information with a study partner. Most participants viewed the study partner as an asset to preclinical AD trial enrollment, including having a partner present during biomarker disclosure.
Comparison of the effectiveness and safety of different regimens of tranexamic acid in complex tibial plateau fracture: a retrospective study
Authors: Wang Zhimeng , Lu Yao , Wang Qian , Song Leilei , Ma Teng , Ren Cheng , Li Zhong , Yang Jiarui , Zhang Kun , Zhang Bing
Published: March 2020

Background Previous studies have demonstrated the effectiveness and safety of tranexamic acid (TXA) in orthopedics. However, no study has investigated TXA in complex tibial plate surgery. Therefore, the purpose of this study was to confirm the safety and effectiveness of IV (intravenous) TXA and topical TXA. Material and methods This was a retrospective analysis of prospectively collected data. The control group received an equal amount of placebo (physiological saline solution); the IV group received 1.0 g TXA by intravenous injection before the tourniquet was inflated and before the surgical incision was closed, and the topical group received 3.0 g TXA in 75 mL of physiological saline solution before 5 min prior to the final tourniquet release. Perioperative blood loss, vascular events, wound complications, and adverse reactions were compared for the three groups. Results Baseline data were comparable for all groups. The IV group showed the best results for total blood loss (TBL) and hidden blood loss (HBL) (424.5 ± 29.4 ml, 219.3 ± 33.4 ml, respectively, all p values < 0.001). The topical group performed excellently with regard to postoperative vascular events, wound complications, and adverse reactions, but there was no statistical significant in the incidence of these between the groups. Conclusion This study presents the first information to show that both IV TXA and topical TXA are safe and effective for complex tibial plateau fractures. The IV regimen effectively reduced blood loss during the perioperative period, whereas the topical regimen had a better safety profile.
An apoptosis-related gene signature for the prognosis of hepatocellular carcinoma
Authors: Zhu Pengfei , Lei Zhang , Zhicheng Du , Yuan Liao , Lei Yan , Wenlong Zhai , Kunlun Chen
Published: March 2020

Hepatocellular carcinoma (HCC) is a major public health burden worldwide owning to high incidence and poor prognosis. Although a mushrooming number of apoptosis-related genes had been disclosed in HCC, the prognostic value and clinical utility of them remain to be illustrated. Here, we defined the data from Gene Expression Omnibus (GEO) as a training cohort and data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma data set (TCGA-LIHC) as a validation cohort. The apoptosis-related differentially expressed genes (AR-DEGs) were identified with the two cohorts and the Gene Set Enrichment Analysis. Then, we constructed a Lasso-penalized Cox regression model using AR-DEGs and conducted a signature including 14 apoptotic genes to calculate the risk score. Patients with a high risk score indicated worse overall survival than those with low risk. Besides, the 3-year and 5-year area under curve (AUC) values of the signature were above 0.7 in both training and validation cohorts (0.762, 0.818, 0.717, 0.745, respectively). Moreover, a nomogram containing the signature and clinical characteristics presented reliable net benefits for the survival prediction. And the nomogram was tested by probability calibration curves and Decision Curve Analysis (DCA). Furthermore, protein-protein interaction (PPI) and Gene Ontology (GO) enrichment analysis disclosed several noticeable pathways that might clarify the hidden mechanism. Collectively, the present study formed a novel signature based on the 14 apoptotic genes and this possibly predicted prognosis and strengthened the communication with HCC patients about the likely treatment.
Effective inhibition of MYC-amplified Group 3 medulloblastoma through targeting translation machinery eIF4F complex
Authors: Zhao Yang , Li Tiantian , Tian Shuaiwei , Meng Wei , Yang Jian , Wang Baocheng , Liang Zhuangzhuang , Zhao Heng , Han Yipeng , Tang Yujie , Ma Jie
Published: March 2020

Background: Medulloblastoma (MB) consists of four major molecular subtypes and group 3 subtype (G3) is the most aggressive one. MYC amplification tends to happen in G3 MB and those patients exhibit the worse prognosis and need novel effective therapeutic approach most urgently. MYC has been shown to be the driver as well as crucial dependency for MYC-amplified G3-MB, thus serving as a promising therapeutic target. Methods: In this study, we tested inhibiting MYC translation in MYC-amplified G3-MB by targeting eIF4F complex. We analyzed multiple MB tumor data sets to identify potential therapeutic target of eIF4F components and utilized genetic or pharmacological approaches for validation. The relevant inhibitory mechanisms were further investigated by Western blot and whole lysate mass spectrometry assays to confirm the targeting of MYC translation. Results: Tumor data set analyses identified eIF4A1, a subunit of eIF4F complex, which was significantly upregulated in G3-MB compared to normal cerebellum and highly correlated with MYC at transcript level. Targeting eIF4A1 with CRISPR/Cas9 approach or small-molecule inhibitor Silvestrol effectively attenuated growth of multiple preclinical models through blocking proliferation and inducing apoptosis. Mechanistically, Silvestrol treatment effectively inhibited MYC expression at protein level and MYC amplification was shown to sensitize MB cells to eIF4A1 inhibition. Moreover, whole proteome mass spectrometry analyses demonstrated additional biological functions or pathways affected by eIF4A1 inhibition, which could help in better understanding its inhibitory mechanisms and revealing combinatory strategies. Conclusion: It is shown in our study that targeting MYC translation by eIF4A1 inhibition could be an effective therapeutic strategy against MYC-amplified G3-MB.
Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPAA2B1
Authors: Zhang Yu-Hui , Huang Wei-Bin , Yuan Yu-Jie , Li Jin , Wu Jing , Yu Jie , He Yu-Long , Wei Zhe-Wei , Zhang Chang-Hua
Published: March 2020

Background Long non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear. Methods Use public database to screen the potential lncRNA crucial for metastasis in colorectal cancer. The expression of H19 in clinical CRC specimens was detected by qRT-PCR. The effect of H19 on the metastasis of CRC cells was investigated by transwell, wound healing assays, CCK-8 assays and animal studies. The potential proteins binding to H19 was identified by LC-MS and verified by RNA immunoprecipitation (RIP). The expression of indicated RNA and proteins were measured by qRT-PCR or western blot. Results We found the expression of lncRNA H19 was significantly upregulated in primary tumor and metastatic tissues, correlated with poor prognosis in CRC. Ectopic H19 expression promoted the metastasis of colorectal cancer cells in vitro and in vivo , and induced epithelial-to-mesenchymal transition (EMT). Mechanistically, H19 directly bound to hnRNPA2B1. Knockdown of hnRNPA2B1 attenuated the H19-induce migration and invasion in CRC cells. Furthermore, H19 stabilized and upregulated the expression of Raf-1 by facilitated the interaction between hnRNPA2B1 and Raf-1 mRNA, resulting in activation of Raf-ERK signaling. Conclusions Our findings demonstrate the role of H19/hnRNPA2B1/EMT axis in regulation CRC metastasis, suggested H19 could be a potential biomarker to predict prognosis as well as a therapeutic strategy for CRC.
Diagnostic accuracy value of intraoperative frozen section for ovarian neoplasms
Authors: Shahmoradi Farinaz , Arab Maliheh
Published: March 2020

Background Accuracy of intraoperative frozen section diagnosis is extremely important in the evaluation of ovarian tumors so that suitable surgical procedures can be chosen. Methods This retrospective diagnostic accuracy study was conducted in the Department of Obstetrics and Gynecology, Emam Hossein Hospital. The case records of patients with ovarian mass who underwent surgery and intraoperatively frozen section assessments between September 2006 and December 2014 were analyzed. Demographic and clinical data, operative details, frozen section and final histopathology Examination (HPE) were reviewed from the medical records. Results one hundred and ninety three patients with ovarian masses undergoing surgery and frozen section were included. The frozen section diagnoses were benign in 155 (80.31%), borderline in 10 (5.18%), and malignant in 28 (14.51%), whereas the final diagnosis was benign in 154 (79.80%), borderline in 9 (4.66%), and malignant in 30 (15.54%). The overall accuracy of intra-operative frozen section diagnosis was 98.9%. The sensitivity for frozen section diagnosis was 100% for benign, 89% for borderline and 93.3% for malignant category, whereas the specificity was 97%, 99%, and 100%, respectively. There were 3 cases with discordance between the frozen section diagnoses and the final diagnoses, all of which were under diagnosed by frozen section. Conclusion Frozen section was found to be accurate and useful in the intraoperative assessment of patients with ovarian neoplasm. The results may help to determine the type and extent of surgery.
System Life and Reliability Modeling of a Multiple Power Takeoff Accessory Gearbox Transmission
Authors: Wang Kai , Wang Xian-Liang , Zhu Jia-Zan , Ou Dai-Song , Pan Dai-Feng
Published: March 2020

A mathematical model for system life and reliability of a multiple power takeoff aeroengine accessory gearbox transmission was presented. The geometry model of accessory gear train system is distributed to multiple subsystems by the different transmitting powers. The subsystem is composed by three basic gear unit cases: spiral bevel gear unit, single mesh cylindrical gear unit and compound cylindrical gear unit. The lives of each component are combined to determine the unit life. The unit transmission and subsystem transmission interface models are defined to dispose the loads of common components in order to get the subsystem and the total system transmission life. A numerical example of a multiple power takeoff accessory gear train illustrates the use of this program. The initial design could not fulfill the design life requirement, and a design modification was performed to improve the system life and to balance the life of each component. The results of the redesign show that the accessory gear train has a more balanced life distribution by strengthening the weak parts of the transmission, and the overall life of total system is increased above the design requirement. This program can help the designer to approach an optimal accessory gearbox transmission design efficiently.
Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis
Authors: Stevens Marc Y , Cropper Haley C , Lucot Katherine L , Chaney Aisling M , Lechtenberg Kendra J , Jackson Isaac M , Buckwalter Marion S , James Michelle
Published: March 2020

Background: B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).Methods: Female C57BL/6J mice were induced with EAE through immunisation with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted.Results: Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/mol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02±0.092 vs. 1.68±0.06 percentage of injected dose per gram, %ID/g, p=0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22±0.020 vs. 0.12±0.003 %ID/g, p=0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry – providing further evidence that [64Cu]CD19-mAb enables visualisation of B cell infiltration into the CNS of EAE mice. Conclusion: CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.
Lung Ultrasound to Quantitatively Evaluate Extravascular Lung Water Content and its Clinical Significance
Authors: Guo Guo , Zhang Xue-Feng , Liu Jing , Zong Hai-Feng
Published: March 2020

Background:B-line assessment with lung ultrasound (LUS) has recently been proposed as a reliable, noninvasive semiquantitative tool for evaluating extravascular lung water (EVLW). Currently, there has been no easy quantitative method to evaluate EVLW by LUS. To establish a simple, accurate and clinically operable method for quantitative assessment of EVLW using LUS. Methods:Forty-five New Zealand rabbits were randomized into 9 groups (n=5). After anesthesia, each group of rabbits was injected with different amounts of warm sterile NS (0 ml/kg, 2 ml/kg, 4 ml/kg, 6 ml/kg, 8 ml/kg, 10 ml/kg, 15 ml/kg, 20 ml/kg, 30 ml/kg) via the endotracheal tube. Each rabbit was examined by LUS before and after NS injection. At the same time, the spontaneous respiratory rate (RR, breaths per minute), heart rate (HR, bpm) and arterial blood gas (ABG) of the rabbits were recorded. Then, both lungs were dissected to obtain the wet and dry weight and conduct a complete histological examination.Results:Injecting NS into the lungs through a tracheal tube can successfully establish a rabbit model with increased EVLW. When theNS injection volume is 2~6 ml/kg, comet-tail artifacts and B-lines are the main patterns found on LUS; as additional NS is injected into the lungs, the rabbits' RR gradually increases, while their HR gradually decreases. Confluent B-lines grow gradually but significantly, reaching a dominant position when the NS injection volume reaches 6~8 ml/kg and predominating almost entirely when the NS injection volume is 8~15 ml/kg; at that time, rabbits' RRs and HRs decrease sharply, and the ABG indicated type I respiratory failure (RF). Compact B-lines occur and predominate almost entirely when the NS injection volume reaches 10 ml/kg and 15~20 ml/kg, respectively. At that time, rabbits begin to enter cardiac and respiratory arrest, and ABG shows type II RF and metabolic acidosis (MA).Conclusion: LUS can estimate EVLW content based on the type of B-line.We can give clinical treatment depending on the type of LUS B-line.
Inhibitory effect of endostar combined with radiotherapy on gastric cancer animal models
Authors: Qitian Chen , Ran Chen , Youhong Dong
Published: March 2020

Background: Inhibitory effect of endostar combined with radiotherapy on gastric cancer (GC) animal models and its effect on transforming growth factor-β (TGF-β)1 and inter- leukin-10 (IL-10) were evaluated.Methods: Forty mouse models of GC xenograft tumors were prepared and randomly divided into blank control group, endostar group, radiotherapy group and endostar combined with radiotherapy group (combina- tion group). From the 14th day, a vernier caliper was used for measuring the long and short diameters of the xenograft tumors. The formula V = ab2/2 was used for calculating the tumor volume and to obtain its average value. Tumor growth curves were plotted to calculate the tumor inhibition rate. The growth of xenograft tumors and the behavioral changes of mice were observed. ELISA was used for detecting the expression levels of IL-10 and TGF-β1.Results: The tumor growth in the combination group was significantly inhibited, and the tumor volume was finally the smallest compared with the other groups (p<0.05). Compared to the blank control group, the tumor inhibition rate was 11.8% in endostar group, 33.0% in radiotherapy group and 52.1% in combination group (p<0.01). Endostar combined with radiotherapy had an interaction in decreasing the expression levels of TGF-β1 and IL‑10 (F=4.35 and 5.12, p<0.05). Leucocyte count was significantly higher in control and combination groups than that in endostar and radiotherapy groups. The body weight of mice in endostar and radiotherapy groups decreased after treatment (p<0.05). The body weight of mice after treatment in control and combination groups increased, with a statistically significant difference compared to that before treatment (p<0.05). There was a statistically significant difference among all groups after treatment (F=198.1, p<0.01).Conclusions: Endostar combined with radiotherapy can inhibit tumor growth and downregulate the expression levels of TGF-β1 and IL-10 through synergistic action.
Clinical investigations of percutaneous vertebroplasty combined with intensity-modulated radiotherapy for patients with spinal metastases
Authors: Xie Xiaoqi , Xin Chen , Hong Zhang , Zhengying Liao , Feng Wang
Published: March 2020

Background: This study aimed to explore the use of percutaneous vertebroplasty (PVP) plus radiotherapy in patients with bone metastases. However, percutaneous vertebroplasty (PVP) combined with intensity modulated radiotherapy (IMRT) has been rarely reported in the treatment of spinal metastases.Methods: The effectiveness and feasibility of this procedure were initially observed in this paper. We retrospectively analyzed the clinical characteristics of 7 patients with spinal metastasis. They were all treated with PVP, followed by IMRT (6 MV-X linear at a dose of 40-60 Gy) for 4-6 weeks. All patients achieved technical success with PVP, and all successfully completed the IMRT program without serious complications or discomfort.Results: After the initial exploration of PVP combined with IMRT in our tumor center, the patients' pain was alleviated, and no pain aggravation or fracture was found. The short-term effect was significant.Conclusions: PVP combined with IMRT seems to be an effective way to improve the quality of life of patients with spinal metastasis of tumor, and the curative effect is definite, which can be further popularized in clinical practice.
Total neoadjuvant chemoradiotherapy (consolidation chemotherapy during the interval after chemoradiotherapy) for distal rectal cancer increases the rates of complete response
Authors: Zhai Zhiwei , Zhang Kunning , Wang Chen , Han Jiagang , Zhang Tian , Wang Lixia , Yao Jiannan , Wang Zhenjun
Published: March 2020

Objective To compare the safety and efficacy between neoadjuvant concurrent chemoradiotherapy (CRT) and total neoadjuvant chemoradiotherapy (TNT) in patients with locally advanced rectal cancer. Methods Patients with cT3/T4 or TxN+M0 rectal cancer were randomized to receive CRT/TNT. In CRT group, we planned pelvic radiotherapy (50.0Gy in 25 fractions) with two cycles of concurrent CAPOX followed by total mesorectal excision (TME). In TNT group, 3 cycles of CAPOX were administered 2 weeks after the completion of CRT before TME. The primary endpoints of my study were pathological complete response (pCR) rates in the two cohorts. Results A total of 197 patients were included in our study. Eighty-one patients received CRT while one hundred and sixteen patients received TNT (consolidation chemotherapy). Nine patients did not undergo surgery because of the distant metastases (1 patient (1.2%) in CRT group, 2 patients (1.7%) in TNT group) or clinical complete response (cCR) (2 patients in CRT group, 4 patients in TNT group). The rate of pathological complete response in TNT was significantly higher than the rate in CRT (32.7% vs12.8%, P =0.002). No grade 4 or serious adverse events were observed. There was no statistically significant difference in the grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups (all P >0.05). Conclusions Our data suggests that total neoadjuvant chemoradiotherapy (consolidation chemotherapy) is effective and safe for patients with locally advanced rectal cancer and is associated with high rates of pathological complete response. The long-term follow-up and survival outcomes for patients are necessary to be evaluated in future prospective randomized trial.
Therapeutic benefits of music for three types of neurological disorders: an fNIRS study protocol for controlled trial in Dalian, China, Part 1 – Parkinson’s Disease
Authors: Pu Lanlan , Qureshi Nauman Khalid , Ly Joanne , Zhang Bingwei , Cong Fengyu , Tang William C. , Liang Zhanhua
Published: March 2020

Background: Music therapy improves neuronal activity and connectivity of healthy persons and patients with clinical symptoms of neurological diseases like Parkinson’s Disease, Alzheimer’s Disease, and Major Depression. Despite the plethora of publications that have reported the positive effects of music interventions, little is known about how music improves neuronal activity and connectivity in afflicted patients. In this three-part series of studies, each of the three neurological disorders – (1) Parkinson’s Disease, (2) Alzheimer’s Disease, and (3) Major Depression – will be treated individually in detail. Methods: For patients suffering from Parkinson’s Disease (PD), we propose a daily 25-minute music-based synchronous finger tapping (SFT) intervention for 8-weeks. Participants will be each split into two groups: an intervention group and a control arm. Assessment of finger tapping performances, the Unified Parkinson’s Disease Rating Scale (UPDRS), an n-back test, the Montreal Cognitive Assessment (MoCA), as well as oxygenated- (HbO 2 ), deoxygenated- hemoglobin (HbR), and total hemoglobin activation collected by functional near-infrared spectroscopy (fNIRS) will be measured at baseline, week 4 (during), week 8 (post), and week 12 (retention) of the study. Data collected from the two PD groups will be compared to baseline performances from healthy controls.Discussion: The trial study investigates the cortical neuronal activity and therapeutic effects associated with an auditory external cue used to induce automatic and implicit synchronous finger tapping in patients diagnosed with PD. The extent to which the intervention is effective may be dependent on the severity of the disease.
Nurses’ attunement to patients’ meaning in life – A qualitative study of experiences of Dutch adults ageing in place
Authors: Hupkens Susan , Goumans Marleen , Derkx Peter , Machielse Anja
Published: March 2020

Background Meaning in life (MiL) is considered to be an important part of health and is associated with many positive outcomes in older adults, such as quality of life and longevity. As health promotors, nurses may take patients’ MiL into account in the care process. There is a knowledge gap in terms of what constitutes good care in relation to older patients’ MiL, and what the benefits may be for patients when nursing is attuned to this aspect. The purpose of this study was to explore the experiences of home nursing older adults in relation to nurses’ attunement to MiL. Methods Gadamerian hermeneutic phenomenological design with semi-structured interviews. Participants were 24 aged home nursing patients. A framework of care ethical evaluation was used in the analysis. Multiple dialogues enhanced understanding. Results Patients did not expect nurses’ regard for their MiL. They rather expected ‘normal contact’ and adequate physical care. Nurses showed that they were open to patients’ MiL by being interested in the patient as a person and by being attentive to specific and hidden needs. Participants explained that the nurse’s behaviour upon arrival set the tone: they knew immediately if there was room for MiL or not. All participants had positive and negative experiences with nurses’ behaviour in relation to MiL. Valued nursing care included maintaining a long, kind and reciprocal relationship; doing what was needed; and skilled personalised care. Participants mentioned ‘special ones’: nurses attuned to them in a special way who did more than expected. Benefits of care that was attuned to patients’ MiL were experiencing a cheerful moment, feeling secure, feeling like a valuable person and having a good day. Older adults also stressed that consideration for MiL helps identify what is important in healthcare. Conclusion Aged homecare patients value nurses’ attunement to their MiL positively. Although patients regard MiL mostly as their own quest, nurses play a modest yet important role. Managers and educators should support nurses’ investment in reciprocal nurse-patient relationships.
Risk factors for acute kidney injury among patients with rhabdomyolysis
Authors: Yang Jia , Zhou Jiaojiao , Wang Xin , Wang Siwen , Tang Yi , Yang Lichuan
Published: March 2020

Background Acute kidney injury (AKI) is a life-threatening complication of rhabdomyolysis (RM). The aim of the present study was to assess patients at high risk for the occurrence of AKI defined by the Kidney Disease Improving Global Outcomes criteria and in-hospital mortality. Methods We performed a retrospective study of patients with creatine kinase levels >1000 U/L, who were admitted to the West China Hospital of Sichuan University between January 2011 and March 2019. The sociodemographic, clinical and laboratory data of these patients were obtained from an electronic medical records database, and univariate and multivariate regression analyses were subsequently conducted. Results For the 329 patients included in our study, the incidence of AKI was 61.4%, and the overall mortality rate was 19.8%; furthermore, patients with AKI tended to have higher mortality rates than those without AKI (24.8% vs. 11.8%; P<0.01). The clinical conditions most frequently associated with RM were trauma (28.3%), sepsis (14.6%), bee sting (12.8%), thoracic and abdominal surgery (11.2%) and exercise (7.0%). Furthermore, patients with RM resulting from sepsis, bee sting and acute alcoholism were more susceptible to AKI. The risk factors for the occurrence of AKI among RM patients included age ≥60 years (OR=3.070), chronic alcoholism (OR=3.256), hypertension (OR=4.252), multiple organ dysfunction syndrome (MODS; OR=7.244), high levels of white blood cell count (OR=1.047) and elevated serum phosphorus (OR=5.526). Age ≥60 years (OR=3.188), MODS (OR=2.262), diabetes (OR=2.746) and elevated prothrombin time (OR=1.079) were independent risk factors for in-hospital mortality in RM patients with AKI. Conclusions AKI is independently associated with mortality in patients with RM, and several risk factors were found to be associated with the occurrence of AKI and in-hospital mortality. These findings suggest that, to improve the quality of medical care, the early prevention of AKI should focus on high-risk patients and more effective management.
Effect of different restorative crown design and materials on stress distribution in endodontically treated molars: A finite element analysis study
Authors: Lin Jie , Lin Zhenxiang , Zheng Zhiqiang
Published: March 2020

Background

The purposes of this simulation study were to evaluate the stresses in the roots of endodontically treated molars with extensive coronal tissue loss which were restored by endocrowns (all-in-one core and crown) and traditional crowns with post-cores, during masticatory simulation using finite element analysis.

Methods

A mesio-distal cross-section of a lower right first molar was digitized and used to create 2-dimensional models of the teeth and supporting tissue; different crown designs, viz ., endocrown with 2 mm occlusal clearance, endocrown with 4 mm occlusal clearance and post-core crown; different crown materials, viz ., zirconia (Zr) and lithia-disilicate reinforced glass ceramic (LDRGC), and different post and core materials, viz. , glass fiber (GF), stainless steel (SS) and metal cast (MC). An axial load of 600 N was applied to the central fossa of occlusal surface.

Results

The stress distributions were similar between Zr and LDRGC for periodontal ligament and alveolar bone. The root canal inner wall maximum principal stresses of SS post (70.8 MPa) and MC post (71.4 MPa) were higher than that of GF post (36.0 MPa) and endocrown (2.4 MPa).

Conclusion

The endocrowns reduced stress concentration for the root canal inner wall in comparison with the conventional post-core crown. Molars restored with endocrowns are less prone to root fracture than those with posts.
Evaluation of resistance to powdery mildew and identification of resistance genes in wheat cultivars
Authors: Wu Xian Xin , Gao Yue , Bian Qiang , Sun Qian , Ni Xin Yu , Sun Yan Qiu , Xu Xiao Feng , Cao Yuan Yin , Li Tian Ya
Published: March 2020

Background: Wheat powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici ( Bgt ), is a serious disease of wheat worldwide that can cause significant yield losses. Growing resistant cultivars is the most cost-effective and eco-soundly strategy to manage the disease. Therefore, a high breeding priority is to identify genes that can be readily used either singly or in combination for effective resistance to powdery mildew and alos in combination with genes for resistance to other diseases. Yunnan Province, with complex and diverse ecological environments and climates, is one of the main wheat growing regions in China. This region provides initial inoculum for starting epidemics of wheat powdery mildew in the region and other regions and thus, plays a key role in the regional and large-scale epidemics of the disease throughout China. The objectives of this study were to evaluate seedling resistance of 69 main wheat cultivars to powdery mildew and to determine the presence of resistance genes Pm3 , Pm8 , Pm13 , Pm16 , and Pm21 in these cultivars using gene specific DNA markers. Results: Evaluation of 69 wheat cultivars with six Bgt isolates showed that only four cultivars were resistant to all tested isolates, indicating that the overall level of powdery mildew resistance of Yunnan wheat cultivars is inadequate. The molecular marker results showed that 27 cultivars likely have at least one of these genes. Six cultivars were found likely to have Pm3 , 18 likely to have Pm8 , 5 likely to have Pm16 , and 3 likely to have Pm21 . No cultivar was found to carry Pm13 . Conclusion: The information on the presence of the Pm resistance genes in Yunnan wheat cultivars can be used in future wheat disease breeding programs. In particular, cultivars carrying Pm21 , which is effective against all Bgt races in China, should be pyramided with other effective genes to developing new cultivars with durable resistance to powdery mildew. Keywords: Blumeria graminis f. sp. tritici , Pm gene, molecular markers, wheat