bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Phase 1 Safety Study of Repeated Doses of Intranasal OP0201 Metered Dose Inhaler Compared to Placebo in Healthy Adults: A Potential Treatment for Otitis Media
Authors: Sirimanne Mai D. , Patel Janak A. , Kankam Martin , Vince Bradley D. , Turkel Catherine C. 
Published: February 2020

Abstract
Background OP0201 Nasal Aerosol is a novel drug-device surfactant product being developed for treatment and prevention of otitis media. The active ingredients in OP0201, dipalmitoylphosphatidylcholine (DPPC) and cholesteryl palmitate (CP), are endogenous to the human nasal and respiratory systems. This phase 1 study evaluated the safety and tolerability of OP0201 in healthy adults. Methods This was a randomized, double-blind, placebo-controlled, parallel-group study with a dose-escalation cohort design to evaluate 30 mg/day (Cohort A) and 60 mg/day (Cohort B) of OP0201. Subjects were randomized 4:1 to receive either OP0201 or placebo 3 times per day for 14 consecutive days. Treatment was administered via a metered dose inhaler and sprayed directly backwards into each nostril. Primary endpoints were adverse events, otoscopy, tympanometry, nasal and epipharynx endoscopy, University of Pennsylvania Smell Identification Test (UPSIT), audiology pure-tone hearing test, 12-lead electrocardiography, physical examination, vital signs, and clinical laboratory tests. Exploratory endpoints included baseline-adjusted maximum serum concentration (Cmax) and time to maximum concentration (tmax) of DPPC and CP on Day 14 in Cohort B. Results 101 participants were screened, and 30 were randomized (15 per cohort; n=12 OP0201, n=3 placebo). No deaths, serious adverse events, or treatment-emergent adverse events leading to study discontinuation were reported. No clinically significant deviations from baseline were found in any of the primary endpoints. Serum DPPC and CP concentrations on Day 14 were comparable to baseline in the OP0201 group and numerically higher in the placebo group. Mean baseline-corrected serum DPPC Cmax on Day 14 was 0.82 µg/mL with OP0201 and 4.51 µg/mL with placebo, with a median tmax observed at 0.05 hours for both groups. Mean baseline-corrected serum CP Cmax on Day 14 was 14.89 µM with OP0201 and 89.50 µM with placebo, with a median tmax observed at 0.05 and 0.22 hours for OP0201 and placebo, respectively. Conclusions OP0201 was safe and well tolerated in healthy adults. There were no supraphysiologic systemic concentrations of DPPC or CP after local intranasal administration of a 60 mg/day dose of OP0201. These outcomes support continued development of OP0201 with future studies in a patient population.
The Effect of Aquatic Exercise and Swimming on Standing Stability of Three Different Clinical Forms of Multiple Sclerosis
Authors: Karimi mohammad , Marvi-Esfahani Mahnaz 
Published: February 2020

Abstract
Objective It was a survey of the effect of a combined program of aquatic exercise and swimming on standing stability of three different clinical forms of Multiple Sclerosis (MS). Design 31 MS subjects were divided into three groups, based on spasticity, ataxia and ataxic-spastic syndromes. Standing stability was assessed in open and closed eyes conditions in quiet standing by use of Kistler force platform. The Ashworth Scale and Brief Ataxia Rating Scale (BARS) were used to determine the rate of spasticity and ataxia rating, respectively. All patients participated in the intervention (3 sessions in week for 2 months). All tests repeated after the exercise. Paired t-test and ANOVAs (repeated measure) were used to determine the effects of exercise on standing stability parameters. Result The total path length of center of pressure (eyes open position) before intervention was 1415.5±575.75mm, 1216.4±817.38mm and 1662.3±540.27mm compared to 1119.7±435.51mm, 655.53±256.31mm and 1169.6±369.67mm after intervention in ataxic, spastic and ataxic-spastic subjects, respectively (p<0.04). The rate of spasticity, EDSS and BARS decreased after the exercise program (p<0.05). Conclusion Aquatic exercise and swimming skill improved MS subjects' standing stability. Therefore, they are recommended to use the aquatic training as a complement treatment aside from medication treatments.
Single berry sampling reveals novel insights into transcriptomic changes induced by leafroll virus infections in grapevine (V. vinifera)
Authors: Ghaffari Sana , Reynard Jean Sébastien , Rienth Markus 
Published: February 2020

Abstract
Background Grapevine leafroll associated viruses (GLRaV), the causing agents of grapevine leafroll disease (GLD) are amongst the most devastating graft and vector transmitted pathogens in viticulture and responsible for important economic losses in the wine industry. Reported fruit alterations caused by GLD consist in a delay of ripening, a reduction in anthocyanins, aroma compounds and sugar concentration. The molecular interactions underlying the quality deteriorating effects are not well understood so far. The few conducted molecular studies on infected berries did associate the lack of anthocyanin and sugar content with a repression of key genes of the respective pathways. However, sampling protocols in such studies never accounted for berry heterogeneity and potential virus induced phenological shifts. Thus, such commonly used sampling strategies could have introduced unquantifiable biases in gene expression studies which would impede the discovery of novel molecular information. The aim of the present study was to investigate the effects of GLRaV-1 and GLRaV-1&3 infections on berry physiology of Pinot Noir vines. Berries of different treatments were individually sampled and analyzed for sugar and organic acids. According to this biochemical analysis 2 homogenous stages were reconstituted to circumvent berry heterogeneity and compensate for virus induced phenological shifts. RNA of 18 reconstituted samples (2 stages and 3 treatments) was extracted, sequenced and analyzed for differentially expressed genes (DEGs). Results A total of 2136 transcripts were modulated by GLRaV-1 and GLRaV-1&3 infections. Interestingly the transcriptome of the early ripening berry was much more affected as the later ripening stage. Several pathways related to abiotic and biotic stress, defense mechanism as well as plant immunity showed a virus-induced upregulation in dependence to ripening stage and infection severity. Surprisingly, the previously reported repression of anthocyanin biosynthesis and sugar metabolism could not be confirmed by gene expression. This illustrates that the main damaging effect on GLRaV infection is rather related to a phenological shift than to a direct impact on metabolism. Conclusions The here reported results give new insight in the mechanism of leafroll infection and emphasize the importance of the sampling protocol of molecular studies investigating berry metabolism.
The down-regulation of PP2Ac demethylation attenuates learning and memory impairment in Manganism
Authors: Wu Bin , Cai Haiqing , Tang Shen , Xu Yilu , Shi Qianqian , Wei Lancheng , Meng Ling , Wang Xinhang , Xiao Deqiang , Zou Yunfeng , Yang Xiaobo , Li Xiyi , Lu Cailing 
Published: February 2020

Abstract
Background: Protein phosphatase 2A (PP2A) is considered a potential therapeutic target for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), and catalytic unit methylation of PP2A that relies on methionine and its intermediate S-adenosylmethionine (SAM) regulates most of protein phosphorylation. Manganese overload caused methionine decrease and tau phosphorylation in brain. However, the relationship between PP2Ac and manganese poisoning is not fully understood. In present study, we concentrate on the ameliorative effect of PP2Ac demethylation on cognitive impairment induced by manganese. Methods: Adult male Sprague-Dawley rats (n = 80; 200-250 g) were divided into Subacute (4W) and chronic (16W) exposure groups. Each exposure group consisted of four treatment groups: control (i.p., saline), Mn, methionine, and methionine plus Mn treatment group. N2a cells with different manganese exposure concentrations were cultured with or without methionine, furthermore, ABL127 is used in follow-up studies. Morris water maze, Alamar Blue assay, flow cytometry, Western blot, liquid chromatography, 2,7-dichlorofluorescein diacetate assay were performed to assess spatial memory, cell viability and apoptosis levels，phosphorylated tau and PP2Ac pathway protein expression, SAM content in brain tissue and cells, oixidative stress related markers. Results: Manganese-exposed rats had elevated levels of phosphorylated Tau and PP2Ac demethylation accompanied by abnormal rise of PPME1 expression in cortex and hippocampus as well as restricted SAM in hippocampus and spatial memory function. Up-regulation of PP2Ac demethylation caused by SAM increase after methionine treatment or PPME1 inhibition after ABL127 treatment significantly reduced p-tau, apoptosis and ROS levels, and increased cell viability and GSH levels. In addition, methionine treatment in vivo significantly increased the number of crossings and reduced the escape latency. Conclusion: Methionine and ABL127 treatment can prevent manganese-induced tau hyperphosphorylation and oxidative stress injury, thus improve spatial memory. This improvement is mediated by down-regulation of PP2Ac demethylation. This study confirms that PP2Ac demethylation plays an important role in manganese neurotoxicity and provides a potentially powerful therapeutic strategy for such neurodegenerative diseases.
Transcriptomic analysis reveals the molecular mechanisms of wheat seedling resistance to Puccinia striiformis f. sp. tritici
Authors: Liu Rong , Lu Jing , Du Mei , Zhou Min , Wang Mingxiu , Xing Jiayi , Zhang Chihong , Li Yunfang , Wu Yu , Zhang Lei 
Published: February 2020

Abstract
Background: Stripe rust or yellow rust (Yr), caused by Puccinia striiformis f. sp. Tritici (Pst), is one of the most globally devastating fungal disease that significantly reduces yield and quality in wheat (Triticum aestivum). Although some Yr genes have been successfully used in wheat breeding and a little number of them have been cloned, large of the regulating networks and the molecular mechanisms of Pst resistance remains unknown. In this study, a pair of Yr-gene pyramiding line L58 and its background parent cv. Chuanyu12 (CY12) were used to study the transcriptome profiles after inoculated with Pst physiological race CYR34. Results: The results revealed that the different expression genes (DEGs) were significantly enriched in phenylpropanoid biosynthesis, phenylalanine metabolism, plant-pathogen interaction and MAPK signaling pathways after Pst-CYR34 inoculation. Compared with CY12, L58 showed greater up-regulated DEGs in those pathways by Pst infection at 24hpi. However, these DEGs became lower expression in L58 and opposite expression in CY12 at 7dpi. Besides, the activities of enzymes (PAL, POD) and products of phenylpropanoid pathway (lignin content) were significantly increased in both CY12 and L58, and the increase was greater and faster in the resistant line L58. Some candidate genes and transcription factors (TFs) associated with Pst resistance were identified, including LRR receptor-like serine/threonine protein kinase, disease resistance protein, MYB, NAC and WRKY transcription factors involved in the fine-tuning of Pst infection responses. Conclusions: Our results give insights into the regulating networks of Pst resistance and pave the way for durable resistant breeding in bread wheat.
Effect of a Mobile Application intervention on Knowledge, Attitude and Practice Related to Healthy Marriage among Youth in Iran
Authors: Torkian Sahebjan , Mostafavi Firoozeh , Pirzadeh Asiyeh 
Published: February 2020

Abstract
Background:Pre-marriage counseling coupled with enriching the couple's relationships skills can lead to better relationships. New approaches and programs are being developed today to improve youth skills. Mobile app education is one of the new educational models in this field. The purpose of this study was to determine the effectiveness of mobile app intervention on knowledge, attitude and practice of youth for healthy marriage.Methods: This quasi-experimental study was conducted in 2019 on 88 young people (44 couples) who were selected by convenience sampling from youth referred to the premarital counseling center of Falavarjan city (Isfahan). At first, the pre-marriage skills training and counseling app was designed and produced, then this app was installed on the intervention group's cellphone. Data were collected using questionnaire based on the content of the app and its validity and reliability were confirmed. Data were analyzed using SPSS (20) and paired t-test and independent t-test were applied. Results:The mean (SD) of couples' age was 21.11 (5.06) years. The results showed that after installation of educational consulting app in the intervention group, the mean score of knowledge (P = 0.001), attitude (P = 0.001), and practice (P = 0.001) after intervention were significantly higher than before the intervention. Conclusion: The results of the study showed that using mobile-based educational and counseling app increases couples' knowledge, attitude and practice in pre-marital education. Therefore, it is recommended that this type of education (mobile app) be used to promote pre-marriage education classes.
Genomic characterization of fecal microbial communities in severely sick humans and broiler chickens using next generation sequencing
Authors: Afridi Ome Kalsoom , Ali Johar , Chang Jeong Ho 
Published: February 2020

Abstract
Background: Microbiota plays an important role in food safety and its alteration poses a serious threat to humans. Comparative microbiome profiling using next-generation sequencing (NGS) enabled the understanding of microbial diversity and similarity between different species. In this study, we used NGS to profile the fecal microbiota of sick human and broiler chickens. A total of 26 fecal samples were collected from severely sick human subjects (n= 13) and broiler chickens (n=13) with similar symptoms. Results: The total number of microbial species detected in broiler chickens fecal microbiota was higher than that of humans. Phylum Proteobacteria was the most abundant in both human and broiler chickens fecal microbiota while Tenericutes was found to be least abundant in both species. Phylum Actinobacteria was found only in the human fecal microbiota. In both humans and broiler chickens, E.coli was found to be phylogenetically related suggesting a microbial association between both species. Conclusion: NGS based taxonomic profiling revealed the association of microbial dysbiosis with extreme sickness in both humans and broiler chickens. The dominance of phylum Proteobacteria in both the species ascertains their altered gut microbiota. Both human and broiler chickens microbial communities were found to be genetically related indicating horizontal transfer of microbes between the two species.
Development and evaluation of an indirect ELISA for the detection of Mycoplasma hyopneumoniae natural infection but not inactivated bacterin vaccination
Authors: Ding Honglei , Wen Yukang , Xu Zuobo , Tlili Chaker , Tian Yaqin , Wang Zhaodi , Ning Yaru , Xin Jiuqing 
Published: February 2020

Abstract
Background: Mycoplasma hyopneumoniae is the primary pathogen of mycoplasmal pneumonia of swine (MPS). Vaccination with inactivated bacterin is the most popular and practical measure to control MPS. However, these commercial vaccines have a limited effect on the transmission of microorganism and cannot prevent colonization. Therefore, after immunization with inactivated bacterin, M. hyopneumoniae colonized on the respiratory tract and lungs stimulates the humoral immune responses and produce IgG and IgA antibodies. ELISA is a widely used serological method to detect M. hyopneumoniae antibodies. However, commercial IgG ELISA kit cannot distinguish between inactivated bacterin-induced hyperimmune sera and convalescent sera stimulated by natural infection. SIgA ELISA method is laborious for nasal swab collection, and the amount of each swab sample obtained from the nasal cavity is less compared to the serum sample. Establishment of a discriminative ELISA detecting humoral IgG from convalescent sera but not hyperimmune sera is facilitating to evaluate the natural infection of Mycoplasma hyopneumoniae after inactivated bacterins vaccination. Result: We expressed and purified a recombinant protein named Mhp366-N which contains an epitope recognized by the convalescent sera but not hyperimmune sera. The developed discriminative IgG-ELISA could discriminate between inactivated bacterin-induced hyperimmune sera and convalescent sera, and was reproducible, sensitive, and specific to M. hyopneumoniae antibody produced by natural infection. Compared to SIgA-ELISA method, discriminative IgG-ELISA was more convenient to detect IgG antibody from sera than IgA from nasal swabs, although it is limited sensitivity in the early stages of infection. Additionally, to some extent, it has a potential to avoid the interference of maternally derived IgG antibodies. Conclusions: The established discriminative IgG-ELISA was efficient to judge the serological IgG antibodies induced from natural infection or inactivated vaccine stimulation and provided a useful method to investigate and evaluate the live organism infection after the application of inactivated bacterin.
Maternal MTHFR C677T polymorphism does not affect live birth rate following IVF in Chinese Han population: a retrospective cohort study of 1265 women
Authors: Zeng Hong , Xie Hebin , He Dongmei , Zhao Yuhao , Liu Nenghui 
Published: February 2020

Abstract
Backgrounds: MTHFR is a key enzyme for folic acid metabolism and is important for reproduction. However, whether MTHFR C677T genotype affect live birth rate following IVF is unknown. This study aims to evaluate the association of MTHFR C677T polymorphism and live birth rate following IVF. Methods: This is a retrospective cohort study of 1265 women undergoing first IVF -ET cycle (2015-2017) in Reproductive Medicine Center of Xiangya Hospital. The patients were followed for a minimum of 2 years and maximum of 5 years, the observation endpoint is live birth, or all the embryos derived from the first stimulation cycle are transferred. The study population was divided into three groups based on MTHFR C677T genotype (MTHFR 677CC, MTHFR 677CT, MTHFR 677TT). The primary outcomes are live birth rate and cumulative live birth. The secondary outcomes including laboratory parameters (number of oocytes, number of 2PNs, number of available embryos, number of good embryos) and clinical parameters (chemical pregnancy rate, clinical pregnancy rate, implantation rate, preclinical pregnancy loss rate, miscarriage rate). The logistic regression analysis with different adjusted models were used to analyze the association of MTHFR C677T genotype and live birth. Results: Among the 1265 participants, 541 were MTHFR 677CC genotype, 585 were MTHFR 677CT genotype, and 139 were MTHFR 677TT genotype. The live birth rate was 43.6%, 44.8%, and 40.3% (p-value = 0.63), and the cumulative live birth rate per stimulation cycle was 54.7%, 53.5%, and 51.8% (p-value =0.81) in MTHFR 677CC group, MTHFR 677CT group, and MTHFR 677TT group, respectively. The secondary laboratory outcomes and clinical outcomes were not significantly different between the three groups. Logistic regression analysis showed no significant association of MTHFR C677T genotype and live birth whether in model 1 (p-value for trend = 0.63) , model 2 (p-value for trend = 0.63), or model 3 (p-value for trend = 0.59). Conclusions: MTHFR C677T genotype does not significantly affect live birth rate and cumulative live birth rate following first IVF in Chinese Han couples.
Outcomes, Complications, and Technical Aspects of One-Level Vertebral Column Decancellation Osteotomy for Thoracolumbar Kyphosis in Ankylosing Spondylitis: Experience of 39 Patients with Minimum 2-Year Follow-Up
Authors: Xin Zhijun , Zheng Guoquan , Feng Xinwen , Huang Peng , Zhang Xuesong , Liao Wenbo , Wang Yan 
Published: February 2020

Abstract
Objective To evaluate the safety and efficacy of one-level vertebral column decancellation (VCD) for the correction of thoracolumbar kyphosis in ankylosing spondylitis (AS) will beneficial for clarify the application of this procedure. Methods With a minimum 2-year follow-up, 39 AS patients with kyphotic deformity who underwent one-level VCD were retrospectively reviewed. The operation time, blood loss, and perioperative complications were investigated to evaluate the technical safety. Pre- and postoperative radiographic and clinical parameters were compared to evaluate the technical efficacy. Results All of the osteotomy sites were located between T12 and L3. With an average operation time of 257.8±49.9 minutes, the average blood loss was 596.1±218 ml. 4 patients (10.3%) experienced complications during the follow-up period, while no deaths or complete paralysis were occurred. With an average correction of 45.07±11.27° have obtained for one-level VCD, the radiographic parameters improved significantly from preoperative to postoperative, including global kyphosis (from 42.05±13.82° to 1.51±12.08°), local kyphosis (from 20.54±15.43° to -24.54±12.83°), lumbar lordosis (from -8.01±16.34° to -42.81±13.98°), and SVA (from 17.47±6.77 cm to 7.45±5.37). At final follow-up, the clinical results were significantly improved compared with the preoperative results, including VAS for back pain (from 6.82±0.91 to 0.15±0.37), CBVA (from 30.44±10.81° to 10.10±3.92°) and all items of SRS-22 questionnaire. Conclusion With an acceptable complication rate, one-level VCD is an effective technique which can provide an average correction of 45° for correcting kyphotic deformity caused by AS, and can achieve good results even for severe AS kyphosis with a necessary correction angular up to 60°.
Circulating exosomal microRNAs as novel detection biomarkers in pancreatic cancer
Authors: Author) Lun Wu(Former Corresponding , Zhou Wen-Bo , Zhou Jiao , Wei Ying , Wang Hong-Mei , Liu Xian-de , Chen Xiao-Chun , Wang Wei , Ye Lin , Yao Li Chao , Chen Qin-Hua , Author) Zhi-Gang Tang(New Corresponding 
Published: February 2020

Abstract
Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantiﬁed using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P<0.001). However, no signiﬁcant difference in the relative serum levels of free miR-21 and miR-210 was observed between these two groups (both P>0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.