bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation biomarker discovery in Parkinson's disease and atypical parkinsonisms
Authors: Santaella Anna , Kuiperij H. Bea , Rumund Anouke van , Esselink Rianne A.J. , Gool Alain J. van , Bloem Bas R. , Verbeek Marcel
Published: December 2019

Background: Parkinson’s disease (PD) and atypical parkinsonisms (APD) have overlapping symptoms challenging an early diagnosis. Diagnostic accuracy is important because PD and APD have different prognosis and response to treatment. We aimed to identify diagnostic inflammatory biomarkers of PD and APD in cerebrospinal fluid (CSF) using the multiplex proximity extension assay (PEA) technology and to study possible correlations of biomarkers with disease progression. Methods: CSF from a longitudinal cohort study consisting of PD and APD patients (PD, n = 44; multiple system atrophy (MSA), n = 14; vascular parkinsonism (VaP), n = 9; and PD with VaP, n = 7) and controls (n = 25) were analyzed. Results: Concentrations of CCL28 were elevated in PD compared to controls (p = 0.0001). Five other biomarkers differentiated both MSA and PD from controls (p < 0.05) and 10 biomarkers differentiated MSA from controls, of which two proteins, i.e. beta nerve growth factor (β-NGF) and Delta and Notch like epidermal growth factor-related receptor (DNER), were also present at lower levels in MSA compared to PD (both p = 0.032). Two biomarkers (MCP-1 and MMP-10) positively correlated with PD progression (rho > 0.650; p < 0.01). Conclusions: PEA technique identified potential new CSF biomarkers to help to predict the prognosis of PD. Also, we identified new candidate biomarkers to distinguish MSA from PD.
Evaluation of the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients
Authors: song jinfang , Zhang Mingzhu , Ni Jiang , Wang Tao , Zhao Yi-Qing
Published: December 2019

Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM.
Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 newly diagnosed T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment.
Result: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). A total of 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a less reduction in fasting plasma glucose (FPG) levels with a less increase in homeostasis model assessment for β cell HOMA-β in the carriers of G allele at rs10830963, when compared with the wild-type CC (P <0.05).
Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.
The efficacy of superior oblique posterior tenectomy in the treatment of A-pattern exotropia without ocular intorsion: A retrospective study
Authors: Wei Yan , Dong Ling-Yan , Kang Xiao-li , Zhao Pei-quan
Published: December 2019

Background: Superior oblique weakening is a common method to treat A-pattern strabismus. This study aims to evaluate the surgical results of the bilateral superior oblique posterior tenectomy procedure to treat A-pattern strabismus patients who had bilateral superior oblique overaction without objective ocular intorsion.
Methods: The records of 18 consecutive patients who underwent surgery of superior oblique posterior tentomy close to its insertion with superior oblique overaction (SOOA)-associated A-pattern strabismus between September 1, 2015 and August 31, 2018 were retrospectively reviewed. Ocular alignment, objective torsion, A-pattern and ocular motility were assessed. Ocular alignment was measured in the primary position, 25° upgaze, and 25° downgaze using the prism bar cover test, and torsion was measured using fundus photographs.
Results: A total of 18 patients (mean age: 15 years; 6 female, 12 male) underwent bilateral superior oblique posterior tenectomy and simultaneous horizontal rectus muscle surgery were included. The mean preoperative A-pattern deviation was 15 PD and the mean postoperative A-pattern deviation was 2.25 PD with a mean reduction of 12.75 PD. The mean preoperative superior oblique overaction was 2.28 and the mean postoperative superior oblique overaction was 0.43 with a mean reduction of 1.85. There was no significant correlation between the ocular torsional, vertical and horizontal alignment change and the superior oblique posterior tenectomy procedure.
Conclusions: Superior oblique posterior tenectomy surgery selectively improved the A-pattern and superior oblique overaction but not affect the primary position vertical and horizontal deviation, as well as the ocular torsion. It is an effective procedure to treat the mild to moderate superior oblique overaction (SOOA)-associated A pattern strabismus without ocular intorsion.
Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study
Authors: Tamura Haruka , Kondo Yoshinobu , Ito Kohei , Hasebe Masanori , Satoh Shinobu , Terauchi Yasuo
Published: December 2019

Background: Among patients with type 2 diabetes and established cardiovascular disease, those receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes and death from any cause. Alternatively, treatment with sulfonylurea reduces microvascular complications in diabetes but appears to increase cardiovascular hospitalization or mortality in combination with metformin. Therefore, in the present study, we assessed the effects of empagliflozin and glimepiride, a sulfonylurea, on endothelial function using flow–mediated dilation (FMD) to estimate arteriosclerosis and cardiovascular events in patients with type 2 diabetes. Methods: In this prospective, open-label, randomized, parallel-group comparison, 58 patients with type 2 diabetes were administered metformin and glargine before bedtime for 12 weeks, followed by the random addition of 10 mg empagliflozin or 0.5 mg glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (DFMDs), which was measured prior to and following 12 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. Results: Analysis of the empagliflozin group (n = 30) and glimepiride group (n = 28) showed no significant differences in DFMDs (empagliflozin, −0.19 ± 2.34%; glimepiride, −0.37 ± 2.77%; P = 0.79). Likewise, glycated hemoglobin (HbA1c) changes were similar between the two groups. Body weight changes significantly differed (empagliflozin, –0.59 ± 2.5 kg; glimepiride, 1.2 ± 3.0 kg; P = 0.02). However, analysis of the body composition revealed that body fluid volume significantly decreased only after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, –0.33 ± 0.72 L; P = 0.03). Conclusions: Empagliflozin did not improve endothelial function compared with glimepiride in patients with type 2 diabetes, but decreased their body fluid volume. This suggested that the coronary protective effect of empagliflozin is not derived by protecting endothelial function but rather from reducing the risk of heart failure.
Gross Motor Developmental Dysfunctional Outcomes in Infantile and Toddler Pediatric Intensive Care Unit Survivors
Authors: Yang Chun-Feng , Xue Yang , Feng Jun-Yan , Jia Fei-Yong , Zhang Yu , Li Yu-Mei
Published: December 2019

Background: Increasing studies have focused on motor function/dysfunction in PICU survivors; however, most studies have focused on adults and older children. This study investigated gross motor developmental function outcomes in infantile and toddler pediatric intensive care unit (PICU) survivors and the factors associated with gross motor developmental functions.
Methods: This observational study was conducted in the PICU of the First Hospital of Jilin University between January 2019 and March 2019. Thirty-five eligible patients were divided into the dysfunctional (n=24) or non-dysfunctional (n=11) group according to the results of the Peabody Developmental Motor Scales, Second Edition (PDMS-2). Baseline gross motor function for all participants before PICU admission was measured via the Age and Stages Questionnaires, Third Edition (ASQ-3). The PDMS-2 was used to evaluate gross motor development function before PICU discharge.
Results: The gross motor developmental dysfunction incidence was 68.6%. Linear correlation analysis showed that the gross motor quotient (GMQ) was positively correlated with the pediatric critical illness score (PCIS, r=0.621, P<0.001), and negatively correlated with length of PICU stay (r=-0.556, P=0.001), days sedated (r=-0.602, P<0.001), days on invasive mechanical ventilation (IMV; r=-0.686, P<0.001), and days on continuous renal replacement therapy (CRRT; r=-0.538, P=0.001). Linear regression analysis showed that IMV days (β=-0.736, P=0.001), sepsis (β=-18.111, P=0.003) and PCIS (β=0.550, P=0.021) were independent risk factors for gross motor developmental dysfunction
Conclusions: Gross motor developmental dysfunction in infantile and toddler PICU survivors is more common and may be exacerbated by experiences associated with longer IMV days and increasing illness severity combined with sepsis.
Planning of Food-Energy-Water-Waste (FEW2) nexus for sustainable development
Authors: Feng Bowen , Dam Koen H. van , Guo Miao , Shah Nilay , Passmore Stephen , Wang Xiaonan
Published: December 2019

It is critical for reliable infrastructure planning to address the Food-Energy-Water-Waste (FEW2) nexus at system level. This paper presents the applicability of resilience.io platform across water, energy and waste sectors (including food and agricultural waste) with focus on waste-to-energy pathway, aiming to establish the optimal FEW2 nexus based on economic and environmental indicators. A rich array of technology options, including water production facilities, clean energy technologies and waste-to-energy conversions are evaluated to meet the demand of water and energy (mainly gas and electricity), and the treatment requirement of waste and wastewater. A case study of Hunter Region, the largest region in Australia, is presented in this study, featuring the supply and demand context of developed countries. A full set of scenarios, including business-as-usual (BAU), water and wastewater, power plant decommission, waste-to-energy and policy intervention, is created to present FEW2 nexus from the perspective of individual nodes and the whole system. The results signal the benefits of biogas and syngas generation from anaerobic digestion and gasification for waste-to-energy pathway, alongside findings in water and energy sectors. The outcome of this analysis can then form the foundation of regional planning involving relevant stakeholders, with the modelling tools supporting scenario evaluation and collaborative learning to reach consensus in view of different performance indicators including financial and environmental metrics.
Do Bacteremic Patients with End-Stage Renal Disease Have a Fever When Presenting to The Emergency Department? A Paired, Retrospective Cohort Study.
Authors: Weatherall Sarah L. , Chambers Alison B. , Mermel Leonard
Published: December 2019

Background Fever is a common symptom when patients present to Emergency Departments. It is unclear if the febrile response of bacteremic hemodialysis-dependent patients differs from bacteremic patients not receiving hemodialysis. The objective of this study was to compare Emergency Departments triage temperatures of patients with and without hemodialysis-dependent end-stage rental disease who have Staphylococcus aureus bacteremia and determine the incidence of afebrile S. aureus bacteremia. Methods: Paired, retrospective cohort study of 37 patients with and 37 patients without hemodialysis hospitalized with Methicillin-resistant or Methicillin-susceptible S. aureus bacteremia. Emergency Department triage temperatures were reviewed for all patients, as were potential confounding variables. Results: 54% (95% CI, 38-70%) and 82% (95% CI 65-91%) of hemodialysis and non-hemodialysis patients did not have a detectable fever (<100.4°F) at triage. Triage temperatures were 100.5°F (95% CI 99.9-101.2°F) and 99.0°F (95% CI 98.4-99.6°F) in the hemodialysis and non-hemodialysis cohorts, respectively (p<0.001). Triage temperature in patients with and without diabetes mellitus was 99.2°F (95% CI 98.4-99.9°F) and 100.4°F (95% CI 99.7-101.0°F), respectively (p=0.03). We were unable to detect a significant effect of diabetes mellitus and other potential confounding variables on differences in temperature between the hemodialysis and non-hemodialysis cohorts (all interactions p > 0.19). Conclusions: Hemodialysis-dependent patients with S. aureus bacteremia had significantly higher temperatures than non- hemodialysis-dependent end stage renal disease patients but more than half of patients were without detectable fever at triage, possibly reflecting use of insensitive methods for measuring temperature. Absence of fever at presentation to the Emergency Department should not delay blood culture acquisition in patients who are at increased risk of S. aureus bacteremia.
Phenolics and related in vitro functional activities of different varieties of fresh waxy corn: a whole grain
Authors: Chen Lirong , Guo Yuqiu , Li Xiaoyue , Gong Kuijie , Liu Kaichang
Published: December 2019

The polyphenol distribution in fresh waxy corns of different color varieties and their functional activities, which may be useful for treating various chronic diseases, were investigated. The in vitro antioxidant activity, and hypoglycemic and hypocholesterolemic effects of the free and bound corn phenolics were determined to evaluate the edible value of fresh waxy corn. The colored varieties contained more phenols than the common varieties (white and/or yellow). The total free phenolic acid content of the six varieties was 6637.73 μg/g DW (dry weight), which was slightly higher (p >0.05) than that of the total bound form (6276.65 μg/g DW). The total free flavonoid content was 5850.09 μg/g DW, which was higher (p < 0.05) than that of the total bound form (4874.51μg/g DW). No bound anthocyanin was detected in the methanol extracts of the tested varieties. For all the varieties, free polyphenols contributed 86-100% and 70-78% of the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging abilities, respectively, and 100% of the ferric reducing capacity. The free phenolics in fresh waxy corn showed significantly better (p< 0.05) hypoglycemic effect than the bound form in terms of inhibition of α-amylase activity, whereas the bound phenolics of most varieties showed higher α-glucosidase inhibitory activity than the free forms. The free phenolics showed significantly better (p < 0.05) glycocholesterol binding than the bound form for all varieties. The bound polyphenols showed better sodium cholate and taurocholate binding than the free form for most varieties. In conclusion, the difference between free and bound polyphenol content and functional activities indicates that fresh waxy corn can be potentially used for the development of functional food.
Genetic mapping and genomic selection for maize stalk strength
Authors: Liu Xiaogang , Hu Xiaojiao , Li Kun , Liu Zhifang , Wu Yujin , Wang Hongwu , Huang Changling
Published: December 2019

Background Maize is one of the most important staple crops and is widely grown throughout the world. Stalk lodging can cause enormous yield losses in maize production. However, rind penetrometer resistance (RPR), which is recognized as a reliable measurement to evaluate stalk strength, has been shown to be efficient and useful for improving stalk lodging-resistance. Linkage mapping is an acknowledged approach for exploring the genetic architecture of target traits. In addition, genomic selection (GS) using whole genome markers enhances selection efficiency for genetically complex traits. In the present study, two recombinant inbred line (RIL) populations were utilized to dissect the genetic basis of RPR, which was evaluated in seven growth stages.Results The optimal stages to measure stalk strength are the silking phase and stages after silking. A total of 66 and 45 quantitative trait loci (QTL) were identified in each RIL population. Several potential candidate genes were predicted according to the maize gene annotation database and were closely associated with the biosynthesis of cell wall components. Moreover, analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway further indicated that genes related to cell wall formation were involved in the determination of RPR. In addition, a multivariate model of genomic selection efficiently improved the prediction accuracy relative to a univariate model and a model considering RPR-relevant loci as fixed effects.Conclusions The genetic architecture of RPR is highly genetically complex. Multiple minor effect QTL are jointly involved in controlling phenotypic variation in RPR. Several pleiotropic QTL identified in multiple stages may contain reliable genes and can be used to develop functional markers for improving the selection efficiency of stalk strength. The application of genomic selection to RPR may be a promising approach to accelerate breeding process for improving stalk strength and enhancing lodging-resistance.
High frequency of benzimidazole resistance alleles in Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis from Austrian sheep flocks in an alpine transhumance management system
Authors: Hinney Barbara , Schoiswohl Julia , Melville Lynsey , Ameen Vahel J. , Wille-Piazzai Walpurga , Bauer Karl , Joachim Anja , Krücken Jürgen , Skuce Philip J. , Krametter-Frötscher Reinhild
Published: December 2019

Infections of small ruminants with trichostrongyloid nematodes often result in reduced productivity and may be detrimental to the host. Anthelmintic resistance (AR) against most anthelmintic drug classes is now widespread amongst the trichostrongyloids. Baseline establishment, followed by regular monitoring of the level of AR, is necessary for farmers and veterinarians to make informed decisions about parasite management. The detection of single nucleotide polymorphisms (SNPs) is a sensitive method to detect AR against benzimidazoles (BZs), one of the most widely used anthelmintic classes. Alpine transhumance constitutes a special type of pasturing of sheep from many different farms, the aim of this study was to investigate the prevalence of benzimidazole resistance alleles in this particular management system. Sixteen sheep flocks in Styria and Salzburg in Austria were examined by pyrosequencing for SNPs at codons 167, 198 and 200 of the isotype-1 β-tubulin gene. The frequency of the resistance-associated mutation F200Y was 87–100% for H. contortus, 77–100% for T. colubriformis and <5–66% for T. circumcincta. Additionally, the F167Y polymorphism was detected in T. colubriformis from two farms at a frequency of 19% and 23% respectively. The high resistance allele frequency in H. contortus and T. colubriformis in the examined sheep population urgently calls for the development of new treatment strategies to sustainably control trichostrongyloid infections for this kind of pasturing, since the frequent mixing of flocks during the alpine summer grazing must be considered an important risk factor for the spread of resistant nematodes to a large number of farms.
The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts
Authors: Venugopal Nisha , Ghosh Ananga , Gala Hardik , Aloysius Ajoy , Vyas Neha , Dhawan Jyotsna
Published: December 2019

Background: Reversible cell cycle arrest (quiescence/G0) is characteristic of adult stem cells and is actively controlled at multiple levels. Quiescent cells also extend a primary cilium, which functions as a signaling hub. Primary cilia have been shown to be important in multiple developmental processes, and are implicated in numerous developmental disorders. Although the association of the cilium with G0 is established, the role of the cilium in the control of the quiescence program is still poorly understood.Results: Primary cilia are dynamically regulated across different states of cell cycle exit in skeletal muscle myoblasts: quiescent myoblasts elaborate a primary cilium in vivo and in vitro , but terminally differentiated myofibers do not. Myoblasts where ciliogenesis is ablated using RNAi against a key ciliary assembly protein (IFT88) can exit the cell cycle but display an altered quiescence program and impaired self-renewal. Specifically, the G0 transcriptome in IFT88 knockdown cells is aberrantly enriched for G2/M regulators, suggesting a focused repression of this network by the cilium. Cilium-ablated cells also exhibit features of activation including enhanced activity of Wnt and mitogen signaling and elevated protein synthesis via inactivation of the translational repressor 4E-BP1.Conclusions: Taken together, our results show that the primary cilium integrates and dampens proliferative signaling, represses translation and G2/M genes, and is integral to the establishment of the quiescence program.
In Silico Design of a Peptide Receptor for Dopamine Recognition
Authors: Rodriguez-Salazar Luna , Pulido James Guevara
Published: December 2019

Background: Dopamine (DA) is an important neurotransmitter with a fundamental role in regulatory functions related to the central, peripheral, renal, and hormonal nervous systems. Dopaminergic neurotransmission dysfunctions are commonly associated with several diseases; thus, in situ quantification of DA is a major challenge. To achieve this goal, enzyme-based biosensors have been employed for substrate recognition in the past. However, owing to their sensitivity to changes in temperature and pH levels. Results: New peptide bioreceptors have been developed. Based on this, 45 in silico bioreceptors were designed to exhibit a higher affinity than that of the DA transporters (DATs). The design was based on the active sites of crystallized enzyme structures that are physiologically related to DA. These affinities were calculated using AutoDock Vina and by assessing the interaction energy between DA and the active DAT site. The controlled variables in the design were amino acids, bond type, steric volume, stereochemistry, affinity, and interaction distances. Conclusions: Three bioreceptor candidates presenting promising values ​​in terms of DA affinity and distance were obtained.
Increased PD-1-positive macrophages in the tissue of gastric cancer are closely associated with poor prognosis in gastric cancer patients.
Authors: Kono Yusuke , Saito Hiroaki , Miyauchi Wataru , Shimizu Shota , Murakami Yuki , Shishido Yuji , Miyatani Kozo , Matsunaga Tomoyuki , Fukumoto Yoji , Nakayama Yuji , Sakurai Chiye , Hatsuzawa Kiyotaka , Fujiwara Yoshiyuki
Published: December 2019

Background: Programmed cell death 1 (PD-1) is one of the immune checkpoint molecules that negatively regulate the function of T cells. Although recent studies indicate that PD-1 is also expressed on other immune cells besides T cells, its role remains unclear. This study aims to evaluate PD-1 expression on macrophages and examine its effect on anti-tumor immunity in gastric cancer (GC) patients. Methods: The frequency of PD-1+ macrophages obtained from GC tissue was determined by multicolor flow cytometry (n = 15). Double immunohistochemistry staining of PD-1 and CD68 was also performed to evaluate the correlations among the frequency of PD-1+ macrophages, clinicopathological characteristicus, and prognosis in GC patients (n = 102). Results: The frequency of PD-1+ macrophages was significantly higher in GC tissue than in non-tumor gastric tissue. The phagocytotic activity of PD-1+ macrophages was severely impaired compared with that of PD-1- macrophages. The 5-year disease specific survival rates in patients with PD-1+ macrophageLow (the frequency of PD-1+ macrophages; < 0.85%) and those with PD-1+ macrophageHigh (the frequency of PD-1+ macrophages; ≥ 0.85%) were 85.9% and 65.8%, respectively (P = 0.008). Finally, multivariate analysis showed the frequency of PD-1+ macrophage to be an independent prognostic factor. Conclusions: The function of PD-1+ macrophage was severely impaired and increased frequency of PD-1+ macrophage worsened the prognosis of GC patients. PD-1–PD-L1 therapies may function through a direct effect on macrophages in GC.
Production of an anti-angiogenic factor sFLT1 is suppressed via promoter hypermethylayion of FLT1 gene in choriocarcinoma cells
Authors: Sasagawa Tadashi , Jinno-Oue Atsushi , Nagamatsu Takeshi , Morita Kazuki , Tsuruga Tetsushi , Mori-Uchino Mayuyo , Fujii Tomoyuki , Shibuya Masabumi
Published: December 2019

Background: Soluble Fms-like tyrosine kinase-1 (sFLT1) as an anti-angiogenic factor is abundantly expressed in placental trophoblasts. Choriocarcinoma, a malignant tumor derived from trophoblasts, is known to be highly angiogenic and metastatic. However, the molecular mechanism underlying angiogenesis in choriocarcinoma pathogenesis remains unclear. We aimed to investigate the mRNA expression and DNA methylation status of the FLT1 gene in human choriocarcinoma cells and trophoblast cells. Methods: qRT-PCR, Western blotting and ELISA were conducted to evaluate the mRNA and protein expression levels of sFLT1. 5-aza-2'-deoxycytidine (5azadC) treatment and bisulphite sequencing were used to study the FLT1 gene promoter methylation. The effect of sFLT1 on choriocarcinoma growth and angiogenesis was evaluated in a xenograft mouse model. Results: Expression of the FLT1 gene was strongly suppressed in choriocarcinoma cell lines compared with that in the primary trophoblasts. Treatment of choriocarcinoma cell lines with 5azadC, a DNA methyltransferase inhibitor, markedly increased in mRNA expression of three FLT1 splice variants and secretion of sFLT1 proteins. Bisulfite sequencing revealed that the CpG hypermethylation was observed at the FLT1 promoter region in choriocarcinoma cell lines and a human primary choriocarcinoma tissue but not in human trophoblast cells. Interestingly, in 5azadC-treated choriocarcinoma cell lines, sFLT1 mRNA expression and sFLT1 production were further elevated by hypoxic stimulation. Finally, as expected, sFLT1-expressing choriocarcinoma cells implanted into nude mice showed significantly slower tumor growth and reduced microvessel formation compared with GFP-expressing control choriocarcinoma cells. Conclusions: Inhibition of sFLT1 production by FLT1 silencing occurs via the hypermethylation of its promoter in choriocarcinoma cells. The stable expression of sFLT1 in choriocarcinoma cells resulted in the suppression of tumor growth and tumor vascularization in vivo. We suggest that the FLT1 gene may be a cell-type-specific tumor suppressor in choriocarcinoma cells.
A LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of osteosarcoma
Authors: Zheng Shengnai , Wan Li , Ge Dawei , Jiang Fan , Qian Zhanyang , Tang Jian , Yang Jin , Yao Yilun , Yan Junwei , Zhao Lei , Li Haijun , Yang Lei
Published: December 2019

Background: To uncover the role of LINC00266-1 in the development of osteosarcoma (OS) and identify the underlying mechanism.Methods: LINC00266-1 levels in OS tissues in the GSE12865 dataset were analyzed. Binding sites between the DNA of LINC00266-1 and SMAD2 and potential miRNAs binding LINC00266-1 were predicted via databases. The effects of LINC00266-1 on the proliferative, migratory, invasive and apoptotic abilities were evaluated by a series of functional experiments. Interactions in the LINC00266-1/miR-548c-3p/SMAD2 feedback loop were assessed by RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (ChIP)-qPCR and dual luciferase reporter assays. Tumorigenesis assay was then conducted in nude mice. The potential influence of LINC00266-1 on the positive expression of Ki67 in nude mice bearing OS xenografts was elucidated through immunohistochemistry.Results: LINC00266-1 was upregulated in OS tissues and cells. SMAD2 was able to bind sites in the LINC00266-1 promoter and thus upregulate LINC00266-1. Knockdown of LINC00266-1 suppressed the proliferative and metastatic abilities but promoted the apoptosis of OS cells. LINC00266-1 sponged miR-548c-3p, an action that partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Moreover, miR-548c-3p bound to the 3’-UTR of SMAD2 and thus downregulated SMAD2. Overexpression of SMAD2 partially reversed the regulatory effects of LINC00266-1 on OS cell phenotypes. Knockdown of LINC00266-1 significantly alleviated the growth of OS in vivo.Conclusions: The LINC00266-1/miR-548c-3p/SMAD2 feedback loop stimulates the development of OS.
In vitro repellency and contact bioassay of aqueous extracts of Cissus quadrangularis and Gomphocarpus physocarpus plants against Rhipicephalus evertsi evertsi ticks
Authors: Mkwanazi Mbusiseni V , Chimonyo Michael , Ndlela Sithembile Z
Published: December 2019

Background The frequent use of acaricides to control ticks and inadequate flock management has led to the development of tick resistance to many acaricidal drugs. Ethno-veterinary plants with acaricidal activities have a major potential to combat this challenge because they are easily biodegradable, user-friendly, and less toxic to the environment and meat products. The objective of the study was to assess the ethnoveterinary properties of Cissus quandrangularis. Lin and Gomphocarpus physocarpus E. Mey to control ticks.Results The 6% v/v of Cissus quadrangularis for each extract were more effective (p<0.01) against Rhipicephalus evertsi evertsi ticks. The repellency percentage was highest at 6% v/v for acetone, methanol and control extracts similar to positive control Amitraz. The acaricidal efficacy of the Gomphocarpus physocarpus at 12% v/v of methanol extracts was as good as that of 6% v/v, however different to that of 18% v/v was relatively low. The mortality rate of the control, acetone was similar (p <0.05) between 6, 12 and 18% v/v at 24hrs. The mortality rate of the positive control reached 100% after 72 hrs (p < 0.05) post-treatment, even though it was similar to that of acetone, methanol and control across different concentrations. The use of acetone and methanol extracts resulted in similar tick mortality at 12 and 18% v/v at 24 hrs post-treatment. The methanol extract of Gomphocarpus physocarpus at 6% v/v reached up to 100% mortality at 72 hours similar to the positive control.Conclusions The bioassays indicated that there was a high efficacy percentage from the lowest concentrations (6% v/v) of both Gomphocarpus physocarpus E. Mey and Cissus quadrangularis. Lin plant extracts, which was similar to the positive control (Amitraz) suggesting that suggesting that 6% v/v could be sufficient for recommendations because less plant material is required.
Profiling Italian cat and dog owners’ perception of pet food quality in purchasing habits
Authors: Vinassa Marica , Vergnano Diana , Valle Emanuela , Giribaldi Marzia , Nery Joana , Prola Liviana , Bergero Domenico , Schiavone Achille
Published: December 2019

Background. In these last years there is a growing sensibility of public opinion towards pet animal, that involves also an in increasing attention on their nutrition, seen as a way to guarantee welfare. However, it is difficult for the consumer to understand the quality of a product because label information is not always clear to the consumer. The aim of the study is to identify through a survey the pet food characteristics that are seen as quality indicators for pet owners. Results. In total 935 surveys were collected. Descriptive statistic showed a higher percentage of female owners (61.8%) among pet food buyers. Participants were divided almost equally between dogs owners (39.4%), cats owners (30.8%) or both dogs and cats owners (29.8%). A quarter of owners (25.5%) asked for advice to veterinary on which pet food to buy and about a third (30.4%) trusts in web sites of major brands, giving both of them an higher responsibility in providing information to the buyer. “Contain natural ingredients” was the characteristic with the highest score (4.3 on 5), confirming nowadays market trends. Correspondence analysis for age showed that older owners (>65 y) put more attention on costs, with low emphasis on food appearance, animal satisfaction and fecal quality. Younger owners (<35 y) put more attention on positive influence on animal feces, high percentage of protein, presence of recyclable packaging and less attention at food appearance, smell and animal satisfaction. Appearance, smell, higher cost and some label indication (protein content, presence of fresh meat, low grains content) are relevant for consumers buying wet pet food. Some differences are showed between owners of different animal species. Cat owners give more importance to appearance, smell and production site, dog owners focus on protein content, presence of meat as a first ingredient and higher cost. Conclusions. Italian pet food buyers, considered as the most important quality indicators the presence of natural ingredients, while the least important was the high price. Information from this survey can help the pet food companies to identify the factors that influence the perceived quality of the products by dog and cat owners.
Cardiovascular findings by echocardiography in canine model of Chagas disease immunized with DNA Trypanosoma cruzi genes.
Authors: Rodríguez-Morales Olivia , Roldán Francisco-Javier , Vargas-Barrón Jesús , Parra-Benítez Enrique , Medina-García María de Lourdes , Vergara-Bello Emilia , Arce-Fonseca Minerva
Published: December 2019

Background: Chagas disease (ChD) is nowadays considered as an emerging disease in the USA and Europe. pBCSP and pBCSSP4 plasmids, containing Trypanosoma cruzi genes encoding a trans -sialidase protein and an amastigote-specific glycoprotein, respectively, were tested as vaccines in canine model. Echocardiography studies for determining the prophylactic effect of these genes in experimentally infected dogs were evaluated to compare with findings obtained by other techniques performed previously. Hemodynamic parameters after DNA-immunization were performed. Results: Low fractional-shortening values of non-vaccinated dogs suggested an impairment in general cardiac function. Low Left-Ventricular-Ejection-Fraction values found in infected dogs suggested myocardial injury regardless of whether they were vaccinated or not. Low Left-Ventricular-Diastolic/Systolic-Diameters in vaccinated dogs suggested that progressive heart damage or heart dilation could be prevented by DNA vaccination. Systolic-Peak-Time was higher in non-vaccinated groups increasing vulnerability to malignant arrhythmias and sudden death. High Left-Ventricular-Volume in infected groups suggested a decrease in wall thickness that might lead to increased size of the heart cavity, except in the pBCSP plasmid-vaccinated dogs. Conclusions: The use of echocardiography allowed a more complete follow-up the pathological process in the living patient than with other techniques like electrocardiography, anatomopathology and histopathology, being the method of choice for characterizing the clinical stages of ChD.
Immune response of horses to inactivated African horse sickness vaccines
Authors: Rodriguez Marina , Joseph Sunitha , Pfeffer Martin , Raghavan Rekha , Wernery Ulrich
Published: December 2019

Background: African horse sickness (AHS) is a devastating disease of equids that has been known for centuries. Many equids mainly in sub-Saharan Africa still die every year from this viral disease. This has an enormous economic impact on the horse industry, notwithstanding the dedication of the individual horse owner in the daily care of their animals. Currently, prevention and control of the disease is based on live attenuated vaccines and control vector arthropods. Results: A total of 29 horses kept in a desert isolation area, divided into 2 groups, were subcutaneously (sc) vaccinated. Horses of Group 1, in total 18 horses divided into 9 subgroups of 2 horses each, were individually immunised with 1 to 9 AHS serotypes, respectively. Eleven horses of Group 2 were immunised with all 9 serotypes simultaneously in 2 different injections as combination of vaccine 1 containing 5 serotypes (1,4,7,8,9) and vaccine 2 containing 4 serotypes (2,3,5,6). This vaccination experiment lasted 12 months. Blood samples were periodically withdrawn for serum antibody tests using ELISA and VNT. Blood was collected for 2 weeks after each vaccination for PCR and virus isolation. After the booster vaccination, these 27 horses seroconverted to the inactivated vaccines, but 2 horses responded poorly as measured by ELISA. In Group 1 ELISA and VN antibodies declined between 5 to 7 months post vaccination (pv). Twelve months later, the antibody level in most of the horses dropped to the negative range, but after the annual booster all horses again seroconverted strongly, already 1 week pv. In Group 2, ELISA antibodies turned positive after the first booster and VN antibodies started to appear for some serotypes after primary vaccination. After booster vaccination, VN antibodies increased in a different pattern for each serotype. Antibodies remained high during 12 months and increased strongly after the annual booster in 78% of the horses. PCR and virus isolation were negative. Conclusions: Horses vaccinated with single serotypes need a booster after 6 months and simultaneously immunised horses after 12 months. Due to the non-availability of a facility in the UAE, no challenge infection could be carried out.
Mixture survival models methodology: an application to cancer immunotherapy assessment in clinical trials
Authors: Sanchez Lizet , Lorenzo-Luaces Patricia , Fonte Claudia , Lage Agustin
Published: December 2019

Progress in immunotherapy revolutionized the treatment landscape for advanced lung cancer, raising survival expectations beyond those that were historically anticipated with this disease. In the present study, we describe the methods for the adjustment of mixture parametric models of two populations for survival analysis in the presence of long survivors. A methodology is proposed in several five steps: first, it is proposed to use the multimodality test to decide the number of subpopulations to be considered in the model, second to adjust simple parametric survival models and mixture distribution models, to estimate the parameters and to select the best model fitted the data, finally, to test the hypotheses to compare the effectiveness of immunotherapies in the context of randomized clinical trials. The methodology is illustrated with data from a clinical trial that evaluates the effectiveness of the therapeutic vaccine CIMAvaxEGF vs the best supportive care for the treatment of advanced lung cancer. The mixture survival model allows estimating the presence of a subpopulation of long survivors that is 44% for vaccinated patients. The differences between the treated and control group were significant in both subpopulations (population of short-term survival: p = 0.001, the population of long-term survival: p = 0.0002). For cancer therapies, where a proportion of patients achieves long-term control of the disease, the heterogeneity of the population must be taken into account. Mixture parametric models may be more suitable to detect the effectiveness of immunotherapies compared to standard models.
Estimating Optimal Dynamic Treatment Strategies Under Resource Constraints Using Dynamic Marginal Structural Models
Authors: Caniglia Ellen , Murray Eleanor , Hernan Miguel , Shahn Zach
Published: December 2019

Background: Existing methods for estimating the optimal treatment or monitoring strategy typically assume unlimited access to resources. However, when a health system has resource constraints, such as limited funds, access to medication, or monitoring capabilities, medical decisions must balance impacts on both individual and population health outcomes. That is, decisions should account for competition between individuals in resource usage. A simple solution is to estimate the (counterfactual) resource usage under the possible interventions and choose the optimal strategy for which resource usage is within acceptable limits. Methods: We propose a method to identify the optimal dynamic intervention strategy that leads to the best expected health outcome accounting for a health system's resource constraints. We then apply this method to determine the optimal dynamic monitoring strategy for people living with HIV when resource limits on monitoring exist using observational data from the HIV-CAUSAL Collaboration. In our example, we identify the optimal CD4 cell count at which to decrease monitoring frequency from every 3-6 months to every 9-12 months among the subset of strategies that satisfy a hypothetical constraint on monitoring. We find the resource constrained dynamic strategy (RCDS) that minimizes the risk of virologic failure given a hypothetical resource constraint where individuals can only be monitored on average every 6 months. Results: Given the hypothetical resource constraint, the optimal monitoring strategy is "monitor CD4 cell count and HIV-RNA every 3-6 months when CD4 is below 320 cells/ml and every 9-12 months when CD4 is above 320 cells/ml." Conclusions: We describe and and apply a method to identify the optimal RCDS given a hypothetical resource constraint. Similar applications may be useful in settings with limited availability of or capacity for monitoring individuals living with HIV or other chronic diseases.
Development of A Guideline for Reporting Mediation Analyses (AGReMA)
Authors: Cashin Aidan Gregory , McAuley James H , Lamb Sarah E , Hopewell Sally , Kamper Steven J , Williams Christopher M , Henschke Nicholas , Lee Hopin
Published: December 2019

Background There are a growing number of studies using mediation analysis to understand the mechanisms of health interventions and exposures. Recent work has shown that the reporting of these studies is heterogenous and incomplete. This problem stifles clinical application, reproducibility, and evidence synthesis. This paper describes the processes and methods that will be used to develop a guideline for reporting studies of mediation analyses (AGReMA).Methods/Design AGReMA will be developed over five overlapping stages. Stage one will comprise a systematic review to examine relevant evidence on the quality of reporting in published studies that use mediation analysis. In the second stage we will consult a group of methodologists and applied researchers by using a Delphi process to identify items that should be considered for inclusion in AGReMA. The third stage will involve a consensus meeting to consolidate and prioritise key items to be included in AGReMA. The fourth stage will involve production of AGReMA and an accompanying explanation and elaboration document. In the final stage we will disseminate the AGReMA statement via journals, conferences, and professional meetings across multiple disciplines.Discussion The development and implementation of AGReMA will improve the standardization, transparency, and completeness in the reporting of studies that use mediation analysis to understand the mechanisms of health interventions and exposures.
A qualitative study exploring the effects of participation in a community-based pre-operative exercise programme on perceived wellbeing and quality of life in people with newly diagnosed prostate cancer: A pilot study
Authors: Loughney Lisa , McGowan Rachel , O'Malley Kiaran , McCaffrey Noel , Furlong Brona , Walsh Deirdre
Published: December 2019

Purpose: People with a newly diagnosed prostate cancer are often treated by surgery. The time window between cancer diagnosis and surgery causes high levels of uncertainty and stress, which negatively impact quality of life (QoL). This study explored the experience of participating in a community-based pre-operative exercise programme (in the time between cancer diagnosis and surgery) and its impact on perceived wellbeing and QoL in people with newly diagnosed prostate cancer.Methods: Eleven men diagnosed with a new prostate cancer diagnosis were recruited and undertook a prescribed community-based pre-operative exercise training programme in the time available prior to surgery. Following completion of the pre-operative exercise programme (within 1 week before surgery), participants took part in one semi-structured interview which explored four broad QoL domains: physical; psychological; social; and spiritual wellbeing. Data were analysed using thematic analysis (a bottom up/inductive analysis).Results: Data supported four main themes. Participation in the community-based pre-operative exercise training programme (over a mean (SD) of 4 (2) weeks) provided participants with: 1) a teachable moment; 2) a journey of preparation; 3) provided them with a sense of optimism; and 4) social connectedness.Conclusion: This community-based pre-operative exercise training programme enhanced wellbeing and served as an opportunity to improve perceived QoL. Further research is required to explore this in a larger sample.
Identification of the biomarker roles of miR-106 family for predicting the risk and poor survival of colorectal cancer
Authors: Peng Qiliang , Shen Yi , Zhao Peifeng , Cheng Ming , Zhu Yaqun , Xu Bo
Published: December 2019

Background: Recent studies have extensively investigated the roles of miR-106 in colorectal cancer (CRC). However, the associations and molecular mechanism underlying the roles of miR-106 in CRC remain unclear. We aimed to thoroughly investigate the biomarker roles of miR-106 for predicting the risk and survival outcome in CRC.Methods: We first conducted a comprehensive meta-analysis to quantitatively evaluate the roles of miR-106 in the diagnosis and prognosis of CRC. Then, we qualitatively explored the biomarker roles of miR-106 in CRC through an integrative bioinformatics analysis. Results: The results indicated that miR-106 yielded a combined AUC of 0.79 (95% CI: 0.76–0.83), with a pooled sensitivity of 0.50 (95% CI: 0.32–0.68) and a pooled specificity of 0.93 (95% CI: 0.79–0.98) for discriminating CRC cases from normal controls. Moreover, patients with higher expression of miR-106 were significantly associated with shorter disease-free survival (HR: 1.73; 95%CI: 1.23-2.44) and overall survival (HR: 1.39; 95%CI: 1.09-1.77). Finally, gene ontology and pathway analysis demonstrated that miR-106 family was highly involved in the initiation and progression of CRC and indicated the potential molecular mechanism for miR-106 in CRC.Conclusions: Our results indicated that miR-106 showed promising potential as diagnostic and prognostic biomarker for CRC. Nevertheless, the underlying molecular mechanism of miR-106 family involved in CRC requires further investigation.