bluuebunny/crossref_metadata_2025_split huggingface dataset:
DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits
Authors: Jiang Lin , Xue Chao , Dai Sheng , Chen Shangzhen , Chen Peikai , Sham Pak Chung , Wang Haijun , Li Miaoxin 
Published: November 2019

AbstractThe driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.
Metabolic engineering Escherichia coli for efficient production of icariside D2
Authors: Liu Xue , Li Lingling , Liu Jincong , Qiao Jianjun , Zhao Guang-Rong 
Published: November 2019

Abstract

Background
Icariside D2 is a plant-derived natural glycoside with pharmacological activities of inhibiting angiotensin-converting enzyme and killing leukemia cancer cells. Production of icariside D2 by plant extraction and chemical synthesis is inefficient and environmentally unfriendly. Microbial cell factory offers an attractive route for economical production of icariside D2 from renewable and sustainable bioresources.

Results
We metabolically constructed the biosynthetic pathway of icariside D2 in engineered Escherichia coli. We screened the uridine diphosphate glycosyltransferases (UGTs) and obtained an active RrUGT3 that regio-specifically glycosylated tyrosol at phenolic position to exclusively synthesize icariside D2. We put heterologous genes in E. coli cell for the de novo biosynthesis of icariside D2. By fine-tuning promoter and copy number as well as balancing gene expression pattern to decrease metabolic burden, the BMD10 monoculture was constructed. Parallelly, for balancing pathway strength, we established the BMT23–BMD12 coculture by distributing the icariside D2 biosynthetic genes to two E. coli strains BMT23 and BMD12, responsible for biosynthesis of tyrosol from preferential xylose and icariside D2 from glucose, respectively. Under the optimal conditions in fed-batch shake-flask fermentation, the BMD10 monoculture produced 3.80 g/L of icariside D2 using glucose as sole carbon source, and the BMT23–BMD12 coculture produced 2.92 g/L of icariside D2 using glucose–xylose mixture.

Conclusions
We for the first time reported the engineered E. coli for the de novo efficient production of icariside D2 with gram titer. It would be potent and sustainable approach for microbial production of icariside D2 from renewable carbon sources. E. coli–E. coli coculture approach is not limited to glycoside production, but could also be applied to other bioproducts.
Integrated strain- and process design enable production of 220 g L−1 itaconic acid with Ustilago maydis
Authors: Hosseinpour Tehrani Hamed , Becker Johanna , Bator Isabel , Saur Katharina , Meyer Svenja , Rodrigues Lóia Ana Catarina , Blank Lars M. , Wierckx Nick 
Published: November 2019

AbstractBackgroundItaconic acid is an unsaturated, dicarboxylic acid which finds a wide range of applications in the polymer industry and as a building block for fuels, solvents and pharmaceuticals. Currently,Aspergillus terreusis used for industrial production, with titers above 100 g L−1depending on the conditions. BesidesA. terreus,Ustilago maydisis also a promising itaconic acid production host due to its yeast-like morphology. Recent strain engineering efforts significantly increased the yield, titer and rate of production.ResultsIn this study, itaconate production byU. maydiswas further increased by integrated strain- and process engineering. Next-generation itaconate hyper-producing strains were generated using CRISPR/Cas9 and FLP/FRT genome editing tools for gene deletion, promoter replacement, and overexpression of genes. The handling and morphology of this engineered strain were improved by deletion offuz7, which is part of a regulatory cascade that governs morphology and pathogenicity. These strain modifications enabled the development of an efficient fermentation process with in situ product crystallization with CaCO3. This integrated approach resulted in a maximum itaconate titer of 220 g L−1, with a total acid titer of 248 g L−1, which is a significant improvement compared to best published itaconate titers reached withU. maydisand withA. terreus.ConclusionIn this study, itaconic acid production could be enhanced significantly by morphological- and metabolic engineering in combination with process development, yielding the highest titer reported with any microorganism.
First report of the influence of temperature on the bionomics and population dynamics of Aedes koreicus, a new invasive alien species in Europe
Authors: Marini Giovanni , Arnoldi Daniele , Baldacchino Frederic , Capelli Gioia , Guzzetta Giorgio , Merler Stefano , Montarsi Fabrizio , Rizzoli Annapaola , Rosà Roberto 
Published: November 2019

Abstract

Background
Aedes koreicus was detected in northern Italy for the first time in 2011, and it is now well established in several areas as a new invasive mosquito species. Data regarding the influence of temperature on mosquito survival and development are not available yet for this species.

Methods
We experimentally investigated the influence of different constant rearing temperatures (between 4 and 33 °C) on the survival rates and developmental times of different life stages of Ae. koreicus under laboratory conditions. The resulting data were subsequently used to inform a mathematical model reproducing the Ae. koreicus life-cycle calibrated to counts of adult females captured in the field in the autonomous province of Trento (northern Italy) between 2016 and 2018.

Results
We found that temperatures above 28 °C are not optimal for the survival of pupae and adults, whereas temperate conditions of 23–28 °C seem to be very favorable, explaining the recent success of Ae. koreicus at establishing into new specific areas. Our results indicate that Ae. koreicus is less adapted to local climatic conditions compared to Ae. albopictus, another invasive species which has been invading the area for the last three decades. Warmer seasons, which are more likely to occur in the future because of climate change, might extend the breeding time and therefore increase the abundance of Ae. koreicus in the study region.

Conclusions
Our findings provide, to our knowledge, the first evidence on how temperature influences the bionomics and dynamics of Ae. koreicus and highlight the need for further studies on the phenology of this species in temperate areas of Europe.
First detection of the kdr mutation (L1014F) in the plague vector Xenopsylla cheopis (Siphonaptera: Pulicidae)
Authors: Liu Nian , Feng Xiangyang , Li Mei , Qiu Xinghui 
Published: November 2019

Abstract

Background
The oriental rat flea, Xenopsylla cheopis, is the most efficient vector of the plague. Pyrethroid insecticides such as cypermethrin, cyhalothrin and deltamethrin have been often used to limit plague transmission via controlling the vector during outbreaks. However, this strategy is threatened by the development of insecticide resistance. Understanding the mechanisms underlying pyrethroid resistance is the prerequisite for successful flea control.

Methods
Partial DNA sequences of X. cheopis voltage gated sodium channel (VGSC) gene were amplified from a total of 111 individuals, collected from a natural plague epidemic foci in Baise City, Guangxi Zhuang Autonomous Region of China. These DNA fragments were sequenced. The frequency and distribution of kdr mutations were assessed in four X. cheopis populations. The origin of kdr mutations was investigated by phylogenetic and network analysis.

Results
The classical knockdown resistance (kdr) mutation (L1014F) was detected in four field populations at frequencies ranging between 0.021–0.241. The mutant homozygote was observed only in one of the four populations. Seven haplotypes were identified, with two of them carrying the resistance L1014F mutation. Phylogenetic tree and network analysis indicated that the L1014F allele was not singly originated. Based on polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) profiling, an easy-to-use and accurate molecular assay for screening individual fleas for the L1014F mutation was developed.

Conclusions
To our knowledge, this work represents the first report of the L1014F mutation in the plague vector X. cheopis. The incidence of the L1014F allele highlights the need of further studies on the phenotypic effect of this mutation in this plague vector. Early detection and monitoring of insecticide resistance is suggested in order to make effective control strategies in case of plague outbreaks in this region.
Liver fluke in Irish sheep: prevalence and associations with management practices and co-infection with rumen fluke
Authors: Munita Maria Pia , Rea Rosemary , Martinez-Ibeas Ana Maria , Byrne Noel , McGrath Guy , Munita-Corbalan Luis Enrique , Sekiya Mary , Mulcahy Grace , Sayers Ríona G. 
Published: November 2019

Abstract

Background
The present study aimed to identify the national prevalence of Fasciola hepatica in Irish sheep and to conduct a risk analysis assessment based on management and treatment practices in participating flocks. Also, co-infection with rumen fluke was quantified and its association with liver fluke and management practices was assessed.

Methods
A total of 305 sheep flocks were selected ensuring even national representation of the sheep population. Participating farms were asked to complete a survey questionnaire on farm management practices and submit faecal samples during the winter of 2014–2015. Pooled faecal samples were analysed for the presence of F. hepatica and co-infection with rumen fluke. Apparent and true prevalence were calculated, additionally, the rate of co-infection with rumen fluke was also obtained. Correlation and regression analyses were used for assessing associations between management practices, liver fluke infection and co-infection with rumen fluke.

Results
The national true prevalence of F. hepatica was 50.4% (n = 305). Regional prevalence varied from 41% in the east to 52% in the south. Co-infection with rumen fluke was observed in 40% of the studied population and correlated with increased F. hepatica egg counts (OR = 2.9; P ≤ 0.001). Predominant breeds were Suffolk, Texel and Horned Mountain breeds. Beef cattle were the most frequent type of other livestock present on farms and mixed species grazing was frequently reported (73%). More than half of the flocks reported a mid-to-late lambing period (March-April). Use of mountain land for grazing was of 32%. Flukicides were most commonly used twice over the autumn-winter period. Regression analyses highlighted significant association of F. hepatica status, with the presence of other livestock on farm, frequency of flukicides used during the winter and clinical presentation of liver fluke. A significant increase in eggs per gram of faeces was observed in Charollais sheep in comparison with all other breeds. Co-infection with F. hepatica and Calicophoron daubneyi was also significantly associated with the presence of other livestock on the farm, type of flukicide used and clinical fasciolosis.

Conclusions
The present study provides up-to-date information on the prevalence of F. hepatica in Irish sheep and adds insight to the epidemiology of the disease. These findings will be useful for designing new holistic control measures for F. hepatica infection.
Inhibition of spinal bone formation in AS: 10 years after comparing adalimumab to OASIS
Authors: van der Heijde Désirée , Landewé Robert 
Published: November 2019

AbstractA decade has passed since the publication on the comparison of the effect of adalimumab with data from a historic cohort on the progression of structural damage in the spine of patients with ankylosing spondylitis (AS). No effect could be observed, and currently, there is still no definite proof that TNF inhibitors (TNFi) inhibit spinal structural damage. The findings of the publication are discussed within the context of the time at the publication and new developments.
Multilevel modelling of factors associated with caesarean section in Ethiopia: community based cross sectional study
Authors: Azene Abebaw Gedef , Aragaw Abiba Mihret , Birlie Mihretie Gedefaw 
Published: November 2019

Abstract

Objective
The aim of this study was to identify socio-demographic and health related factors associated with caesarean section in Ethiopia.

Results
A total of 256 mothers undergoing to CS among 7193 delivery. Average maternal age of a participant was 29.26 years and 80% of mothers having two and more children. A woman delivered in private institution was 30% (AOR = 1.29; 95% CI 1.25, 1.32) more likely undergoing CS as compared to home delivery. Factors associated with CS were higher education level (AOR = 1.09, 95% CI 1.07, 1.12), preceding birth interval (AOR = 1.01; 95% CI 1.00. 1.03), multiple pregnancy (AOR = 1.11; 95% CI 1.08, 1.15), multiple parity (AOR = 0.98; 95% CI 0.97, 0.99), large size the child (AOR = 1.01; 95% CI 1.001, 1.02), richest households (AOR = 0.98; 95% CI 0.97, 0.99), rural residence (AOR = 0.98 95% CI 0.96, 0.99) and Addis Ababa (AOR = 1.06; 95% CI 1.04,1.09). As a conclusion and recommendation, the prevalence of CS higher in private institutions and Addis Ababa, so professionals should apply CS alone medical indication.
Rapid diagnostics of orthopedic implant-associated infections using Unyvero ITI implant and tissue infection application is not optimal for Staphylococcus species identification
Authors: Aamot Hege Vangstein , Johnsen Bjørn Odd , Skråmm Inge 
Published: November 2019

Abstract

Objectives
This pilot study aimed to compare the commercial Unyvero ITI multiplex PCR application (U-ITI, Curetis GmbH) with conventional culturing concerning (a) detection of pathogens, (b) time to detection of pathogens and (c) time to and quality of antibiotic treatment recommendation in diagnostics of orthopedic implant-associated infections (OIAI).

Results
72 tissue biopsies from 15 consecutive patients with deep OIAI infections were analyzed with conventional culturing including phenotypic antibiotic susceptibility testing and the U-ITI. U-ITI showed lower sensitivity than conventional culturing concerning detection of pathogens (73% vs 93%). 4/15 patients would have been given false negative results by U-ITI, all of which were culture-positive for Staphylococcus species. Median time to detection of pathogens was 47 h and antibiotic resistance 89 h by conventional methods compared to 13.5 h with the U-ITI. The U-ITI did not detect antibiotic resistance, whereas conventional culturing showed resistance to antibiotics covered by the U-ITI panel in 2 patients. Time to detection of pathogens was improved, but the detection limit for staphylococci was unsatisfactory. Although the time to antibiotic treatment recommendation was significantly reduced, the U-ITI would have resulted in incorrect antibiotic recommendation in 2 patients. Our data do not support use of this assay in diagnostics.
Alterations of mental defeat and cognitive flexibility during cognitive behavioral therapy in patients with major depressive disorder: a single-arm pilot study
Authors: Murata Tomokazu , Hiramatsu Yoichi , Yamada Fuminori , Seki Yoichi , Nagata Shinobu , Shibuya Takayuki , Yokoo Mizue , Noguchi Remi , Tanaka Mari , Oshiro Keiko , Matsuzawa Daisuke , Hirano Yoshiyuki , Shimizu Eiji 
Published: November 2019

Abstract
Objective
Mental defeat affects the occurrence and chronicity of depression and cognitive flexibility. This study aimed to examine changes in mental defeat and cognitive flexibility scores after cognitive behavioral therapy including IR. In the intervention group, patients with depression (n = 18, mean age = 37.89 years) received 15 cognitive behavioral therapy sessions. Patients completed the Beck Depression Inventory-II; Mental Defeat Scale; Cognitive Flexibility Scale; EuroQol five dimensions questionnaire; Patient Health Questionnaire-9 and seven-item Generalized Anxiety Disorder Scale before the intervention, after six sessions, and post-intervention. The healthy control group (n = 33, mean age = 37.91) completed all scales once and did not receive treatment.

Results
Post-cognitive behavioral therapy, a significant decrease was observed in Beck Depression Inventory-II, Mental Defeat Scale, Cognitive Flexibility Scale, and Patient Health Questionnaire-9 scores. Although mental defeat and cognitive flexibility did not reach the level of the healthy control group, they demonstrated improvement. Therefore, when treating depression, mental defeat and cognitive flexibility should be measured in addition to depressive symptoms.
Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 25, 2016 (registration ID: UMIN000023320)
Missed opportunities in large scale comparison of QSAR and conformal prediction methods and their applications in drug discovery
Authors: Krstajic Damjan 
Published: November 2019

Abstract
Recently Bosc et al. (J Cheminform 11(1): 4, 2019), published an article describing a case study that directly compares conformal predictions with traditional QSAR methods for large-scale predictions of target-ligand binding. We consider this study to be very important. Unfortunately, we have found several issues in the authors’ approach as well as in the presentation of their findings.
Optimal interference range for minimum Bayes risk in binomial and Poisson wireless networks
Authors: Ouyang Min , Shi Wenxiao , Zhang Ruidong , Liu Wei 
Published: November 2019

Abstract
Interference is the main performance-limiting factor in most wireless networks. Protocol interference model is extensively used in the design of wireless networks. However, the setting of interference range, a crucial part of the protocol interference model, is rather heuristic and remains an open problem. In this paper, we use the stochastic geometry and the direct approach to obtain the associated feasibility distributions. After that, we use the binary hypothesis testing to achieve the Bayes risk under binomial point process (BPP) and Poisson point process (PPP), respectively. According to the first derivative of the Bayes risk, we provide the equation to achieve the optimal interference range for minimum Bayes risk. We extend the method proposed by Wildman et al. to a more general situation. Furthermore, we show that for infinite PPP, those two methods converge to the same results. Several numerical results for wireless networks under BPP, finite PPP, and infinite PPP are given. Simulation results show that in the finite wireless network, the BPP method performs better than the PPP method.
Fixed point results in $M_{\nu }$-metric spaces with an application
Authors: Asim Mohammad , Uddin Izhar , Imdad Mohammad 
Published: November 2019

Abstract
In this paper, we introduce the concept of $M_{\nu}$

M
ν

-metric as a generalization of M-metric and ν-generalized metric and also prove an analogue of Banach contraction principle in an $M_{\nu}$

M
ν

-metric space. Also, we adopt an example to highlight the utility of our main result which extends and improves the corresponding relevant results of the existing literature. Finally, we use our main result to examine the existence and uniqueness of solution for a Fredholm integral equation.
Blow-up results for a quasilinear von Karman equation of memory type
Authors: Lee Mi Jin , Kang Jum-Ran 
Published: November 2019

Abstract
In this paper, we consider the blow-up result of solution for a quasilinear von Karman equation of memory type with nonpositive initial energy as well as positive initial energy. For nonincreasing function $g>0$
g
>
0
and nondecreasing function f, we prove a finite time blow-up result under suitable condition on the initial data.
Effect of bFGF and fibroblasts combined with hyaluronic acid-based hydrogels on soft tissue augmentation: an experimental study in rats
Authors: Lee Su Yeon , Park Yongdoo , Hwang Soon Jung 
Published: November 2019

Abstract

Background
Hyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane®).

Methods
The hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane® group (HGF), the hydrogel was replaced with Restylane® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR.

Results
The hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane® filler could not be observed, even though no inflammatory reactions were observed.

Conclusion
This study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.