bluuebunny/crossref_metadata_2025_split huggingface dataset:
PET quantification of brain O-GlcNAcase with [18F]LSN3316612 in healthy human volunteers
Authors: Lee Jae-Hoon , Liow Jeih-San , Paul Soumen , Morse Cheryl L. , Haskali Mohammad B. , Manly Lester , Shcherbinin Sergey , Ruble J. Craig , Kant Nancy , Collins Emily C. , Nuthall Hugh N. , Zanotti-Fregonara Paolo , Zoghbi Sami S. , Pike Victor W. , Innis Robert B. 
Published: March 2020

Abstract
Background
Previous studies found that [18F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of [18F]LSN3316612 for human clinical research.

Methods
Kinetic evaluation of [18F]LSN3316612 was conducted in a combined set of baseline brain scans from 17 healthy human volunteers and test-retest imaging was conducted in 10 of these volunteers; another 6 volunteers had whole-body scans to measure radiation exposure to body organs. Total distribution volume (VT) estimates were compared for the one- and two-tissue compartment models with the arterial input function. Test-retest variability and reliability were evaluated via mean difference and intraclass correlation coefficient (ICC). The time stability of VT was assessed down to a 30-min scan time. An alternative quantification method for [18F]LSN3316612 binding without blood was also investigated to assess the possibility of eliminating arterial sampling.

Results
Brain uptake was generally high and could be quantified as VT with excellent identifiability using the two-tissue compartment model. [18F]LSN3316612 exhibited good absolute test-retest variability (12.5%), but the arithmetic test-retest variability was far from 0 (11.3%), reflecting a near-uniform increase of VT on the retest scan in nine of 10 volunteers. VT values were stable after 110 min in all brain regions, suggesting that no radiometabolites accumulated in the brain. Measurements obtained using only brain activity (i.e., area under the curve (AUC) from 150–180 min) correlated strongly with regional VT values during test-retest conditions (R2 = 0.84), exhibiting similar reliability to VT (ICC = 0.68 vs. 0.64). Estimated radiation exposure for [18F]LSN3316612 PET was 20.5 ± 2.1 μSv/MBq, comparable to other 18F-labeled radioligands for brain imaging.

Conclusions
[18F]LSN3316612 is an excellent PET radioligand for imaging O-GlcNAcase in the human brain. Alternative quantification without blood is possible, at least for within-subject repeat studies. However, the unexplained increase of VT under retest conditions requires further investigation.
The impact of additive or substitutive clinical study design on the negotiated reimbursement for oncology pharmaceuticals after early benefit assessment in Germany
Authors: Dintsios C. M. , Beinhauer I. 
Published: March 2020

Abstract
Background
We analysed the impact of clinical study design for oncological pharmaceuticals on the subsequent price negotiations after early benefit assessment between pharmaceutical companies and the German National Association of Statutory Health Insurance Funds. The analysis was conducted for all oncology pharmaceuticals that underwent the early benefit assessment in Germany since its introduction in 2011 up to September 2016.

Methods
It was differentiated between additive (new therapy in addition to baseline therapy) and substitutive study designs (baseline therapy to be replaced). The study design was derived from the dossiers of the pharmaceutical companies submitted to the Federal Joint Committee. Subgroup specific costs in case of granted added benefit were calculated as annual therapy costs and compared with the costs of the appropriate comparators to quantify price premiums. Further price influencing factors were analysed in univariate and multivariate regression analysis considering the budget impact for the statutory health insurance as well.

Results
The mean and the median of the additive premiums for substitutive designs (€50,477.68 and €49,841.24) were higher than for additive designs, if the comparator was different to best supportive care (€48,750.00 and €42,820.44). The mean multiplicative premium for the substitutive designs was 15.07 versus 2.29 for the additive designs. EU-Prices and target population size had a significant effect on the reimbursement. The adjusted R-square in the log Premium OLS-regressions reached 0.708 when including all explanatory variables and considering interaction between target population and annual costs of the comparator.

Conclusions
Study design as an additional important influencing factor of the negotiations next to those stated in the framework agreement was identified and verified. Therefore, study design should be considered by pharmaceutical companies and by decision makers and payers within strategic price planning as a potential predictor. For some specific categories the number of cases was small. Further analyses should be performed when more oncology pharmaceuticals have passed the early benefit assessment.
The costs of disability in Australia: a hybrid panel-data examination
Authors: Vu Binh , Khanam Rasheda , Rahman Maisha , Nghiem Son 
Published: March 2020

Abstract
Background
Over four million people in Australia have some form of disability, of whom 2.1 million are of working age. This paper estimates the costs of disability in Australia using the standard-of-living approach. This approach defines the cost of disability as additional income required for people with a disability to achieve a similar living standard to those without a disability. We analyse data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey using a hybrid panel data model. To the best of our knowledge, this is the first study to examine the costs of disability in Australia using a high quality, large, nationally-representative longitudinal data set.

Methods
This study estimates the costs of disability in Australia by using the Standard of Living (SoL) and a dynamic model approach. It examines the dynamics of disability and income by using lagged disability and income status. The study also controls for unobserved individual heterogeneity and endogeneity of income. The longitudinal specification in this study allows us to separate short- and long-run costs of disability using a hybrid panel data regression approach.

Results
Our results show that people with a disability need to increase their adult-equivalent disposable income by 50% (in the short-run) to achieve the same standard of living as those without a disability. This figure varies considerably according to the severity of the disability, ranging from 19% for people without work-related limitations to 102% for people with severe limitations. Further, the average cost of disability in the long-run is higher and it is 63% of the adult-equivalent disposable income.

Conclusions
Firstly, our results show that with the same level of income, the living standard is lower in households with people with a disability compared to households without members with a disability. This indicates a strong relationship between poverty and disability. However, current poverty measures do not take into account disability, therefore, they fail to consider substantial differences in poverty rates between people with and without a disability. Secondly, the estimated costs reflected in this study do consider foregone income due to disability. Therefore, policymakers should seriously consider adopting disability-adjusted poverty and inequality measurements. Thirdly, increasing the income (e.g. through government payments) or providing subsidised services for people with a disability may increase their financial satisfaction, leading to an improved living standard. The results of this study can serve as a baseline for the evaluation of the National Disability Insurance Scheme (NDIS).
Transmission of influenza A virus and porcine reproductive and respiratory syndrome virus using a novel nurse sow model: a proof of concept
Authors: Garrido-Mantilla Jorge , Culhane Marie R. , Torremorell Montserrat 
Published: March 2020

AbstractThe mechanisms of transmission of influenza A virus (IAV) and porcine reproductive and respiratory syndrome virus (PRRSV) in pigs during the pre-weaning period are not fully elucidated. Since viable IAV and PRRSV can be found on the udder skin of lactating sows and the use of nurse sows is a common management practice, we developed a novel nurse sow model to evaluate the transmission of IAV and PRRSV from lactating sows to their adopted piglets. In two studies, we infected pigs with either IAV or PRRSV who then contaminated the udder skin of lactating dams with their nasal and oral secretions while suckling. Once the skin was confirmed virus positive for IAV and PRRSV, the sows were moved to separate empty clean rooms to adopt IAV and PRRSV negative suckling piglets. After adoption, 1 out of eight (12.5%) piglets tested IAV positive 1-day post-adoption (dpa) and the entire litter (8 out of 8) became positive by 4 dpa. In the case of PRRSV, 3 out of 11 (27.3%) pigs tested rRT-PCR positive 2 dpa and there were 7 out of 11 (63.6%) pigs positive at the termination of the study at 7 dpa. This study documented the transmission of IAV and PRRSV between litters of piglets by nurse sows and highlights the importance of the nurse sow-piglet as a unit that contributes to the maintenance of endemic infections in breeding herds. The use of nurse sows in pig farms, though beneficial for minimizing pre-weaning mortality and maximizing farm productivity, is seemingly detrimental as this practice may facilitate the transmission of IAV and PRRSV to piglets prior to weaning.
Protective immunity in mice vaccinated with a novel elastase-1 significantly decreases Trichinella spiralis fecundity and infection
Authors: Zhang Xin Zhuo , Sun Xiang Yuan , Bai Ying , Song Yan Yan , Hu Chen Xi , Li Xiangrui , Cui Jing , Wang Zhong Quan 
Published: March 2020

AbstractTrichinella spiralis is an important foodborne parasitic nematode that represents an enormous threat to the food safety of pork meat. The development of a preventive vaccine is valuable for the prevention and control of Trichinella infection in domestic pigs to ensure pork safety. Elastase is a trypsin-like serine protease that hydrolyzes the host’s diverse tissue components and participates in parasite penetration, and it might be a novel vaccine target molecule. The aim of this study was to assess the protective immunity produced by vaccination with a novel Trichinella spiralis elastase-1 (TsE) in a mouse model. The results demonstrate that subcutaneous vaccination of mice with rTsE elicited a systemic humoral response (high levels of serum IgG and subclass IgG1/IgG2a and IgA) and significant local enteral mucosal sIgA responses. Anti-rTsE IgG recognized the native TsE at the cuticle, stichosome of intestinal infective larvae and adult worm (AW), and intrauterine embryos of female AW. The rTsE vaccination also produced a systemic and local mixed Th1/Th2 response, as demonstrated by clear elevation levels of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4, IL-10) after spleen, mesenteric lymph node and Peyer’s patch cells from immunized mice were stimulated with rTsE. The immunized mice exhibited a 52.19% reduction in enteral AW and a 64.06% reduction in muscle larvae after challenge infection. The immune response triggered by rTsE vaccination protected enteral mucosa from larval intrusion, suppressed larval development and reduced female fecundity. The results indicate that TsE may represent a novel target molecule for anti-T. spiralis vaccines.
Diversity of active root-associated methanotrophs of three emergent plants in a eutrophic wetland in northern China
Authors: Cui Jing , Zhao Ji , Wang Zheng , Cao Weiwei , Zhang Shaohua , Liu Jumei , Bao Zhihua 
Published: March 2020

AbstractRoot-associated aerobic methanotrophs play an important role in regulating methane emissions from the wetlands. However, the influences of the plant genotype on root-associated methanotrophic structures, especially on active flora, remain poorly understood. Transcription of the pmoA gene, encoding particulate methane monooxygenase in methanotrophs, was analyzed by reverse transcription PCR (RT-PCR) of mRNA isolated from root samples of three emergent macrophytes, including Phragmites australis, Typha angustifolia, and Schoenoplectus triqueter (syn. Scirpus triqueter L.) from a eutrophic wetland. High-throughput sequencing of pmoA based on DNA and cDNA was used to analyze the methanotrophic community. Sequencing of cDNA pmoA amplicons confirmed that the structure of active methanotrophic was not always consistent with DNA. A type I methanotroph, Methylomonas, was the most active group in P. australis, whereas Methylocystis, a type II methanotroph, was the dominant group in S. triqueter. In T. angustifolia, these two types of methanotroph existed in similar proportions. However, at the DNA level, Methylomonas was predominant in the roots of all three plants. In addition, vegetation type could have a profound impact on root-associated methanotrophic community at both DNA and cDNA levels. These results indicate that members of the genera Methylomonas (type I) and Methylocystis (type II) can significantly contribute to aerobic methane oxidation in a eutrophic wetland.
Effect of sodium and calcium on polysaccharide production and the activities of enzymes involved in the polysaccharide synthesis of Lentinus edodes
Authors: Adil Bilal , Xiang Quanju , He Maolan , Wu Yuetong , Asghar Muhammad Ahsan , Arshad Muhammad , Qin Peng , Gu Yunfu , Yu Xiumei , Zhao Ke , Zhang Xiaoping , Ma Menggen , Chen Qiang , Chen Xiaoqiong , Yan Yanhong 
Published: March 2020

AbstractLentinan is a Lentinus edodes secondary metabolite that can regulate human immune function, but yields are low. Here, the effects of Ca2+ and Na+ on L. edodes lentinan content were investigated. Metal ion concentrations and induction times were optimized according to mycelial biomass, and intracellular polysaccharide (IPS), extracellular polysaccharide (EPS), and total polysaccharide (TPS) content. The activities and gene expression of phospho-glucose isomerase (PGI), phosphoglucomutase (PGM), and UDP-glcpyrophosphorylase (UGP) were also measured. Ca2+ and Na+ concentration and induction time affected biomass, IPS, and EPS concentrations. Na+ increased EPS, IPS and TPS, while Ca2+ increased biomass, IPS, and TPS. During fermentation, mycelial biomass varied greatly under Ca2+ induction, while IPS, EPS and TPS varied greatly under Na+ induction. PGM and UGP activities increased in the presence of Na+, while PGI increased with Ca2+. Compared to control samples, pgi and pgm expression under Na+ was greater at days 45 and 60, respectively, while under Ca2+, ugp expression was greater at day 45. IPS content correlated significantly with enzyme activity, while EPS correlated with PGM activity. Our data contributes to better understanding how Na+ and Ca2+ affect mycelial growth and secondary metabolite production, and of polysaccharide biosynthesis mechanisms of L. edodes.
Production and identification of monoclonal antibodies and development of a sandwich ELISA for detection of the H3-subtype avian influenza virus antigen
Authors: Luo Sisi , Deng Xianwen , Xie Zhixun , Huang Jiaoling , Zhang Minxiu , Li Meng , Xie Liji , Li Dan , Fan Qing , Wang Sheng , Zeng Tingting , Zhang Yanfang , Xie Zhiqin 
Published: March 2020

AbstractThe H3 subtype of avian influenza virus (AIV) is widespread in avian species and is frequently isolated in surveillance projects; thus, we have developed a more effective diagnostic approach of a monoclonal antibody (mAb)-based sandwich ELISA for the H3 AIV detection. First, we have produced the essential reagent of mAb against AIV H3 strains with the development of an mAb-Mouse immunization with a purified H3-subtype AIV strain and cell fusion to generate hybridoma cells. These cells were screened with hemagglutination inhibition (HI) tests, and optimal cells were subcloned. We chose a hybridoma cell line that steadily secreted a specific H3-subtype AIV mAb, designated 9F12, that belongs to the IgG1 subclass and has a K-type light chain. 9F12 was shown to bind specifically to the H3-subtype AIV antigen by both immunofluorescence assay and Western blot analysis. Finally, a 9F12-based sandwich ELISA was successfully developed and used to specifically test for this antigen. The sandwich ELISA conditions were optimized, and the specificity and sensitivity were validated. The results for clinical sample detection were consistent with viral isolation. Consequently, the 9F12-based sandwich ELISA is a specific, sensitive, robust, rapid and versatile diagnostic tool for H3-subtype AIV and provides a promising strategy for effective influenza virus prevention and control.
Probiotics mitigating subclinical necrotic enteritis (SNE) as potential alternatives to antibiotics in poultry
Authors: Khalique Abdul , Zeng Dong , Shoaib Muhammad , Wang Hesong , Qing Xiaodan , Rajput Danish Sharafat , Pan Kangcheng , Ni Xueqin 
Published: March 2020

AbstractSubclinical necrotic enteritis (SNE) caused byClostridium perfringens(CP), is an important disease in chickens, which causes huge economic losses by damaging the intestinal mucosa, decreasing digestion and absorption of nutrients. Use of antibiotics at a sub-therapeutic level as antimicrobial growth promoters in poultry feed prevents the birds from SNE and improves growth. Due to the ban on the use of antibiotics in 2006 as antimicrobial growth promoters have led to the reemergence of the disease. Worldwide numerous studies have been carried out to investigate the alternatives to antibiotics for the prevention of SNE. Possible alternatives to control SNE include probiotics, prebiotics, bacteriophages, essential oils, organic acids, secondary metabolites and other microbial products. Currently, probiotics are most extensively used in poultry production as an alternative to antibiotics. This review summarizes recent insights and experimental evidence on the use of different microorganisms likeBacillus, Lactic acid bacteria, Bifidobacteria, Enterococcus, yeast, etc. as valuable probiotics for prevention of SNE and potential molecular mechanisms responsible for ameliorating effects of probiotics against SNE.
Remarks on infinitely many solutions for a class of Schrödinger equations with sign-changing potential
Authors: Cheng Rong , Wu Yijia 
Published: March 2020

AbstractIn this paper, we study the existence of infinitely many nontrivial solutions for the following semilinear Schrödinger equation: $$ \textstyle\begin{cases} -\Delta u+V(x)u=f(x,u), \quad x\in\mathbb{R}^{N},\\ u\in H^{1}(\mathbb{R}^{N}), \end{cases} $${−Δu+V(x)u=f(x,u),x∈RN,u∈H1(RN), where the potential V is continuous and is allowed to be sign-changing. By using a variant fountain theorem, we obtain the existence of infinitely many high energy solutions under the condition that the nonlinearity $f(x,u)$f(x,u) is of super-linear growth at infinity. The super-quadratic growth condition imposed on $F(x,u)=\int _{0}^{u}f(x,t)\,dt$F(x,u)=∫0uf(x,t)dt is weaker than the Ambrosetti–Rabinowitz type condition and the similar conditions employed in the references.
A novel noise-tolerant Zhang neural network for time-varying Lyapunov equation
Authors: Sun Min , Liu Jing 
Published: March 2020

AbstractThe Zhang neural network (ZNN) has become a benchmark solver for various time-varying problems solving. In this paper, leveraging a novel design formula, a noise-tolerant continuous-time ZNN (NTCTZNN) model is deliberately developed and analyzed for a time-varying Lyapunov equation, which inherits the exponential convergence rate of the classical CTZNN in a noiseless environment. Theoretical results show that for a time-varying Lyapunov equation with constant noise or time-varying linear noise, the proposed NTCTZNN model is convergent, no matter how large the noise is. For a time-varying Lyapunov equation with quadratic noise, the proposed NTCTZNN model converges to a constant which is reciprocal to the design parameter. These results indicate that the proposed NTCTZNN model has a stronger anti-noise capability than the traditional CTZNN. Beyond that, for potential digital hardware realization, the discrete-time version of the NTCTZNN model (NTDTZNN) is proposed on the basis of the Euler forward difference. Lastly, the efficacy and accuracy of the proposed NTCTZNN and NTDTZNN models are illustrated by some numerical examples.
Dynamical analysis of a stochastic toxin-producing phytoplankton–fish system with harvesting
Authors: Liao Tiancai , Dai Chuanjun , Yu Hengguo , Ma Zengling , Wang Qi , Zhao Min 
Published: March 2020

AbstractIn this paper, we analytically and numerically study the dynamics of a stochastic toxin-producing phytoplankton–fish system with harvesting. Mathematically, we give the existence and stability of the positive equilibrium in the deterministic system (i.e., the system without environmental noise fluctuations). In the case of the stochastic system (i.e., the system with environmental noise fluctuations), in addition to the existence and uniqueness of the positive solution, we provide the properties of the stochastic dynamics including the stochastic extinction and persistence in the mean, almost sure permanence and uniform boundedness, and the existence of ergodic stationary distribution for the phytoplankton and fish. Ecologically, via numerical analysis, we find that (1) the small random environmental fluctuations can ensure the persistence of phytoplankton and fish, but the larger one can result in the extinction of these populations; (2) an appropriate increase in harvest rate can reduce the irregular random variation of phytoplankton and fish; (3) the increase of toxin liberate rate is capable to decrease the height of probability density function of phytoplankton. These results may help us to better understand the phytoplankton–fish dynamics.
Gut microbiota and cardiovascular disease: opportunities and challenges
Authors: Kazemian Negin , Mahmoudi Morteza , Halperin Frank , Wu Joseph C. , Pakpour Sepideh 
Published: March 2020

AbstractCoronary artery disease (CAD) is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Over the past decade, it has become clear that the inhabitants of our gut, the gut microbiota, play a vital role in human metabolism, immunity, and reactions to diseases, including CAD. Although correlations have been shown between CAD and the gut microbiota, demonstration of potential causal relationships is much more complex and challenging. In this review, we will discuss the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Uncovering the causal relationship of gut microbiota and CAD development can lead to novel microbiome-based preventative and therapeutic interventions. However, an interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms (e.g., using advanced nanomedicine technologies and incorporation of demographic factors such as age, sex, and ethnicity) to enable efficacious and high-precision preventative and therapeutic strategies for CAD.