bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycinin-induced porcine IPEC-J2 cell damage via the NF-κB/MAPK signaling pathway
Authors: Peng Chenglu , Sun Zhifeng , Wang Lei , Shu Yingshuang , He Mengchu , Ding Hongyan , Li Yu , Wang Xichun , Feng Shibin , Li Jinchun , Wu Jinjie 
Published: March 2020

Abstract
Background: Glycinin, a protein found in soybean, is a human and animal allergen. It been previously shown to damage the intestinal barrier. However, its mechanisms of action remain unclear. Therefore, in this study, the intestinal porcine epithelial cell line IPEC-J2 was used to study the effect of glycinin concentration on the intestinal epithelium and identify the related signaling pathways. Results: IPEC-J2 cells were divided into seven treatment groups and a control group; the cells were treated for 24 h with 1, 5, or 10 mg/mL glycinin or with 5 mg/mL glycinin after 30 min of pre-treatment with 1 μmol/L nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), inducible nitric oxide synthase inhibitor (N-ω-nitro-l-arginine methyl ester), Jun N-terminal kinase (JNK) inhibitor (SP600125), or p38 inhibitor (SB202190). A series of molecular and biochemical experiments revealed that the levels of NF-κB, p38, and JNK, as well as their downstream proteins, increased after the treatment compared with those in the control group.
Associations of serum sodium levels with mortality in very elderly acute kidney injury patients
Authors: Li Qinglin , Pan Liang , Mao Zhi , Kang Hongjun , Zhou Feihu 
Published: March 2020

Abstract
Background: Patients suffering from acute kidney injury (AKI) have been associated with impaired sodium. However, studies on the association of dysnatremia with all-cause mortality risk in AKI patients are particularly lacking. We examined the relationship between different levels of serum sodium and mortality among very elderly patients with AKI. Methods: We retrospectively enrolled very elderly patients (≥ 75 years) from Chinese PLA General Hospital from 2007, to 2018. All-cause mortality was examined according to eight predefined sodium levels: <130.0 mmol/L, 130.0–134.9 mmol/L, 135.0–137.9 mmol/L, 138.0–141.9 mmol/L, 142.0–144.9 mmol/L, 145.0–147.9 mmol/L, 148.0–151.9 mmol/L, and ≥152.0 mmol/L. We estimated the risk of all-cause mortality using a multivariable adjusted Cox proportional hazard model, with a normal serum potassium level of 135.0–137.9 mmol/L as a reference. Results: In total, 744 geriatric patients were suitable for the final evaluation. Among them, 260 (34.9%) died within 90 days; during the 1-year follow-up, 5 patients were lost to follow-up, and 383 (51.8%) died. After 90 days, the mortality rates in the eight strata were 36.1, 27.8, 19.6, 24.4, 30.7, 48.6, 52.8, and 57.7%, respectively. In the multivariable adjusted analysis, patients with sodium levels <130.0 mmol/L [hazard ratio (HR): 2.247; 95% confidence interval (CI): 1.117–4.521], from 142.0 to 144.9 mmol/L (HR: 1.964; 95% CI: 1.100–3.508), from 145.0 to 147.9 mmol/L (HR: 2.942; 95% CI: 1.693–5.114), from 148.0 to 151.9 mmol/L (HR: 3.455; 95% CI: 2.009–5.944), and ≥152.0 mmol/L (HR: 3.587; 95% CI: 2.151–5.983) had an increased risk of all-cause mortality. After 1 year, the mortality rates in the eight strata were 58.3, 47.8, 33.7, 38.9, 45.5, 64.3, 69.4, and 78.4%, respectively. In the multivariable adjusted analysis, patients with sodium levels <130.0 mmol/L (HR: 1.944; 95% CI: 1.125–3.360), from 142.0 to 144.9 mmol/L (HR: 1.681; 95% CI: 1.062–2.660), from 145.0 to 147.9 mmol/L (HR: 2.631; 95% CI: 1.683–4.112), from 148.0 to 151.9 mmol/L (HR: 2.411; 95% CI: 1.552–3.744), and ≥152.0 mmol/L (HR: 3.037; 95% CI: 2.021–4.563) had an increased risk of all-cause mortality. Conclusion: Sodium levels outside the interval of 130.0–141.9 mmol/L were associated with increased risks of 90-day mortality and 1-year mortality in very elderly AKI patients.
Asymmetric Price Transmission of World Prices to Kenyan Tea Market
Authors: Ngeno Vincent 
Published: March 2020

Abstract
The use of asymmetrical threshold cointegration test is adopted in this study to investigate whether any significant relationship or asymmetric adjustment exists in transmission of prices between the world tea market and domestic prices in Kenya. The empirical results obtained are as follows. First, we verify a close link between the Kenya’s tea price and its international counterparts under the current period of market liberalization. Second, empirical results demonstrate that in both long run and short run, the price transmission between world tea market and Kenyan domestic market are nonlinear and asymmetric, suggesting long run and short run dynamic inefficiencies and presence of transaction costs.JEL classification: C32, Q13, Q17
Adiponectin inhibits palmitic acid-induced NLRP3 inflammasome activation in hepatocytes through AMPK-JNK/ErK1/2-NFκB/ROS signaling pathways
Authors: Dong Zhixia , Zhuang Qian , Ye Xin , Ning Min , Wu Shan , Lu Lungen , Wan xinjian 
Published: March 2020

Abstract
Background Adiponectin, an adipose-derived adipokine, possesses a hepatoprotective role in various liver disorders. Inflammasome activation has been recognized to play a major role during the progression of non-alcoholic fatty liver diseases (NAFLD). However, the effect of adiponectin on NLRP3 inflammasome activation in liver and the exact mechanism remains largely unclear. Here, we assessed the effect of adiponectin on NLRP3 inflammasome activation and its potential molecular mechanisms through both in vivo and in vitro experiments. Methods Male adiponectin-knockout (adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-alcoholic steatohepatitis (NASH). Serum biochemical markers, liver histology and inflammasome-related gene and protein expression were determined. In addition, the hepatocytes isolated from SD rats were exposed to palmitic acid(PA) in the absence or presence of adiponectin and/or AMPK inhibitor. The activation of NLRP3 inflammasome was assessed by mRNA and protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. Results In the in vivo experiments, we found that adiponectin deficiency mice fed with HFD presented excessive hepatic steatosis with increased NLRP3 inflammasome activation compared to wild-type mice. Moreover, the expression levels of NLRP3 inflammasome activation pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK and Erk1/2 were downregulated in adiponectin-knockout mice compared with wild-type mice. In the in vitro study, PA significantly promoted NLRP3 inflammasome activation in hepatocytes. Additionally, PA increased lipid droplet deposition, NF-kB signaling and ROS production, while adiponectin could abolish PA-mediated NLRP3 inflammasome activation and decrease ROS production, which was reversed by AMPK inhibitor (compound C). The results indicated that the inhibitory effect of adiponectin on PA-mediated NLRP3 inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway. Conclusion Adiponectin inhibited PA-mediated NLRP3 inflammasome activation in hepatocytes. Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and NAFLD.
Development of Drug Resistance among Comorbid and Non-Comorbid HIV-Negative Relapsed Cases of Tuberculosis in Lahore, Pakistan
Authors: Salam Arslan Ahmed , Ikram Aamer , Fatima Maha , Awan Najma Javed 
Published: March 2020

Abstract
Background: Mycobacterium tuberculosis sometimes become resistant to the drugs that are used to treat it. Drug resistant TB (DR-TB) is spread in the same way as drug susceptible TB. DR-TB is a public health crisis. This study aims to find the pattern of drug resistance and correlations between drug resistance and comorbid/non-comorbid conditions in patients with a relapse of TB. Methodology: A cross-sectional study was conducted among 200 HIV-negative relapsed TB patients from 2016-2017 in Mayo Hospital Lahore. The patients’ sputum samples were tested by Ziehl-Neelsen staining to observe acid-fast bacilli. The demographics and medical history of patients was recorded, who were positive for AFB in their sputum samples. Molecular procedure of Gene-Xpert assay was conducted to detect the presence of MTB and rifampicin resistance in the samples. Whereas, the drug susceptibility test (DST) was conducted on the LJ culture medium containing drugs.Results: Out of 200 relapsed TB cases; 97 were comorbid, 99 were non-comorbid. The most prevalent comorbidities were hypertension (42 cases- 43.3%), diabetes (45 cases-46.4%) and hepatitis B (14 cases-14.4%). Among 97 comorbid patients; 37 worked as laborers, 43 earned less than 20,000 PKR and 23 were found to have a history of imprisonment. Whereas in non-comorbid patients; 20 worked as laborers, 28 earned less than 20,000 PKR and 12 had been in prison before. The Gene-Xpert test detected rifampicin resistance (RR) in 20 comorbid (20.6%) and 33 non-comorbid (33.3%) patients. Whereas, the drug susceptibility test (DST) showed that 22 comorbid (22.7%) and 33 non-comorbid (33.3%) patients were RR. A contrast was seen in the results of Gene-Xpert and DST; Gene-Xpert detected 3 cases of RR-negative whereas the same 3 cases were found to be RR-positive on DST. Only 1 case was RR-positive on Gene-Xpert but RR-negative on DST. 17 comorbid patients (17.5%) were diagnosed with MDR-TB and 5 (5.2%) with XDR-TB. Whereas, in non-comorbid patients, there were 26 cases of MDR-TB (26.3%) and 5 cases of XDR-TB (5.1%). There were 2 patients (2.1%) resistant to all drugs.Conclusion: There was a deviation in the results of molecular Gene-Xpert assay compared to the conventional culture methods. Drug resistance was relatively higher in non-comorbid patients than comorbid patients, however, the difference between the two is not very significant.
Evaluation of six different protocols for protein extraction from rice young panicles by two-dimensional electrophoresis
Authors: Huang Xiaoping , Zhou Hui-wen 
Published: March 2020

Abstract
Background: For most reported proteomics approaches, protein extraction are of crucial importance for optimal results. However, extraction of protein from plant tissues still exist great challenges due to low protein content and many secondary metabolites that prominently interfering with isoelectric focusing. Up to now, no attempts are focused on comparison of protein extraction from rice young panicles.Methods: To establish a higher efficiency protein extraction protocol suited for two-dimensional electrophoresis in rice young panicles, six protocols for protein preparation were evaluated in terms of protein concentration, the molecular weight range of protein, gel image resolution, the number of protein spots: 1) Phenol extraction; 2) Mg/Nonidet P-40 (NP-40) extraction; 3) Tris-Base/acetone extraction; 4) SDS extraction; 5) trichloroacetic acid (TCA)/acetone/phenol extraction; 6) TCA/acetone precipitation.Results: The result explicitly demonstrated that TCA/acetone/phenol method provided a high-enhanced protein extraction efficacy from rice young panicles than other protocols in terms of the protein concentration (9.79±0.23 SD), the most comprehensive proteins (10 KDa to 150 KDa), the maximum number of protein spots (450±53 SD), the greater gel image resolution and spot abundance. In addition, these methods also generated remarkably differential 2-DE protein patterns. Twenty-nine of 30 visible differentially extracted proteins were identified by MS analysis and were divided into eight categories. Prediction for protein subcellular localization and grand average of hydropathy (GRAVY) analysis showed that certain special proteins respectively necessitate different extraction methods due to different physicochemical properties of each protocol.Conclusions: Overall, this paper will facilitate to provide a cornerstone of comparative proteomic analysis from rice young panicles, including other complicated plant tissues.
Generative Enhancement of 3D Image Classifiers
Authors: Varga Michal , Jadlovský Ján , Jadlovská Slávka 
Published: March 2020

Abstract
In this paper, we propose a methodology for generative enhancement of existing 3D image classifiers. This methodology is based on combining the strengths of both non-generative classifiers and generative modeling. Its purpose is to streamline the creation of new classifiers by embedding existing compatible classifiers in a generative network architecture. The demonstration of this process and evaluation of its effects is performed using a 3D convolutional classifier and its generative equivalent - a conditional generative adversarial network classifier. The results show that the generative model achieves greater classification performance, gaining a relative classification accuracy improvement of 7.43%. Improvement of accuracy is also present when compared to a plain convolutional classifier trained on a dataset augmented with examples produced by a trained generator. This suggests there is a desirable knowledge sharing within the hybrid discriminator-classifier network.
Hypoxia preconditioning promotes mesenchymal stem cells survival and vascularization through the activation of MALAT1/miR-195/VEGFA axis
Authors: Hou Jingying , Wang Lingyun , Yang Zhengfei , Zheng Guanghui , Guo Tianzhu , Yu Menglei 
Published: March 2020

Abstract
Background: Previous studies have demonstrated that hypoxia preconditioning (HP) can promote mesenchymal stem cells (MSCs) survival and vascularization. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a newly discovered regulator of MSCs viability and differentiation. Evidences have indicated that MALAT1 can be strongly induced by hypoxia. This study aimed to investigate the role of MALAT1 in HP mediated MSCs survival and vascularization as well as the relevant underlying mechanism in vitro.Methods: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells at the third passage were divided into the following groups: normoxia (N), hypoxia preconditioning (HP), HP + MALAT1, HP + MALAT1 NC, HP+si-MALAT1 and HP +si-MALAT1 NC. The normoxia group was cultured in 20% O2 for 24 h. All the other groups were exposed to hypoxia (1% O2) for 24 hours. MALAT1 and relevant scramble RNA were transfected in the HP+MALAT1 and HP+MALAT1 NC groups respectively. HP+si-MALAT1 and HP +si-MALAT1 NC groups were transfected with MALAT1 siRNA and relevant siRNA scramble respectively. MSCs proliferation, apoptosis and vascular densities were evaluated. Bioinformatics and dual luciferase reporter assay were performed. Relevant biomarkers were examined in different experimental groups.Results: MSCs survival and vascularization were significantly enhanced in the HP group. Transfection of MALAT1 further strengthened the viability and angiogenic potential of MSCs in the condition of HP, whereas its knockdown attenuated cells survival and vascularization. MALAT1 and vascular endothelial growth factor A (VEGFA) were obviously increased after hypoxia exposure, while miR-195 was decreased. miR-195 targeted and downregulated VEGFA. miR-195 was a target of MALAT1. Overexpression of MALAT1 led to a decreased level of miR-195, accompanied with an augmented expression of VEGFA. However, both miR-195 and VEGFA exhibited contrary alterations after MALAT1 blockage. Conclusion: HP enhanced MSCs survival and vascularization potential in vitro, and the activation of MALAT1/miR-195/VEGFA axis might be involved in this procedure. This study reveals a new molecular mechanism of HP mediated MSCs survival and vascularization. It will be conducive for the development of novel strategies to improve the therapeutic efficiency of MSCs based on HP.
Keeping the faith: Receptiveness, capacity and acceptability of Islamic religious settings to deliver childhood obesity prevention intervention
Authors: Dogra Sufyan Abid , Rai Kiran , Barber Sally , McEachan Rosemary RC , Adab Peymane , Sheard Laura 
Published: March 2020

Abstract
Keeping the faith: Receptiveness, capacity and acceptability of Islamic religious settings to deliver childhood obesity prevention interventionBackground: Childhood obesity rates among South Asian populations in the UK are significantly high. 10% of childhood population in the UK are of South Asian origin, majority of them follow Islamic faith and attend Islamic religious settings (IRS) daily after school. IRS may be appropriate channels for obesity prevention initiatives; however there is limited evidence for this approach. Methods: Using a qualitative research methodology, we conducted 20 indepth interviews with parents of 5-11 years old children attending IRS, 20 indepth interviews with Islamic leaders, and 3 focus group discussions with 26 managers and workers of IRS in Bradford and Birmingham in the UK. The guides for interviews and focus groups, tailored to each group of participants, were developed from a literature review and prior learning from the results of other work packages in the same study. Interviews and focus group discussions were audio-recorded, transcribed, and analysed thematically. Results: IRS are receptive to delivering a childhood obesity prevention intervention. Most of them have the capacity and the delivery would be acceptable to parents of children attending these settings. All participants viewed Prophet Muhammad’s physical fitness, food and his attitude towards physical activity and maintaining healthy lifestyle as the best role model to follow. Managers and workers in IRS showed willingness to conduct physical activity sessions for South Asian boys and girls and emphasised the need to have female instructors and role models to encourage South Asian girls. Practical barriers for the intervention delivery were poor funding systems and time constraints for managers and workers. Conclusion: IRS can deliver childhood obesity prevention interventions. Interventions should be co-designed, culturally/religiously sensitive and combine the scientific guidelines on healthy living with Islamic narrative on importance of physical activity and healthy diet consumption and should involve local place-based groups for delivery.
Assessment of the impact of pesticide usage in groundwater aquifer of an agriculturally dominated area in North West India
Authors: Chaubey Jyoti , Singh S. K. , Singh Sukhwant , Arora H. 
Published: March 2020

Abstract
Groundwater pollution due to several anthropogenic activities has been a worldwide problem, one such activity being injudicious pesticide usage in agriculture. Assessment of pesticide impact on groundwater is a prerequisite step towards the formulation of regulatory policies related to the pesticides' application. The present study deals with assessment of the impact of pesticide usage in the groundwater aquifer of an agriculturally dominated area in North West India. The relationship between the pesticide usage and its impact on the quality of groundwater has been established by employing a model named Pesticide Impact Rating Index (PIRI). For illustration, seven farms lying in Nakodar tehsil of Punjab state in India were considered. Based on the frequency of usage of various pesticides in the study area, four pesticides namely atrazine, chlorophyrifos, phorate and monocrotophos were selected for detailed analysis. Groundwater samples were collected and analyzed for observed values of pesticide residues. The observed residues were compared with the PIRI model estimates and results showed that though the observed values were higher corresponding to the estimated values, the ratio seemed to be fluctuating within a consistent range. Therefore multiplicative correction factors were introduced for the model estimates so as to predict realistic pesticide residues in an area.
Further Considerations Towards an Effective and Efficient Oncology Drug Discovery DMPK Strategy
Authors: Williamson Beth , Colclough Nicola , Fretland Adrian John , Jones Barry Christopher , Jones Rhys Dafydd Owen , McGinnity Dermot Francis 
Published: March 2020

Background:
DMPK data and knowledge are critical in maximising the probability of developing successful
drugs via the application of in silico, in vitro and in vivo approaches in drug discovery.

Methods:
The evaluation, optimisation and prediction of human pharmacokinetics is now a mainstay within drug
discovery. These elements are at the heart of the ‘right tissue’ component of AstraZeneca’s ‘5Rs framework’ which,
since its adoption, has resulted in increased success of Phase III clinical trials. With the plethora of DMPK related
assays and models available, there is a need to continually refine and improve the effectiveness and efficiency of
approaches best to facilitate the progression of quality compounds for human clinical testing.

Results:
This article builds on previously published strategies from our laboratories, highlighting recent discoveries
and successes, that brings our AstraZeneca Oncology DMPK strategy up to date. We review the core aspects of
DMPK in Oncology drug discovery and highlight data recently generated in our laboratories that have influenced our
screening cascade and experimental design. We present data and our experiences of employing cassette animal PK,
as well as re-evaluating in vitro assay design for metabolic stability assessments and expanding our use of freshly
excised animal and human tissue to best inform first time in human dosing and dose escalation studies.

Conclusion:
Application of our updated drug-drug interaction and central nervous system drug exposure strategies
are exemplified, as is the impact of physiologically based pharmacokinetic and pharmacokinetic-pharmacodynamic
modelling for human predictions.
Analysis of Inhibitor Binding Combined with Reactivity Studies to Discover the Potentially Inhibiting Phytochemicals Targeting Chikungunya Viral Replication
Authors: Rasool Nouman , Bakht Afreen , Hussain Waqar 
Published: March 2020

Background:Chikungunya fever is a challenging threat to human health in various parts of the world nowadays. Many attempts have been made for developing an effective drug against this viral disease and no effective antiviral treatment has been developed to control the spread of the Chikungunya virus (CHIKV) in humans.Objective:This research is aimed at the discovery of potential inhibitors against this virus by employing computational techniques to study the interactions between non-structural proteins of Chikungunya virus and phytochemicals from plants.Method:Four non-structural proteins were docked with 2035 phytochemicals from various plants. The ligands having binding energies ≥ -8.0 kcal/mol were considered as potential inhibitors for these proteins. ADMET studies were also performed to analyze different pharmacological properties of these docked compounds and to further analyze the reactivity of these phytochemicals against CHIKV, DFT analysis was carried out based on HOMO and LUMO energies.Results:By analyzing the binding energies, Ki, ADMET properties and band energy gaps, it was observed that 13 phytochemicals passed all the criteria to be a potent inhibitor against CHIKV in humans.Conclusion:A total of 13 phytochemicals were identified as potent inhibiting candidates, which can be used against the Chikungunya virus.