bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment
Authors: Ntari Lydia , Nikolaou Christoforos , Kranidioti Ksanthi , Papadopoulou Dimitra , Chouvardas Panagiotis , Meier Florian , Geka Christina , Denis Maria C , Karagianni Niki , Kollias George
Published: November 2020

Background
Medications for Rheumatoid Arthritis (RA) have emerged in the last two decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients.
Methods
We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy.
Results
Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-depended manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy.
Conclusion
Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of this combination therapy may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.
Immunoinformatics approach for multi-epitope vaccine design against structural proteins and ORF1a polyproteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)
Authors: Adam Khalid Mohamed
Published: November 2020

Background
The lack of effective treatment and a protective vaccine against the highly infectious SARS-CoV-2 has aggravated the already catastrophic global health issue. Here, in an attempt to design an efficient vaccine, a vigorous immunoinformatics approach was followed to predict the most suitable viral proteins epitopes for building that vaccine.
Methods
The amino acid sequences of four structural proteins (S, M, N, E) along with one potentially antigenic accessory protein (ORF1a) of SARS-CoV-2 were inspected for the most appropriate epitopes to be used for building the vaccine construct. Several immunoinformatics tools were used to assess the antigenicity, immunogenicity, allergenicity, toxigenicity, interferon-gamma inducing capacity, and the physicochemical properties of the product.
Results
The final candidate vaccine construct consisted of 468 amino acids, encompassing 30 epitopes. All the vaccine properties and its ability to trigger the humoral and cell-mediated immune response were validated computationally. Molecular modeling, docking to TLR3, simulation, and molecular dynamics were also carried out. Finally, a molecular clone using pET28: :mAID expression plasmid vector was prepared.
Conclusion
The overall results of the study suggest that the final multi-epitope chimeric construct is a potential candidate for an efficient protective vaccine against SARS-CoV-2.
Analysis of Determinants of Postpartum Mood Disorders
Authors: Iwanowicz-Palus Grażyna Jolanta , Marcewicz Agnieszka Ewa , Bień Agnieszka Maria
Published: November 2020

BackgroundThe birth of a child entails major changes in a woman’s life. In the perinatal period, the woman is particularly susceptible to emotional problems. The objective of the present paper was to investigate the relationship between global orientation to life and its components on the one hand, and socio-demographic factors on the other, with regard to early postpartum emotional disorders. MethodsThe study included 643 patients hospitalized in obstetric departments who had had a spontaneous vaginal delivery. Research instruments included: the Edinburgh Postnatal Depression Scale (EPDS), the Orientation to Life Questionnaire (SOC-29), and the authors’ own survey questionnaire to record participants’ characteristics.ResultsThe study findings indicate an association between lower levels of postpartum blues and higher levels of global sense of coherence, as well as a stronger sense of meaningfulness, manageability, and comprehensibility. More severe mood disorders were found in patients who were single. Postpartum blues symptoms were more intense in less educated respondents.Conclusions Postpartum mood disorders are associated with a global sense of coherence and its components. Higher levels of SOC reduce the risk of postpartum blues.
Foreign Development Assistance and Macroeconomic Policy Stance: The Underlying Levers of Growth in Emerging SSA Countries
Authors: Edo Samson , Matthew Oluwatoyin , Ogunrinola Ifeoluwa
Published: November 2020

The role of foreign development assistance and macroeconomic policy stance, in economic growth performance of the emerging Sub-Saharan African economies, is investigated in this study. The GMM and VECM methods are employed in estimating the relationships and impacts, for the period 1980-2019. Results from the two estimation methods are comparable and consistent. The effect of foreign development assistance is revealed to be positive, and more significant than that of monetary policy, but less significant than fiscal policy. The control variable, exchange rate, exerts significant negative effect on growth. The results also reveal that economic growth is unable to significantly reinforce itself. Generally, the estimation results conform to theoretical expectations of the relationships that exist between economic growth and the underlying variables. The results are also considered to be significantly reliable for forecasting and policy making.
Can Primary palliative care education change life-sustaining treatment intensity of older adults at the end of life? A retrospective study
Authors: Liu Qian , Qin Mingzhao , Zhou Jian , Zheng Hui , Liu Weiping , Shen Qi
Published: November 2020

Background

In recent years, palliative care has gradually developed in mainland China. Since 2018, primary palliative care education has been carried out in the department of geriatrics at Beijing Tongren Hospital. This study aimed to explore the changes to the intensity of end-of-life care in hospitalized older adults before and after the implementation of primary palliative care education.
Methods

A retrospective study was conducted. 203 decedents were included from Beijing Tongren Hospital’s department of geriatrics between January 1, 2014 to December 31, 2019. Patients were split into two cohorts with regards to the start of palliative care education. Patient demographics and clinical characteristics as well as analgesia use, other medical resources use and provision of life-sustaining treatments were compared between the two groups. We used a chi-square test to compare categorical variables, a t test to compare continuous variables with normal distributions and a Mann–Whitney U test for continuous variables with skewed distributions.
Results

Of the total participants in the study, 157(77.3%) patients were male. The median age was 88 (interquartile range; Q1-Q3 83–93) and the majority of patients (N = 172, 84.7%) aged 80 years or older. The top 3 causes of death were malignant solid tumor (N = 74, 36.5%), infectious disease (N = 74, 36.5%), and cardiovascular disease (N = 23, 11.3%). Approximately two thirds died of non-cancer diseases. There was no significant difference in age, gender, cause of death and functional status between the two groups (p > 0.05). After primary palliative care education, pain controlling drugs were used more (p < 0.05), fewer patients received electric defibrillation, bag mask ventilation and vasopressors ( p༜0.05). There was no change in the length of hospitalization, intensive care admissions, polypharmacy, use of broad-spectrum antibiotics, blood infusions, albumin infusions, nasogastric/nasoenteric tubes, parenteral nutrition, renal replacement and mechanical ventilation (p > 0.05).
Conclusions

Primary palliative care education promotes symptom control and DNR implementation. In the future, more efforts should be put on education about symptom assessment, prognostication, advance care planning, code status discussion with particular focus on patients with end stage non-cancer diseases.
In-hospital Emergencies Versus Out-of-hospital Emergencies Admitted to ICU: Is the Outcome Different? An Observational Study
Authors: Cauchois Emi , Bourenne Jérémy , Saux Audrey Le , Bouzana Fouad , Tilmont Antoine , Allez Charlotte , Pauly Vanessa , Gainnier Marc , CARVELLI Julien
Published: November 2020

Background: Rapid Response Systems (RRS) are now commonly implemented throughout hospital health systems to manage in-hospital emergencies (IHE). There is limited data on characteristics and outcomes of such patients admitted to an intensive care unit (ICU). The goal was to determine whether the hospital mortality of ICU patients was different depending on their admission pathway: in-hospital via rapid response teams (RRT), or out-of-hospital emergencies (OHE) via prehospital emergency medical systems. Results: Out of 422 ICU admissions (Timone University Hospital ICU), 241 patients were retrospectively (2019-2020) included: 74 IHE versus 167 OHE. In-hospital mortality rates did not differ between both cohorts (n = 31(42%) vs. 63(39%) respectively, NS). IHE patients were older and had more comorbidities (immunosuppression and ongoing malignancy). OHE patients had more severe organ failures at presentation with more frequent mechanical ventilation support. Independent global hospital mortality risk factors were ongoing malignancy (OR = 10.4 [2.7-40], p < 0.001), SAPS II (OR = 1.05 [1.03-1.08], p < 0.0001) and SOFA scores (OR = 1.14 [1.01-1.3], p < 0.05), hemorrhagic stroke as admission diagnosis (OR = 8.4 [2.7-26], p < 0.001), and arterial lactate on arrival (OR = 1.11 [1.03-1.2], p < 0.01). Conclusion: This study provides a thorough and comprehensive analysis of characteristics and outcomes of ICU admissions following a mature rapid response activation system, compared to the “conventional” out-of-hospital admission pathway. Despite the more vulnerable background of IHE patients, hospital mortality does not differ, supporting the use of early RRS to identify deteriorating ward patients.
iTRAQ-based Comparative Proteomic Analysis Provides Insights Into Tobacco Callus Response to Carbon Nanoparticles
Authors: Zhenjie Zhao , Hu Liwei , Chen Qiansi , Dai Huaxin , Meng Xiangyu , Yin Qisheng , Liang Taibo
Published: November 2020

Background: Carbon nanomaterials (CNMs) have attracted a great deal of research interest for their potential application in plants. Some types of CNMs have exhibited the ability on regulating the growth of plants, which showed a promising future in agriculture. However, detailed mechanism of their application in plants is still not well characterized especially at the molecular level.Methods: The biomass variation of tobacco callus was investigated to exposure of carbon nanoparticles (CNPs). During the incubation period, proteomic profiling in tobacco callus was investigated by using the isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The function of differentially expressed proteins were achieved by using a gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis by InterproScan, and qRT-PCR was used to confirm the results of the proteomic data.Results: The results showed that the growth of tobacco callus was enhanced by CNPs, with the optimal concentration at 50 mg/L. The expression levels of 198 cellular proteins were significantly up- or down- regulated after CNPs treatment. These differentially expressed proteins were involved in mitochondria and calcium-mediated signaling. Conclusions: We demonstrated CNPs have the ability to enhance the growth of tobacco callus. The proteomic profile changes of tobacco callus provided a deeper understanding of the highly complex regulatory mechanisms in tobacco callus exposed to CNPs.
Continuous Cropping Regulates Fungal Community Structures and Functional Groups in Rhizosphere Soil of Tibet Barley
Authors: Yao Youhua , Zhao Yuan , Yao Xiaohua , Bai Yixiong , An Likun , Li Xin , Wu Kunlun
Published: November 2020

Continuous cropping regulates the community structure of rhizosphere soil microbes; however, the effects of continuous cropping on the community structure and function of rhizosphere fungal communities of plants cultivated in high-altitude regions are not well understood. In this study, 18S rRNA gene high-throughput sequencing was applied to examine the rhizosphere fungal community structure during continuous cropping of Tibet barley (a principal cereal cultivated on the Qinghai-Tibetan Plateau). The results showed that the Chao1 and phylogenetic diversity (PD) indices declined as cropping years increased. Additionally, relative abundance of the genera Cystofilobasidium, Mucor, and Ustilago increased, whereas the abundance of Fusarium decreased during continuous cropping. Furthermore, identification of ecological groups using FUNGuild revealed that saprotrophs, pathogens, and symbiotrophs were the dominant groups in rhizosphere soil, and these three trophic modes all increased significantly with continuous cropping. During continuous cropping, the fungal plant-pathogens Parastagonospora and Ustilago also increased remarkably, as did the endophyte fungi Verticillium. Collectively, continuous cropping of Tibet barely increased the potential for plant-pathogenic and endophyte fungi in rhizosphere soil. Thus, the development of sustainable farming practices to reduce the abundance of harmful fungi is vital to Tibet barley growth and production during continuous cropping of plants cultivated in high-altitude regions.
A highly sensitive octopus-like azobenzene fluorescent probe for determination of abamectin B1 in apples
Authors: Guo Zhenlong , Su YiFei , Li Kexin , Tang MengYi , Li Qiang , Xu Shandong
Published: November 2020

The development of detecting residual level of abamectin B1 in apples is of great importance to public health. Herein, we synthesized a octopus-like azobenzene fluorescent probe 1,3,5-tris (5'-[(E)-(p-phenoxyazo) diazenyl)] benzene-1,3-dicarboxylic acid) benzene (TPB) for preliminary detection of abamectin B1 in apples. The TPB molecule was characterized by ultraviolet-visible absorption spectrometry, 1H-nuclear magnetic resonance, fourier-transform infrared (FT-IR), electrospray ionization mass spectroscopy (ESI-MS) and fluorescent spectrum. A proper determination condition was optimized, with limit of detection and limit of quantification of 1.3 µg L-1 and 4.4 μg L-1, respectively. The mechanism of this probe to identify abamectin B1 was illustrated in terms of undergoing aromatic nucleophilic substitution, by comparing fluorescence changes, FT-IR and ESI-MS. Furthermore, a facile quantitative detection of the residual abamectin B1 in apples was achieved. Good reproducibility was shown based on relative standard deviation of 2.20%. Six carboxyl recognition sites, three azo groups and unique fluorescence signal towards abamectin B1 of this fluorescent probe decided ideal sensitivity, specificity and selectivity. The results show that the octopus-like azobenzene fluorescent probe may be promising for evaluating abamectin B1 in agricultural foods.
NLRP3 inflammasome-mediated cerebrospinal fluid hypersecretion in choroid plexus contributes to hydrocephalus after hemorrhage
Authors: Zhang Zhaoqi , Tan Qiang , Guo Peiwen , Jia Zhengcai , Liu Xin , Feng Hua
Published: November 2020

BackgroundHydrocephalus is a severe complication of intracerebral hemorrhage with ventricular extension (ICH-IVH). The choroid plexus epithelium plays an important role in cerebrospinal fluid (CSF) secretion and constitutes blood-CSF barrier adjusting brain–immune system interface. NLRP3 inflammasome is a key component of the innate system which promotes neuroinflammation. However, the role of NLRP3 inflammasome in the pathogenesis of hydrocephalus after hemorrhage has not been investigated.MethodsHydrocephalus after ICH-IVH rat model was accomplished by autologous blood infusion. Then, we investigated the relationship between NLRP3 inflammasome and CSF hypersecretion in choroid plexus.ResultsThe NLRP3 inflammasome activated and CSF hypersecretion in choroid plexus epithelium were found after ICH-IVH. NLRP3 inhibition with MCC950 decreased CSF secretion, ventricles dilation and attenuated neurofunction deficits after ICH-IVH. In addition, MCC950 decreased NKCC1 phosphorylation which was the major protein adjusting CSF secretion and improved blood-CSF barrier integrity after ICH-IVH.ConclusionsThis study demonstrates that NLRP3 inflammasome mediated CSF hypersecretion by influencing NKCC1 phosphorylation in choroid plexus epithelium plays an important role in the pathogenesis of hydrocephalus after hemorrhage and provides a new therapeutic strategy.
Correlation of the Lipid Ratios With Hepatic Steatosis and Liver Fibrosis in Non-alcoholic Fatty Liver Disease Patients
Authors: Guo Wen , Qin Pei , Li Xiaona , Lu Jing , Zhu Wenfang , Wu Juan , Xu Nainzhen , Zhang Qun
Published: November 2020

Background: The work intends to investigate the correlation of the lipid ratios to the severity of hepatic steatosis and the presence of liver fibrosis among non-alcoholic fatty liver disease (NAFLD) patients.Methods: Randomly selected 3402 participants were differentiated into the NAFLD (n =2036) and the non-NAFLD group (n =1366) in accordance with the outcomes of the liver ultrasonography. The related anthropometric and biochemical parameters were measured, while the severity of hepatic steatosis and the presence of liver stiffness were appraised by transient elastography.Results: The triglycerides/ high-density lipoprotein cholesterol (TG/HDL-C) and total cholesterol/HDL-C (TC/HDL-C) ratios exhibited a close connection with the severity of hepatic steatosis. Furthermore, higher area under the receiver operator characteristic (AUROC) value for TG/HDL-C than those of TC, TG, LDL-C, HDL-C, TC/HDL-C and non-HDL-C, was observed. Accordingly, the AUROC and optimal cut-off point of TG/HDL-C for NAFLD were 0.771 (95%CI: 0.755-0.787), 1.08 (sensitivity: 72.2 %, specificity: 68.3%), respectively. TG/HDL-C and TC/HDL-C were independent risk factors for the presence of liver fibrosis in NAFLD. Notably, the fact of relatively high AUROC while low AUROC (0.610) values of TG/HDL-C for detecting the presence of liver fibrosis relative to other lipid indexes indicated that it could not function as a desirable indicator of the presence of liver fibrosis in NAFLD.Conclusions: TG/HDL-C can be an independent risk factor for the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD, furthermore, it possesses predictive significance to NAFLD but not to liver fibrosis.
Determinants of Market Outlet Choices by Smallholder Chickpea Farmers in Estie District Amhara Region, Ethiopia
Authors: Erkie Chernet Worku , Adugna Marlign , Chanie Essa
Published: November 2020

In Ethiopia, chickpea is an important plus crop, particularly in Estie district. It is a source of food and provides cash income for majority of smallholder farmers. To commercialize chickpea producers, selecting an appropriate market channel is mandatory. However, selecting an appropriate market channel is not an easy task because there are different factors that affect market outlet choices in the district. Hence, this study aimed to identify factors that affecting chickpea market outlet choices. Both primary & secondary sources of data were used. A two-stage random sampling procedure was used and a total of 122 smallholder farmers were randomly and proportionally selected to collect primary data. Multivariate probit model was employed to identify factors affecting chickpea market outlet choices. The result shows that five major chickpea marketing channels were identified and among them wholesalers and retailers purchased about (61.84%) and (18.2%) respectively. The estimation result of multivariate probit model showed that the likelihood of sampled households to select collectors, consumers, retailers and wholesalers were 25.3%, 35.4%, 30.5% and 36%, respectively. The joint probability of success and failure to select all market outlets was 0.01537% and 13.4% respectively. It also indicated that sex of household, education status, family size, off-farm income, access to credit; lagged price and distance to market significantly affected the market channel choice decision of producers. Based on the findings, Government and concerned stakeholders need to focus more on enhancing accessibility of infrastructures facilities, strengthening credit access and improving yield through extension service to accelerate selecting appropriate market channel.
Physical Layer Security Transmission Scheme Based on Artificial Noise in Cooperative SWIPT NOMA System
Authors: Jin Yong , Hu Zhentao , Xie Dongdong , Wu Guodong , Zhou Lin
Published: November 2020

Physical layer security of non-orthogonal multiple access (NOMA) system which uses simultaneous wireless information and power transfer (SWIPT) technique is deeply dicussed in this paper. Generally, eavesdropper in the downlink of NOMA system may use successive interference cancellation technology (SIC) to obtain the secrecy information of receiver. To tackle this problem, we propose a physical layer security scheme to minimize the transmit power of the base station (BS) while the secrecy rates of receivers are guaranteed. Moreover, semidefinite relaxation (SDR) method and successive convex approximation (SCA) technique are combined to solve above non-convex problem. Simulation results show that in comparison with other methods, our method can effectively reduce the transmit power of the BS.
Elite Squash Players Nutrition Knowledge and Influencing Factors
Authors: Turner Ollie , Mitchell Nigel , Ruddock Alan , Purvis Alison , Ranchordas Mayur
Published: November 2020

Background: There is a reported mismatch between macronutrient consumption and contemporary macronutrient guidelines in elite standard squash players. Suboptimal dietary practices could be due to a lack of nutrition knowledge among players. Subsequently, the purpose of this study was to assess the sports nutrition knowledge of elite squash players through the RNSKQ and provide an indication of whether players require nutrition support to increase their nutrition knowledge.Methods: This cross-sectional study assessed the nutrition knowledge of 77 elite squash players via the RNSKQ over the period of June 2020 to August 2020.Results: Players conveyed average nutrition knowledge with a mean RNSKQ score of 48.78 ± 10.06 (56.07 % ± 11.56 %). There were no significant differences in RNSKQ score between male and female players (p = .532). There was found to be a weak positive correlation between world ranking and RNSKQ score (r = .208) and age and RNSKQ score (r = .281). Players who had a relevant undergraduate degree (e.g. BSc Sport & Exercise Science) had significantly greater RNSKQ score than players with no qualifications (p = .022). Players who consulted a sports nutritionist to obtain their main source of nutrition information were shown to have significantly greater knowledge than those who acquired knowledge from a sports scientist (p = .01) or the internet / social media (p = .007).Conclusions: Players should consult with a sports nutritionist to increase their sport nutrition knowledge. Future research should quantify the effectiveness of a nutritional education intervention at increasing nutrition knowledge in players.
Light-induced Inversion of Na+ Uptake in Rice (Oryza sativa L.) under Salt Stress
Authors: Lee Imshik , Sun Yajun , Ye Xiaoxue , Cao Yipeng , Gao Deng
Published: November 2020

Background: Rice is a salt-sensitive crop, and salinity is a major negative constraint on rice production, while light has a major positive effect on plant growth and development. How plants integrate the external salinity and light signals remains poorly understood. Results: Here, we demonstrated that light exposure enhanced the cation (Na+, K+, H+, and Ca2+) efflux from the rice (Oryza sativa L.) root for both salt-free and NaCl-treated rice. Surprisingly, net flux of Na+, J(Na+), in NaCl-treated rice was inverted in the light-on state. This inverted light-inducible J(Na+) signal suggests crosstalk between salt stress and light signals, with salt stress interfering with Na+ transport via down regulation of the light receptors. PPI network of this crosstalk suggested that there were key players, phytochrome A and B, phototropin 1A and 1B, and 2 at the bridging group and AKT1 potassium channel, monovalent cation/H+ antiporter and Na+/K+ antiporter (SOS1) at the interface between bridging group and cation transport group. Conclusions: Crosstalk between light and salt stress caused the inverted light-inducible J(Na+) signals. Phytochrome A and B, phototropin 1A and 1B, and 2 at the light-responding group and AKT1 potassium channel, monovalent cation/H+ antiporter and Na+/K+ antiporter (SOS1) at salt-stress responding group play an important role in this unique inverted light-inducible J(Na+) switch, which offers a new paradigm to understand the crosstalk between salt-stress and light signals.
The effects of gestational diabetes mellitus with advanced maternal age on the metabolite profiles of serum and urine
Authors: He Xiaoling , Hu Xiaojing , Luo Bai-yu , Xia Yinyin , Zhang Ting , Saffery Richard , Seymour Jamie De , Zou Zhen , Xu Ge , Zhao Xue , Qi Hongbo , Han Ting-Li , Zhang Hua , Baker Philip N
Published: November 2020

Background: Gestational diabetes mellitus (GDM) is characterized by impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. It can lead to adverse maternal and neonatal outcomes. The incidence of GDM is closely related to maternal age, but there are only a few pregnancy-related metabolomic studies involving advanced maternal age (AMA) in China.Methods: 20 GDM and 20 normal pregnant participants(≥35 years old) were recruited from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine metabolomes collected at the first and third trimester were analyzed using gas chromatography-mass spectrometry (GC-MS). Results: Of the metabolites identified using GC–MS, 165 metabolites and 192 metabolites were found in plasma and urine respectively. However, urine metabolomic profiles were unable to distinguish GDM from controls, while there were 14 and 39 significantly different metabolites in plasma of the two groups in first and third trimester. Especially, by combining seven metabolites including cysteine, malonic acid, stearic acid, alanine, 11,14-eicosadienoic acid, 2-methyloctadecanoic acid, and arachidic acid using multivariant receiver operating characteristic(ROC) models, we were capable of discriminating GDM from healthy pregnancies with an area under curve (AUC) of 0.928 at early gestation.Conclusion: This study explores metabolomic profiles between GDM and normal pregnancies longitudinally. Several metabolites have the potential to be biomarkers to predict GDM with AMA. Besides, the discordant metabolome profiles between the two groups could be helpful to understand the etiology of elderly GDM.
Niclosamide Suppresses the Expansion of Follicular Helper T Cells and Alleviates Disease Severity in Two Murine Models of Lupus via STAT3
Authors: Jang Se Gwang , Lee Jaeseon , Hong Seung-Min , Song Young-Seok , Kim Min Jun , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan
Published: November 2020

Background. Autoantibody production against endogenous cellular components is pathogenic feature of systemic lupus erythematosus (SLE). Follicular helper T (TFH) cells aid in B cell differentiation into autoantibody-producing plasma cells (PCs). The IL-6 and IL-21 cytokine-mediated STAT3 signaling are crucial for the differentiation to TFH cells. Niclosamide is an anti-helminthic drug used to treat parasitic infections but also exhibits a therapeutic effect on autoimmune diseases due to its potential immune regulatory effects. In this study, we examined whether Niclosamide treatment could relieve lupus-like autoimmunity by modulating the differentiation of TFH cells in two murine models of lupus.Methods. 10-week-old MRL/lpr mice were orally administered with 100 mg/kg of Niclosamide or with 0.5% methylcellulose (MC, vehicle) daily for 7 weeks. TLR7 agonist, resiquimod was topically applied to an ear of 8-week-old C57BL/6 mice 3 times a week for 5 weeks. And they were orally administered with 100 mg/kg of Niclosamide or with 0.5% MC daily for 5 weeks. Every mouse was analyzed for lupus nephritis, proteinuria, autoantibodies, immune complex, immune cell subsets at the time of the euthanization.Results. Niclosamide treatment greatly improved proteinuria, anti-dsDNA antibody levels, immunoglobulin subclass titers, histology of lupus nephritis, and C3 deposition in MRL/lpr and R848-induced mice. In addition, Niclosamide inhibited the proportion of TFH cells and PCs in the spleens of these animals, and effectively suppressed differentiation of TFH-like cells and expression of associated genes in vitro.Conclusions. Niclosamide exerted therapeutic effects on murine lupus models by suppressing TFH cells and plasma cells through STAT3 inhibition.
Climate Change Scenario Analysis for Baro-Akobo River Basin, Southwestern Ethiopia
Authors: MULETA TERESSA NEGASSA
Published: November 2020

BackgroundRelatively few studies have addressed water management and adaptation measures in the face of changing water balances due to climate change. Projection of the future climate variables is done using General Circulation Model (GCM). But GCM cannot capture finer scale forcing variables at regional and basin levels. Hence Regional Climate Model (RCM) downscaled data for A1B emission scenario is bias corrected at basin level using observed data. The current study has developed future climate trends using the bias corrected RCM output data for Baro-Akobo River Basin with the basic objective of producing informative data for sustainable water resource development and management in the basin. ResultThe projected future climate shows an increasing trend for both maximum and minimum temperatures; however, for the case of precipitation it doesn’t manifest a systematic increasing or decreasing trend in the next century. The projected mean annual temperature increases from the baseline period by an amount of 1oC and 3.5oC respectively, in 2040s and 2090s. Similarly, evapotranspiration has been found to increase to an extent of 25% over the basin. The precipitation experiences a mean annual decrease by 1.8% in 2040s and increases by 1.8% in 2090s over the basin for the A1B emission scenario. ConclusionIrrespective of whether there is a trend or not, it can be concluded from these results that considerable change in climate is expected to happen over the basin as per the A1B emission scenario. In addition to quantitative change, the results of this study have depicted a considerable climate change in terms of timing and frequency and hence calls for an attention on the possible future risks of sustainable water resources development and management in the basin.
Plasma Extracellular Vesicle Long RNA Profiles in the Diagnosis and Prediction of Treatment Response for Breast Cancer
Authors: Su Yonghui , Zhao Jingjing , Guo Rong , Lai Hongyan , Chi Weiru , Li Yuchen , Wang Jia , Wang Zhen , Li Lun , Sang Yuting , Hou Jianjing , Xue Jingyan , Shao Zhimin , Chi Yayun , Huang Shenglin , Wu Jiong
Published: November 2020

Background: The utility of extracellular vesicle long RNAs (exLRs) as noninvasive biomarkers in breast cancer remains elusive. The purpose of this study was to explore the potential of exLRs as clinically actionable biomarkers for breast cancer diagnosis, classification, and neoadjuvant therapy efficacy prediction. Methods: One hundred and seventy-two participants, including 112 breast cancer patients, 19 benign patients and 41 healthy controls, were enrolled in this case-control study. The exLR profile of the plasma samples was analyzed by exLR sequencing. The d-signature was identified using a support vector machine algorithm with a training cohort (n=120) and was validated using an internal validation cohort (n=52). Treatment efficacy prediction was conducted with 48 patients who received neoadjuvant chemotherapy.Results: We constructed a breast cancer diagnostic signature that showed high accuracy with an area under the curve (AUC) of 0.960 in the training cohort and 0.900 in the validation cohort. The signature was able to identify early stage BC (I/II) with an AUC of 0.940. Integrating the signature could increase the diagnosis accuracy by up to 91.9% for breast cancer patients with the corresponding predictive results based on the Breast Imaging Reporting and Data System classification of 4 or 5. Moreover, the exLRs could provide a strong indication of the breast cancer subtypes, and exMSMO1 is employable as a predictive biomarker in response to neoadjuvant chemotherapy.Conclusions: This study demonstrated the value of exLR profiling to provide potential biomarkers for early detection and treatment efficacy prediction of breast cancer.
The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production
Authors: Wang Hao , Sun Jia-Lin , Xu Ying-Xing , Sui Zhong-Guo
Published: November 2020

Background: A novel curcumin (Cur) derivative 1g can inhibit the proliferation of colon cancer in vitro and in vivo. The purpose of this study was to explore the role of 1g in inducing apoptosis of colon cancer cells, especially mitochondrial apoptosis and endoplasmic reticulum (ER)-stress caused by reactive oxygen species (ROS).Methods: Bioinformatics was used to analyze differentially expressed mrnas. Gene expression was measured by using qRT-PCR and protein expression was measured by using western blotting. Cell apoptosis, cycle, mitochondrial membrane potential and ROS were analyzed by flow cytometry. Experiments on transplanted tumors in animals.Results: The mechanism of this effect was a change in mitochondrial membrane potential caused by 1g that increased its pro-apoptotic activity. In addition, 1g produced ROS, induced G1 checkpoint blockade, and enhanced ER-stress in colon cancer cells. On the contrary, pretreatment with the ROS scavenging agent N-acetyl-l-cysteine (NAC) inhibited the mitochondrial dysfunction caused by 1g and reversed ER-stress, cell cycle stagnation, and apoptosis. Additionally, pretreatment with the p-PERK inhibitor GSK2606414 significantly reduced ER-stress and reversed the apoptosis induced by colon cancer cells.Conclusions: This study not only found that 1g inherits the safety of Cur and has a more inhibitory effect on colon cancer cells than Cur, but also revealed that excessive production of ROS is one of the mechanisms of anti-tumor action.
NeoCLEAN: a multimodal strategy to enhance environmental cleaning in a resource-limited neonatal unit
Authors: Dramowski Angela , Aucamp M , Bekker A , Pillay S , Moloto K , Whitelaw AC , Cotton MF , Coffin S
Published: November 2020

Background: Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings.Methods: A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention (NeoCLEAN) for surfaces and equipment in a 30-bed neonatal ward. The intervention included cleaning audits with feedback, cleaning checklists, in-room cleaning wipes and training of staff and mothers in cleaning methods. Cleaning adequacy was evaluated for 100 items (58 surfaces, 42 equipment) using quantitative bacterial surface cultures, adenosine triphosphate (ATP) bioluminescence assays and fluorescent ultraviolet (UV) markers, performed at baseline (P1, October 2019), early intervention (P2, November 2019) and late intervention (P3, February 2020). Results: Environmental swabs (55/300; 18.3%) yielded growth of 78 potential neonatal pathogens with Enterococci, S. marcescens, K. pneumoniae, S. aureus and A. baumannii predominating. Highest aerobic colony counts were noted from moist surfaces such as sinks, milk kitchen surfaces, humidifiers and suction tubing. The proportion of surfaces and equipment exhibiting no bacterial growth increased between phases (P1=49%, P2=66%, P3=69%; p=0.007). The proportion of surfaces and equipment meeting the ATP “cleanliness” threshold (<200 relative light units) increased over time (P1=40%, P2=54%, P3=65%; p=0.002), as did the UV marker removal rate (P1=23%, P2=71%, P3=74%; p<0.001).Conclusion: Routine environmental cleaning of this neonatal ward was sub-optimal at baseline but improved significantly following a multimodal cleaning intervention. Involving mothers and nursing staff was key to achieving improved environmental and equipment cleaning in this resource-limited neonatal unit.
An Association Between Visceral or Subcutaneous Fat Accumulation and Diabetes Mellitus Among Japanese Subjects
Authors: Yokokawa Hirohide , Fukuda Hiroshi , Saita Mizue , Goto Kento , Kaku Tengen , Miyagami Taiju , Takahashi Yuichi , Hamada Chieko , Hisaoka Teruhiko , Naito Toshio
Published: November 2020

Background: The impact of subcutaneous fat accumulation remains controversial. This study assessed the association between visceral or subcutaneous fat area (VFA and SFA, respectively) and diabetes mellitus (DM) among Japanese subjects.Methods: This was a cross-sectional study involving 1,907 eligible participants (men, 1,050; women, 883) who participated in a voluntary health check-up conducted at Juntendo University Hospital from January 2017 to December 2018, in Tokyo, Japan. Associations between VFA or SFA quartiles and DM were identified using adjusted odds ratios (AORs) and 95% confidence intervals (CIs) with multivariable logistic regression analysis adjusted for confounders. Receiver operating characteristic (ROC) curve analysis was used to assess appropriate cut-off values of VFA or SFA.Results: Multivariate analyses showed that Q4 (≥125 cm2) of VFA was significantly positively associated with DM compared to Q1 (<65 cm2) (AOR=1.94, 95% CI=1.02-3.71), whereas there was no association between SFA and DM in men. Among women, Q4 (≥85 cm2) of VFA was significantly positively associated with DM compared to Q1 (Q4, AOR=6.15, 95% CI=1.65-22.99). Also, Q3 and Q4 (≥135 cm2) of SFA were significantly positively associated with DM compared to Q1 (<90 cm2) (Q3, AOR=5.64, 95% CI=1.21-26.25; Q4, AOR=7.81, 95% CI=1.71-35.65). The appropriate cut-off value of VFA in men was 101.5 cm2. Those of VFA and SFA in women were 72.5 cm2 and 165.3 cm2, respectively.Conclusion: Our results suggest the importance of considering SFA as well as VFA, especially in women, for primary and secondary prevention of DM.
Detection of High Risk People for Diabetes by American Diabetes Association Risk Score in PERSIAN Guilan Cohort Study
Authors: Hasandokht Tolou , Joukar Farahnaz , Marroufizadeh Saman , Sibevey Sahar , Naghipour Mohammadreza , Mansour-Ghanaei Fariborz
Published: November 2020

Background: To determine prevalence of high risk individuals for diabetes mellitus (DM) and pre DM based on American Diabetes Association (ADA) risk score among Iranian people. Methods: Present study was based on 7989 non diabetic subjects aged 35–70 years from 10520 PERSIAN Guilan Cohort Study (PGCS) participants. ADA risk score was calculated for every individual through online calculator. Receiver operating characteristic (ROC) curves was used to study diagnostic accuracy of the anthropometric indices for detecting individuals with high risk ADA score for developing DM, represented by area under the curve (AUC).Results: From 7989 study subjects, ADA risk score found 3874 (48.5%) and 19122 (23%) at risk for developing PreDM and DM, respectively. The results of ROC curve analyses showed the highest diagnostic value was related to waist circumference (WC) followed by Body Mass Index (BMI) (0.695 and 0.693, respectively). The cut-points of WC and BMI for identifying high risk people for DM were 97 and 29, respectively.Conclusions: A large number of our participants had high ADA risk score for developing DM and PreDM that provide the importance of prevention strategies. WC seems to be highest diagnostic value in identifying people (men and women) with DM.
Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity
Authors: He Yuting , Deng Zhi , Jin Jianjun , Mao Ruolin , Gao Lei , Zhang Yi , Wang Gang , Gao Peng , Xie Min , Li Huayin , Chen Zhihong
Published: November 2020

Background: The progression of an abnormal inflammatory response plays a crucial role in the functional decline that occurs in COPD patients[1].Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of the inflammatory processes in the airways. Based on this, we explored the association of inflammatory biomarkers in induced sputum with lung function in COPD patients.Methods: 102 patients with COPD were recruited and underwent spirometry. According to the percentage of the predicted forced expiratory volume in 1 second value (FEV1%pred), participants with COPD were divided into a mild and moderate group (FEV1%pred≥ 50%, n=57) and a severe and extremely severe group (FEV1%pred<50%, n=45). Then we analyzed a series of inflammatory biomarkers in induced sputum and determined their association with lung function in COPD patients.Results: We found an increased levels of eosinophils percentage, MMP9 mRNA, LTB4R mRNA, and decreased levels of CC16 mRNA and miR-155 in the induced sputum of patients with severe and extremely severe COPD. In our analysis, sputum cell CC16 mRNA expression, but not CC16 secretion in the supernatant of the sputum, was closely and independently correlated with lung function decline in patients with COPD. Conclusion: The levels of numerous inflammatory biomarkers in induced sputum were associated with lung function decline in COPD，and the relative CC16 mRNA expression level with a cutoff of 1.09 could be a predictive biomarker of the severity of COPD.
Association between Host Genetics of Sheep and the Rumen Microbial Composition
Authors: Mani Sinalo , Aiyegoro Olayinka Ayobami , Adeleke Matthew Adeniyi
Published: November 2020

Background: The gut microbiome is very significant in the stability of the rumen ecosystem, also in the maintenance of the host’s health. The gut flora influences the nutritional, physiological, immunological, and directly or indirectly affects the host’s well-being. A synergy between the rumen microbiota and the host genetics creates a symbiotic relationship, beneficial to the host’s health. In this study, the association between the host genetics and rumen microbiome of Damara and Meatmaster sheep was investigated. The composition of rumen microbiota was estimated through the analysis of the V3-V4 region of the 16S rRNA gene, while the sheep blood DNA was genotyped with Illumina OvineSNP50 BeadChip and the genome-wide association (GWA) was analyzed. Results: Sixty significant SNPs dispersed in 21 regions across the Ovis aries genome were found to be associated with the relative abundance of seven genera: Acinetobacter, Bacillus, Clostridium, Flavobacterium, Prevotella, Pseudomonas and Streptobacillus. A total of eighty-four candidate genes were identified, and their functional annotations were mainly associated with immunity responses and function, metabolism, and signal transduction. Conclusion: We are of the opinion, as evident from our results that candidate genes identified may be modulating the composition of rumen microbiota and, thus further indicate the significance of comprehending the interactions between the host and rumen microbiota to gain better insight into the health of sheep. We conclude that host genetics is important in modulating microbial composition; though various factors may alter the rumen microbiota. More studies are necessary to help determine genetic combinations favorable for the propagation of beneficial microbiota and provide excellent intestinal health.
Timing of early laparoscopic cholecystectomy for acute calculous cholecystitis: a meta-analysis of randomized clinical trials.
Authors: Borzellino Giuseppe , Khuri Safi , Pisano Michele , Mansour Subhi , Allievi Niccolò , Ansaloni Luca , Kluger Yoram
Published: November 2020

Background Early cholecystectomy for acute cholecystitis is reported in the literature to be performed up to 96 hours of admission or up to 1 week of the onset of symptoms. Based on the natural history of acute cholecystitis such timing may have missed some potential benefits that could have been expected by performing cholecystectomy in an earlier phase of the disease. The study aimed to explore the hypothesis that an immediate cholecystectomy performed within 24 hours of admission could reduce post-operative complications when compared with delayed cholecystectomy. Methods The literature search was conducted based on the Patient Intervention Comparison Outcome Study (PICOS) strategy. Randomized trials comparing post-operative complications at different timings of cholecystectomy for acute cholecystitis were included. The main outcome was the post-operative complication rate. Studies were grouped based on the timing of cholecystectomy which was defined immediate when performed within 24 hours of admission, early when performed up to 96 hours of admission and delayed when surgery was elective after medical treatment. Pooled data of studies comparing post-operative complications after immediate versus delayed and early versus delayed cholecystectomy were analysed within a sub-group analysis. The literature search finding allowed the performance of a second analysis in which immediate cholecystectomy did not refer to a cholecystectomy performed within 24 hours of admission but within 72 hours of the onset of symptoms. Results Immediate cholecystectomy performed within 24 hours of admission did not prove to reduce post-operative complications with relative risk (RR) 1.89 and its 95% confidence interval (CI) [0.76; 4.71]. When the timing was based on the onset of symptoms, immediate cholecystectomy performed within 72 hours of the onset of symptoms was found to reduce post-operative complications compared to delayed cholecystectomy with RR 0.57 [95% CI: 0.37;0.89]. Conclusion The present study did not confirm the hypothesis that immediate cholecystectomy performed within 24 hours of admission may reduce post- operative complications. However, the finding of studies in which timing referred not to admission but to the onset of symptoms, allows to favour immediate cholecystectomy if performed within 72 hours of the onset of symptoms.