bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a self-limiting model of Methotrexate-induced mucositis reinforces butyrate as a potential therapy
Authors: Ferreira Ana Rita da Silva , Aa Stijn A.J. van der , Wehkamp Tjalling , Wardill Hannah R. , Klooster Jean Paul Ten , Garssen Johan , Harthoorn Lucien F. , Hartog Anita , Harmsen Hermie J.M. , Tissing Wim J.E. , Bergenhenegouwen Jeroen van 
Published: May 2020

Abstract
Background: Gastrointestinal mucositis remains a significant complication of anticancer treatment, with limited anti-mucositis interventions. Currently, there are few validated in vitro systems suitable to study the mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Methods: Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX), ranging from 0-1000 ng/ml. Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. To link the model to clinical practices, the protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005-50 µg/mL) folinic acid. Given the impact of microbial-derived short-chain fatty acids in epithelial health, we also evaluated the impact of short-chain fatty acid supplementation on MTX toxicity in the organoid model. Results: MTX treatment caused a dose-dependent reduction in cell metabolic activity and citrulline production. Folinic acid treatment reduced MTX toxicity when applied simultaneously or up to 24 hours after treatment. Supplementation of the growth medium with butyrate reduced MTX toxicity. Analysis of organoid gene expression suggests that butyrate may reduce intracellular MTX concentrations by increasing the expression of MTX transporters, including the ABCC1 transporter.Conclusion: MTX causes significant organoid damage, which can be reversed upon removal of MTX. The specific readouts and the protective effects of folinic acid suggest that the model is clinically relevant, and can be used in the future to study mucositis, diminishing the need for animal models. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.
Symptoms at disease onset predict prognosis in COVID-19 disease
Authors: Zhou Aiyuan , Peng Yating , Price David R , Peng Hong , Liao Xin , Huang Peng , Liu Wenlong , Xiang Zhi , Liu Qimi , Jiang Mingyan , Xiang Xudong , Guo Peipei , Deng Dingding , Chen Ping 
Published: May 2020

Abstract
Background: The main clinical manifestations of coronavirus disease 2019 (COVID-19) onset are respiratory symptoms, including cough, sputum and dyspnea. However, a significant proportion of patients initially manifested extra-respiratory symptoms, such as fever, myalgia and diarrhea. Here we compared the different characteristics and outcomes between the patients with respiratory symptoms and extra-respiratory symptoms at illness onset.Methods: The patients admitted to the respiratory departments from eight hospitals out of Wuhan with nucleic acid-positive of severe acute respiratory syndrome coronavirus (SARS-CoV-2) were recruited. Epidemiological information, clinical manifestations, laboratory findings, and radiological characteristics, treatment regimens and outcomes data were recorded and analyzed.Results: The median age of the recruited 541 subjects was 43 years (IQR, 33-55). Of the 541 subjects, 404 (74.5%) subjects had initial symptom that were respiratory, while 137 (25.5%) subjects had extra-respiratory symptoms. Respiratory COVID-19 subjects had more secondary bacterial infections (p<0.001), needed the intensive care unit more (p=0.005), non-invasive ventilation more (p=0.004), developed ARDS more (p=0.001) and needed longer to recover (p=0.003) compared to predominately extra-respiratory COVID-19 subjects. The multivariate model showed that age (OR = 1.04, p = 0.01) dyspnea (OR = 4.91, p < 0.001) and secondary bacterial infection (OR = 19.8, p < 0.001) were independently associated with development of ARDS among COVID-19 patients.Conclusion: we identify COVID-19 subjects with dyspnea at disease onset have worse prognosis. We also demonstrate age and secondary bacterial infections to be independently associated with ARDS development in subjects with COVID-19.
Does physiotherapy applied in conjunction with compression brace treatment in patients with pectus carinatum have efficacy? A randomized controlled study
Authors: ALACA Nuray , ALACA İhsan , Yüksel Mustafa 
Published: May 2020

Abstract
Background Non-invasive treatment of pectus carinatum (PC) deformity includes the use of a compression brace and exercises. In this study, we aimed to examine the effect of a physiotherapy protocol applied as adjunct to compression brace treatment in patients with PC.Methods The study included 30 male patients between 11–18 years of age. Patients were randomly assigned into two groups: a brace treatment only group (Group 1) and a brace and physiotherapy group (Group 2). Patient demographics and disease related properties, protrusion measurements, postural evaluations, deformity perceptions, life quality and treatment satisfaction were evaluated (before and after 12 weeks).Results Although both groups showed improvements based on external chest measurements related to PC protrusion following treatment (p < 0.001), Group 2 had more benefit from the treatment (effect size > 0.36) and displayed greater improvement in maximum protrusion degree and lateral length values (p < 0.05). Additionally, we found that patient perception of deformity, posture, psychological life quality, and treatment satisfaction scores were significantly better in Group 2 (p < 0.05).Conclusion Owing to the satisfaction and additional benefits observed in the physiotherapy group, we think a proper cardiopulmonary and musculoskeletal exercise program should be applied concurrently with brace treatment for patients with PC deformity. Nevertheless, long- term outcomes need to be clarified in future studies.Trial registration:The study was approved by the ethics committee (ATADEK-2019-14/11) and retrospectively registered as a clinical trial (ClinicalTrials.gov Identifier: NCT04167800, 20 November 2019)
Identification of genomic alterations of perineural invasion in patients with stage II colorectal cancer
Authors: Su Hao , Chang Chen , Hao Jiajie , Xu Xin , Bao Mandula , Luo Shou , Zhao Chuanduo , Wang Xishan , Liu Qian , Zhou Zhixiang , Zhou Haitao 
Published: May 2020

Abstract
Background The molecular mechanism of perineural invasion (PNI) in stage Ⅱ colorectal cancer (CRC) remains not to be defined clearly. This study aims to identify the genomic aberrations related to PNI in stage Ⅱ CRC.Methods Using array-based comparative genomic hybridization (array-CGH), primary tumor tissues and paracancerous normal tissues of stage Ⅱ CRC from 5 patients with PNI and 5 patients without PNI were analyzed. We also identified genomic aberrations by using Genomic Workbench and MD-SeeGH. Furthermore, Gene ontology (GO) and Pathway analysis for these array-CGH data was performed to determine the most likely biological effects of these genes.Results The most frequent gains in stage Ⅱ CRC were at 7q11.21-q11.22, 8p11.21, 8p12-p11.23, 8q11.1-q11.22, 13q12.13-q12.2, and 20q11.21-q11.23 and the most frequent losses were at 17p13.1-p12, 8p23.2, and 118q11.2-q23. Four high-level amplifications at 8p11.23-p11.22, 18q21.1, 19q11-q12, and 20q11.21-q13.32 and homozygous deletions at 20p12.1 were discovered in Stage II CRC. Gains at 7q11.21-q22.1, 16p11.2, 17q23.3-q25.3, 19p13.3-p12, and 20p13-p11.1, and losses at 11q11-q12.1, 11p15.5-p15.1, 18p11.21, and 18q21.1-q23 were more commonly found in patients with PNI by frequency plot comparison together with detailed genomic analysis. It is also observed that gains at 8q11.1-q24.3, 9q13-q34.3, and 13q12.3-q13.1, and losses at 3q26.1, 8p23.3-p12, 17p13.3-p11.2, and 21q22.12 occurred more frequently in patients without PNI. GO and Pathway analysis revealed that the genes in two groups were enriched in specific pathways.Conclusions These involved genomic changes in the PNI of stage Ⅱ CRC will contribute to reveal the mechanisms underlying PNI and provide candidate biomarkers.
Leishmanicidal effects of resveratrol and its derivatives: a systematic review and meta-Analysis
Authors: Dashatan Nasrin Amiri , Ashrafmansouri Marzieh , Koushki Mehdi , Ahmadi Nayebali 
Published: May 2020

Abstract
Background

Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies.
Methods

The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review.
Results

Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species.
Conclusions

Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.
Exploitation of siderophore producing bacteria Acinetobacter soli (MTCC-5918) for lipids and reactive oxygen species in Chlorella variabilis (ATCC- PTA 12198) through co-cultivation
Authors: Rajapitamahuni Soundarya , Bachani Pooja , Bharadwaj Vamsi , Mishra Sandhya 
Published: May 2020

Abstract
Background

Increased iron uptake via siderophores triggers a series of physiological processes and generation of reactive oxygen species (ROS) which causes damage to proteins, lipids, carbohydrates, resulting into micro algal cell lysis. Moreover, there are reports mentioning oxidative stress is a mediator for increased lipid accumulation in microalgae. The main aim of this study is co-cultivation of the bacteria Acinetobacter soli (MTCC- 5918) and the microalgae Chlorella variabilis (ATCC-PTA 12198) under iron limiting conditions and the threshold value of iron that trigger oxidizing stress to microalgae. Further, the ROS generation in the microalgae C. variabilis was determined in terms of OH, SO2 and H2O2 concentration in the cells while co-cultivation.
Results

The co-cultured biomass contains (45.92 ± 0.74%) lipid content which was about 21% higher than that of the axenically grown microalgae. Carbohydrate content also increased to 40% than that of the control culture. Oxidative stress is a mediator for increased lipid accumulation in microalgae. As growth inhibition triggered due to the generation of high ROS toxicity during iron deficiency an increase in concentration of OH and H2O2 content was observed. In iron sufficient medium ash content of co-cultivated microalgae showed 32% and in iron deficient medium showed 14.23% which shows 44% decrease of ash content. Our novel approach significantly outperforms the involvement of different reactive oxygen species (ROS) in induction and in regulation of chelator release from cells at adequate Fe supply, which is also affecting the growth,lipids, carbohydrates, proteins, pigments, etc.
Conclusions

The findings of the present study highlights that oxidative stress is a mediator for increased lipid accumulation in microalgae that simultaneously becomes an alternative strategy for the improvement of biofuel potential in C. variabilis. The study portraysthe significance of co-cultivation of A. soli and C. variabilis induced oxidative stress (ROS generation) in microalgae caused due to higher uptake of iron via siderophore
Optical properties of doping electrochromic M0.125W0.875O3 (M=Mo, Nb, Ta, Ti, V): A first-principles study
Authors: Cui Yuanyuan , Wang Qinfan , Liu Bin , Gao Yanfeng 
Published: May 2020

Abstract
Tungsten trioxide (WO3) is a representative electrochromic material that can change their optical properties under the action of a voltage pulse and has attracted great interest in the applications of energy efficient windows. Models of various W0.125M0.875O3 and LixM0.125W0.875O3 (M=Mo, Nb, Ta, Ti, V) were built to simulate the bleached and colored state of WO3 materials by first-principles calculations, respectively. The calculations show that doping systems of LixM0.125W0.875O3 (M= Nb, Ta, V) lead to an enhancement of the modulation efficiency in invisible light and a decrease in the modulation efficiency in near infrared region (NIR). Ti doping boosts an excellent high efficiency of NIR modulation, while no modulation was observed in the visible light region. Mo doping remarkably promotes the coloration efficiency in both NIR and visible regions. The specific characteristics of doped WO3 systems deserve more exploration of their application in green house or thermal modulation smart window.
Performance of PURE-LAMP to Detect Declining Prevalence of Malaria in Haiti
Authors: VINCENT Jeanne Perpétue , Existe Alexandre Valcena , Komaki-Yasuda Kanako , Boncy Jacques , Kano Shigeyuki 
Published: May 2020

Abstract
Background Malaria continues to cause burden in various parts of the world. Endemic countries are developing schemes to end this nuisance in accordance with the World Health Organization’s Global Technical Strategy for Malaria 2016–2030. Haiti, a Caribbean country, is among those aiming to eliminate malaria within a few years. Two surveys were conducted in Haiti in the summers of 2017 and 2018, respectively, during which we aimed to evaluate the performance of the simple and rapid PURE-LAMP (procedure for ultra-rapid extraction–loop-mediated isothermal amplification) method with dried blood spots as an alternative diagnostic method for malaria in the context of low to very low rates of transmission.Methods Febrile and asymptomatic subjects were recruited from three administrative divisions within Haiti. Their blood samples were tested by microscopy, rapid diagnostic tests (RDT), PURE-LAMP and nested PCR to detect Plasmodium infection. The positive rates for the two study periods as determined by the different methods were compared. Sensitivity, specificity, positive and negative predictive values and kappa statistics were estimated with the nested PCR results as the gold standard.Results Among 1074 samples analyzed, a positive rate of 8.3% was calculated based on the nested PCR results. Among symptomatic subjects, the rates in 2017 and 2018 were 14.6% and 1.4%, respectively. Three positives were detected among 172 asymptomatic participants in 2018 by PURE-LAMP and nested PCR, and all three were from the same locality. No asymptomatic subjects were recruited in 2017. The PURE-LAMP, RDT and microscopy had respective sensitivities of 100%, 85.4% and 49.4%. All of the testing methods had specificities over 99%.Conclusion The prevalence of malaria was found to have substantially decreased in 2018 in Haiti. A specific focus of infection appeared to require intervention with a sensitive malaria diagnostic method and treatment. This study confirmed the high performance of the PURE-LAMP method with dried blood spots and recommends its use in targeted mass screening and treatment activities in low endemic areas of malaria.
Emergency Department Utilization of Case Managed Patients Following Benign Gynecologic Surgery
Authors: Kelly Elizabeth A. , Keller Cara C. , Sax Megan R , Rossi Rocco A. 
Published: May 2020

Abstract
Background Case management has been shown to reduce the amount of unnecessary emergency department visits among Medicaid or uninsured patients. This study aims to determine whether case management is associated with decreased unnecessary emergency department visits among benign gynecology surgical patients in the first thirty days following surgery.Results Out of 875 patients, there were a total of 58 return visits to the Emergency Department within thirty days and only 6 readmissions. Twenty-four emergency department visits occurred in the case managed group and thirty-eight emergency department visits occurred in the non-case managed group. The two factors that were statistically significant for increase odds of return to the emergency department were type of surgery (inpatient versus outpatient) and case management. The odds for returning to the Emergency Department for those not receiving case management was found to be 4.53 that of the case managed group when controlling for BMI, age, marital status, and type of surgery.Conclusion In an effort to reduce healthcare costs, case management is a promising intervention to help postoperative patients manage their care while minimizing emergency department visits.
Correlation between serum uric acid level and central body fat distribution in patients with type 2 diabetes
Authors: Zong Jing , Sun Yi , Zhang Yiqian , Yuan Jin , Wang Xinlei , Zhang Rongping , Zhao Xiaoqin , Zhao Xuying , Gu Yunjuan 
Published: May 2020

Abstract
Background The aim of this study was to investigate the correlation between serum uric acid level and central body fat distribution in patients with type 2 diabetes (T2DM).Methods A total of 867 patients with T2DM were enrolled. Measurements of central fat distribution were obtained by dual energy X-ray absorptiometry. Patients were stratified into three groups according to their levels of serum uric acid (SUA). Multiple linear regression analysis was used to determine the association between SUA and central body fat distribution. Logistic regression analysis was used to estimate the risk factors for hyperuricemia (HUA). Mediation analysis was applied to assess the overall, direct, and indirect mediators of SUA levels.Results Multiple linear regression analysis showed that SUA levels were significantly positively correlated with waist circumference (WC), body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue(SAT), Android fat mass, Gynoid fat mass, fasting c-peptide (F-CP), and area under the curve of C-peptide (P < 0.05 for all). VAT [odds ratio (OR), 2.367; 95% confidence interval (CI), 1.078–5.197; P < 0.001)], WC (OR, 1.041; 95% CI, 1.011–1.072; P < 0.001), high-density lipoprotein (OR, 0.274; 95% CI, 0.104–0.727; P < 0.001), and estimated glomerular filtration rate (OR, 0.966; 95% CI, 0.959–0.973; P < 0.001) were found to be independent risk factors for T2DM patients with HUA. After mediation analysis, BMI and central obesity were found to have different partial effects on the association between SUA and F-CP (P < 0.001).Conclusions In patients with T2DM, HUA was positively correlated with F-CP and central body fat distribution, especially VAT. These results suggest that central obesity may play a role in the positive correlation between HUA and insulin resistance (IR).
Wire Arc Additive Manufactured CuMn13Al7 High-Manganese Aluminium Bronze
Authors: Guo Chun , Hu Bai-Song , Wei Bao-Li , Chen Feng 
Published: May 2020

Abstract
In this work, high-manganese aluminium bronze CuMn13Al7 samples were prepared by arc additive manufacturing technology. The phase composition, microstructure, and crystal structure of the high-manganese aluminium bronze CuMn13Al7 arc additive manufactured samples were analysed using direct-reading spectrometer, metallographic microscope, scanning electron microscope, and transmission electron microscope. The micro-hardness tester, tensile tester, impact tester, and electrochemical workstation were also used to test the performance of the CuMn13Al7 samples. By studying the microstructure and properties of the CuMn13Al7 samples, it was found that preparation of the samples by the arc additive manufacturing technology ensured good forming quality, almost no defects, and good metallurgical bonding inside the sample. The metallographic structure (α + β + point phase) mainly comprises the following: the metallographic structure in the equiaxed grain region has an obvious grain boundary α; the metallographic structure in the remelting region has no obvious grain boundary α; the thermal influence on the metallographic structure produced a weaker grain boundary α than the equiaxed grain region. The transverse and longitudinal cross sections of the sample had uniform microhardness distributions, and the average microhardness values were 190.5 HV0.1 and 192.7 HV0.1, respectively. The sample also had excellent mechanical properties: yield strength of 301 MPa, tensile strength of 633 MPa, elongation of 43.5%, reduction of area by ​​58%, Charpy impact value of 68 J at –20 ℃, and dynamic potential polarisation curve test results. Further, it was shown that the average corrosion potential of the sample was –284.5 mV, and the average corrosion current density was 4.1 × 10–3 mA/cm2.
ATO /miRNA-885-5p/MTPN axis induced reversal of drug-resistance in cholangiocarcinoma
Authors: Wang Yuting , Zhang Wen , Chen Lin , Chen Wei , Xu Shufen , Tang Lingyu , Yang Yang , Li Quanpeng , Jiang Qi , Miao Lin 
Published: May 2020

Abstract
Backgroud:

In recent years, the incidence of cholangiocarcinoma (CCA) has increased, and it has become the second most malignant tumor of the hepatobiliary system. Chemotherapy has become the main treatment for cholangiocarcinoma due to its difficulty in diagnosis and rapid progress. Primary drug resistance is the main reason for the poor efficacy of chemotherapeutic drugs.
Methods

Western blot and quantitative real-time PCR assays were used to detect the expression levels of myotrophin (MTPN) and microRNA-885-5p(miR-885-5p) in CCA tissues and cells; Cell viabilities treated with arsenic trioxide (ATO), 5-fluorouracil (5-Fu) and cisplatin (CDDP) were analyzed by a CCK-8 kit. Luciferase reporter assay detected the relationship between miR-885-5p and MTPN. Kaplan-Meier analysis showed survival time curve.
Results

We found that ATO can reduce the resistance of CCA cells to 5-Fu and CDDP and promote the killing effect of 5-Fu and CDDP. Low-dose ATO played an anti-drug-resistance role through up-regulating the expression of miR-885-5p. Combined with sequencing results and database prediction, we found that MTPN was a direct target gene of miR-885-5p. The sensitivity of CCA cells to 5-Fu and CDDP was increased after MTPN was knocked out. After MTPN knockout, the sensitivity of cholangiocarcinoma cells to 5-FU and CDDP was increased. ATO can reverse chemotherapy resistance induced by overexpression of MTPN.
Conclusions

Our study suggests that the ATO/miR-885-5p/MTPN axis is a potential therapeutic strategy for improving the sensitivity of CCA to chemotherapy.