bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey
Authors: yang xiaolong , Xu Yue , Wang Yun , Li Chang , Zhang Xiaofeng 
Published: January 2020

Abstract
Background Ovariectomized cynomolgus monkey 30 months after surgery was selected as the research object to identify protein changes in tears and serum to provide a reference for the diagnosis and pathogenesis of dry eye in menopausal women. Methods Six cynomolgus monkey were randomly divided into an experimental group and a control group (3 in each group). The experimental group underwent bilateral ovariectomy, while the control group underwent sham surgery with their ovaries reserved. Proteomic analysis was performed by LC-MS/MS on tears and serum collected from two groups. Differentially expressed proteins were identified and were performed cluster analysis, which included gene ontology, the Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction. Results 33 differentially expressed proteins have been identified in tears and17 differentially expressed proteins have been identified in serum. Kyoto Encyclopedia of Genes and Genomes enrichment analysis in tears has discovered Glucagon signaling pathway and neurotrophin signaling pathway may play an important role in the pathogenesis of dry eye. Gene ontology enrichment analysis in serum has discovered insulin-like growth factor binding and growth factor binding in molecular function probably make effort in pathogenesis of dry eye. KEGG analysis in serum has discovered salivary secretion may be the key pathway in pathogenesis of dry eye. Conclusions Protein G7PCH4, Q2PG17 and G7PT55 in tears may be the key protein in pathogenesis of dry eyes. Protein G7P1T1, G7PUN9 and G8F302 in serum may play an important role in pathogenesis of dry eyes.
Evaluating influence of customer and scheme qualities in selecting a medical scheme by using choice and loglinear modelling: Case of healthcare services in Zimbabwe
Authors: Mwembe Desmond , Khamis Harry J , Jones Brian , Chagwiza Wilbert 
Published: January 2020

Abstract
Background Marketing of medical aid schemes in Zimbabwe after the hyperinflationary period before 2008 has been a mammoth task due to the loss of trust in insurance companies, medical aid companies included. Selecting an affordable scheme that best suits a client's needs is not easy due to the wide variety of medical schemes that are available. Methods Purposive sampling of people with medical aid schemes was conducted. Random sampling was done to select the sample from which information was obtained using questionnairs. Results A number of factors are considered to understand the behaviour of clients in this industry. Correspondingly, scheme characteristics are examined through a random sample of 1222 Zimbabwean medical aid society clients to understand preferences by clients in relation to the medical schemes. It was established that experience, contribution, sex, family size, employment, education and salary are the main drivers in selecting medical aid schemes. Age was found to be nonsignificant in influencing choice of a medical aid scheme. Type of scheme and quality were also seen to be independent and these two were highly associated with rejection. Conclusion It is recommended that, to ease the difficulty of selling medical aid schemes, client characteristics need to be understood so as to increase uptake of medical aid schemes in Zimbabwe. Choosing a low or high premium medical aid scheme is recommended to clients to reduce the rejection rate by medical practitioners, and hence improve access to healthcare services.
Naringin suppressing the PI3K/Akt signaling pathway as a drug target in BIU87 cells
Authors: Li Jianzhong , Zhao Jing , Zhang Huayang , Liu Meixia , Li Xin 
Published: January 2020

Abstract
Background: Flavonoids are regarded as potential anti-cancer drugs due to their toxicity and anti-proliferation functions. Naringin, which is a kind of flavanone compounds targeting anti-tumor treatment, has been focused on reliving several types of cancers, besides of bladder cancer. This paper was aimed to investigate whether and how naringin induced bladder cancer cells. Method: MTT, cell-cycle, transwell and cell apoptosis were used to assess the cellular responses. Molecular expressions and the signaling pathway of naringin inducing BIU87 cells were evaluated by western blot and real-time quantitative PCR. Results: It was found that naringin effectively suppressed proliferation and invasion of BIU87 cells by downregulating the expression of PI3K and its downstream pathway. The corresponding proteins related to viability and motility, including CDK2, Bcl-2 and Fascin, were inhibited. Conclusion: It can be concluded that naringin targeting to PI3K in bladder tumor cells expressed abundantly and inhibited the growth and invasive ability of tumor cells.
Engineering the CBB cycle and hydrogen utilization pathway of Ralstonia eutropha H16 for improved autotrophic growth and PHB production
Authors: Li Zhongkang , Hu Muzi , Xiong Bin , Zhao Dongdong , Zhang Chunzhi , Bi Changhao , Zhang Xueli 
Published: January 2020

Abstract
CO 2 is fixed by all living organisms with an autotrophic metabolism, among which the Calvin-Benson-Bassham ( CBB) cycle is the most important and widespread carbon fixation pathway. Thus, studying and engineering the CBB cycle with the associated energy providing pathways to increase the CO 2 fixation efficiency of cells is an important subject of biological research with significant application potential. In this work, the autotrophic microbe Ralstonia eutropha H16 was selected as a research platform for CBB cycle optimization engineering. By knocking out either CBB operon genes on the operon or mega-plasmid of R. eutropha , we found that both CBB operons were active and contributed almost equally to the carbon fixation process. With similar knock-out experiments, we found while both soluble and membrane-bound hydrogenases (SH and MBH), belonging to the energy providing hydrogenase module, were f unctional d uring autotrophic growth of R. eutropha. And SH played a more significant role. By introducing a heterologous cyanobacterial RuBisCO with the endogenous GroES/EL chaperone system and RbcX, the culture OD 600 of engineered strain increased 89.15% after 72 hours of autotrophic growth, indicating cyanobacterial RuBisCO with a higher activity was functional in R. eutropha and improved upon original CBB pathway. Meanwhile, expression of hydrogenases were optimized by modulating the expression of MBH and SH, which could further increase the R. eutropha H16 culture OD 600 to 93.4% at 72 hours. Moreover, the autotrophic yield of its major industrially relevant product, polyhydroxybutyrate (PHB), was increased by 99.71%. To our best knowledge, this is the first report of successfully engineering the CBB pathway of R. eutropha for improved activity , and is one of only a few cases where the efficiency of CO 2 assimilation pathway was improved. Our work demonstrates that R. eutropha is an extremely useful platform for studying and engineering the CBB for applications in more important organisms, such as agricultural crops, and a potential microbial cell factory to develop industrial biotechnology for sequestrating CO 2 .
Development of a nomogram to predict in-hospital mortality of sepsis-associated encephalopathy: a retrospective cohort study
Authors: Yang Yang , Liang Shengru , Geng Jie , Wang Qiuhe , Wang Pan , Cao Yuan , Li Rong , Gao Guodong , Li Lihong 
Published: January 2020

Abstract
Background Sepsis-associated encephalopathy (SAE) is related to an increased in-hospital mortality in patients with sepsis. We aim to establish a user-friendly nomogram for individual prediction of in-hospital death probability in patients with SAE. MethodsData were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database. SAE was defined by a Glasgow Coma Score (GCS) <15 at the presence of sepsis. Prediction model with a nomogram was constructed in the training set by Logistic regression analysis and then internally validated. A decision curve analysis (DCA) was performed to evaluate the net benefit of intervention with the nomogram. Results A total of 669 and 287 patients with SAE were randomly assigned to training set and internal validation set according to an allocation ratio of 7:3, respectively. Parameters eligible for the nomogram included age, Sequential Organ Failure Assessment (SOFA) score, red blood cell distribution width (RDW) and the mean values of heart rate, temperature and respiratory rate at first day of ICU admission. The nomogram exhibited good discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.773 (95%CI: 0.729–0.818) in the training set and 0.741 (95%CI 0.673–0.809) in the validation set, respectively. Calibration of the derived model was also excellent, with Brier score of 0.136 (95%CI: 0.12­–0.153) and 0.168 (95%CI: 0.144–0.192) in both sets. The DCA of the nomogram indicated greater net benefit than SOFA. X-tile analysis showed that the nomogram can clearly stratify patients into three subgroups with different risks of in-hospital death. Conclusions The nomogram presents excellent performance in predicting in-hospital mortality of SAE patients, which can guide the prevention of SAE progression and may be more beneficial once specific treatments towards SAE are developed.
Pediatric hypophosphatasia: a retrospective single-centre chart review of 50 children
Authors: Vogt Marius , Girschick Hermann , Schweitzer Tilmann , Benoit Clemens , Holl-Wieden Annette , Seefried Lothar , Jakob Franz , Hofmann Christine 
Published: January 2020

Abstract
Background: Hypophosphatasia (HPP) is a rare, inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene that encodes the tissue-nonspecific alkaline phosphatase TNAP (ORPHA 436). Its clinical presentation is highly heterogeneous with a remarkably wide-ranging severity. HPP affects patients of all ages. Therefore, diagnosis is often difficult and delayed. To improve the understanding of HPP in children and in order to shorten the diagnostic time span in the future we studied the natural history of the disease in our large cohort of pediatric patients. In light of the enzyme replacement therapy (Asfotase alfa, a recombinant mineral-targeted TNAP), HPP patients may benefit from early and patient severity orientated calculated treatment in the course of the disease. Methods: This single centre retrospective chart review included longitudinal data from 50 patients with HPP diagnosed and followed at the University Children`s Hospital Wuerzburg, Germany over the last 25 years. Results: The cohort comprises 4 (8%) perinatal, 17 (34%) infantile and 29 (58%) childhood onset HPP patients. Two patients were deceased at the time of data collection. Diagnosis was based on available characteristic clinical symptoms (in 88%), low alkaline phosphatase (AP) activity (in 96%), accumulating substrates of AP (in 58%) and X-ray findings (in 48%). Genetic analysis was performed in 48 patients (35 compound heterozygous, 11 heterozygous, 2 homozygous mutations per patient), allowing investigations on genotype-phenotype correlations. Based on anamnestic data, median age at first clinical symptoms was 3.5 months (min. 0, max. 107), while median time to diagnosis was 13 months (min. 0, max. 103). Common symptoms included: impairment of motor skills (78%), impairment of mineralization (72%), premature loss of teeth (64%), musculoskeletal pain and craniosynostosis (each 64%) and failure to thrive (62%). Up to now 20 patients started medical treatment with Asfotase alfa. Conclusions: Reported findings support the clinical perception of HPP being a chronic multi-systemic disease with often delayed diagnosis. Our natural history information provides detailed insights into the prevalence of different symptoms, which can help to improve and shorten diagnostics and thereby lead to an optimised medical care, especially with promising therapeutic options like enzyme-replacement-therapy with Asfotase alfa in mind.
Analysis of the primary and post-treatment antibiotic resistance of Helicobacter pylori in Nanjing area
Authors: zongdan jiang , He Bang-Shun , Zhang Zhen-Yu , Wang Shu-Kui , Ran Dan , WANG Zhi-Bing 
Published: January 2020

Abstract
Background To investigate the current status and trend of Helicobacter pylori(H. pylori)antibiotics resistance over 5 years in Nanjing area.Then we evaluated the primary and post-treatment antibiotic resistance of H. pylori in Nanjing area. Methods During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by breath test or rapid urease test were collected for isolation and identify H. pylori. The agar dilution method was used for antibiotic resistance test. The antibiotic resistance of H. pylori were compared with that in the period from May 2014 to May 2015. Results The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. Compared with the period of May 2014 to May 2015, the resistance rate of metronidazole was the most obvious, from 60.5% to 80.76% in the period of July 2017 to December 2019, followed by clarithromycin from 29.5% to 47.03%, and levofloxacin from 14.7% to 33.59%. The resistance rates of H. pylori (primary Vs post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% Vs 6.08%, 38.62% Vs 77.81%, 27.41% Vs 56.23%, 0.58% Vs 2.13%, 0.33% Vs 1.22%, 78.57% Vs 88.75%, respectively during the period of July 2017 to December 2019. Conclusions Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in Nanjing area. For post-treatment eradication patients, clinicians should took into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects.
Understanding transmission and control of the pork tapeworm with CystiAgent: a spatially explicit agent-based model
Authors: Pray Ian Wright , Wakeland Wayne , Pan William , Lambert William E. , Garcia Hector H. , Gonzalez Armando E. , O’Neal Seth E. 
Published: January 2020

Abstract
BackgroundThe pork tapeworm (Taenia solium) is a serious public health problem in rural low-resource areas of Latin America, Africa, and Asia, where the associated conditions of nuerocysticercosis (NCC) and porcine cysticercosis cause substantial health and economic harms. An accurate and validated transmission model for T. solium would serve as an important new tool for control and elimination, as it would allow for comparison of available intervention strategies, and prioritization of the most effective strategies for control and elimination efforts. MethodsWe developed a spatially-explicit agent-based model (ABM) for T. solium (“CystiAgent”) that differs from prior T. solium models by including a spatial framework and behavioral parameters such as pig roaming, open human defecation, and human travel. In this article, we introduce the structure and function of the model, describe the data sources used to parameterize the model, and apply sensitivity analyses (Latin hypercube sampling–partial rank correlation coefficient (LHS-PRCC)) to evaluate model parameters. ResultsLHS-PRCC analysis of CystiAgent found that the parameters with the greatest impact on model uncertainty were the roaming range of pigs, the infectious duration of human taeniasis, use of latrines, and the set of “tuning” parameters defining the probabilities of infection in humans and pigs given exposure to T. solium.ConclusionsCystiAgent is a novel ABM that has the ability to model spatial and behavioral features of T. solium transmission not available in other models. There is a small set of impactful model parameters that contribute uncertainty to the model and may impact the accuracy of model projections. Field and laboratory studies to better understand these key components of transmission may help reduce uncertainty, while current applications of CystiAgent may consider calibration of these parameters to improve model performance. These results will ultimately allow for improved interpretation of model validation results, and usage of the model to compare available control and elimination strategies for T. solium.
Lung Radiofrequency Ablation: Post-procedure Imaging Patterns and Late Follow-up
Authors: Araujo-Filho Jose , Menezes Raonne Souza Almeida Alves , Horvat Natally , Panizza Pedro Sergio Brito , Bernardes João Paulo Giacomini , Damasceno Rodrigo Stanford , Oliveira Brunna Clemente , Menezes Marcos Roberto 
Published: January 2020

Abstract
Background: Radiofrequency ablation (RFA) is a safe and effective minimally invasive treatment for primary or secondary malignancies of the lung. This study aims to describe imaging features on chest computed tomography (CT) after RFA of primary and secondary lung tumors, and their frequency over the time after the procedure.Methods: In this double-center retrospective study, we reviewed 69 patients with primary and secondary lung tumors who underwent percutaneous RFA. Patients were excluded if they had received concomitant radiation therapy or chemotherapy, and if there was no CT follow-up. The imaging features were assessed in four different time points: immediate post-procedure, <4 weeks, 5-24 weeks, 25-52 weeks and >52 weeks. Late follow-up (3 and 5 years after procedure) was assessed clinically in 48 patients.Results: The study population consisted of 69 patients and 144 pulmonary tumors. Six out of 69 (8.7%) patients had primary lung nodules (stage I) and 63/69 (91.3%) had metastatic pulmonary nodules. Based on per patient analysis, immediately after lung RFA, the most common CT features were consolidation (56/69, 81.1%), reversed halo (55/69, 79.7%), and hyperdensity (47/69, 68.1%). Less than 4 weeks, reversed halo was demonstrated in 19/22 (86.3%) patients, and consolidation and pleural thickening in 17/22 (77.2%). Between 5-24 weeks, 25-52 weeks and after 52 weeks, the most common imaging features were parenchymal bands. Conclusions: Our study demonstrated the expected CT features after lung RFA, a procedure which use has been progressively growing. Diagnostic and interventional radiologists should be familiar with the expected imaging features immediately after RFA and their change during follow-up in order to avoid misinterpretation and inadequate treatments.
Sennoside A induces GLP-1 secretion through activation of the ERK1/2 pathway in L-cells
Authors: Ma Li , Cao Xinyu , Ye Xiaotong , Ye Jianping , Sun Yongning 
Published: January 2020

Abstract
Background Glucagon-like peptide-1 (GLP-1) is secreted from the intestinal L-cells to stimulate insulin secretion in the control of blood glucose. Sennoside A (SA), derived from Rhubarb extract of traditional Chinese medicine, is often used to treat constipation and lose weight. Our previous study suggests that SA can increase the plasma GLP-1 level in a mouse model of type 2 diabetes. However, the mechanism of SA activity remains unknown. This issue was addressed in this study. Methods C57bl/6 mice were divided randomly into four groups at n = 12. Group one was used as a control group without drug treatment. The other three groups were treated with (SA) at three dosages: a low dose (15 mg/kg/day), medium dose (30mg/kg/day) or high dose (45 mg/kg/day). SA was delivered into the mice through drinking water. Bodyweight was monitored. After treatment, blood glucose was assayed by OGTT. Plasma GLP-1 and insulin were determined at 15 mins of oral glucose challenge. Colon tissues were collected for mRNA or western blot analysis. Immunofluorescence staining assays was used to evaluate the number of β-cells and L-cells. NCI-H716 cells were employed to investigate the mechanism of SA-induced GLP-1 secretion, and the cells were subjected to western blot analysis. In the study of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, NCI-H716 cells were pretreated with ERK1/2 inhibitors (PD98059, 50 μM) for 30 min in the presence of SA (100 μM). Results In the current study, SA can reduce body weight during 5 weeks of weight monitoring and improve OGTT in C57BL/6 mice on the Chow diet. Furthermore, plasma GLP-1 was significantly elevated in the mouse treated by SA at the dosage of 45 mg/kg/day. The SA activity was supported by improving glucose-induced insulin secretion. Meanwhile, increased expression of EKR1/2 and prohormone convertase 1/3 (PC1/3) proteins was observed in the large intestine of SA-treated mice. The number of L-cells was not altered in each group. In the NCI-H716 cells, GLP-1 secretion was induced by SA with activation of the ERK1/2 pathway and elevation of PC1/3 protein. The SA effect was blocked by the ERK1/2 inhibitor. These data suggest that SA induced GLP-1 secretion in L-cells through activation of the ERK1/2 pathway in the mouse intestine. Conclusion Our study provides direct evidence that SA interacts with L cells for GLP-1 secretion. The data suggest that the SA effect is dependent on the ERK1/2 signaling pathway. Therefore, SA is a new drug candidate for the treatment of type 2 diabetes by induction of GLP-1 secretion.
Goal-directed dehydration therapy in sepsis and acute respiratory distress syndrome guided by volumetric hemodynamic monitoring
Authors: Khromacheva N. O. , Fot E. V. , Kuzkov V. V. , Kirov M. Yu. 
Published: January 2020

The aim of our study was to improve results of treatment of critically ill patients with sepsis and acute respiratory distress syndrome (ARDS) using the goal-directed dehydration therapy (DT).Sixty adult patients with sepsis and ARDS receiving mechanical ventilation for at least 24 hours were enrolled into a prospective randomized study. The patients were randomized into groups of dehydration guided either by extravascular (group of extravascular lung water index ‒ EVLWI,n= 30) or intravascular (group of global end-diastolic volume index ‒ GEDVI,n= 30) compartment. Dehydration was performed over 48 hours by administering diuretics or controlled extracorporeal ultrafiltration. We measured ventilation parameters, blood gases, and parameters of volumetric monitoring. The baseline characteristics of the patients did not differ between the groups. By 48 hours, the target fluid balance was achieved in both groups. In the EVLWI group at 48 hours, we found reduction of EVLWI by 15.4% (p< 0.001) and increase in PaO2/FiO2by 23.3% as compared with baseline (p< 0.001). In parallel, we observed decrease in creatinine and urea (p< 0.05). In the GEDVI group, PaO2/FiO2 rose by 12.5% (p = 0.021), whereas EVLWI remained unchanged (p= 0.4). Maximal decrease in EVLWI and improvement of PaO2/FiO2 were achieved in direct ARDS.Thus, in patients with sepsis and ARDS the de-escalation goal-directed therapy resulted in the improvement of arterial oxygenation and organ function. The efficacy of dehydration was increased in direct ARDS. The extravascular compartment dehydration algorithm attenuated pulmonary edema and acute kidney injury more efficiently. Therefore, sepsis-induced ARDS may require personalized therapeutic approach.