bluuebunny/crossref_metadata_2025_split huggingface dataset:
A case of pheochromocytoma presenting with cardiac manifestation: case report
Authors: Molaei Akbar , Abarzadeh-Bairami Vahideh , Sadat-Ebrahimi Seyyed-Reza 
Published: June 2020

Abstract
Background
Pheochromocytomas are rare tumors originating in chromaffin cells which predominantly are located in adrenal glands. Sustained or paroxysmal hypertension (HT) is the most frequent sign of pheochromocytoma. In some cases, it is associated with the classic triad including episodic headaches, sudoresis, and tachycardia; however, we present a case of pheochromocytoma with first presentation of cardiomyopathy.

Case presentation
The authors describe a rare case of a pheochromocytoma which was first presented with cardiomyopathy in a 7-year-old patient. The patient was admitted with malaise, abdominal pain, polydipsia, and myalgia. Further evaluations revealed hyperglycemia, mild dehydration and sinus tachycardia but no HT. Echocardiography demonstrated some of the signs of cardiomyopathy which was incorrectly diagnosed as viral myocarditis. The patient was discharged with this diagnosis but he presented again with HT crisis a few months later. A diagnosis of pheochromocytoma was assigned after the evaluation of the HT secondary causes. The diagnosis was confirmed by metanephrine assay and the tumor was localized in the adrenal gland using the abdominal MRI.

Conclusion
Pheochromocytoma can present itself with normotensive cardiomyopathy. Therefore, the possibility of pheochromocytoma should be considered in patients with cardiomyopathy especially in those with positive familial history.
Health inequality: a longitudinal study on geographic variations in lung cancer incidence and mortality in Taiwan
Authors: Hsu Jason C. , Tseng Yu-Chi , Chang Sheng-Mao , Lee Yang-Cheng , Lin Peng-Chan , Chu Hone-Jay 
Published: June 2020

Abstract
Background
This study is aimed toward an analysis of the variations in lung cancer incidence and mortality, adjusted by population factors (age, gender, and year), between administrative areas.

Methods
This is a retrospective study, using 2005–2014 data in each administrative area from the Taiwan Cancer Registry database organized by the Health Promotion Administration. The yearly age-standardized (overall) and crude (stratified by gender and age) incidence/mortality (and their growth rates) for each administrative area were collected and calculated. We used a mixed model to analyze the repeated measurements of yearly incidence and mortality rates and used general linear regression to analyze their growth rates.

Results
It was found that male and elderly populations had significantly higher lung cancer incidence and mortality in Taiwan. After adjusting for gender, age, and calendar year, there were no significant variations in incidence among the administrative areas, while the mortality in Yilan County was significantly higher than that in Taipei City (the capital city of Taiwan). On the other hand, the incidence in the female and younger population and mortality growth rates were higher. The incidence growth rate in Keelung City was significantly lower than that in Taipei City, while there were no significant variations in mortality growth rate among administrative areas.

Conclusions
This study found an inequality in the lung cancer burden among cities in Taiwan, which can serve as the basis for future resource allocations for lung cancer prevention and treatment in Taiwan.
Interference chromatography: a novel approach to optimizing chromatographic selectivity and separation performance for virus purification
Authors: Santry Lisa A. , Jacquemart Renaud , Vandersluis Melissa , Zhao Mochao , Domm Jake M. , McAusland Thomas M. , Shang Xiaojiao , Major Pierre M. , Stout James G. , Wootton Sarah K. 
Published: June 2020

AbstractBackgroundOncolytic viruses are playing an increasingly important role in cancer immunotherapy applications. Given the preclinical and clinical efficacy of these virus-based therapeutics, there is a need for fast, simple, and inexpensive downstream processing methodologies to purify biologically active viral agents that meet the increasingly higher safety standards stipulated by regulatory authorities like the Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. However, the production of virus materials for clinical dosing of oncolytic virotherapies is currently limited—in quantity, quality, and timeliness—by current purification technologies. Adsorption of virus particles to solid phases provides a convenient and practical choice for large-scale fractionation and recovery of viruses from cell and media contaminants. Indeed, chromatography has been deemed the most promising technology for large-scale purification of viruses for biomedical applications. The implementation of new chromatography media has improved process performance, but low yields and long processing times required to reach the desired purity are still limiting.ResultsHere we report the development of an interference chromatography-based process for purifying high titer, clinical grade oncolytic Newcastle disease virus using NatriFlo® HD-Q membrane technology. This novel approach to optimizing chromatographic performance utilizes differences in molecular bonding interactions to achieve high purity in a single ion exchange step.ConclusionsWhen used in conjunction with membrane chromatography, this high yield method based on interference chromatography has the potential to deliver efficient, scalable processes to enable viable production of oncolytic virotherapies.
The impact of flavonoids-rich Ziziphus jujuba Mill. Extract on Staphylococcus aureus biofilm formation
Authors: Miao Weiwei , Sheng Lei , Yang Tao , Wu Guizhen , Zhang Minfang , Sun Juan , Ainiwaer Aikemu 
Published: June 2020

AbstractBackgroundTo evaluate the in vitro antibacterial effect of flavonoids-richZiziphus jujubaMill. extract (FZM) against the formation of bacterial biofilms (BBFs) inStaphylococcus aureus.ResultsFZM can effectively inhibit the formation ofS. aureusbiofilms in vitro. Morphological observation showed a decrease in both biofilm adhesion and thickness. Results of confocal laser scanning microscopy used to detect the thickness of the BBFs showed that FZM treatment reduced the thickness of the BBFs. Furthermore, after the Image-Pro Plus v.6.0 analysis of the fluorescence intensity, FZM treatment reduced the thickness of the BBFs as well as the proportion of green fluorescence. Scanning electron microscopy showed that FZM can disrupt the channels available for substance exchange in the biofilm, thus exposing the bacterial cells and damaging its three-dimensional structures.ConclusionFZM can inhibit biofilm formation, improve the bacterial pH environment, and eliminate the hydrophobic effect of reactive oxygen species and flavonoids.
Professional advice for primary healthcare workers in Ethiopia: a social network analysis
Authors: Sabot Kate , Blanchet Karl , Berhanu Della , Spicer Neil , Schellenberg Joanna 
Published: June 2020

AbstractBackgroundIn an era of increasingly competitive funding, governments and donors will be looking for creative ways to extend and maximise resources. One such means can include building upon professional advice networks to more efficiently introduce, scale up, or change programmes and healthcare provider practices. This cross-sectional, mixed-methods, observational study compared professional advice networks of healthcare workers in eight primary healthcare units across four regions of Ethiopia. Primary healthcare units include a health centre and typically five satellite health posts.MethodsOne hundred sixty staff at eight primary healthcare units were interviewed using a structured tool. Quantitative data captured the frequency of healthcare worker advice seeking and giving on providing antenatal, childbirth, postnatal and newborn care. Network and actor-level metrics were calculated including density (ratio of ties between actors to all possible ties), centrality (number of ties incident to an actor), distance (average number of steps between actors) and size (number of actors within the network). Following quantitative network analyses, 20 qualitative interviews were conducted with network study participants from four primary healthcare units. Qualitative interviews aimed to interpret and explain network properties observed. Data were entered, analysed or visualised using Excel 6.0, UCINET 6.0, Netdraw, Adobe InDesign and MaxQDA10 software packages.ResultsThe following average network level metrics were observed: density .26 (SD.11), degree centrality .45 (SD.08), distance 1.94 (SD.26), number of ties 95.63 (SD 35.46), size of network 20.25 (SD 3.65). Advice networks for antenatal or maternity care were more utilised than advice networks for post-natal or newborn care. Advice networks were typically limited to primary healthcare unit staff, but not necessarily to supervisors. In seeking advice, a colleague’s level of training and knowledge were valued over experience. Advice exchange primarily took place in person or over the phone rather than over email or online fora. There were few barriers to seeking advice.ConclusionInformal, inter-and intra-cadre advice networks existed. Fellow primary healthcare unit staff were preferred, particularly midwives, but networks were not limited to the primary healthcare unit. Additional research is needed to associate network properties with outcomes and pilot network interventions with central actors.
Cost objects: How is your ED performing?
Authors: Fuentes-Cáceres Verónica , Neriz Liliana , Núñez-Mondaca Alicia , Mateo Ricardo 
Published: June 2020

Abstract
Background
The aim of this study is to a propose a standardized methodology to identify a list of cost objects that can be used by any ED to compute costs considering that the resulting data must facilitate unit management by improving the information available for decision-making.

Methods
This study considers two stages, first, we analyzed the case-mix of two hospitals collecting their data to define and diagram their processes, activities and to obtain their cost objects, second, we used four additional hospitals to validate our initial findings.

Results
We recognized 59 cost objects. Hospitals may have all these cost objects or just a subset of them depending on the services they provide.

Conclusions
Among the main benefits of our cost objects definition are: the possibility of tracing the processes generated by the services delivered by EDs, the economic sense in its grouping, the chance of using any costing methodology, the flexibility with other classification systems such as DRGs and ICDs, and the opportunity of costing for both diseases and treatments. Furthermore, cost comparison among hospitals using our final 59 cost objects list is more accurate and based on comparable units. In different EDs, each cost object will be the result of a similar combination of activities performed. We also present the results of applying this cost objects list to a particular ED. A total of 53 out of 59 cost objects were identified for that particular unit within a calendar year.
Medical insurance and health equity in health service utilization among the middle-aged and older adults in China: a quantile regression approach
Authors: Fan Guorui , Deng Zhaohua , Wu Xiang , Wang Yang 
Published: June 2020

Abstract
Background
China has achieved nearly universal coverage of the Social Basic Medical Insurance (SBMI), which aims to reduce the disease burden and improve the utilization of health services. We investigated the association between China’s health insurance schemes and health service utilization of middle-aged and older adults at different quantiles, and then explored whether the SBMI could help reduce the underutilization of health services among the middle-aged and older adults in China.

Methods
Survey data of middle-aged and older adults were drawn from the China Health and Retirement Longitudinal Study (CHARLS). A linear quantile mixed regression model was utilized to provide a comprehensive understanding of the relationship between SBMI and health service utilization, which was measured by the total medical expenditure. We took the New Rural Cooperative Medical Scheme (NCMS) as the reference level and examined the associations of the Urban Employee Basic Medical Insurance (UEBMI) and the Urban Resident Basic Medical Insurance (URBMI) with health service utilization.

Results
The quantile regression analysis revealed a significant positive association between URBMI and health service utilization at the 0.75 (β = 1.608, p < 0.01), 0.8 (β = 1.578, p < 0.01), 0.85 (β = 1.473, p < 0.01), 0.9 (β = 1.403, p < 0.01) and 0.95 (β = 1.152, p < 0.01) quantiles, and also a significant positive association between UEBMI and health service utilization at the 0.85 (β = 1.196, p < 0.01), 0.9 (β = 1.070, p < 0.01) and 0.95 (β = 0.736, p < 0.01) quantiles. Results showed that URBMI was significantly associated with an improvement in inpatient health service utilization of the middle-aged and older adults, and a significant positive association between UEBMI and inpatient health service utilization was observed at 0.1 (β = 0.559, p < 0.01), 0.25 (β = 0.420, p < 0.05), 0.5 (β = 0.352, p < 0.05), and 0.75 (β = 0.306, p < 0.05) quantiles.

Conclusions
Inequity in health service utilization exists among the middle-aged and older adults across urban and rural Chinese areas, and it can be explained by the different reimbursement benefits of SBMI types.
Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma
Authors: Guo Lingyun , Wang Zhenjiang , Du Yuanyuan , Mao Jie , Zhang Junqiang , Yu Zeyuan , Guo Jiwu , Zhao Jun , Zhou Huinian , Wang Haitao , Gu Yanmei , Li Yumin 
Published: June 2020

Abstract
Background
Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients.

Methods
We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients’ database, and obtained the data and results of immunohistochemistry.

Results
We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis.

Conclusion
Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.
Long non-coding RNA SNHG22 facilitates the malignant phenotypes in triple-negative breast cancer via sponging miR-324-3p and upregulating SUDS3
Authors: Fang Xuan , Zhang Jin , Li Chunyan , Liu Jinjin , Shi Zhendong , Zhou Peng 
Published: June 2020

AbstractBackgroundIncreasing evidence has indicated the important role of long non-coding RNAs (lncRNAs) in regulating the development and progression of cancers, including triple-negative breast cancer (TNBC). Small nucleolar RNA host gene 22 (SNHG22) is a novel lncRNA that has been identified as tumor-contributor in ovarian carcinoma. However, its function has not been explored in TNBC.MethodsqRT-PCR was used to identify gene expression at mRNA level while western blot was utilized to analyze the protein level. Functional assays were implemented to identify changes on the proliferation, apoptosis and motility of TNBC cells under different conditions. Additionally, mechanistic assays, such as RIP assay, RNA pull down assay and luciferase reporter assay, were applied to assess relationships between molecules.ResultsSNHG22 represented a high expression level in TNBC tissues and cells. Besides, SNHG22 silencing restrained the proliferation, migration and invasion of TNBC cells. Furthermore, miR-324-3p that was lowly expressed in TNBC cells was conformed to be sponged by SNHG22. Moreover, upregulated miR-324-3p inhibited cell proliferation and motility in TNBC. Subsequently, we identified that SUDS3, a tumor-facilitator with elevated expression in TNBC, was the downstream target of SNHG22/miR-324-3p axis. Of note, miR-324-3p repression or SUDS3 overexpression could rescue the anti-tumor effect of SNHG22 silencing on the malignant phenotypes of TNBC cells.ConclusionLncRNA SNHG22 facilitated cell growth and motility in TNBC via sponging miR-324-3p and upregulating SUDS3, highlighting a new promising road for TNBC treatment development.
Arsenic trioxide potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK-mediated endoplasmic reticulum stress
Authors: Hu Xiaoli , Cai Jiayi , Zhu Jianyi , Lang Wenjing , Zhong Jihua , Zhong Hua , Chen Fangyuan 
Published: June 2020

Abstract
Background
Acute myeloid leukemia (AML) patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) have a high relapse rate and poor prognosis. This study aims to explore the underlying mechanism of combining Gilteritinib with ATO at low concentration in the treatment of FLT3-ITD positive leukemias.

Methods
We used both in vitro and in vivo studies to investigate the effects of combination of Gilteritinib with ATO at low concentration on FLT3-ITD positive leukemias, together with the underlying molecular mechanisms of these processes.

Results
Combination of Gilteritinib with ATO showed synergistic effects on inhibiting proliferation, increasing apoptosis and attenuating invasive ability in FLT3-ITD-mutated cells and reducing tumor growth in nude mice. Results of western blot indicated that Gilteritinib increased a 160KD form of FLT3 protein on the surface of cell membrane. Detection of endoplasmic reticulum stress marker protein revealed that IRE1a and its downstream signal phosphorylated JNK were suppressed in Gilteritinib-treated FLT3-ITD positive cells. The downregulation of IRE1a induced by Gilteritinib was reversed with addition of ATO. Knockdown of IRE1a diminished the combinatorial effects of Gilteritinib plus ATO treatment and combination of tunicamycin (an endoplasmic reticulum pathway activator) with Gilteritinib achieved the similar effect as treatment with Gilteritinib plus ATO.

Conclusions
Thus, ATO at low concentration potentiates Gilteritinib-induced apoptosis in FLT3-ITD positive leukemic cells via IRE1a-JNK signal pathway, targeting IRE1a to cooperate with Gilteritinib may serve as a new theoretical basis on FLT3-ITD mutant AML treatment.
DNA methylation-based classification and identification of bladder cancer prognosis-associated subgroups
Authors: Tian Zijian , Meng Lingfeng , Long Xingbo , Diao Tongxiang , Hu Maolin , Wang Miao , Liu Ming , Wang Jianye 
Published: June 2020

Abstract
Background
Bladder cancer (BCA) is the most common urinary tumor, but its pathogenesis is unclear, and the associated treatment strategy has rarely been updated. In recent years, a deeper understanding of tumor epigenetics has been gained, providing new opportunities for cancer detection and treatment.

Methods
We identified prognostic methylation sites based on DNA methylation profiles of BCA in the TCGA database and constructed a specific prognostic subgroup.

Results
Based on the consistent clustering of 402 CpGs, we identified seven subgroups that had a significant association with survival. The difference in DNA methylation levels was related to T stage, N stage, M stage, grade, sex, age, stage and prognosis. Finally, the prediction model was constructed using a Cox regression model and verified using the test dataset; the prognosis was consistent with that of the training set.

Conclusions
The classification based on DNA methylation is closely related to the clinicopathological characteristics of BCA and determines the prognostic value of each epigenetic subtype. Therefore, our findings provide a basis for the development of DNA methylation subtype-specific therapeutic strategies for human bladder cancer.
Determining a critical threshold for G6PD activity below which red blood cell response to oxidative stress is poor
Authors: Swastika Maria , Harahap Alida R. , Panggalo Lydia V. , Jusman Sri Widia A. , Satyagraha Ari W. 
Published: June 2020

Abstract
Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine, which has a long half-life, screening for G6PD deficiency becomes a necessity where those with < 70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.

Methods
RBC models were developed to analyse the effect of oxidant on RBC oxidative markers namely total glutathione (GSH)and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from two G6PD heterozygous women with different G6PD activities were also analysed for comparison.

Results
There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, the CuCl RBC model showed that in low G6PD activities (10–30%) cells, the MDA level is lower compared to the rest of the models (p < 0.05). The ex vivo models however were in line with the hypothesis, although the result was not significant (p = 0.5). There was a significant difference between RBC with < 60% and those with > 80% G6PD activities in CuCl RBC model, but not in ex vivo RBC (p = 0.5). Genotyping heterozygous subjects showed G6PDViangchan variant with 2.97 U/gHb (33% activity) and 6.58 U/gHb (74% activity).

Conclusions
The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old World Health Organization threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex vivo model.