bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations
Authors: Takeda Yuichiro , Naka Go , Yamaguchi Yoh , Hashimoto Masao , Suzuki Manabu , Izumi Shinyu , Sugiyama Haruhito 
Published: August 2020

Abstract
Background: Osimertinib, a third - generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as a second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy, and limited information is available regarding genetic diagnostic approaches after EGFR-TKI naïve treatment. This study investigated the characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistance to EGFR-TKIs and the advantages of rebiopsy and liquid biopsy for these patients.
Methods: The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy.
Results: From April 2016 through May 2019, 113 patients were determined to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among which 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had new lesions, and were administered gefitinib as first-line therapy, patients harboring an EGFR mutation were suspected of harboring the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with co-existing original mutations, brain metastases, tumor enlargement by ≥ 12 mm, or metastases at minor sites.
Conclusion: Repeated biopsy can help maximize the detection rate of the T790M substitution. Furthermore, the advantages of repeated tissue or liquid biopsy should be considered among patients with positive T790M factors , and these biopsies can be repeated numerous times .
Data Processing Scheme Based on Blockchain
Authors: Fu Jinhua , Xu Mixue , Huang Yongzhong , Si Xueming , Yuan Chao 
Published: August 2020

Abstract
In the white paper written on Bitcoin, a chain of blocks was proposed by Satoshi Nakamoto. Since then, blockchain has been rapidly developed. Blockchain is not only limited to the field of cryptocurrency but also has been extensively applied to the Internet of Things (IoT), supply chain finance, electronic evidence storage, data sharing, and e-government fields. Both the public chain and the alliance chain have been extensively developed. In the data processing field, blockchain has a particularly good application potential. The Square Kilometre Array (SKA) is a proposal consisting of a joint venture of more than ten countries, resulting in the world’s largest synthetic aperture radio telescope. In the SKA, the processing scale of the data is large, and it consists of several data processing nodes. The data will be processed in the cloud computing mode. Taking the SKA under consideration, this report proposes a data processing scheme based on blockchain for the anti-counterfeiting, anti-tampering and traceability of data. Furthermore, the authenticity and integrity of the data are assured. The primary aspects include data distribution, data operation and data sharing, which correspond to the data reception, data algorithm processing and result sharing of data operation in the SKA. With this process, the integrity, reliability and authenticity of the data are guaranteed. Additionally, smart contracts, homomorphic hashing, secure containers, aggregate signatures and one-way encrypted channels are implemented to ensure the intelligence, security and high performance of the process.
Dietary nutrient intake related to higher grade cervical intraepithelial neoplasia risk: A Chinese population-based study
Authors: Wang Zhe , Yang Aimin , Yang Jing , Zhao Weihong , Wang Zhilian , Wang Wei , Wang Jintao , Song Jinghui , Li Li , Lv Weiguo , Li Dongyan , Liu Huiqiang , Wang Chen , Hao Min 
Published: August 2020

Abstract
Background: Dietary nutrient intake plays a significant role in carcinogenesis. Few studies have investigated the association between dietary nutrient intake and cervical intraepithelial neoplasia (CIN) risk in China. Methods: Data on 2,304 women from an ongoing cohort comprising 40,000 women from China in 2014 were included. We randomly selected 218 out of 2304 people as subjects during 2019. All participants were surveyed through in-person interviews, physical examinations, and laboratory tests. Clinical data were obtained from physical examinations and laboratory tests. Dietary intakes were assessed using a semiquantitative food frequency questionnaire. Nutrition intakes from 26 food sources were calculated using a comprehensive validated database. Descriptive statistics were used to describe the frequency and proportion, and mean and standard deviation of the demographic characteristics. Characteristics were examined for significant differences, and Pearson chi-square tests were used for categoric variables. Logistic regression was used to obtain odds ratios (ORs) and confidence intervals (CIs) for CIN risk in each nutritional ingredient quartile relative to that in the highest quartile. Results: The food frequency questionnaire exhibited acceptable reproducibility and reasonable validity in assessing nutrient intakes among these women. After adjusting for multiple confounders, several dietary nutrients showed significant associations with CIN2+ risk. Low dietary folate intake was associated with the risk of CIN2+ (first versus fourth quartile: OR=1.55, 95% CI: 1.03-2.33). Similar results were also observed for vitamin B6 (OR=1.63, 95% CI: 1.08-2.46), vitamin C (OR=1.59, 95% CI: 1.05-2.42), niacin (OR=1.65, 95% CI: 1.08-2.51), and vitamin K (second versus fourth quartile: OR=1.60, 95% CI: 1.05-2.44).Conclusions: Low folate; vitamin B6, C, and K; and niacin intakes were associated with CIN2+ risk. Nutrients may influence the development of higher grade CIN and cervical cancer.Trial registration: The study was registered in the Chinese Clinical Trial Register (ChiCTR-ROC-15006479) (http://www.chictr.org.cn).
Transcriptome Analysis of Aedes aegypti Aag2 Cells in Response to Dengue Virus-2 Infection
Authors: Li Man-jin , Lan Ce-jie , Gao He-ting , Xing Dan , Gu Zhen-yu , Su Duo , Zhao Tong-yan , Yang Hui-ying , Li Chun-xiao 
Published: August 2020

Abstract
Background: Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model.Methods: RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: The transcriptome analysis generated 8866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed and that the transcriptome sequencing data were reliable.Conclusions: This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.
Staging Procedures Fail to Benefit Women with Borderline Ovarian Tumours Who Want to Preserve Fertility: A Retrospective Analysis of 448 cases
Authors: Li Na , Gou Jinhai , Li Lin , Ming Xiu , Hu Tingwenyi , Li Zhengyu 
Published: August 2020

Abstract
Background: To evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients.Methods: We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated.Results: 448 patients were included; 52 recurrences were observed. 92 patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation.Conclusion: Patients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.Keywords: Borderline Ovarian Tumour, Surgery Staging, Fertility-Sparing Surgery, Disease-Free Survival
Assessing the acceptability of a text messaging service and smartphone app to support patient adherence to medications prescribed for high blood pressure: a pilot study.
Authors: Kassavou Aikaterini , Court Charlotte A , Chauhan Jagmohan , Brimicombe James , Bhattacharya Debbi , Naughton Felix , Hardeman Wendy , Mascolo Cecilia , Sutton Stephen 
Published: August 2020

Abstract
Aims and objectives. This paper describes a pilot non-randomised controlled study of a highly tailored 56-days text message and smartphone app prototype intervention to increase adherence to anti-hypertensive medication in primary care. The aim of this study was to evaluate the acceptability of the intervention and obtain patients views about the intervention content, delivery mode, and the mechanisms by which the intervention supported medication adherence. Methods. Patients diagnosed with hypertension were invited to the study via general practice text messages and were recruited face to face by the researcher team. Participants were asked to test the text message intervention for 28 consecutive days and switch to the smartphone app for 28 more days. Participants completed baseline and follow up questionnaires and took part in semi-structured telephone interviews. Digital log files captured patients’ usage of the intervention. Participant transcripts were analysed using thematic analysis. Descriptive statistics were used to summarize data from questionnaires and log files. A mixed methods analysis generated data to respond to the research questions. Results. 79 patients expressed interest to participate in this study, of whom 23 (64% male, 82% above 60 years old) were recruited to take part. With one drop-out, 22 participants tested the text message delivery mode (with 20 being interviewed) and four of them (17%) switched to the app (with 3 being interviewed). All participants engaged and interacted with the text message and app notifications, and most participants found the intervention content and delivery mode acceptable. They also self-reported that the interactive elements of the intervention motivated them to take their medications as prescribed. Conclusion. This study provides evidence that the digital intervention is acceptable by hypertensive patients recruited in primary care. Future research could usefully investigate its feasibility and effectiveness using rigorous research methods.
"The inflammation link between periodontal disease and coronary atherosclerosis in patients with acute coronary syndromes - case-control study".
Authors: Wojtkowska Agnieszka , Zapolski Tomasz , Wysokinska-Miszczuk Joanna , Wysokinski Andrzej P. 
Published: August 2020

Abstract
Background Coronary atherosclerosis and periodontal disease, due to their prevalence, are a serious epidemiological problem. Pathophysiological evidence points to their possible common inflammatory etiopathological background. The aim of the study was to analyze the relationship between the presence and severity of periodontitis, systemic inflammation and selected parameters of myocardial injury and heart function in patients with acute myocardial infarction. Methods The study group consisted of 71 patients 54.22(7.05) - year - old hospitalized due to acute myocardial infarction. The patients underwent a coronary angiographic examination and echocardiography. The following laboratory parameters were determined: blood morphology, hsCRP, ESR, fibrinogen, troponin I, CK-MB, BNP, lipidogram, glucose, creatinine, GFR, TSH, HbA1c. Dental assessment of the patients was performed and the following indicators were included: the number of teeth preserved, approximal plaque index (API), bleeding on probing (BoP), pocket depth (PD), the number of bleeding periodontal pockets ≥ 4 mm in depth (NoPD≥4 mm), the percentage of bleeding periodontal pockets ≥ 4 mm in depth (%PD≥4 mm), clinical attachment loss (CAL). The control consisted of 40 patients 52 (± 8.43)- year-old without a history of coronary heart disease. These patients were subjected to a periodontal examination using the above parameters and classification methods. Results The BI (bleeding index) significantly correlated with fibrynogen. All indices regarding the pocket depth (PD, NoPD≥4mm,% PD4≥mm) correlated significantly with the number of leukocytes. PD and NoPD≥4mm were also associated significantly with the level of hsCRP. The BI is correlated closely with the levels of BNP. The multifactorial analysis showed that significant predictors of myocardial infarction are API and BI. The analysis showed that API and BI are important predictors of troponin levels. Linear regression analysis showed that only CAL is a significant predictor of BNP. Conclusions Patients with acute myocardial infarction have worse periodontal status compared to people without coronary heart disease. Higher severity of periodontal disease, poorer oral hygiene and increased activity of the periodontitis leads to greater manifestation of systemic inflammation in patients with acute myocardial infarction. Periodontitis is a risk factor for myocardial infarction and also affects the degree of post-infarction left ventricular damage, which means that there is an inflammatory link between these two diseases.
Correlation between immunity from BCG and the morbidity and mortality of COVID-19
Authors: Wickramasinghe Dakshitha , Wickramasinghe Nilanka , Kamburugamuwa Sohan Anjana , Arambepola Carukshi , Samarasekera Dharmabandhu N 
Published: August 2020

Abstract
Background To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis(TB)) and the morbidity and mortality of COVID-19. Methods Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating immunity from BCG using linear regression analysis. Results Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p<0.0001) and deaths (p<0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients >65-years (Cases(rs=-0.785,p=0.0001)) and deaths (rs=-0.647,p=0.0001).Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were inversely affected by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients >65-years. Conclusion Significant inverse correlations observed between cases and deaths of COVID-19 and BCG related parameters highlights immunity from BCG as a likely explanation for the variation in COVID-19 across countries.
The modules of mental health programs implemented in schools in low- and middle-income countries: Findings from a systematic literature review
Authors: Gimba Solomon Musa , Harris Paul , Saito Amornrat , Udah Hyacinth , Martin Averil , Wheeler Amanda J. 
Published: August 2020

Abstract
Background Secondary schools in low- and middle-income countries (LMICs) provide promotional, preventive, and early intervention services. Nevertheless, literature indicates that the modules of these services are either adapted or modified from existing mental health programs in developed countries. The literature also highlights the provision of non-comprehensive services (mental health promotion, prevention, and early intervention), in LMICs such as Nigeria. These findings inform the need for undertaking this systematic literature review. The aim of this review was thus to identify the modules of school-based mental health programs (SBMHP) that have been implemented in LMICs to guide the development of a culturally sensitive comprehensive mental health program for adolescents in a LMIC. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to guide this review. The following databases were searched in September 2018, to identify the relevant literature: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and ERIC. The search was conducted by the first author and reviewed by the authors.Results Following the screening process, a total of 11 papers were identified and reviewed for quality. The systematic review highlighted that the mental health programs provided in schools included: an introduction module, a communication and relationship module, a psychoeducation module, a cognitive skills module, a behavioral skills module, establishing social networks for recovery and help seeking behavioral activities and a summary/conclusion module.Conclusion This review sheds light on the characteristics of the programs in LMICs. Two programs were found to be universal in nature. Five programs were directed at key risk factors or at-risk groups, and four were early intervention programs. The review also revealed that only one program out of the 11 programs included modules for parents. The synthesis indicated that all the identified programs were adapted or modified from existing programs. The dearth of comprehensive programs in LMICs was also revealed. Lastly, the review revealed modules that can be useful for developing a SBMHP.
Production of peptides and amino acids from microbial biomass in food and feed industries: biotechnological aspects
Authors: Serba Elena , Rimareva Liubov , Overchenko Marina , Ignatova Nadezhda , Tadzhibova Polina , Zorin Sergey 
Published: August 2020

Introduction. Microbial biomass is a popular source of food ingredients and feed additives. Its high use has made it focus of many relevant studies. Yeast and fungal biomasses proved to be useful substrates that improve the quality and biological value of functional products. They differ in the content and composition of proteins and polysaccharides. The present research dealt with the enzymatic decomposition of proteins found in a novel fungal and yeast biomass. The research objective was to describe the peptide and amino acid composition of their enzymatic hydrolysates.
Study objects and methods. The research featured a new fungal and yeast biomass mix. Aspergillus oryzae is a mycelial fungus and a popular industrial producer of hydrolytic enzymes in food industry. As for the yeast, it was the Saccharomyces cerevisiae strain, which is often used in baking.
Results and discussion. The total content of identified amino acids in the fungal and yeast biomass was 306.0 mg/g, which was 1.5 times higher than in the fungal biomass alone. The biomass mix demonstrated a higher biological value of proteins than the yeast biomass. A set of experiments made it possible to compile a scheme for the biocatalytic destruction of polymers in the fungal and yeast biomass under the effect of fungal intracellular and endogenous enzymes. The article also contains a thorough description of the obtained enzymatic hydrolysates with various fractional compositions of peptides and free amino acids. Peptides with the molecular weight in the range of up to 29.0 kDa decreased by 2.1 times after 5 h of hydrolysis and by 10.7 times after 18 h. The designed conditions doubled the release of amino acids and increased the content of low-molecular-weight peptides up to 75.3%.
Conclusion. The research provided a new algorithm for the biocatalytic conversion of microbial biomass. Regulating the conditions of enzymatic hydrolysis made it possible to obtain enzymatic hydrolysates with a desired degree of protein degradation. They could serve as peptides and amino acids in functional food and feed products.
The Identification of Three Key Genes Related to Stemness in Thyroid Carcinoma through Comprehensive Analysis
Authors: Zhang Tonglong , Yan Chunhong , Ye Zhengdu , Yin Xingling , Jiang Tian-an 
Published: August 2020

Background:
Tumor heterogeneity imposes great challenges on cancer treatment.
Cancer stem cells (CSCs) are a leading factor contributing to tumor occurrence. However, the
mechanisms underlying the growth of thyroid cancer (TCHA) are still unclear.

Methods:
Key genes regulating the characteristics of THCA, such as stemness were identified by
combining gene expressions of samples downloaded from the Cancer Genome Atlas (TCGA) and
were used to establish an mRNA expression stemness index (mRNAsi) through machine learningbased
methods. The relationships of mRNAsi, THCA clinical features and molecular subtypes
were analyzed. Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to
obtain mRNAsi-related gene modules and determine mRNAsi-related differentially co-expressed
genes. Key genes related to mRNAsi were screened by protein interaction network. Functional
analysis was conducted and expressions of key genes were verified in multiple external data sets.

Results:
The mRNAsi score, which was found to be lower in the TCHA tissues than that in
normal tissues (p<0.05), was positively correlated with a slow progression of tumor prognosis
(p=0.0085). We screened a total of 83 differentially co-expressed genes related to mRNAsi and
multiple tumor pathways such as apoptosis, tight junction, cytokine-cytokine receptor interaction, and
cAMP signaling pathway (p<0.05). Finally, 28 protein interaction networks incorporating 32 genes
were established, and 3 key genes were identified through network mining. 3 core genes were finally
determined, as their low expressions were strongly correlated with the progression of THCA.

Conclusion:
The study found that NGF, FOS, and GRIA1 are closely related to the characteristics
of THCA stem cells. These genes, especially FOS, are highly indicative of the prognosis of THCA
patients. Thus, screening therapy could be used to inhibit the stemness of TCHA.