bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma
Authors: Keam Bhumsuk , Park Jin Young , Kim Jinpyo , Kim Gun Do , Yu Yunsuk , Cho Sang Hee , Kim Sangwoo , Ahn Hee Kyung , Chun Sang Hoon , Kwon Jung Hye , Yun Tak , Kim Ji-Won , Kim Ji Eun , Ahn Myung-Ju , Kim Joo-Hang , Yun Hwan Jung 
Published: July 2020

Abstract
Background: Over- or under-expression of mRNA results from genetic alterations. Comprehensive pathway analyses based on mRNA expression are as important as single gene level mutations. This study aimed to compare the mutation-and mRNA expression-based signaling pathways in head and neck squamous cell carcinoma (HNSCC), and to match these with potential drug or druggable pathways.Methods: Altogether, 93 recurrent/metastatic HNSCC patients were enrolled. We performed targeted gene sequencing using Agilent 244 customized gene panel for NGS, and nanostring nCounter® for mRNA expression. mRNA expression was classified into over- or under expression groups based on the expression levels that showed 2-fold change in tumor compared with non-tumor tissues. We investigated mutational and nanostring data using the CBSJukebox® system, which is a big-data driven platform to analyze druggable pathways, genes, and protein-protein interaction. Analyses were based on 14 databases related to protein interaction, signaling pathways and drugs such as NCBI, Uniprot, KEGG, Biogrid, DIP, HPRD, and Drugbank. High score interaction genes were mapped to investigate druggable pathways. We calculated Treatment Benefit Prediction Score (TBPS) to identify suitable drugs. Results: By mapping the high score interaction genes to identify druggable pathways, we found that highly related signaling pathways with mutation mapping were Influenza A, pathways in cancer, EBV, HPV, HTLV-1 pathways. Based on mRNA expression and interaction gene scoring model, several pathways were found to be associated with over- and under-expression. Comparison between mutation-based pathway and over-/under-expressed genes-based pathways, we observed that 19.8% of NGS based pathways matched with mRNA over-expressed genes-based pathways, and 43.2% of NGS based pathways consist with mRNA under-expressed genes-based pathways. TBPS found several matching drugs such as immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors.Conclusions: Mutation-based pathway was associated with mRNA under-expressed genes-based pathway. These results suggest that HNSCCs are mainly caused by the loss-of-function mutations. However, big data based platform for druggable pathway can find potential matching drugs.
Establishment and Verification of the Nomogram That Predicts the 3-year Recurrence Risk of Epithelial Ovarian Carcinoma
Authors: Hu Jun , Jiao Xiaobing , Zhu Lirong , Guo Hongyan , Wu Yumei 
Published: July 2020

Abstract
Background As we all know, patients with epithelial ovarian carcinoma have poor prognosis and high recurrence rate. It is critical and challenging to screen out the patients with high risk of recurrence. At present, there are some models predicting the overall survival of epithelial ovarian carcinoma, however, there is no widely accepted tool or applicable model predicting the recurrence risk of epithelial ovarian carcinoma patients. The objective of this study was to establish and verify a nomogram to predict the recurrence risk of EOC. Methods We reviewed the clinicopathological and prognostic data of 193 patients with EOC who achieved clinical complete remission after cytoreductive surgery and chemotherapy between January 2003 and December 2013 in Peking University First Hospital. The nomogram was established with the risk factors selected by LASSO regression. The medical data of 187 EOC patients with 5-year standard follow-up in Peking University Third Hospital and Beijing Obstetrics and Gynecology Hospital were used for external validation of the nomogram. AUC curve and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration.Results The nomogram for 3-year recurrence risk was established with FIGO stage, histological grade, histological type, lymph node metastasis status and serum CA125 level at diagnosis. The total score can be obtained by adding the grading values of these factors together. In the external validation, the AUC (C statistics) was 0.803 [95%CI, 0.738-0.867] and the Chi-square value is 11.04 (P=0.135>0.05). With the threshold value of 198, the sensitivity, specificity, positive predictive value, negative predictive value and correct index of the monogram were 75.7%, 77.0%, 83.2%, 67.9%, and 0.52 respectively.Conclusions We established and validated a nomogram to predict 3-year recurrence risk of patients with EOC who achieved clinical complete remission after cytoreductive surgery and chemotherapy. This nomogram with good discrimination and calibration might be useful for screening out the patients with high risk of recurrence.Precis: Establishment and verification of the nomogram predicting the 3-year recurrence risk of EOC
Deferasirox Shows Inhibition Activity Against Cervical Cancer in vitro and in vivo
Authors: Zhou Nan , Cui Yan , Kuang Yuhuan , Hou Jianyuan , Zhu Yumeng , Chen ShuBo , Xu Xin , Tan Ke , Cao Pengxiu , Duan Xianglin , yumei Fan 
Published: July 2020

Abstract
Background: Iron depletion may be a novel therapeutic strategy for cancer. As an oral iron chelator, deferasirox (DFX) is expected to become an anticancer agent. This study aimed to assess the effects of DFX on cervical cancer.Methods: The effects of DFX on cellular iron metabolism, cell viability, cell cycle and apoptosis, and cell invasion were assessed in two cervical cancer cell lines. The effects of DFX on the expression of cell cycle regulators cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) were examined. The expression of N-myc downstream regulated gene 1 (NDRG1) and c-myc, and the activation of the MEK/ERK signaling pathway were investigated. The effect of DFX on tumor burden was assessed using a murine xenograft model.Results: DFX decreased the viability of HeLa and SiHa cells, induced cell cycle and apoptosis, and decreased cell invasion. The expression of NDRG1 was upregulated while that of c-myc was downregulated. The activation of the MEK/ERK signaling pathway was inhibited by DFX. DFX also significantly suppressed xenograft tumor growth with no serious side effects, decreased ferritin levels in nude mice serum, and decreased ferritin heavy chain (FTH) expression in xenograft tumor tissue.Conclusions: The inhibitory effect of DFX on cervical cancer cells and xenograft tumor growth was related to its effective depletion of iron in tumor cells. These results demonstrate that DFX has potential as a therapeutic agent for cervical cancer.
Expression, Purification, Refolding and Characterization of A Neverland Protein from Caenorhabditis Elegans
Authors: Mao Shuhong , Song Zhan , Wu Mian , Wang Xiaorui , Lu Fuping , Qin Hui-Min 
Published: July 2020

Abstract
Background: Steroid hormones serving as vital compounds are required for a variety of organisms’ development and metabolism. The neverland (NVD) family genes encode conserved Rieske-type oxygenases, which are accountable for the dehydrogenation during the synthesis and regulation of steroid hormones. However, the His-tagged NVD protein from Caenorhabditis elegans expresses as inclusion bodies in E. coil BL21(DE3). This neck bottle can be solved through refolding by urea or introduction of maltose-binding protein (MBP) tag at N-terminus. Results: Further research on purification after introduction of maltose-binding protein (MBP) tag at N-terminus, CD measurement and fluorescence-based thermal shift assay indicated that MBP was favorable for the NVD proteins’ solubility and stability, which may be beneficial for large-scale manufacture of NVD protein for further research. The structural model contained Rieske [2Fe-2S] domain and non-heme iron-binding motif, which were similar with 3-ketosteroid 9 α-hydroxylase.Conclusions: The successful introduction of maltose-binding protein (MBP) tag at N-terminus could increase the soluble expression of CeNVD, is advantageous for further purification and improvement of thermostability. Our study provides a persuasive case for soluble expression of Rieske-domain oxygenase in E. coli.
An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theranostics
Authors: Vargas Clarita Saldarriaga , Bauwens Matthias , Pooters Ivo NA , Pommé Stefaan , Peters Steffie MB , Segbers Marcel , Jentzen Walter , Vogg Andreas , Velden Floris HP van , Viol Sebastiaan L Meyer , Gotthardt Martin , Mottaghy Felix M , Wildberger Joachim E , Covens Peter , Wierts Roel 
Published: July 2020

Abstract
Background: Personalized molecular radiotherapy based on theranostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theranostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu and 90Y.Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theranostic setting was evaluated for 5 clinically-relevant theranostic pairs: 131I/123I, 131I/124I, 177Lu/111In, 90Y/99mTc and 90Y/111In.Results: For 99mTc, 131I, and 177Lu, a small minority of measurements were not within ±5% range from the reference activity (percentage of measurements not within range: 99mTc: 6%, 131I: 14%, 177Lu: 24%) and almost none were outside ±10% range. However, for 111In, 123I, 124I and 90Y more than half of all measurements were not accurate within ±5% range (111In: 51%, 123I: 83%, 124I: 63%, 90Y: 61%) and not all were within ±10% margin (111In: 22%, 123I: 35%, 124I: 15%, 90Y: 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ±10%) for the investigated theranostic pairs, in particular for 90Y/111In, 131I/123I and 90Y/99mTc.Conclusions: Our study shows that substantial over- or under-estimation of therapeutic patient doses are likely to occur in a theranostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically-relevant radionuclide and sample geometry.
Clinical application of pedicled thoracoacromial artery perforator flaps for tracheal reconstruction
Authors: Deng Di , Xu Feng , Liu Jifeng , Li Bo , Li Linke , Liu Jun , Chen Fei 
Published: July 2020

Abstract
Background
Large or complex trachea defects often require some tissue to reconstruct,various flaps have been reported for reconstructing this defect.However, pedicled thoracoacromial artery perforator flap have not been reported in tracheal reconstruction.Therefore,this study is to assess the efficacy and clinical application of pedicled thoracoacromial artery perforator flaps for tracheal reconstruction.
Methods
Eight patients who underwent tracheal reconstructions with pedicled TAAP flaps between December 2017 and October 2019 were retrospectively reviewed.
Results
All of the pedicled TAAP flaps in our study survived. The flap size ranged from 5 cm by 2 cm to 4 cm by 10 cm, and the size of each island of one double-island flap was 2.5 cm by 2 cm. The mean thickness was 0.6 cm, and the pedicle length varied between 6 cm and 9 cm (mean 7.9 cm). The mean time of flap harvest was 17 min. The mean age of the patients was 62.4 years and five elderly patients had comorbidities,such as diabetes,hypertension and asthma. One patient received a double-island flap for tracheal and esophageal reconstruction, and the other patient received simple tracheal reconstruction. One patient died due to cancer metastasis.Six patients obtained functional recovery of breathing, except one patients who did not experience closure of the tracheostomy opening due to uncompleted I131 treatment.
Conclusion
Pedicled TAAP flaps provide a hairless inner lining, short harvesting time, thin thickness and stable blood supply, and they do not require microsurgical skills. This flap is a good choice for the reconstruction of tracheal defects,especially in the aged or patients with comorbidities who are not able to tolerate prolonged surgery.
Long-term outcomes and prognostic factor analysis of resected Siewert type II adenocarcinoma of esophagogastric junction in China: a seven-year study
Authors: Feng Yiding , Jiang Youhua , Zhao Qiang , Liu Jinshi , Zhang Hangyu , Chen Qixun 
Published: July 2020

Abstract
BACKGROUND
The incidence rate of adenocarcinoma of esophagogastric junction (AEG) was significantly increased over the past two decades. Surgery remians the only way to cure. Indeed, there are currently few studies on Chinese AEG patients. The purpose of this study was to retrospectively analyze the survival and prognostic factors of AEG patients in our center.
METHODS
Between January 2008 and September 2014, 249 AEG patients who underwent radical resection were enrolled in this retrospective study, including 196 males and 53 females, with a median age of 64 (range 31–82). Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analysis.
RESULTS
The 5-year survival rate of all patients was 49%. The median survival time of all enrolled patients was 70.1 months. Pathology type, intraoperative blood transfusion, tumor size, adjuvant chemotherapy, hospital stay days, serum CA199, CA125, CA242 and CEA, pTNM stage, lymphovascular or perineuronal invasion, and the ratio of positive to negative lymph nodes (PNLNR) were significant associated with overall survival when analyzed with univariate analysis.
CONCLUSIONS
Our study found that intraoperative blood transfusion, tumor size, adjuvant chemotherapy, serum CEA and PNLNR, postoperative hospital stays were independent risk factors.
Cost-effectiveness of the Adaptive Implementation of Effective Programs Trial (Adept): Approaches to Adopting Implementation Strategies
Authors: Eisman Andria B , Hutton David , Prosser Lisa , Smith Shawna , Kilbourne Amy 
Published: July 2020

Abstract
Background
Theory-based methods to support clinician uptake of evidence-based practices (EBPs) are critical to improving mental health outcomes. Costs associated with effective implementation strategies can be substantial, and few have been rigorously evaluated. The purpose of this study is to conduct a cost-effectiveness analysis to identify the most cost-effective approach to deploying implementation strategies to enhance the uptake of Life Goals, a mental health EBP.
Methods
We used data from a previously conducted randomized trial to compare the cost-effectiveness of different augmentations to Replicating Effective Programs (REP) combined with external and/or internal facilitation to enhance uptake of Life Goals. REP is a low-level strategy that includes EBP packaging, training, and technical assistance. External facilitation (EF) involves external expert support, and internal facilitation (IF) augments EF with protected time for internal staff to support EBP implementation. We developed a decision tree to assess 1-year costs and outcomes for four implementation strategies: 1) REP only, 2) REP + EF 3) REP + EF add IF if necessary, 4) REP + EF/IF. The analyses used a 1-year time horizon and assumes a health payer perspective. Our outcome was quality-adjusted life years (QALYs). The economic outcome was the incremental cost-effectiveness ratio (ICER). We conducted deterministic and probabilistic sensitivity analysis (PSA).
Results
Our results indicate that REP + EF add IF is the most cost-effective option with an ICER of $593/QALY. The REP + EF/IF and REP + EF only conditions are dominated. One-way sensitivity analyses indicate that results are sensitive to utilities for REP + EF and REP + EF add IF. The PSA results indicate that REP + EF, add IF is the optimal strategy in 30% of iterations at the threshold of $100,000/QALY.
Conclusions
Our results suggest that the most cost-effective implementation support begins with a less intensive, less costly strategy initially and increases as needed to enhance EBP uptake. Using this approach, implementation support resources can be judiciously allocated to those clinics that would most benefit. Our results were not robust to changes in the utility measure. Further research is needed that incorporates robust and relevant utilities in implementation research to identify the most cost-effective strategies. This research advances economic evaluation of implementation by assessing costs and utilities across multiple implementation strategy combinations.
Trial registration:
ClinicalTrials.gov Identifier: NCT02151331, 05/30/2014
Vitamin D status in adults and children in Transcarpathia, Ukraine
Authors: Shchubelka Khrystyna 
Published: July 2020

Abstract
Background: Vitamin D deficiency is a global health problem, it is assessed by measuring serum 25(OH)D, nevertheless epidemiological data for many countries remains underreported.Objectives: To study the prevalence of vitamin D deficiency throughout the calendar year in a large cohort recruited in a multiethnic Transcarpathian region of Ukraine.Methods: In this retrospective study 25(OH)D serum concentration was measured during all 12 months of the years 2019 by electrochemoluminescent assay “Elecsys Vitamin D total”, Roche® (Germany) on the automatic analyzer Cobas e411 in 1,823 subjects, including both children and adults (1551 females (85.03%) and 273 males (14.97%)).Results: Mean 25(OH) D concentration in adults shows significantly lower levels compared to children (22.67±8.63 ng/ml vs. 26.00±10.72 ng/ml respectively, p=0.00001). Adult women expressed significantly lower mean year serum 25(OH) D concentration in comparison to men (22.29±8.46 ng/ml vs. 25.75±9.38 ng/ml respectively, p= 0.0000003). On the other hand, children did not show a significant difference between sexes (girls 24.98±10.38 ng/ml vs. boys 27.01±11.01 ng/ml, p=0.2003). In the winter months, 25(OH)D levels fell below 20 ng/ml in 51,74 % of adult population of Thranscarpathia, and in 12.91%, - below 12 ng/ml.Conclusions: The results of this study contradict the previously reported evaluations of the vitamin D levels in Ukraine assessed by measuring serum 25(OH)D. Specifically, only around half of the studied population is vitamin D deficient during “low” winter season. This study features the most representative sample size in Ukraine to date.
Systematic Review and Bibliometric Analysis of African Anesthesia and Critical Care Medicine Research Part II: A Scientometric Analysis of the 116 Most Cited Articles
Authors: Kanmounye Ulrick Sidney , Tochie Joel Noutakdie , Mbonda Aime , Solam Cynthia Wafo , Daya Leonid , Atem Thompson Hope , Nyalundja Arsène Daniel , Eyaman Daniel Cheryl 
Published: July 2020

Abstract
Background Scientometrics is used to assess the impact of research in several health fields, including Anesthesia and Critical Care Medicine. The purpose of this study was to define the landscape and key players of Anesthesia and Critical Care Medicine research in Africa.Methods The authors searched Web of Science from inception to May 4, 2020, for articles on and about Anesthesia and Critical Care Medicine in Africa with ≥ 2 citations. Quantitative (H-index) and qualitative (descriptive analysis of yearly publications and interpretation of document, co-authorship, author country, and keyword) bibliometric analyses were done.Results The search strategy returned 116 articles that had a median of 5 (IQR: 3-12) citations on Web of Science. The most frequent journals were Anesthesia and Analgesia (18, 15.5%), World Journal of Surgery (13, 11.2%), and South African Medical Journal (8, 6.9%). Most (74, 63.8%) articles were published on or after 2013, and seven authors had more than 1 article in the top 116 articles: Epiu I (3, 2.6%), Elobu AE (2, 1.7%), Fenton PM (2, 1.7%), Kibwana S (2, 1.7%), Rukewe A (2, 1.7%), Sama HD (2, 1.7%), and Zoumenou E (2, 1.7%). The bibliometric coupling analysis of documents highlighted 10 clusters with the most significant nodes being Biccard BM, 2018; Baker T, 2013; Llewellyn RL, 2009; Nigussie S, 2014; and Aziato L, 2015. Dubowitz G (5) and Ozgediz D (4) had the highest H-indices among the authors referenced by the most-cited African Anesthesia and Critical Care Medicine articles. The U.S.A. had the largest global node, while South Africa and Uganda had the largest African nodes. The most prominent keywords were anesthesia, mortality, and surgery. Conclusion This study highlighted a decline in the number of top-cited African articles and the roles of the U.S.A, Southern African, and East African countries in scholarly output. Future studies should focus on understanding the time trends of the publications.
Atherogenic Index of Plasma is Associated with the Severity of Hidradenitis Suppurativa: A Case Control Study
Authors: Hernández José Luis , Baldeón Cristina , López-Sundh Ana Elísabet , Ocejo-Vinyals J Gonzalo , Blanco Ricardo , González-López Marcos Antonio 
Published: July 2020

Abstract
Background. Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with several comorbidities and vascular risk factors, such as dyslipidemia. The aim of the present study was to assess the possible associations between the lipid profile and atherogenic indexes and the severity of HS. Methods. This case-control study enrolled 78 HS patients and 62 healthy controls. Classic lipid profile and lipoprotein ratios, including the atherogenic index of plasma (AIP) (log10[triglycerides/HDL-c]) were evaluated. Severity of HS was measured by the HS Physician Global Assessment (PGA). Results. HS-patients had lower serum total cholesterol and HDL-c levels and higher AIP than the control group. AIP was positively correlated to BMI, waist perimeter, systolic and diastolic blood pressure, LDL-c, triglycerides, non-HDL-C, ApoB, HOMA and hs-CRP and negatively to HDL-c and ApoA1. For the overall lipid profile, only AIP was related to a more severe HS (PGA≥3) after controlling for age, sex, BMI, insulin resistance (IR), active smoking and statin use (r=0.268; p=0.023). Multivariable logistic regression adjusted for age, sex, BMI, IR, smoking status and statin use, showed that AIP≥0.5 was significantly associated with the severity of HS (OR, 4.38; CI 95%, 1.09-17.50; p=0.037). Conclusions. In conclusion, our results showed that AIP was significantly and independently associated with HS severity.