bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative identification of clinicopathological prognostic factors for relapse-free survival in clinical N1 non-small cell lung cancer: A retrospective single center-based study
Authors: Aragaki Masato , Kato Tatsuya , Fujiwara-Kuroda Aki , Hida Yasuhiro , Kaga Kichizo , Wakasa Satoru 
Published: May 2020

Abstract
Background
Given the difficulty of preoperative diagnosis of lymph node metastasis, patients with Stage I–III non-small cell lung cancer (NSCLC) are likely to be included in the clinical N1 (cN1) group. However, better treatment options may be selected through further stratification. This study aimed to identify preoperative clinicopathological prognostic and stratification factors for patients with cN1 NSCLC.
Methods
This retrospective evaluated 60 patients diagnosed with NSCLC from 2004 to 2014. Clinical nodal status had been evaluated using routine chest computed tomography (CT) and/or positron emission tomography (PET). To avoid the bias of the fluorodeoxyglucose uptake values based on inter-institution or inter-model differences, we historically used only two different models for PET instruments (one PET and one PET/CT). Relapse-free survival (RFS) and overall survival (OS) were the primary study outcomes. The maximum standardized uptake value (SUVmax) was calculated for the tumors and categorized as low or high based on the median value. Patient sex, age, histology, tumor size, and tumor markers were also assessed.
Results
Poor OS was associated with older age (P = 0.0159) and high SUVmax values (P = 0.0142). Poor RFS was associated with positive carcinoembryonic antigen (CEA) expression (P = 0.0035) and high SUVmax values (P = 0.015). Multivariate analyses confirmed that poor OS was independently predicted by older age (hazard ratio [HR] = 2.751, confidence interval [CI]: 1.300-5.822; P = 0.0081) and high SUVmax values (HR = 5.121, 95% CI: 1.759–14.910; P = 0.0027). Furthermore, poor RFS was independently predicted by positive CEA expression (HR = 2.376, 95% CI: 1.056–5.348; P = 0.0366) and high SUVmax values (HR = 2.789, 95% CI: 1.042–7.458; P = 0.0410). The primary tumor’s SUVmax value was also an independent prognostic factor for both OS and RFS.
Conclusions
For patients with cN1 NSCLC, preoperative prognosis and stratification might be performed based on the CEA expression, age, and the primary tumor’s SUVmax. In particular, regarding SUVmax, minimizing the bias between facilities and models could lead to a more accurate prognosis.
Advance Directives and End-of-Life Care: Knowledge and Preferences Among Brain Cancer Patients in Anhui,China
Authors: Wang Yi Xin , Zhang Yong Kang , Hong Yang , Zeng Ping , Hu Zong Tao , Xu Xiu Li , Wang Hong Zhi 
Published: May 2020

Abstract
Background: Advance directives and end-of-life care has not been well acknowledged among tumor patients in China Mainland,especially in brain tumor patients who may have unconsciousness at the early stage of illness.Thus,this study aims to clarify the knowledge and preferences of advance directives and end-of-life care of brain tumor patients and to investigate the predictors of patients’ preferences.Methods: This was a population-based cross-sectional survey conducted by a face-to-face interviews. Information on sociodemographic factors, brain tumor diseases, knowledge and preferences of advance decisions, end-of-life care were collected.Results: 88.61% participants had never heard of AD but 65.18% would like to make an AD. Knowledge of AD, receiving the treatment of surgery or radiotherapy, less than 70 years old, male, educational qualification of college or more, without children, medical insurance for non-working or working urban residents, pay their medical expenses by themselves as predictors of preferring to make an AD .79.43% participants would like to discuss end-of-life arrangements with medical staff and 63.29% were willing to receive end-of-life care though it cannot delay death. 65.82% brain tumor patients wanted resuscitation, as high as 45.45% thought they didn’t need life support if they were in a persistent vegetative state. Brain primary tumor, less than 70 years old, male, educational qualification of junior middle school or less, have children, new rural cooperative medical insurance, pay their medical expenses by their children or spouse as predictors of choosing end of life care though it cannot delay death.Conclusions: Advance directives and end-of-life care has not been well acknowledged among brain tumor patients in China Mainland. More efforts should be encouraged in the patients with primary brain tumors, who undergoing surgery and radiotherapy and low socioeconomic status, and an appropriate decision-making timing with a technology-based communication is encouraged in promoting advance directives in Chinese brain tumor patients.Key PointsAdvance directives and end-of-life care has not been systematically applied to Chinese brain cancer patients and the knowledge of advance directives is limited.More efforts should be made for the participants with primary brain tumors, who undergoing surgery and radiotherapy and low socioeconomic status.An appropriate decision-making timing with a technology-based communication is encouraged in promoting advance directives in Chinese brain tumor patients.
Cost-Effectiveness Analysis of Proton Beam Therapy for Treatment Decision Making in Paranasal Sinus and Nasal Cavity Cancers in China
Authors: Li Guo , Qiu Bo , Huang Yi-Xiang , Doyen Jerome , Bondiau Pierre-Yves , Benezery Karen , Xia Yun-Fei , Qian Chao-Nan 
Published: May 2020

Abstract
Background: Cost-effectiveness is a pivotal consideration for clinical decision making of advanced cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings.Methods:A 3-state Markov modelwas designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective scenarios of IMPT were further identified by one-way sensitivity analyses and stratified analyses were performed for different age levels. The outcome measure of the model was the incremental cost-effectiveness ratio (ICER). A strategy was defined as cost-effective if the ICER was below the societal willingness-to-pay (WTP) threshold of China (30,828 US dollars ($) / quality-adjusted life year (QALY)).Results: IMPT was identified as being cost-effective for the base case at the WTP of China, providing an extra 1.65 QALYs at an additional cost of $38,928.7 compared with IMRT, and had an ICER of $23,611.2 / QALY. Of note, cost-effective scenarios of IMPT only existed in the following independent conditions: probability of IMPT eradicating cancer ≥ 0.867; probability of IMRT eradicating cancer ≤ 0.764; or cost of IMPT ≤ $52,163.9. Stratified analyses for different age levels demonstrated that IMPT was more cost-effective in younger patients than older patients, and was cost-effective only in patients ≤ 56-year-old.Conclusions: Despite initially regarded as bearing high treatment cost, IMPT could still be cost-effective for patients with paranasal sinus and nasal cavity cancers in China. The tumor control superiority of IMPT over IMRT and the patient’s age should be the principal considerations for clinical decision of prescribing this new irradiation technique.
Radiobiological Model-based approach to determine the potential of dose-escalated robust intensity-modulated proton radiotherapy in reducing gastrointestinal toxicity in the treatment of locally advanced unresectable pancreatic cancer of the head.
Authors: Raturi Vijay Parshuram , Hojo Hidehiro , Hotta Kenji , Baba Hiromi , Takehashi Ryo , Rachi Toshiya , Nakamura Naoki , Zenda Sadamoto , Motegi Atsushi , Tachibana Hidenobu , Ariji Takaki , Motegi kana , Nakamura Masaki , Okumura Masayuki , Hirano Yasuhiro , Akimoto Tetsuo 
Published: May 2020

Abstract
Background: The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model. Methods: For 9 patients, IMRT was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (StoDuo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison. Result: The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs . 13.97%, P = 0.007), duodenum (1.87% vs . 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT – ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to <10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCP ro-IMPT /NTCP IMRT ) reduction was noted (0.16-0.81) for all GI-OARs except for duodenum (>1) with endpoint grade ≥3 GI toxicity (using parameters from Holyoake et al .). Conclusion: With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.
PDGF-BB and IL-4 co-overexpression is a potential strategy to enhance mesenchymal stem cell-based bone regeneration
Authors: Zhang Ning , Lo Chi-Wen , Utsunomiya Takeshi , Maruyama Masahiro , Huang Ejun , Gao Qi , Yao Zhenyu , Goodman Stuart B. 
Published: May 2020

Abstract
Background
Mesenchymal stem cell (MSC)-based therapy has the potential for immunomodulation and enhancement of tissue regeneration. Genetically modified (GM) MSCs that over-express specific cytokines, growth factors or chemokines have shown great promise in pre-clinical studies. In this regard, the anti-inflammatory cytokine Interleukin (IL)-4 converts pro-inflammatory M1 macrophages into an anti-inflammatory M2 phenotype; M2 macrophages could potentially enhance osteogenesis by MSC lineage cells. However, IL-4 inhibits osteogenesis during the acute inflammatory period. Platelet-derived growth factor (PDGF)-BB has been shown to enhance osteogenesis of MSCs with a dose-dependent effect.
Methods
In this study, we generated a lentiviral vector that produces PDGF-BB under a weak promoter (phosphoglycerate kinase, PGK) and lentiviral vector producing IL-4 under a strong promoter (cytomegalovirus, CMV). We infected the MSCs with the PDGF-BB and IL-4-producing lentiviral vectors separately or in combination to investigate protein expression, cell proliferation and viability as well as the capability for osteogenesis.
Results
Co-overexpression of PDGF-BB and IL-4 was observed in the co-infected MSCs and shown to enhance cell proliferation and viability, and osteogenesis compared to IL-4 overexpressing MSCs alone.
Conclusions
Thus, overexpression of both PDGF-BB and IL-4 may be a potential strategy to facilitate osteogenesis in scenarios of both acute and chronic inflammation.
High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction
Authors: Zhang Yue , Ding Xiaosong , Hua Bing , Liu Qingbo , Gao Hui , Chen Hui , Zhao Xue-Qiao , Li Weiping , li Hongwei 
Published: May 2020

Abstract
Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. Clinical characteristics,biochemical parameters, and the incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2]. Results Compared with the TyG index<8.88 group, the TyG index≥8.88 group had significantly higher incidences of non-fatal MI, revascularization, cardiac rehospitalization and composite MACEs. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), P=0.010], cardiac death [HR (95%CI): 1.68 (1.19,2.38), P=0.004], revascularization [HR (95%CI): 1.50 (1.16,1.94), P=0.002], cardiac rehospitalization [HR (95%CI): 1.25 (1.05,1.49), P=0.012], and composite MACEs [HR (95%CI): 1.19 (1.01,1.41), P=0.046] in patients with AMI. The independent predictive effect of TyG index on all-cause death and cardiac death was mainly reflected in the subgroups of male gender, body mass index ≥25kg/m 2 , smoker, diabetes mellitus, estimated glomerular filtration rate (eGFR) ≥60ml/min/1.73m 2 , high-density lipoprotein cholesterol ≥1.01mmol/L and left ventricular ejection fraction (LVEF) ≥0.50. The results also revealed that diabetes mellitus, previous AMI, eGFR, LVEF, and multi-vessel/left main coronary artery lesions were independent predictors of MACEs in patients with AMI (all P<0.05). Conclusions High TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.
Head &amp; Neck Acinar Cell Carcinoma: A Population-Based Study Using the Seer Registry
Authors: Yibulayin Feiluore , Wang Meng , Lu Meng-meng , Luo Yuan , Liu Hui , Feng Lei , Yang Zhi-cheng , Wushou Alimujiang 
Published: May 2020

Abstract
Background:to explorethe clinicopathologic characteristics, treatment and prognostic factors of head and neck acinar cell carcinoma (HNACC) comprehensively.Methods:A population-based study was conductedusing data from the Surveillance, Epidemiology, and End Results database (1975- 2016). Overall survival (OS) and HNACC-specific survival of patients with different clinicopathologic variables were compared using the Kaplan-Meier method and Cox multivariate regression.Results:A total of 2624 primary HNACC cases (1052 males, 1572 females) were identified. There was a significant difference in gender distribution. Among the total cohort, 2416 cases originated from salivary glands, including 2325 parotid gland ACC cases. Regardless of confounding factors, the 10-year and 20-year disease-specific survival (DSS) was 93.6% and 90%, respectively. Surgery was favourably associated with better DSS and OS [HR= 0.13, P = 0.0092 andHR = 0.23, P = 0.0203]. Gender was the only demographic independent prognostic factor for both DSS and OS [male vs female, HR = 3.3, P = 0.0028 for DSS; HR = 2.44, P = 0.0376 for OS]. Higher pathological grade was adversely associated with DSS and OS [Grade II, HR= 4.03, P = 0.0444; Grade III + IV, HR = 35.64, P = 0.0000 for DSS; Grade III + IV, HR = 4.49, P = 0.0000 for OS, Grade I as reference]. In addition, TNM/AJCC stage was commonly associated with prognosis.Conclusion:Surgerywasthe only favourable prognostic indicator for both DSS and OS. Gender, age, pathological differentiation and TNM/AJCC stage were independent prognostic factors for survival.
Genome-scale metabolic modelling underscores the potential of Cutaneotrichosporon oleaginosus ATCC 20509 as a cell factory for biofuel production
Authors: Pham Nhung TT , Reijnders Maarten , Suarez-Diez Maria , Nijsse Bart , Springer Jan , Eggink Gerrit , Schaap Peter 
Published: May 2020

Abstract
Background: Cutaneotrichosporon oleaginosus ATCC 20509 is a fast growing oleaginous basidiomycete yeast that is able to grow in a wide range of low-cost carbon sources including crude glycerol, a byproduct of biodiesel production. When glycerol is used as a carbon source, this yeast can accumulate more than 50% lipids (w/w) with high concentrations of mono-unsaturated fatty acids. Results: To increase our understanding of this yeast and to provide a knowledge base for further industrial use, a FAIR re-annotated genome was used to build a genome-scale, constraint-based metabolic model containing 1553 reactions involving 1373 metabolites in 11 compartments. A new description of the biomass synthesis reaction was introduced to account for massive lipid accumulation in conditions with high carbon to nitrogen (C/N) ratio in the media. This condition-speciﬁc biomass objective function is shown to better predict conditions with high lipid accumulation using glucose, fructose, sucrose, xylose, ethanol and glycerol as sole carbon source. Conclusion: Contributing to the economic viability of biodiesel as renewable fuel, C. oleaginosus ATCC 20509 can eﬀectively convert crude glycerol waste streams in lipids as a potential bioenergy source. Performance simulations are essential to identify optimal production conditions and to develop and ﬁne tune a cost-eﬀective production process. Our model suggests ATP-citrate lyase as a target for overexpression to further improve lipid production.
MELK inhibition effectively suppresses growth of glioblastoma and cancer stem-like cells by blocking AKT and FOXM1 pathways
Authors: Liu Xuejiao , Wang Jie , Wang Yifeng , Zhang Xu , Liu Guanzheng , Li Huan , Yu Jiefeng , Wu Runqiu , Gao Shangfeng , Liang Jun , Niu Mingshan , Yu Rutong 
Published: May 2020

Abstract
Background: Glioblastoma multiforme (GBM) is a devastating disease yet no effective drug treatment has been established to date. Glioblastoma stem-like cells (GSCs) are insensitive to treatment and may be one of the reasons for the relapse of GBM. Maternal embryonic leucine zipper kinase gene (MELK) plays an important role in the malignant proliferation and the maintenance of GSC stemness properties of GBM. However, the therapeutic effect of targeted inhibition of MELK on GBM remains unclear. Methods: This study analyzed the effect of a MELK oral inhibitor, OTSSP167, on GBM proliferation and the maintenance of GSC stemness. Results: OTSSP167 significantly inhibited cell proliferation, colony formation, invasion, and migration of GBM. OTSSP167 treatment reduced the expression of cell cycle G2/M phase-related proteins, Cyclin B1 and Cdc2, while up-regulation the expression of cell cycle inhibitor protein p21 and subsequently induced cell cycle arrest at the G2/M phase. OTSSP167 effectively prolonged the survival of tumor-bearing mice and inhibited tumor cell growth in an in vivo mouse model. It also reduced protein kinase B (Akt) phosphorylation by inhibiting MELK, thereby disrupting the proliferation and invasion of GBM cells. Furthermore, OTSSP167 inhibited the proliferation and neurosphere formation of GSCs by reducing forkhead box M1 (FOXM1) phosphorylation and transcriptional activity. Interestingly, the inhibitory effect of OTSSP167 on the proliferation of GSCs was 4-fold more effective than GBM cells. Conclusion: In conclusion, MELK inhibition suppresses the growth of GBM and GSCs by double-blocking AKT and FOXM1 signals. Targeted inhibition of MELK may thus be potentially used as a novel treatment for GBM.
Intravenous Bolus Fentanyl vs. Rectal Acetaminophen in Outcome and Quality of Anesthesia in Infants Undergoing Pyloromyotomy: A Randomized Clinical Trial
Authors: Sharabiani Behzad Aliakbari , Sheikhzadeh Daryosh , Akbari Sahar , Arjmand Nasim , Parsay Sina , hejazi Mahin Seyed 
Published: May 2020

Abstract
Background

Hypertrophic Pyloric Stenosis (HPS) is one of the most common diseases requiring surgery in infants. Regardless of recruited surgical reconstruction techniques, preoperative evaluation, using proper anesthesia induction, perioperative, and postoperative care are the main determining factors in the outcome of these patients. This study aimed to evaluate and compare the premedication with intravenous fentanyl versus rectal acetaminophen on the anesthesia-related outcome of patients.
Methods

In this double-blinded randomized clinical trial, 24 infants who were managed to underwent a pyloromyotomy surgery due to the HPS were enrolled. Patients then randomly allocated into two groups of Fentanyl (F) or Acetaminophen (A). Anesthesia procedure was initiated with premedication with midazolam (0.03 mg/kg) co-administrated with fentanyl (1 µg/kg) in group F, and rectal acetaminophen (40 mg/kg) administrated 20 minutes prior to midazolam (0.03 mg/kg) in group A individuals. All patients’ vital signs, the period of each step of anesthesia, and the incidence of apnea were measured and recorded.
Results

Although the time duration from anesthesia termination till extubation and the recovery time were relatively shorter among the patients of the acetaminophen group, there were no statistically significant differences between the two groups. Patients in the acetaminophen group showed a lower level of pain in all evaluated timelines than those who were treated with fentanyl (p < 0.05). There was no statistically significant difference between the apnea incidence in two groups.
Conclusion

The use of rectal acetaminophen in infants who are planning to undergo pyloromyotomy due to HPS offers a better treatment outcome than fentanyl.
Trial Registration:

This study was approved by the Ethics Committee of Tabriz University of Medical Sciences under the registry code of IR.TBZMED.REC.1397.511. It was also registered in Iranian Registry of Clinical Trials (IRCT). The trial’s registration number (TRN) is IRCT20180726040601N1 ‘retrospectively registered’