bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Vitamin E and the Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study
Authors: Song Yun , Li Jingyi , Liu Lishun , Xu Richard , Zhou Ziyi , Xu Benjamin , Lin Tengfei , Chen Ping , Li Huan , Li Youbao , Liu Chengzhang , Huang Xiao , Wang Binyan , Zhang Yan , Li Jianping , Huo Yong , Ren Fazheng , Xu Xiping , Zhang Hao , Qin Xianhui 
Published: November 2021

Background: The association between plasma vitamin E levels and first stroke risk in men and women remains unclear.Objective: We aimed to examine the prospective association between plasma vitamin E and first stroke, and evaluate the effect modifiers for the association, among hypertensive patients.Design: The study sample was drawn from the China Stroke Primary Prevention Trial (CSPPT), which randomized a total of 20,702 hypertensive patients to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. This nested case-control study, including 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site, was conducted after the completion of the CSPPT.Results: The median follow-up duration was 4.5 years. Among men, a significantly higher risk of first stroke (adjusted OR, 1.67; 95%CI: 1.01, 2.77) was found for those with plasma vitamin E ≥7.1 μg/mL (≥quartile 1) compared with those with plasma vitamin E &lt; 7.1 μg/mL. Subgroup analyses further showed that the association between vitamin E (≥7.1 vs. &lt;7.1 μg/mL) and first stroke in men was significantly stronger in non-drinkers (adjusted OR, 2.64; 95%CI: 1.41, 4.96), compared to current drinkers (adjusted OR, 0.84; 95% CI: 0.43, 1.66, P-interaction = 0.008). However, there was no significant association between plasma vitamin E and first stroke in women (P-interaction between sex and plasma vitamin E = 0.048).Conclusions: Among Chinese hypertensive patients, there was a statistically significant positive association between baseline plasma vitamin E and the risk of first stroke in men, but not in women.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT00794885, Identifier: NCT00794885.
Dietary Intake and Biomarkers of α-Linolenic Acid and Mortality: A Meta-Analysis of Prospective Cohort Studies
Authors: Chen Li-Hua , Hu Qingjing , Li Guijie , Zhang Li , Qin Li-Qiang , Zuo Hui , Xu Guangfei 
Published: November 2021

Background: The association between α-linolenic acid (ALA) and mortality is inconsistent and has not been summarized systematically.Objective: The purpose was to conduct a meta-analysis that synthesized the results of prospective cohort studies to investigate associations between ALA intake and mortality.Methods: We conducted a comprehensive search on PubMed, Embase, and Web of Science databases on May 1, 2021, for relevant prospective cohort studies which reported associations of ALA (assessed by dietary surveys and/or ALA concentrations in body tissues) with mortality from all-cause, cardiovascular disease (CVD), and other diseases. Multivariable-adjusted relative risks (RRs) were pooled by a random or fixed-effects model.Results: A total of 34 prospective cohort studies, of which 17 reported dietary ALA intake, 14 for ALA biomarkers, and the remaining 3 reported both of intake and biomarkers. The studies included 6,58,634 participants, and deaths were classified into all-cause mortality (56,898), CVD mortality (19,123), and other diseases mortality (19,061). Pooled RRs of ALA intake were 0.93 (95% CI: 0.86, 1.01, I2 = 71.2%) for all-cause mortality, 0.90 (95% CI: 0.83, 0.98, I2 = 22.1%) for CVD mortality, and 0.94 (95% CI: 0.83, 1.06, I2 = 73.3%) for other diseases mortality. The two-stage random-effects dose-response analysis showed a linear relationship between dietary ALA intake and CVD-mortality and each 0.5% energy increment of ALA intake was associated with a 5% lower risk of CVD-mortality (RR: 0.95; 95% CI: 0.90, 1.00). Pooled RRs per SD increment of ALA biomarkers were 0.99 (95% CI: 0.96, 1.01, I2 = 27%) for all-cause mortality, 1.00 (95% CI: 0.98, 1.03, I2 = 0%) for CVD mortality and 0.98 (95% CI: 0.95, 1.01, I2 = 0%) for other diseases mortality.Conclusions: This meta-analysis summarizing the available prospective cohort studies indicated that ALA intake was associated with reduced risk of mortality, especially CVD mortality. Our findings suggest that ALA consumption may be beneficial for death prevention. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO; identifier: CRD42021264532.
Assessment and Prognostic Value of Immediate Changes in Post-Ablation Intratumor Density Heterogeneity of Pulmonary Tumors via Radiomics-Based Computed Tomography Features
Authors: Liu Bo , Li Chunhai , Sun Xiaorong , Zhou Wei , Sun Jing , Liu Hong , Li Shuying , Jia Haipeng , Xing Ligang , Dong Xinzhe 
Published: November 2021

ObjectivesTo retrospectively observe the instantaneous changes in intratumor density heterogeneity after microwave ablation (MWA) of lung tumors and to determine their prognostic value in predicting treatment response and local tumor progression (LTP).MethodsPre- and post-MWA computed tomography (CT) images of 50 patients (37-males; 13-females; mean-age 65.9 ± 9.7y, 39 primary and 11 metastasis) were analyzed to evaluate changes in intratumor density. Global, regional, and local scale radiomics features were extracted to assess intratumor density heterogeneity. In four to six weeks, chest enhanced CT was used as the baseline evaluation of treatment response. The correlations between the parametric variation immediately after ablation and the visual score of ablation response (Rvisu) were analyzed by nonparametric Spearman correlation analysis. The 1-year LTP discrimination power was assessed using the area under the receiver operating characteristic (ROC) curves. A Cox proportional hazards regression model was used to identify the independent prognostic features.ResultsAlthough no significant volume changes were observed after ablation, the radiomics parameters changed in different directions and degrees. The mean intensity value from baseline CT image was 30.3 ± 23.2, and the post-MWA CT image was -60.9 ± 89.8. The ratio of values change was then calculated by a unified formulation. The largest increase (522.3%) was observed for cluster prominence, while the mean CT value showed the largest decline (321.4%). The pulmonary tumors had a mean diameter of 3.4 ± 0.8 cm. Complete ablation was documented in 36 patients. Significant correlations were observed between Rvisu and quantitative features. The highest correlations were observed for changes in local features after MWA, with r ranging from 0.594 to 0.782. LTP developed in 22 patients. The Cox regression model revealed Δcontrast% and response score as independent predictors (Δcontrast%: odds ratio [OR]=5.61, p=0.001; Rvisu: OR=1.73, p=0019). ROC curve analysis showed that Δcontrast% was a better predictor of 1-year LTP. with higher sensitivity (83.5% vs. 71.2%) and specificity (87.1% vs. 76.8%) than those for Rvisu.ConclusionsThe changes in intratumor density heterogeneity after MWA could be characterized by analysis of radiomics features. Real-time density changes could predict treatment response and LTP in patients with pulmonary tumors earlier, especially for tumors with larger diameters.
Intertumoural Heterogeneity and Branch Evolution of Synchronous Multiple Primary Lung Adenocarcinomas by Next-Generation Sequencing Analysis
Authors: Zhang Qinleng , Jia Hui , Wang Zhendan , Hao Shaoyu , Huang Haiyan , Yang Airong , Han Lu , Song Pingping 
Published: November 2021

ObjectivesMultiple primary lung cancers (MPLCs) are an increasingly well-known clinical phenomenon, but there is a lack of high-level evidence for their optimal clinical diagnosis and therapeutic approaches. Thus, we analysed genetic variation to determine the intertumoural heterogeneity and branch evolution of synchronous multiple primary lung adenocarcinomas.MethodsWe performed multiplex mutational sequencing on 93 synchronous multiple primary lung adenocarcinoma lesions from 42 patients who underwent surgical resection.ResultsThe high discordance rate of mutation was 92.9% (n=39) between tumours in individual patients. EGFR, TP53 and KRAS mutations were detected in 57 (61.3%), 19 (20.4%) and 11 (11.8%) of the 93 tumours, respectively. 16 cases of multiple primary lung adenocarcinomas simultaneously harboured EGFR mutations and TP53 mutations. Matching mutations between paired tumours were observed in 1 (2.4%) patient for P20. The genotypes were all EGFR L858R mutations, but the pathological type of P20T1 was lepidic predominant, and P20T2 was adenocarcinoma in situ. In the phylogenetic tree, genetic variations were divided into trunk, shared and branch subtypes. Branch mutations accounted for 91.09% of variations in sMPLA, while the ratio of trunk (4.95%) and shared (3.96%) variations was significantly lower.ConclusionsRemarkable intertumoural heterogeneity and frequent branch mutations were found in synchronous multiple primary lung adenocarcinomas.
Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008–2015)
Authors: Sabaté M. , Vidal X. , Ballarin E. , Rottenkolber M. , Schmiedl S. , Grave B. , Huerta C. , Martin-Merino E. , Montero D. , Leon-Muñoz L. M. , Gasse C. , Moore N. , Droz C. , Lassalle R. , Aakjær M. , Andersen M. , De Bruin M. L. , Souverein P. , Klungel O. H. , Gardarsdottir H. , Ibáñez L. 
Published: November 2021

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries.Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008–2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases.Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases.Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).
Evaluation of Efficacy and Safety for Kanglaite Injection in the Control of the Malignant Pleural Effusions via Thoracic Perfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Guanghui , Wang Xinmiao , Li Jie , Zhang Ying , Gao Ruike , Zhang Xiaoxiao , Xu Bowen , Hu Jiaqi , Dai Minghao , Chen Jiayang 
Published: November 2021

Background: Kanglaite injection (KLTI) is a traditional Chinese medicine (TCM) preparation with anti-tumor activity, which has been used to treat malignant tumors in China. The purpose of this study was to evaluate the efficacy and safety of intrapleural infusion with KLTI in the treatment of malignant pleural effusion (MPE).Methods: Randomized controlled trials (RCTs) on the efficacy and safety of intrathoracic infusion with KLTI in the treatment of MPE were searched from the PubMed, EMBASE, the Cochrane Library, CNKI, VIP, Wanfang and CBM databases. The primary outcome was objective remission rate (ORR). Secondary outcomes included quality of life (QOL) and incidence of adverse events (AEs). The Stata15.1 software and RevMan5.3 software were used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis.Results: This meta-analysis included 20 RCTs, involving 1,291 patients. The ORR of intrapleural infusion with KLTI + chemotherapy drugs in the treatment of MPE was higher than that of chemotherapy alone (RR) 1.23; 95%CI; 1.11–1.36, I2 = 0%, z = 3.876, p = 0.000]. When KLTI is combined with cisplatin or KLTI 200 ml is used in every time, it is more advantageous to improve ORR. Moreover, compared with intrapleural infusion of chemotherapy drugs alone, KLTI combined with chemotherapy drugs significantly improved the QOL of patients with MPE (RR 1.28; 95%CI; 1.70–1.53, I2 = 0%, z = 2.70, p = 0.007). In addition, the participation of KLTI reduced the gastrointestinal reaction (RR 0.79; 95% CI; 0.66–0.96; I2 = 0%, z = 2.37, p = 0.018) and renal damage (RR 0.468; 95% CI; 0.23–0.945, I2 = 0%, z = 2.11, p = 0.035) caused by chemotherapy drugs, but did not increase other adverse reactions (p &gt; 0.05).Conclusion: The efficacy and safety of traditional chemotherapy drugs plus KLTI was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that KLTI can be used to treat MPE. However, a more rigorous RCT should be designed and completed before it is widely recommended.
XPC Protein Improves Lung Adenocarcinoma Prognosis by Inhibiting Lung Cancer Cell Stemness
Authors: Wang Weiyu , Ma Shengyao , Ding Zhenyu , Yang Yang , Wang Huaijie , Yang Kunning , Cai Xiaoshan , Li Hanyue , Gao Zhiqin , Qu Meihua 
Published: November 2021

Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients.Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers.Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (PXPC &lt; 0.0001, PCD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities.Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.
Prevalence of Antibiotic Purchase Online and Associated Factors Among Chinese Residents: A Nationwide Community Survey of 2019
Authors: Sun Na , Gong Yanhong , Liu Jiaming , Wu Jianxiong , An Rongrong , Dong Yue , Zhu Yi , Mu Ketao , Zhang Guopeng , Yin Xiaoxv 
Published: November 2021

Introduction: Online sales of antibiotics have increased public access to these medicines. This study aimed to analyze the online antibiotic purchase behavior of the Chinese residents and identify its associated factors.Methods: We conducted a nationwide cross-sectional online survey among Chinese community residents from January 20 to February 28, 2019. A structured questionnaire was used to collect data on their sociodemographic characteristics, health-related variables, and the online antibiotic purchase behavior in the past 3 months. Descriptive statistics and logistic regression analyses were used. The statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.).Results: A total of 101,120 respondents were included in the analysis. The weighted prevalence of antibiotic purchase online was 3.71% (95% CI, 3.53–3.88%). Residents who purchased antibiotics online were more likely to be older (age≥65 years), be a male, live in rural areas, have a higher education level, report an excellent economic status, suffer from chronic diseases, and search for health information on the internet.Conclusion: Numerous residents had purchased antibiotics online in the past 3 months throughout China. We should pay more attention to this behavior. There is a need to strengthen regulation of antibiotic sales online and improve public education on antibiotic purchase online. More comprehensive information on antibiotic purchase online as well as the advantages and disadvantages of online sales of antibiotics should be investigated in the future studies.
Pharmacokinetics and Disposition of Heparin-Binding Growth Factor Midkine Antisense Oligonucleotide Nanoliposomes in Experimental Animal Species and Prediction of Human Pharmacokinetics Using a Physiologically Based Pharmacokinetic Model
Authors: Bai Haihong , Cheng Yuanguo , Che Jinjing 
Published: November 2021

Encapsulating the antisense oligonucleotide drug MK-ASODN with nanoliposomes greatly improved its potency and targeting to the heparin-binding growth factor midkine. The disposition and pharmacokinetic (PK) parameters of MK-ASODN nanoliposomes were studied in monkeys and rats, and the human PK parameters were predicted based on preclinical data using a physiologically based pharmacokinetic (PBPK) model. Following intravenous injection, the drug plasma concentration rapidly declined in a multiexponential manner, and the drug was rapidly transferred to tissues from the circulation. The terminal t1/2 in plasma was clearly longer than that of the unmodified antisense nucleic acid drug. According to the AUC,MK-ASODN nanoliposomes were mainly distributed in the kidney, spleen, and liver. . MK-ASODN nanoliposomes were highly plasma protein bound, limiting their urinary excretion. Very little MK-ASODN nanoliposomes were detected in urine or feces. The plasma disposition of MK-ASODN nanoliposomes appeared nonlinear over the studied dose range of 11.5–46 mg kg−1. The monkey PBPK model of MK-ASODN nanoliposomes was well established and successfully extrapolated to predict MK-ASODN nanoliposome PK in humans. These disposition and PK data support further development in phase I clinical studies.
Development and Benchmarking of a Monte Carlo Dose Engine for Proton Radiation Therapy
Authors: Lysakovski Peter , Ferrari Alfredo , Tessonnier Thomas , Besuglow Judith , Kopp Benedikt , Mein Stewart , Haberer Thomas , Debus Jürgen , Mairani Andrea 
Published: November 2021

Dose calculation algorithms based on Monte Carlo (MC) simulations play a crucial role in radiotherapy. Here, the development and benchmarking of a novel MC dose engine, MonteRay, is presented for proton therapy aiming to support clinical activity at the Heidelberg Ion Beam Therapy center (HIT) and the development of MRI (magnetic resonance imaging)-guided particle therapy. Comparisons against dosimetric data and gold standard MC FLUKA calculations at different levels of complexity, ranging from single pencil beams in water to patient plans, showed high levels of agreement, validating the physical approach implemented in the dose engine. Additionally, MonteRay has been found to match satisfactorily to FLUKA dose predictions in magnetic fields both in homogeneous and heterogeneous scenarios advocating its use for future MRI-guided proton therapy applications. Benchmarked on 150 MeV protons transported on a 2 × 2 × 2 mm3 grid, MonteRay achieved a high computational throughput and was able to simulate the histories of more than 30,000 primary protons per second on a single CPU core.
Exploring Optimality of Piecewise Polynomial Interpolation Functions for Lung Field Modeling in 2D Chest X-Ray Images
Authors: Kumar Rohit , Bhattacharya Subrata , Murmu Govind 
Published: November 2021

In this paper, a landmark based approach, using five different interpolating polynomials (linear, cubic convolution, cubic spline, PCHIP, and Makima) for modeling of lung field region in 2D chest X-ray images have been presented. Japanese Society of Radiological Technology (JSRT) database which is publicly available has been used for evaluation of the proposed method. Selected radiographs are anatomically landmarked using 17 and 16 anatomical landmark points to represent left and right lung field regions, respectively. Local, piecewise polynomial interpolation is then employed to create additional semilandmark points to form the lung contour. Jaccard similarity coefficients and Dice coefficients have been used to find accuracy of the modeled shape through comparison with the prepared ground truth. With the optimality condition of three intermediate semilandmark points, PCHIP interpolation method with an execution time of 5.04873 s is found to be the most promising candidate for lung field modeling with an average Dice coefficient (DC) of 98.20 and 98.54% (for the left and right lung field, respectively) and with the average Jaccard similarity coefficient (JSC) of 96.47 and 97.13% for these two lung field regions. While performance of Makima and cubic convolution is close to the PCHIP with the same optimality condition, i.e., three intermediate semilandmark points, the optimality condition for the cubic spline method is of at least seven intermediate semilandmark points which, however, does not result in better performance in terms of accuracy or execution time.