bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Postoperative Adjuvant Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients With Microscopic Portal Vein Invasion
Authors: Qiu Yiwen , Yang Yi , Wang Tao , Shen Shu , Wang Wentao 
Published: June 2022

BackgroundMicroscopic portal vein invasion (MPVI) strongly predicts poor prognosis in patients with hepatocellular carcinoma (HCC). This study aims to investigate the impact of MPVI on the efficacy of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE).MethodsFrom April 2014 to July 2019, a total of 512 HCC patients who underwent curative liver resection (LR) with microscopic vascular invasion (MVI) confirmed by histopathological examination were enrolled and divided into LR alone and PA-TACE groups. They were subsequently stratified into subgroups according to the presence of MPVI. Recurrence-free survival (RFS) and overall survival (OS) were compared using Kaplan–Meier curves and the log-rank test. The efficacy of PA-TACE was tested using univariate and multivariate Cox regression analyses. Sensitivity analysis was conducted after propensity score matching (PSM).ResultsAmong all patients, 165 (32.3%) patients underwent PA-TACE, and 196 (38.2%) patients presented MPVI. In the entire cohort, PA-TACE and the presence of MPVI were identified as independent predictors for RFS and OS (all p&lt;0.05). In the subgroup analysis, patients without MPVI who received PA-TACE had significantly better outcomes than those who underwent LR alone before and after PSM (all p&lt;0.05). For patients with MPVI, PA-TACE displayed no significant benefit in terms of improving either RFS or OS, which was consistent with the results from the PSM cohort.ConclusionAmong the HCC patients without MPVI who underwent curative liver resection, those who received PA-TACE had better RFS and OS outcomes than those who underwent LR alone. For patients with MPVI, PA-TACE had no significant effect on either RFS or OS outcomes.
Anti-Angiogenetic and Anti-Lymphangiogenic Effects of a Novel 2-Aminobenzimidazole Derivative, MFB
Authors: Hsu Ming-Jen , Chen Han-Kun , Chen Cheng-Yu , Lien Jin-Cherng , Gao Jing-Yan , Huang Yu-Han , Hsu Justin Bo-Kai , Lee Gilbert Aaron , Huang Shiu-Wen 
Published: June 2022

Background and PurposeBenzimidazoles have attracted much attention over the last few decades due to their broad-spectrum pharmacological properties. Increasing evidence is showing the potential use of benzimidazoles as anti-angiogenic agents, although the mechanisms that impact angiogenesis remain to be fully defined. In this study, we aim to investigate the anti-angiogenic mechanisms of MFB, a novel 2-aminobenzimidazole derivative, to develop a novel angiogenesis inhibitor.Experimental ApproachMTT, BrdU, migration and invasion assays, and immunoblotting were employed to examine MFB’s effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration, invasion, as well as signaling molecules activation. The anti-angiogenic effects of MFB were analyzed by tube formation, aorta ring sprouting, and matrigel plug assays. We also used a mouse model of lung metastasis to determine the MFB’s anti-metastatic effects.Key ResultsMFB suppressed cell proliferation, migration, invasion, and endothelial tube formation of VEGF-A-stimulated human umbilical vascular endothelial cells (HUVECs) or VEGF-C-stimulated lymphatic endothelial cells (LECs). MFB suppressed VEGF-A and VEGF-C signaling in HUVECs or LECs. In addition, MFB reduced VEGF-A- or tumor cells-induced neovascularization in vivo. MFB also diminished B16F10 melanoma lung metastasis. The molecular docking results further showed that MFB may bind to VEGFR-2 rather than VEGF-A with high affinity.Conclusions and ImplicationsThese observations indicated that MFB may target VEGF/VEGFR signaling to suppress angiogenesis and lymphangiogenesis. It also supports the role of MFB as a potential lead in developing novel agents for the treatment of angiogenesis- or lymphangiogenesis-associated diseases and cancer.
The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis
Authors: Lin Qi , Bao Jia-Hao , Xue Fei , Qin Jia-Jun , Chen Zhen , Chen Zhong-Rong , Li Chao , Yan Yi-Xuan , Fu Jin , Shen Zhao-Li , Chen Xian-Zhen 
Published: June 2022

BackgroundDespite improved overall survival outcomes, chemotherapy has brought concerns for heart disease–related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear.MethodsWe obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan–Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias.ResultsAA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736–0.83, P&lt;0.001). For competing risk regression analysis, the cumulative incidence of HDRD in non-chemotherapy exceeded HDRD in the chemotherapy group (P&lt;0.001) and multivariable analysis showed a lower HDRD risk in AA patients with chemotherapy (adjusted SHR=0.574, 95%CI=0.331–0.991, P=0.046). In the PSM-after cohort, there were no significant association between chemotherapy and the increased HDRD risk (adjusted SHR=0.595, 95%CI=0.316−1.122, P=0.11). Landmark analysis showed that AA patients who received chemotherapy had better heart disease–specific survival than those in the non-chemotherapy group (P=0.007) at the follow-up time points of 216 months. No difference was found when the follow-up time was more than 216 months.ConclusionAA patients with chemotherapy are associated with a lower risk of HDRD compared with those without chemotherapy. Our findings may help clinicians make a decision about the management of AA patients and provide new and important evidence for applying chemotherapy in AA patients as the first-line treatment. However, more research is needed to confirm these findings and investigate the correlation of the risk of HDRD with different chemotherapy drugs and doses.
Anti-Angiogenic Drugs Inhibit Interstitial Lung Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer
Authors: Wang Yanning , Gong Xiaoling , Hu Yuxuan , Yi Qing , Zhang Qianning , Miao Liyun , Zhou Yujie 
Published: June 2022

BackgroundInterstitial lung disease (ILD) is the most serious complication of chemotherapy in lung cancer patients with pre-existing ILD. The effect of anti-angiogenic drugs in lung cancer patients with ILD remains unclear. We examined the effect of anti-angiogenic drugs on reducing the risk of ILD progression in non-small cell lung cancer (NSCLC) patients receiving chemotherapy.MethodsWe analyzed the risk of ILD progression in 52 patients with advanced NSCLC with ILD who received first-line chemotherapy with (anti-angiogenic group, n = 22) and without (non-anti-angiogenic group, n = 30) anti-angiogenic drugs between August 2014 and January 2021.ResultsThe incidences of chemotherapy-related ILD progression were significantly lower in the anti-angiogenic than in the non-anti-angiogenic groups (0% vs. 20.0%, p = 0.033). However, there were no differences in other events as the competing risk factors of ILD progression between the two groups. The overall-cumulative incidence of ILD progression during the first-line and subsequent chemotherapy was 30.8% (16 of the 52). The median progression-free survival had no significant difference between the anti-angiogenic and the non-anti-angiogenic groups (10.3 vs. 8.1 months, p = 0.386).ConclusionsThe addition of anti-angiogenic drugs to chemotherapy regimens may reduce the risk of chemotherapy-related ILD progression in patients with NSCLC-ILD.
Urine Exosomal AMACR Is a Novel Biomarker for Prostate Cancer Detection at Initial Biopsy
Authors: Jin Xin , Ji Jin , Niu Decao , Yang Yuchen , Tao Shuchun , Wan Lilin , Xu Bin , Chen Shuqiu , Wang Fubo , Chen Ming 
Published: June 2022

ObjectivesThe aim of this study is to identify and validate urine exosomal AMACR (UE-A) as a novel biomarker to improve the detection of prostate cancer (PCa) and clinically significant PCa (Gleason score ≥ 7) at initial prostate biopsy.MethodsA total of 289 first-catch urine samples after the digital rectal exam (DRE) were collected from patients who underwent prostatic biopsy, and 17 patients were excluded due to incomplete clinical information. Urine exosomes were purified, and urinary exosomal AMACR (UE-A) was measured by enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of UE-A was evaluated by receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots.ResultsThe expression of AMACR in PCa and csPCa was significantly higher than that in BPH and non-aggressive (p &lt; 0.001). The UE-A presented good performance in distinguishing PCa from BPH or BPH plus non-significant PCa (nsPCa) from csPCa with an area under the ROC curve (AUC) of 0.832 and 0.78, respectively. The performance of UE-A was further validated in a multi-center cohort of patients with an AUC of 0.800 for detecting PCa and 0.749 for detecting csPCa. The clinical utility assessed by DCA showed that the benefit of patients using UE-A was superior to PSA, f/t PSA, and PSAD in both the training cohort and the validation cohort in terms of all threshold probabilities. Setting 95% sensitivity as the cutoff value, UE-A could avoid 27.57% of unnecessary biopsies, with only 4 (1.47%) csPCa patients missed.ConclusionsWe demonstrated the great performance of UE-A for the early diagnosis of PCa and csPCa. UE-A could be a novel non-invasive diagnostic biomarker to improve the detection of PCa and csPCa.
Efficacy and Safety of Conversion Therapy by Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis: A Prospective Phase II Study
Authors: Yang Zhong-Yin , Yuan Fei , Lu Sheng , Xu Wei , Wu Jun-Wei , Xi Wen-Qi , Shi Min , Wang Zhen-Qiang , Ni Zhen-Tian , He Chang-Yu , Yao Xue-Xin , Zheng Ya-Nan , Zhu Zheng-Lun , Liu Wen-Tao , Zhang Jun , Zhang Huan , Li Chen , Yan Chao , Yan Min , Zhu Zheng-Gang 
Published: June 2022

BackgroundNeoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients.MethodsEligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST).ResultsSixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery.ConclusionThe NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS.Clinical Trial Registrationhttp://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ (&lt;ChiCTR2200056029&gt;).
Myopia Control With Multifocal Lens in School-Aged Children: A Meta-Analysis
Authors: Chen Meilan , Xu Lu , Li Hongyang , Cai Fengping , Wang Hao , Hu Chun , Wu Yi 
Published: June 2022

BackgroundMyopia is one of the most common eye diseases in school-aged children. Multifocal lens (MFL) is one of the interventions that has being widely applied to control the progress of myopia. However, the treatment effects of MFLs in school-aged children require to be systematically evaluated.MethodsA systematic analysis on qualified randomized controlled trials (RCTs) in which MFLs were prescribed as the intervention and single-vision lenses (SVLs) as the control was conducted. The treatment effects referring to the mean differences in spherical equivalent refraction (SER) and axial length (AL) between MFLs and SVLs groups were analyzed.ResultsWith annual visit (3-years follow-up), the weighted mean differences (WMDs) in SER between MFLs and SVLs were 0.29 D (95% CI, 0.21 ∼ 0.37, p &lt; 0.00001), 0.46 D (95% CI, 0.32 ∼ 0.60, p &lt; 0.00001), and 0.64 D (95% CI, 0.40 ∼ 0.88, p &lt; 0.00001) at the first, second, and third year; in AL were −0.12 mm (95% CI, −0.14 ∼−0.11, p &lt; 0.00001), −0.19 mm (95% CI, −0.22 ∼−0.16, p &lt; 0.00001), and −0.26 mm (95% CI, −0.31 ∼−0.21, p &lt; 0.00001) at the first, second, and third year. With 6-months interval trials (2-years follow-up), the WMDs in SER from MFLs were 0.14 D (95% CI, 0.08 ∼ 0.20, p &lt; 0.0001), 0.19 D (95% CI, 0.11 ∼ 0.28, p &lt; 0.0001), 0.24 D (95% CI, 0.16 ∼ 0.33, p &lt; 0.0001), 0.31 D (95% CI, 0.18 ∼ 0.44, p &lt; 0.0001) and in AL from MFLs were −0.08 mm (95% CI, −0.09 ∼−0.07, p &lt; 0.00001), −0.10 mm (95% CI, −0.12 ∼−0.09, p &lt; 0.00001), −0.14 mm (95% CI, −0.17 ∼−0.11, p &lt; 0.00001), and −0.18 mm (95% CI, −0.22 ∼−0.14, p &lt; 0.00001) slower comparing with SVLs at follow up of 6, 12, 18, and 24 months, respectively.ConclusionThe treatment effects of MFLs to slow down the myopic progress are positive in both 6-months and annual-visit trials and which could be sustained till 36 months. While a slight weaker treatment effect was observed after the first visit in 6-months visit, a slight rebound was observed at the following visit points. Furthermore, the treatment effects in annual visit are more profound than 6-months visit at almost all stages especially in SER. Our analysis encourages the MFLs users to maintain a long-term treatment with annual visit.
A Phase I, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Tolerance of Oil Palm Phenolics (OPP) in Healthy Volunteers
Authors: Muhammad Ismail Tadj Nur Balqis , Ibrahim Nurul ‘Izzah , Haji Mohd Saad Qodriyah , Tg Abu Bakar Sidik Tg Mohd Ikhwan , Leow Soon-Sen , Fairus Syed , Naina Mohamed Isa 
Published: June 2022

Background and aim: Oil palm aqueous by-products rich in phenolic content are known as oil palm phenolics (OPP), and pre-clinical research has shown that OPP has great potential to be further developed as an anti-hyperlipidemic agent. Hence, in order to introduce OPP into market, its safety profile needs to be established by undergoing a phase I clinical trial on healthy humans.Methods: A parallel, placebo-controlled, randomized, and double-blinded clinical trial was conducted for 2 months on 100 healthy subjects aged 20–40 years old. This trial was registered atclinicaltrials.gov(NCT04164446). The subjects were randomly allocated to four treatment arms with 25 participants each: placebo, 250, 1,000, and 1,500 mg of OPP. During the trial, subjects were required to consume four capsules simultaneously per day. Withdrawal of fasting blood for hematology, liver and renal function analysis, and medical examination were conducted at baseline (day 1), day 30, and day 60. For monitoring, vital signs (blood pressure and pulse rate) and weight measurements were taken during each visit.Results: Minor adverse events (AEs) were reported in all groups especially at high dose (1,500 mg) but none were serious adverse events (SAEs). Fasting blood parameters between control and all OPP-treated groups demonstrated no statistically significant difference from baseline to day 60.Conclusion: With no major AEs and SAEs reported and no abnormal findings in biochemistry and hematology results, OPP supplementation in capsule form is safe to be taken up to 1,500 mg a day.
Utilization of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacoepidemiological Studies: A Systematic Review on Antiarrhythmic and Glucose-Lowering Medicines
Authors: Mohammadi Jouabadi Soroush , Nekouei Shahraki Mitra , Peymani Payam , Stricker Bruno H. , Ahmadizar Fariba 
Published: June 2022

Introduction:In human pharmacology, there are two important scientific branches: clinical pharmacology and pharmacoepidemiology. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is important in preclinical studies and randomized control trials. However, it is rarely used in pharmacoepidemiological studies on the effectiveness and medication safety where the target population is heterogeneous and followed for longer periods. The objective of this literature review was to investigate how far PK/PD modeling is utilized in observational studies on glucose-lowering and antiarrhythmic drugs.Method:A systematic literature search of MEDLINE, Embase, and Web of Science was conducted from January 2010 to 21 February 2020. To calculate the utilization of PK/PD modeling in observational studies, we followed two search strategies. In the first strategy, we screened a 1% random set from 95,672 studies on glucose-lowering and antiarrhythmic drugs on inclusion criteria. In the second strategy, we evaluated the percentage of studies in which PK/PD modeling techniques were utilized. Subsequently, we divided the total number of included studies in the second search strategy by the total number of eligible studies in the first search strategy.Results:The comprehensive search of databases and the manual search of included references yielded a total of 29 studies included in the qualitative synthesis of our systematic review. Nearly all 29 studies had utilized a PK model, whereas only two studies developed a PD model to evaluate the effectiveness of medications. In total, 16 out of 29 studies (55.1%) used a PK/PD model in the observational setting to study effect modification. The utilization of PK/PD modeling in observational studies was calculated as 0.42%.Conclusion:PK/PD modeling techniques were substantially underutilized in observational studies of antiarrhythmic and glucose-lowering drugs during the past decade.
Cost-Effectiveness Analysis of Rivaroxaban in Chinese Patients With Stable Cardiovascular Disease
Authors: Feng Tianyu , Zheng Zhou , Gao Shang , Xu Jiaying , Cao Pen , Jia Huanhuan , Yu Xihe 
Published: June 2022

Objective:This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the China.Methods:We used TreeAge 2019 to construct a Markov model to assess the direct healthcare costs and quality-adjusted life years for three therapies, namely low-does rivaroxaban plus aspirin, rivaroxaban alone, and aspirin alone. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Chinese Health Care Statistical Yearbook and published studies. Use the Incremental cost-effectiveness ratio to describe the results. The willingness-to-pay threshold is set at US$11,000 (China’s 2020 Gross National Product per capita).Result:In patients with stable cardiovascular disease, the increased cost per quality-adjusted life year gained in the low-dose rivaroxaban combined with aspirin group compared to the aspirin alone group was US$7937.30. The increased cost per quality-adjusted life year gained in the rivaroxaban alone group versus the aspirin alone group was US$15,045.78.Conclusion:A low-does rivaroxaban plus aspirin therapy may be cost-effective in the secondary prevention of stable cardiovascular disease in patients.
High-Throughput Imaging of Blood Flow Reveals Developmental Changes in Distribution Patterns of Hemodynamic Quantities in Developing Zebrafish
Authors: Maung Ye Swe Soe , Kim Jung Kyung , Carretero Nuria Taberner , Phng Li-Kun 
Published: June 2022

Mechanical forces from blood flow and pressure (hemodynamic forces) contribute to the formation and shaping of the blood vascular network during embryonic development. Previous studies have demonstrated that hemodynamic forces regulate signaling and gene expression in endothelial cells that line the inner surface of vascular tubes, thereby modifying their cellular state and behavior. Given its important role in vascular development, we still know very little about the quantitative aspects of hemodynamics that endothelial cells experience due to the difficulty in measuring forces in vivo. In this study, we sought to determine the magnitude of wall shear stress (WSS) exerted on ECs by blood flow in different vessel types and how it evolves during development. Utilizing the zebrafish as a vertebrate model system, we have established a semi-automated high-throughput fluorescent imaging system to capture the flow of red blood cells in an entire zebrafish between 2- and 6-day post-fertilization (dpf). This system is capable of imaging up to 50 zebrafish at a time. A semi-automated analysis method was developed to calculate WSS in zebrafish trunk vessels. This was achieved by measuring red blood cell flow using particle tracking velocimetry analysis, generating a custom-made script to measure lumen diameter, and measuring local tube hematocrit levels to calculate the effective blood viscosity at each developmental stage. With this methodology, we were able to determine WSS magnitude in different vessels at different stages of embryonic and larvae growth and identified developmental changes in WSS, with absolute levels of peak WSS in all vessel types falling to levels below 0.3 Pa at 6 dpf. Additionally, we discovered that zebrafish display an anterior-to-posterior trend in WSS at each developmental stage.
Association Between Exercise Self-Efficacy and Health-Related Quality of Life Among Dialysis Patients: A Cross-Sectional Study
Authors: Zhang Fan , Liao Jing , Zhang Weihong , Huang Liuyan 
Published: June 2022

BackgroundExercise self-efficacy is a vital determinant of an individual’s active participation in regular exercise, and exercise is a critical component of improving health-related quality of life (HRQOL) in dialysis patients. This study aimed to describe the relationship between exercise self-efficacy and HRQOL in dialysis patients.Materials and MethodsA cross-sectional study was conducted in Shanghai, China. Structured questionnaires distributed to the patients collected socio-demographic and disease-related information. Physical activity was assessed by a self-administered questionnaire, and the exercise self-efficacy scale (ESES) was used to measure exercise self-efficacy. HRQOL was evaluated by the kidney disease quality of life instrument-short form version 1.3 (KDQOL-SF™ v1.3). Data were analyzed using a univariate generalized linear model, Spearman correlation, and hierarchical multiple regression.ResultsA positive association was observed between exercise self-efficacy and HRQOL (r = 0.310, p &lt; 0.001). Physical activity as a predictor variable explained 9.8% of the variance in overall HRQOL (p &lt; 0.001). Exercise self-efficacy explained an additional 7.1% of the HRQOL variance. In total, 24.6% of the variation in the HRQOL was explained by the socio-demographic variables, disease-related factors, physical activity, and exercise self-efficacy.ConclusionOverall, only 16.9% of the change in HRQOL was explained by physical activity and exercise self-efficacy. Future research is still needed to further explore the factors influencing the HRQOL in dialysis patients. However, this finding suggests the need to consider the importance of HRQOL and physical activity as well as exercise self-efficacy when developing intervention programs.