bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations
Authors: Yang Zhengyu , Chen Ya , Wang Yanan , Wang Shuyuan , Hu Minjuan , Zhang Bo , Han Baohui 
Published: August 2021

BackgroundCo-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.ObjectiveThis retrospective study aimed to explore whether EGFR-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.Patients and MethodsWe retrospectively collected data of 137 EGFR-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.ResultsConcurrent TP53 mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months vs. 16.6 months, P=0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with TP53: 11.4 months vs. 19.1 months, P=0.001, HR=0.407; without TP53: 16.6 months vs. 18.9 months, P=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53% vs. 53%, P=0.985).ConclusionsIn our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.
Are the Growth Standards of the World Health Organization Valid for Spanish Children? The SONEV Study
Authors: Pérez-Bermejo Marcelino , Alcalá-Dávalos Luisa , Pérez-Murillo Javier , Legidos-García Maria Ester , Murillo-Llorente Maria Teresa 
Published: August 2021

Background: The use of different growth tables to assess the population's nutritional status has given rise to a series of limitations arising from the lack of consensus and uniform methodological criteria. This leads to a disparity of results that prevent an accurate and reliable diagnosis of whether a child is overweight or obese.Objective: The purpose of this study was to develop growth references for weight, height, and body mass index for Eastern-Spanish children from 6 to 16 years of age.Methods: The final sample used to fit the growth curves was made up of 1,102 observations. The 2007 WHO curves are currently used for Child Health Service Cards. Therefore, to make the comparison of the internal values obtained as realistic as possible, the same construction method has been used for the internal curves, modeling age as a continuous variable and simultaneously adjusting the curves, smoothing them using cubic splines and further smoothing the edge effects by means of data extending above or below the upper and lower age limits.Results: Growth curves for percentiles were constructed for both sexes and higher values were noticeably found to set as growth-standard compared to WHO-standards.Conclusion: Our analysis shows that the WHO 2007 standard references are not suitable for Eastern-Spanish children. The standards shown in this study are much more realistic and current, and we believe that their use will help healthcare professionals more effectively combat the current epidemic of overweight and obesity.
Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers
Authors: Pieterman Elsbet J. , Princen Hans M. G. , Jarke Annica , Nilsson Ralf , Cavallin Anders , Bergenholm Linnéa , Henricsson Marcus , Gopaul V. Sashi , Agrawal Rahul , Nissen Steven E. , Hurt-Camejo Eva 
Published: August 2021

We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 μL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 μg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 μg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 μg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 μg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.
Liraglutide via Activation of AMP-Activated Protein Kinase-Hypoxia Inducible Factor-1α-Heme Oxygenase-1 Signaling Promotes Wound Healing by Preventing Endothelial Dysfunction in Diabetic Mice
Authors: Huang Huiya , Wang Linlin , Qian Fanyu , Chen Xiong , Zhu Haiping , Yang Mei , Zhang Chunxiang , Chu Maoping , Wang Xiaorong , Huang Xiaozhong 
Published: August 2021

Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance.Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h.Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α–heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α–HO-1 axis.
Mobile Phone Use “on the Road”: A Self-Report Study on Young Drivers
Authors: Fraschetti Angelo , Cordellieri Pierluigi , Lausi Giulia , Mari Emanuela , Paoli Elena , Burrai Jessica , Quaglieri Alessandro , Baldi Michela , Pizzo Alessandra , Giannini Anna Maria 
Published: August 2021

BackgroundExtensive research showed that multitasking negatively affects driving performance. Multitasking activities can range from talking and texting to listening to music; particularly among young drivers, multitasking behavior is caused mainly from mobile phone use while driving which is one of the main causes of road accidents.ObjectiveThe main purpose of this study was to investigate whether some variables (e.g., Sensation-Seeking, preferences of Multitasking) could affect mobile phone use while driving in young drivers and whether any gender differences were present among the examined variables.Setting and participantsThe sample consists of 424 Italian students (56% males) with an age range of 18–21 years. A self-report questionnaire was specifically developed to assess variables such as: Attitude toward Multitasking, Perceived Self-efficacy in Multitasking, Accident Risk Perception, General Multitasking Habits, and Sensation Seeking.ResultsThrough SEM modeling, we found the attitude to multitasking while driving to be largely explained by the considered variables. Using multigroup analysis (MGSEM), the model we developed appears to be suitable for explaining the behaviors of both male and female young drivers. Furthermore, data comparison showed that females were more likely to risk perception toward multitasking, and risk perception when using a mobile phone while driving, while males obtained higher mean scores in Sensation Seeking, Perceived Self-Efficacy in Multitasking, and in Multitasking caused by mobile phone use while driving.ConclusionOur research showed how some variables may influence the inclination of some subjects to engage in multitasking while driving. Furthermore, we discussed the importance of considering these variables in the implementation of effective road safety education projects on driving multitasking.
Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
Authors: Campbell Kayleigh S. J. , Collier Abby C. , Irvine Michael A. , Brain Ursula , Rurak Dan W. , Oberlander Tim F. , Lim Kenneth I. 
Published: August 2021

Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood.Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed (n = 31), SRI-Non-Depressed (n = 18), Depressed (unmedicated; n = 42), and Control (n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects.Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls.Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development.
Prediction of Clinical Outcomes With EEG Microstate in Patients With Major Depressive Disorder
Authors: Yan Danfeng , Liu Jin , Liao Mei , Liu Bangshan , Wu Shibin , Li Xueqin , Li Haolun , Ou Wenwen , Zhang Li , Li Zexuan , Zhang Yan , Li Lingjiang 
Published: August 2021

Background: The difficulty in timely evaluating patient response to antidepressants has brought great challenge to the treatment of major depressive disorder (MDD). Some studies found that the electroencephalogram (EEG) microstates might be a reliable marker to evaluate patient response to treatment. The present study aims to evaluate the relationship between EEG microstate parameters and MDD symptoms before and after treatment to identify predictive biological markers for patient response.Methods: Thirty drug-naïve MDD patients (20 females and 10 males) were enrolled in this study. All the patients received effective dosages of selective serotonin reuptake inhibitors, and EEG recordings were collected at baseline and 2 weeks of treatment. Brain activities during the eyes-closed state were recorded using 64-channel electroencephalography, and the patients' microstates were clustered into four maps according to their topography (labeled A, B, C, and D). The differences of EEG microstates before and after treatment were compared using paired t-test. Spearman correlation coefficients were calculated to identify the relationships between the improvement of depression and anxiety symptoms and microstate parameters.Results: The mean duration (69.67 ± 10.33 vs. 64.00 ± 7.70, p &lt; 0.001) and occurrence (4.06 ± 0.69, vs. 3.69 ± 0.70, p = 0.002) of microstate B decreased significantly after treatment. The proportion of microstate B also decreased (27.53 ± 5.81, vs. 23.23 ± 4.61, p &lt; 0.001), while the occurrence of microstate A increased after treatment. A significant negative correlation was found between the change of score of Hamilton Rating Scale for Anxiety and the increase of the occurrence of microstate A (r = −0.431, p &lt; 0.05) after 2 weeks of treatment. The reduction of the duration of microstate B was found to be predictive of patient response to antidepressants after 3 months.Conclusion: This study explored the relationship between changes of EEG microstates and patient response to antidepressants. Depression symptoms might be associated with the duration of microstate B and anxiety symptoms related to the occurrence of microstate A. Therefore, the duration of microstate B and the occurrence of microstate A are potential biological markers for MDD patients' early response and further clinical outcomes.
The Prevalence, Risk Factors and Clinical Correlates of QTc Prolongation in Chinese Hospitalized Patients With Chronic Schizophrenia
Authors: Cao Haiyan , Zhou Yongjie , Li Tao , Yao Cong , Yang Weiliang , Kong Siying , Wang Yanyan , Yu Baoping , Jiao Qingyan , Sun Yun , Jia Xiaoju , Wang Yuting , Wang Zhonggang , Zhang Xiangyang , Li Jie 
Published: August 2021

Background: The QTc interval may be significantly prolonged in schizophrenia patients taking antipsychotics. Few studies have addressed QTc prolongation (QTP) in Chinese patients.Objectives: This study was designed to evaluate the prevalence of QTP and its clinical correlates in Chinese hospitalized patients with chronic schizophrenia.Methods: A total of 436 inpatients and 291 normal controls matched with age and sex were included. QTc prolongation was defined as 2 standard deviations (SD) above the mean value of normal controls. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to evaluate psychopathological symptoms.Results: QTc interval was significantly longer in patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. More women than men displayed QTP. Compared with patients without QTP, the patients with QTP had significantly higher concrete/disorganized subscore, lower low density lipoprotein (LDL) and lower total protein (TP). Furthermore, binary logistic regression analysis showed that higher number of hospitalizations, higher concrete/disorganized subscore and lower LDL were risk factors for QTP. Correlation analysis indicated significant association between QTc interval and the following variables: sex, age, duration of illness, the number of hospitalizations, PANSS total score, fasting blood glucose (FPG). Finally, a multiple regression analysis showed that older age, antipsychotic polypharmacy, higher PANSS total score, and lower LDL were risk factors for QTP. Among them, LDL seemed to be a protective factor for QTP.Conclusions: QTc interval was longer in schizophrenia patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. Some clinical characteristics were risk factors for QTP. And LDL seemed to be a protective factor for QTP.
Research on Financing Mechanism of Long-Term Care Insurance in Xiamen, China: A System Dynamics Simulation
Authors: Zhang Liangwen , Fu Sijia , Fang Ya 
Published: August 2021

Objective: This study aimed to predict the changing trend of long-term care insurance (LTCI) funds by clarifying the linkage between revenue and expenditure and its influencing factors and to provide evidence for the establishment of a sustainable LTCI financing mechanism in China.Method: We have taken Xiamen as an example, based on the data from Xiamen Special Economic Zone Yearbook and field survey. The changing trend of LTCI funds is predicted from 2020 to 2030 based on the system dynamics model (SDM) of the LTCI financing system. Also, through literature research and expert consultation, we found the intervention goals and analyzed their impact on the balance of LTCI funds.Results: In the current situation, according to the forecast, the revenue and the expenditure of the LTCI funds will increase year by year from 2020 to 2030 in Xiamen, an increase of about 3.7 times and 8.8 times, respectively. After 2029, the expenditure will exceed the revenue of the LTCI funds and the balance will turn into a deficit. From the perspective of fund revenue, by adjusting the individual payment rate, government financial subsidies, and enterprise payment rate, the proportion of LTCI funds can be increased to alleviate the balance deficit under the original forecast. On the contrary, from the perspective of fund expenditure, increasing the proportion of reimbursement and the rate of severe disability will lead to an increase in fund expenditure. In this case, the balance of the funds will turn into a deficit, 7 years in advance. In addition, it was found that the severe disability rate has the greatest impact on the balance of funds.Discussion: The SDM can objectively reflect the structure and the behavior of the LTCI financing system and has good applicability. By increasing the individual payment rate, government financial subsidies, and enterprise contribution rate, reasonable setting of the reimbursement ratio of nursing services, especially for the prevention of disability among the elderly, to maintain the sustainability of the funds. This study provides strong evidence for policymakers to establish a sustainable LTCI system in China.
Right Ventricular Myocardial Adaptation Assessed by Two-Dimensional Speckle Tracking Echocardiography in Canine Models of Chronic Pulmonary Hypertension
Authors: Yuchi Yunosuke , Suzuki Ryohei , Kanno Haruka , Teshima Takahiro , Matsumoto Hirotaka , Koyama Hidekazu 
Published: August 2021

Background: Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by an increase in pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. Right ventricle adapts to its pressure overload through various right ventricular (RV) compensative mechanisms: adaptive and maladaptive remodeling. The former is characterized by concentric hypertrophy and increased compensatory myocardial contractility, whereas the latter is distinguished by eccentric hypertrophy associated with impaired myocardial function.Objectives: To evaluate the RV adaptation associated with the increase of PAP using two-dimensional speckle tracking echocardiography.Animals: Seven experimentally induced PH models.Methods: Dogs were anesthetized and then a pulmonary artery catheter was placed via the right jugular vein. Canine models of PH were induced by the repeated injection of microspheres through the catheter and monitored pulmonary artery pressure. Dogs were performed echocardiography and hemodynamic measurements in a conscious state when baseline and systolic PAP (sPAP) rose to 30, 40, 50 mmHg, and chronic phase. The chronic phase was defined that the sPAP was maintained at 50 mmHg or more for 4 weeks without injection of microspheres.Results: Pulmonary artery to aortic diameter ratio, RV area, end-diastolic RV wall thickness, and RV myocardial performance index were significantly increased in the chronic phase compared with that in the baseline. Tricuspid annular plane systolic excursion was significantly decreased in the chronic phase compared with that in the baseline. The RV longitudinal strain was significantly decreased in the sPAP30 phase, increased in the sPAP40 and sPAP50 phases, and decreased in the chronic phase.Conclusions: Changes in two-dimensional speckle tracking echocardiography-derived RV longitudinal strain might reflect the intrinsic RV myocardial contractility during the PH progression, which could not be detected by conventional echocardiographic parameters.
Rotating Microtab Implementation on a DU91W250 Airfoil Based on the Cell-Set Model
Authors: Ballesteros-Coll Alejandro , Portal-Porras Koldo , Fernandez-Gamiz Unai , Zulueta Ekaitz , Lopez-Guede Jose Manuel 
Published: August 2021

Flow control device modeling is an engaging research field for wind turbine optimization, since in recent years wind turbines have grown in proportions and weight. The purpose of the present work was to study the performance and effects generated by a rotating microtab (MT) implemented on the trailing edge of a DU91W250 airfoil through the novel cell-set (CS) model for the first time via CFD techniques. The CS method is based on the reutilization of an already calculated mesh for the addition of new geometries on it. To accomplish that objective, the required region is split from the main domain, and new boundaries are assigned to the mentioned construction. Three different MT lengths were considered: h = 1%, 1.5% and 2% of the airfoil chord length, as well as seven MT orientations (β): from 0° to −90° regarding the horizontal axis, for five angles of attack: 0°, 2°, 4°, 6° and 9°. The numerical results showed that the increases of the β rotating angle and the MT length (h) led to higher aerodynamic performance of the airfoil, CL/CD = 164.10 being the maximum ratio obtained. All the performance curves showed an asymptotic trend as the β angle reduced. Qualitatively, the model behaved as expected, proving the relationship between velocity and pressure. Taking into consideration resulting data, the cell-set method is appropriate for computational testing of trailing edge rotating microtab geometry.