bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of LC-MS/MS and EMIT methods for the precise determination of blood sirolimus in children with vascular anomalies
Authors: Zhao Yue-Tao , Dai Hao-Ran , Li Yue , Zhang Yuan-Yuan , Guo Hong-Li , Ding Xuan-Sheng , Hu Ya-Hui , Chen Feng 
Published: September 2022

Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor. The whole blood concentration of SRL is routinely monitored to tailor dosage and prevent toxicity. Currently, the enzyme multiplied immunoassay technique (EMIT) is often applied to perform therapeutic drug monitoring (TDM) of SRL, but the cross-reactivity with various metabolites is of great concern. A more specific method is required, such as liquid chromatography–tandem mass spectrometry (LC-MS/MS). However, no study on the method comparison of the EMIT and LC-MS/MS for the measurement of whole blood SRL concentration in children with vascular anomalies has been reported. This study developed a simple and sensitive LC-MS/MS assay for the determination of SRL. Meanwhile, consistency between LC-MS/MS and the EMIT was evaluated by linear regression and Bland–Altman analysis. Whole blood samples were deproteinized with methanol for erythrocyte lysis, and the resulting solution was injected into the LC-MS/MS system using the positive electrospray ionization mode. The multiple reaction monitoring transitions of m/z 931.7 → 864.6 and m/z 934.7 → 864.6 were used for SRL and SRL-d3 as the internal standards, respectively. The analytes were separated on a C18 column with a gradient mobile phase (0.1 mM formic acid and 0.05 mM ammonium acetate in methanol/ultrapure water). Blood samples collected from children with vascular anomalies undergoing SRL therapy were tested by EMIT and by LC-MS/MS. The linear range of LC-MS/MS was 0.500–50.0 ng/ml and that of the EMIT was 3.50–30.0 ng/ml. A significant positive correlation between the two assays was established with a regression equation described as [EMIT] = 1.281 × [LC−MS/MS] + 2.450 (r = 0.8361). Bland–Altman plots showed a mean concentration overestimation of 4.7 ng/ml [95% CI: (−3.1, 12.6)] and a positive bias of 63.1% [95% CI: (−36.1, 162.3)] generated by the EMIT more than that of by LC-MS/MS. In conclusion, the two methods were closely correlated, indicating that switching between the two methods is feasible. Considering the overestimation nature of the EMIT assay, switching from the EMIT to the LC-MS/MS method deserves close attention and necessary re-evaluation for the target therapeutic reference range, may be required when methods are switched within the same clinical laboratory or results are compared between different laboratories.
Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer
Authors: Li Lingling , Liu Tingting , Liu Qingyan , Mu Shuai , Tao Haitao , Yang Xuhui , Li Yao , Xiong Qi , Wang Lijie , Hu Yi 
Published: September 2022

Background: Rechallenge of immunotherapy beyond progression (RIBP) has been demonstrably effective in a variety of cancers. Our study aims to investigate the efficacy of RIBP in small-cell lung cancer (SCLC) patients under real-world conditions.Methods: SCLC patients who experienced progressive disease after receiving programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors combined with chemotherapy from January 2017 to October 2021 were enrolled. The study population was divided into two groups: the RIBP group and the discontinuation of immunotherapy beyond progression (DIBP) group. Inverse propensity score weighting (IPSW) method was used to balance the clinical baseline characteristics. The short-term and long-term efficacy of the two groups was compared.Results: 100 SCLC patients were included in this study. There were 45 patients in the RIBP group and 55 patients in the DIBP group. The disease control rate (DCR) and the proportion of durable clinical benefit (DCB) were significantly higher in the RIBP group (DCR: 79.7% vs. 55.7%, p = 0.027; DCB: 40.7 vs. 20.7%, p = 0.025) after weighting. The median progressive-free survival (PFS) in the RIBP group was significantly longer than the DIBP group in the total population (mPFS: 4.8 vs. 2.4 months, p = 0.002), while there was no significant difference in overall survival (OS) of the two groups (mOS: 17.4 vs. 8.0 months, p = 0.098). In the weighted first-line initial immunotherapy subgroup, PFS and OS were significantly improved in the RIBP group (mPFS: 4.5 vs. 2.8 months, p = 0.017; mOS: 11.6 vs. 5.4 months, p = 0.028). After weighting, the RIBP group had a significantly longer PFS than the DIBP group in the SD/PD response to the initial immunotherapy subgroup (mPFS: 6.8 vs. 1.8 months, p = 0.026).Conclusion: Rechallenge of PD-1/PD-L1 inhibitors could bring benefits to SCLC patients, especially in the first-line initial immunotherapy subgroup or SD/PD response to the initial immunotherapy subgroup.
Novel TrueVue series of 3D echocardiography: Revealing the pathological morphology of congenital heart disease
Authors: Sun Feifei , Sun Aijiao , Chen Yixin , Xiao Yangjie , Zhang Xintong , Qiao Wei , Tan Xueying , Liang Yanxiao , Li Dongyu , Yang Shu , Ren Weidong 
Published: September 2022

Aims: This study explored the advantages and limitations of novel series of three-dimensional (3D) echocardiographic techniques and summarized their application methods for congenital heart diseases (CHDs).Method and result: Two-dimensional (2D), traditional 3D echocardiography, and TrueVue plus light and/or Glass novel 3D technologies were performed on 62 patients with CHD, and a clinical survey was designed to judge whether the novel 3D images were more helpful for understanding the cardiac condition and guide treatment than traditional 3D images. TrueVue increased the visual resolution and simulated the true texture of cardiac tissue, significantly improving the display ability of abnormal anatomical structures in CHDs. TrueVue Glass displayed the blood channel and the internal structure of cardiac cavity more intuitively, indicating a new observation aspect not shown by conventional echocardiography. The clinical survey results showed that the new 3D imaging methods effectively increased the diagnostic confidence of echocardiographers, enabled surgeons to better understand the details of lesions, promoted efficient communication, and improved the confidence of both doctors and patients in treatment.Conclusion: The combined application of TrueVue, TrueVue Light, and TrueVue Glass more closely simulated real anatomical features, showed more comprehensive and subtle blood flow in the lumen, not only increased the visual effect but also provided more useful diagnostic information, improved the accuracy of evaluation and treatment of CHD when compared to traditional imaging techniques, indicating that this combined application has significant clinical value.
Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele
Authors: Flück Martin , Vaughan David , Rittweger Jörn , Giraud Marie-Noëlle 
Published: September 2022

Homozygous carriers of the deletion allele in the gene for angiotensin-converting enzyme (ACE-DD) demonstrate an elevated risk to develop inactivity-related type II diabetes and show an overshoot of blood glucose concentration with enduring exercise compared to insertion allele carriers. We hypothesized that ACE-DD genotypes exhibit a perturbed activity of signaling processes governing capillary-dependent glucose uptake in vastus lateralis muscle during exhaustive cycling exercise, which is associated with the aerobic fitness state. 27 healthy, male white Caucasian subjects (26.8 ± 1.1 years; BMI 23.6 +/− 0.6 kg m−2) were characterized for their aerobic fitness based on a threshold of 50 ml O2 min−1 kg−1 and the ACE-I/D genotype. Subjects completed a session of exhaustive one-legged exercise in the fasted state under concomitant measurement of cardiorespiratory function. Capillary blood and biopsies were collected before, and ½ and 8 h after exercise to quantify glucose and lipid metabolism-related compounds (lipoproteins, total cholesterol, ketones) in blood, the phosphorylation of 45 signaling proteins, muscle glycogen and capillaries. Effects of aerobic fitness, ACE-I/D genotype, and exercise were assessed with analysis of variance (ANOVA) under the hypothesis of a dominant effect of the insertion allele. Exertion with one-legged exercise manifested in a reduction of glycogen concentration ½ h after exercise (−0.046 mg glycogen mg−1 protein). Blood glucose concentration rose immediately after exercise in association with the ACE-I/D genotype (ACE-DD: +26%, ACE-ID/II: +6%) and independent of the fitness state (p = 0.452). Variability in total cholesterol was associated with exercise and fitness. In fit subjects, the phosphorylation levels of glucose uptake-regulating kinases [AKT-pT308 (+156%), SRC-pY419, p38α-pT180/T182, HCK-pY411], as well as cytokine/angiotensin 1-7 signaling factors [(STAT5A-pY694, STAT5B-pY699, FYN-pY420, EGFR-pY1086] were higher in angiotensin converting enzyme I-allele carriers than ACE-DD genotypes after exercise. Conversely, the AKT-S473 phosphorylation level (+117%) and angiotensin 2’s blood concentration (+191%) were higher in ACE-DD genotypes. AKT-S473 phosphorylation levels post-exercise correlated to anatomical parameters of muscle performance and metabolic parameters (p &lt; 0.05 and │r│&gt;0.70). The observations identify reciprocal alterations of S473 and T308 phosphorylation of AKT as gatekeeper of a post-translational dysregulation of transcapillary glucose uptake in ACE-DD genotypes which may be targeted in personalized approaches to mitigate type II diabetes.
Non-invasive prognostic biomarker of lung cancer patients with brain metastases: Recurrence quantification analysis of heart rate variability
Authors: Li Guangqiao , Wu Shuang , Zhao Huan , Guan Weizheng , Zhou Yufu , Shi Bo 
Published: September 2022

Background: It has previously been shown that the time-domain characteristic of heart rate variability (HRV) is an independent prognostic factor for lung cancer patients with brain metastasis (LCBM). However, it is unclear whether the nonlinear dynamic features contained in HRV are associated with prognosis in patients with LCBM. Recurrence quantification analysis (RQA) is a common nonlinear method used to characterize the complexity of heartbeat interval time series. This study was aimed to explore the association between HRV RQA parameters and prognosis in LCBM patients.Methods: Fifty-six LCBM patients from the Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, were enrolled in this study. Five-minute ECG data were collected by a mini-ECG recorder before the first brain radiotherapy, and then heartbeat interval time series were extracted for RQA. The main parameters included the mean diagonal line length (Lmean), maximal diagonal line length (Lmax), percent of recurrence (REC), determinism (DET) and Shannon entropy (ShanEn). Patients were followed up (the average follow-up time was 19.2 months, a total of 37 patients died), and the relationships between the RQA parameters and survival of LCBM patients were evaluated by survival analysis.Results: The univariate analysis showed that an Lmax of &gt;376 beats portended worse survival in LCBM patients. Multivariate Cox regression analysis revealed that the Lmax was still an independent prognostic factor for patients with LCBM after adjusting for confounders such as the Karnofsky performance status (KPS) (HR = 0.318, 95% CI: 0.151–0.669, p = 0.003).Conclusion: Reduced heartbeat complexity indicates a shorter survival time in patients with LCBM. As a non-invasive biomarker, RQA has the potential for application in evaluating the prognosis of LCBM patients.
From child social impairment to parenting stress in mothers of children with ASD: The role of parental self-efficacy and social support
Authors: Li Fēi , Xu Mingyu , Wu Danping , Tang Yun , Zhang Lingli , Liu Xin , Zhou Li , Li Fei , Jiang Liping 
Published: September 2022

ObjectivesChildren with autism spectrum disorder (ASD) can exhibit persistent deficits in social communication, causing their mothers to experience elevated parenting stress during the childrearing process. Some internal and external psychosocial resources may mediate or moderate the mother-child relationship, though the underlying mechanisms remain unclear. This study aimed to explore the predictors of parenting stress in mothers of children with ASD and elucidate the mechanisms underlying the relationship between child social impairment and parenting stress.MethodsA cross-sectional study was conducted between October 2020 and March 2022 in Shanghai, China. Mothers of children with ASD completed a survey investigating child social impairment, parenting stress, parental self-efficacy, and social support.ResultsA total of 185 mothers of children with ASD were included in the final analysis. 70.27 percent of mothers experienced a clinically significant level of parenting stress. Child social impairment (r = 0.46, P &lt; 0.001), parental self-efficacy (r = −0.58, P &lt; 0.001), and social support (r = −0.35, P &lt; 0.001) were significantly correlated with parenting stress. Parental self-efficacy completely mediated the relationship between child social impairment and parenting stress (B = 0.51, P &lt; 0.001), after controlling for socioeconomic status (SES) correlated with parenting stress. There was no significant moderating effect of social support between child social impairment and parenting stress (B = 0.01, P = 0.09).ConclusionFuture early intervention programs that focused on child's social communication skills and empowered mothers with related strategies through group-based parent training programs may help reduce parenting stress.
E-cigarettes and non-suicidal self-injury: Prevalence of risk behavior and variation by substance inhaled
Authors: Striley Catherine W. , Nutley Sara K. , Hoeflich Carolin C. 
Published: September 2022

BackgroundNicotine and cannabis inhalation through vaping or electronic delivery systems has surged among young adults in the United States, particularly during the coronavirus disease pandemic. Tobacco and marijuana use are associated with select adverse mental health outcomes, including symptoms of major depressive disorder and suicidal behaviors. Given the need for addiction specialists to treat problematic substance use with an integrated approach, the association between non-suicidal self-injury (NSSI) and use of e-cigarettes, tobacco, marijuana, and alcohol was examined among a diverse sample of college students.MethodsHealthy Minds Study data from 47,016 weighted observations, collected from college students in the 2018–2019 academic year, was used to explore associations between NSSI-related behaviors and past 30-day use of a vaping product (nicotine or marijuana). These relationships were assessed among those using vaping products only, and then among individuals using vaping products and alcohol, conventional cigarettes, and/or marijuana. Hierarchical logistic regression models estimating the relationship between vaping and NSSI were computed to adjust for the effects of demographic factors, symptomatology of psychiatric disorders, and concurrent use of other substances.ResultsA fifth (22.9%) of respondents disclosed past 12-month NSSI; they were significantly more likely to screen positive for depression or anxiety compared to young adults without NSSI. Rates of using vaping products, conventional cigarettes, marijuana, or other substances were higher among students with NSSI even after controlling for potential cofounders. Additionally, students who used a THC-based liquid in their e-cigarettes were more likely to endorse NSSI in comparison to those who used “just flavoring.” However, young adults who vaped were less likely to disclose frequent NSSI-related behaviors than their peers who did not vape.ConclusionsThese findings revealed an association between past 12-month NSSI and past 30-day vaping in a sample of young adults. Further surveillance among college populations and examination of potential sociodemographic confounders is necessary to confirm these findings and advance the substance use and addiction field.
Decreased resting-state functional connectivity of the habenula-cerebellar in a major depressive disorder
Authors: Jung Ju-Yeon , Cho Seo-Eun , Kim Nambeom , Kang Chang-Ki , Kang Seung-Gul 
Published: September 2022

BackgroundIn animal experiments, the habenula and septal nuclei are known as the key brain areas of depression. However, there are few magnetic resonance imaging (MRI) studies on the functional connectivity between these areas and the subcortical areas in humans with major depression. We aimed to investigate the difference in resting-state functional connectivity (RSFC) among the major regions of interest (ROI) in the subcortical areas, including both the habenula and septal nuclei.MethodsWe performed the seed-to-voxel analysis to investigate the RSFC between both the habenula and septal nucleus, as well as other subcortical regions. Furthermore, ROI-to-ROI analysis was performed among the combinations of ROI pairs in the subcortical areas.ResultsThe seed-to-voxel analysis showed a lower RSFC between the left habenula and the cerebellum in major depressive disorder (MDD) than in healthy controls (HCs). As a result of ROI-to-ROI analysis in subcortical areas, a total of 31 pairs of FCs in the MDD group showed a lower RSFC than in the HCs group.ConclusionThis study revealed a lower RSFC between the left habenula and cerebellum in patients with MDD and reduced RSFC among numerous subcortical areas. These new findings on the neural circuitry of MDD might contribute to an in-depth understanding of depression.
Family economic hardship and adolescent mental health during the COVID-19 pandemic
Authors: Kim Bomgyeol , Kim Do Hee , Jang Suk-Yong , Shin Jaeyong , Lee Sang Gyu , Kim Tae Hyun 
Published: September 2022

ObjectiveThis study examined whether pandemic related family economic hardships influenced adolescents' mental health during the COVID-19 pandemic in Korea.MethodsData were collected from 54,948 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-Based Survey. We performed a multiple logistic regression analysis to examine the association between family economic hardship and mental health (anxiety, depressive symptoms, and suicidal ideation).ResultsAmong the adolescents, 39.7, 24.7, and 5.9% reported slight, moderate, and severe economic hardship, respectively. COVID-19 related family economic hardship was significantly associated with higher odds of adolescents reporting anxiety, depressive symptoms, and suicidal ideation. This association was stronger among adolescents with low to middle family economic status.ConclusionsThis study suggests that adolescents from more economically vulnerable families are likely to be at a higher risk for long-term mental health effects due to the financial consequences of the COVID-19 pandemic.
Rational medication management mode and its implementation effect for the elderly with multimorbidity: A prospective cohort study in China
Authors: Tang Qi , Wan Litao , Lu Jing , Wu Wenhui , Wu Huanyun , Liu Zhenwei , Zhao Sitang , Li Chengyue , Chen Gang , Lu Jun 
Published: September 2022

BackgroundAs one of the countries with the most serious degree of aging, the incidence of potentially inappropriate drug use among the elderly is as high as 30. 4% in Chinese communities, and the lack of effective medication management and poor medication compliance at home are the main factors. Given these situations, we constructed a Rational Medication Management Mode based on family physician service, carried out an empirical research and evaluated the implementation effect.MethodsA prospective cohort study was conducted from September to December 2021 to analyze the implementation effect of the Rational Medication Management Mode by comparing the outcome indicators between the intervention group and control group. The primary outcome of this study was medication number and polypharmacy (taking 5 or more medications) at 90 days. The secondary outcomes included the situation for behavioral self-management and knowledge-belief-behavior of rational medication use.ResultsA total of 618 elderly patients (309 in the intervention group and 309 in the control group) with multimorbidity were included in this study, those were all available at follow-up at 90 days. At 90 days, the number of medications was achieved by 3.88 (1.48), and patients with polypharmacy were reduced by 59.55% in the intervention group, having a significant difference compared with the control group (P &lt; 0.001). Patients with medication reminders, intermittent medication and adverse drug reactions were achieved in 294 (95.15%), 47 (15.21%), and 51 (16.51%) respectively in the intervention group (P &lt; 0.001). The knowledge, belief, behavior security and behavior compliance of rational medication use of elderly patients were all greatly improved in the intervention group at 90 days (P &lt; 0.0001).ConclusionThe Rational Medication Management Mode based family physician service, which provides the support of manuals and pillboxes, can decrease the elderly patients' number of drugs with multimorbidity, reduce the incidence of polypharmacy, enhance behavioral self-management, increase the knowledge and belief of rational medication use, and improve the security and compliance of medication usage behavior. In order to provide a practical basis for rational medication management of elderly patients with multimorbidity under the background of long-term prescriptions in China.