bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CpG Methylation Signature as a Potential Marker for Early Diagnosis of Hepatocellular Carcinoma From HBV-Related Liver Disease Using Multiplex Bisulfite Sequencing
Authors: Li Kang , Song Yi , Qin Ling , Li Ang , Jiang Sanjie , Ren Lei , Zang Chaoran , Sun Jianping , Zhao Yan , Zhang Yonghong 
Published: October 2021

BackgroundAberrant methylation of CpG sites served as an epigenetic marker for building diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC).MethodsUsing Illumina 450K and EPIC Beadchip, we identified 34 CpG sites in peripheral blood mononuclear cell (PBMC) DNA that were differentially methylated in early HCC versus HBV-related liver diseases (HBVLD). We employed multiplex bisulfite sequencing (MBS) based on next-generation sequencing (NGS) to measure methylation of 34 CpG sites in PBMC DNA from 654 patients that were divided into a training set (n = 442) and a test set (n = 212). Using the training set, we selected and built a six-CpG-scorer (namely, cg14171514, cg07721852, cg05166871, cg18087306, cg05213896, and cg18772205), applying least absolute shrinkage and selection operator (LASSO) regression. We performed multivariable analyses of four candidate risk predictors (namely, six-CpG-scorer, age, sex, and AFP level), using 20 times imputation of missing data, non-linearly transformed, and backwards feature selection with logistic regression. The final model’s regression coefficients were calculated according to “Rubin’s Rules”. The diagnostic accuracy of the model was internally validated with a 10,000 bootstrap validation dataset and then applied to the test set for validation.ResultsThe area under the receiver operating characteristic curve (AUROC) of the model was 0.81 (95% CI, 0.77–0.85) and it showed good calibration and decision curve analysis. Using enhanced bootstrap validation, adjusted C-statistics and adjusted Brier score were 0.809 and 0.199, respectively. The model also showed an AUROC value of 0.84 (95% CI 0.79–0.88) of diagnosis for early HCC in the test set.ConclusionsOur model based on the six-CpG-scorer was a reliable diagnosis tool for early HCC from HBVLD. The usage of the MBS method can realize large-scale detection of CpG sites in clinical diagnosis of early HCC and benefit the majority of patients.
Longitudinal Assessment of Physical Activity, Fitness, Body Composition, Immunological Biomarkers, and Psychological Parameters During the First Year After Diagnosis in Women With Non-Metastatic Breast Cancer: The BEGYN Study Protocol
Authors: Zemlin Cosima , Stuhlert Caroline , Schleicher Julia Theresa , Wörmann Carolin , Altmayer Laura , Lang Marina , Scherer Laura-Sophie , Thul Ida Clara , Müller Carolin , Kaiser Elisabeth , Stutz Regine , Goedicke-Fritz Sybelle , Ketter Laura , Zemlin Michael , Wagenpfeil Gudrun , Steffgen Georges , Solomayer Erich-Franz 
Published: October 2021

BackgroundModerate physical activity is associated with an improved prognosis and psychosocial outcome in breast cancer patients. Although exercise and physical activity are associated with multiple physiological and psychological effects, many of the underlying mechanisms remain obscure. The BEGYN study (Influence of physical activity in breast cancer patients on physiological and psychological parameters and on biomarkers) aims at identifying potential associations between the extent of physical activity, fitness, body composition, immunological biomarkers, psycho-emotional parameters, and the course of treatment during the first year after diagnosis of breast cancer.MethodsThe prospective observational BEGYN study will include 110 non-metastatic breast cancer patients. The patients will be assessed during a base line visit prior to the initiation of the antineoplastic therapy and after 3, 6, 9 and 12 months. The physical activity will be measured using a fitness tracker and a self-assessment diary during the entire study. Each visit will include the assessment of (i) cardiorespiratory fitness measured by spiroergometry, (ii) body composition, (iii) psycho-emotional parameters (quality of life, mental health, fatigue, depression, distress, anxiety, well-being), and (iv) extensive blood tests including routine laboratory, vitamin D, selenium and immunologically relevant biomarkers (e.g., leukocyte subpopulations and cytokine profiles).DiscussionWhereas most studies investigating the influence of physical activity in breast cancer patients focus on specific activities for three months or less, the BEGYN study will quantify the daily physical activity and cardiorespiratory fitness of breast cancer patients based on objective measurements in the context of the oncological therapy for 12 months after diagnosis. The study will reveal potential associations between exercise, immune status and physical as well as psycho-emotional outcome and the clinical course of the disease. Moreover, complementary therapies such as Vit D and Selenium supplementation and parameters investigating the motivation of the patients are part of the study. Due to this holistic approach, the BEGYN study will guide towards confirmatory studies on the role of physical activity in breast cancer patients to develop individualized counselling regarding the recommended type and extent of exercise.Trial RegistrationThis study has been registered at the German Clinical Trials Register DRKS00024829.
Stool Saponified Fatty Acid, Behavior, Growth, and Stool Characteristics in Infants Fed a High-OPO Formula: A Randomized, Double-Blind Clinical Trial
Authors: Shen Lili , Huang Weihua , Xu Xuebing , Wang Li , Wang Qingyun , Li Shengqi , Yuan Xuewei 
Published: October 2021

Objective: 1,3-Dioleoyl-2-palmitoylglycerol (OPO) is an ideal structured triglyceride for infant formula, with a similar structure to human milk fat. We conducted this randomized, double-blind controlled, single-center trial to evaluate the effects of an OPO formula in infants.Study Design: One hundred seventy-four healthy term infants &lt;14 days old were assigned to the standard formula-fed group (n = 55), high sn-2 palmitic acid (OPO) formula-fed infants (n = 58), and breastfed (BF) group (n = 61). The primary endpoint was the total saponified fatty acid content in feces at week 6 and week 12.Results: Infants from the OPO group had lower concentrations of fecal saponified fatty acids than those from the standard formula group (p &lt; 0.0001) at week 6 and week 12. The frequencies of crying per day and per night of infants in the OPO group were significantly less than those of infants in the standard formula group (p &lt; 0.0001). After 12 weeks of feeding, the length of infants was significantly higher in the OPO group than in the other two groups (p = 0.002). Infants in the OPO group had a significantly lower stool calcium concentration and a higher stool frequency per day than infants in the standard formula group.Conclusion: In summary, a high concentration of OPO in formula is beneficial to the growth and development of infants.
Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis
Authors: Sugimoto Kazuo , Liu Jia , Li MingXuan , Song YueBo , Zhang Chi , Zhai ZhiGuang , Gao Ying 
Published: October 2021

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2–related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer.Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS.Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed.Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p &lt; 0.001) and astrocytic activation (p &lt; 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p &lt; 0.05) and increasing the levels of superoxide dismutase (p &lt; 0.05), Nrf2 (p &lt; 0.05), heme oxygenase-1 (p &lt; 0.05), and glutathione S-transferase (p &lt; 0.05) in the SOD1-G93A mice.Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.
Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies
Authors: Singla Rajeev K. , Sharma Pooja , Dubey Ankit Kumar , Gundamaraju Rohit , Kumar Dinesh , Kumar Suresh , Madaan Reecha , Shri Richa , Tsagkaris Christos , Parisi Salvatore , Joon Shikha , Singla Shailja , Kamal Mohammad Amjad , Shen Bairong 
Published: October 2021

Background:With prostate cancer being the fifth-greatest cause of cancer mortality in 2020, there is a dire need to expand the available treatment options. Castration-resistant prostate cancer (CRPC) progresses despite androgen depletion therapy. The mechanisms of resistance are yet to be fully discovered. However, it is hypothesized that androgens depletion enables androgen-independent cells to proliferate and recolonize the tumor.Objectives:Natural bioactive compounds from edible plants and herbal remedies might potentially address this need. This review compiles the available cheminformatics-based studies and the translational studies regarding the use of natural products to manage CRPC.Methods:PubMed and Google Scholar searches for preclinical studies were performed, whileClinicalTrials.govand PubMed were searched for clinical updates. Studies that were not in English and not available as full text were excluded. The period of literature covered was from 1985 to the present.Results and Conclusion:Our analysis suggested that natural compounds exert beneficial effects due to their broad-spectrum molecular disease-associated targets.In vitroandin vivostudies revealed several bioactive compounds, including rutaecarpine, berberine, curcumin, other flavonoids, pentacyclic triterpenoids, and steroid-based phytochemicals. Molecular modeling tools, including machine and deep learning, have made the analysis more comprehensive. Preclinical and clinical studies on resveratrol, soy isoflavone, lycopene, quercetin, and gossypol have further validated the translational potential of the natural products in the management of prostate cancer.
Factors Associated With Off-Label Oncology Prescriptions: The Role of Cost and Financing in a Universal Healthcare System
Authors: Gordon Noa , Goldstein Daniel A. , Tadmor Boaz , Stemmer Salomon M. , Greenberg Dan 
Published: October 2021

Purpose: Various solutions have been put forward for prescribing and reimbursing treatments outside their registered indications within universal healthcare systems. However, most off-label oncology prescriptions are not reimbursed by health funds. This study characterized the financing sources of off-label oncology use and the predictors of the decision to forego treatment.Materials and Methods: All 708 off-label oncology requests submitted for approval in a large tertiary cancer center in Israel between 2016 and 2018 were examined for disease and patient sociodemographic characteristics, costs and financing sources, and the factors predicting actual off-label drug administration using multivariate logistic regression analysis.Results: The mean monthly cost of a planned off-label treatment was ILS54,703 (SD = ILS61,487, median = ILS39,928) (approximately US$ 15,500). The main sources of funding were private health insurance (25%) and expanded access pharma company plans (30%). Approximately one third (31%) of the requests did not have a financing source at the time of approval. Of the 708 requests, 583 (or 82%) were filled and treatment was initiated. Predictors for forgoing treatment were the impossibility of out-of-pocket payments or the lack of a financing solution (OR = 0.407; p = 0.005 and OR = 0.400; p &lt; 0.0005).Conclusion: Although off-label recommendations are widespread and institutional approval is often granted, a large proportion of these prescriptions are not filled. In a universal healthcare system, the financing sources for off-label treatments are likely to influence access.
Aberrant ROS Mediate Cell Cycle and Motility in Colorectal Cancer Cells Through an Oncogenic CXCL14 Signaling Pathway
Authors: Zeng Jun , Li Mei , Xu Jun-Yu , Xiao Heng , Yang Xian , Fan Jiao-Xiu , Wu Kang , Chen Shuang 
Published: October 2021

Background: Reactive oxygen species (ROS) act as signal mediators to induce tumorigenesis.Objective: This study aims to explore whether chemokine CXCL14 is involved in the proliferation and migration of ROS-induced colorectal cancer (CRC) cells.Methods: The proliferative and migratory capacities of CRC cells treated with or without H2O2 were measured by various methods, including the CKK-8 assay, colony formation assay, flow cytometry, wounding healing assay, and migration assay.Results: The results revealed that H2O2 promoted the proliferation and migration of CRC cells by regulating the cell cycle progression and the epithelial to mesenchymal transition (EMT) process. Furthermore, we noted that the expression level of CXCL14 was elevated in both HCT116 cells and SW620 cells treated with H2O2. An antioxidant N-Acetyl-l-cysteine (NAC) pretreatment could partially suppress the CXCL14 expression in CRC cells treated with H2O2. Next, we constructed CRC cell lines stably expressing CXCL14 (HCT116/CXCL14 and SW620/CXCL14) and CRC cell lines with empty plasmid vectors (HCT116/Control and SW620/Control) separately. We noted that both H2O2 treatment and CXCL14 over-expression could up-regulate the expression levels of cell cycle-related and EMT-related proteins. Moreover, the level of phosphorylated ERK (p-ERK) was markedly higher in HCT116/CXCL14 cells when compared with that in HCT116/Control cells. CXCL14-deficiency significantly inhibited the phosphorylation of ERK compared with control (i.e., scrambled shNCs). H2O2 treatment could partially restore the expression levels of CXCL14 and p-ERK in HCT116/shCXCL14 cells.Conclusion: Our studies thus suggest that aberrant ROS may promote colorectal cancer cell proliferation and migration through an oncogenic CXCL14 signaling pathway.
Individual vs. Group Cognitive Behavior Therapy for Anxiety Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials
Authors: Guo Tingting , Su Jing , Hu Jiayi , Aalberg Marianne , Zhu Yinglin , Teng Teng , Zhou Xinyu 
Published: October 2021

Background: Anxiety disorder is the most prevalent mental disorder in children and adolescents. However, evidence for efficacy and acceptability between individual cognitive behavior therapy (I-CBT) and group cognitive behavior therapy (G-CBT) in anxiety disorders in children and adolescents remains unclear.Methods: Eight electronic databases (PubMed, Embase, Cochrane, Web of Science, CINAHL, PsycINFO, ProQuest, and LILACS) were searched from inception to October 2019. Randomized controlled trials comparing I-CBT with G-CBT for anxiety disorders in children and adolescents were included. The primary outcomes were efficacy (mean change in anxiety symptom scores) at post-treatment and acceptability (all-cause discontinuation). The secondary outcome was remission at post-treatment. Subgroup analyses were also conducted to examine whether the result would be influenced by age, number of treatment sessions, parental involvement, male/female sex, and number of participants.Results: Nine studies were selected in this meta-analysis. The pooled analyses indicated no significant difference between I-CBT and G-CBT for efficacy at post-treatment [standardized mean difference (SMD), −0.14; 95% confidence interval (CI), −0.37 to 0.09], acceptability [odds ratio (OR), 1.30; 95% CI, 0.61–2.77], and remission at post-treatment (OR, 1.15; 95% CI, 0.79–1.66). In the subgroup analysis of age, I-CBT was significantly more effective than G-CBT in adolescents at post-treatment (SMD, −0.77; 95% CI, −1.51 to −0.02), but not in children (SMD, 0.00; 95% CI, −0.02 to 0.20). However, the findings were not materially different from those of the efficacy subgroup analysis of number of treatment sessions, parental involvement, male/female sex, and number of participants.Conclusions: Based on those current evidence, I-CBT was shown to be more beneficial than G-CBT for anxiety disorders in adolescents, but not in children. However, further well-designed clinical studies should be performed to confirm these findings.Systematic Review Registration:http://osf.io/xrjkp, identifier: 10.17605/OSF.IO/XRJKP.
The Influence of Online Game Behaviors on the Emotional State and Executive Function of College Students in China
Authors: Zhao Wei , Wei Tao , Zhou Ruidong , Wang Yujing , Wang Yan , Ren Zixuan , Shao Wenyi , Luo Hanrun , Zhou Yiding , Chen Nuo , Lu Qiao , Song Xun , Zhang Ziyao , Fang Yinnuo , Zhang Xinyi , Jiao Dongliang 
Published: October 2021

Background and Objective: Since the classification of gaming disorder (GD) by the World Health Organization (WHO) as “mental disorder caused by addictive behaviors,” there has been controversy regarding whether online game behaviors can lead to mental disorder. This study aims to clarify the correlation between the online game behaviors of college students and anxiety, depression, and executive function of college students in China, from a questionnaire-based investigation.Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from March 7 to March 27, 2020. The questionnaires included the Internet Game Addiction (IGA) Scale, Behavior Rating Inventory of Executive Function (Adult Version, BRIEF-A), Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire Scale (PHQ-9).Results: A total of 850 participants completed the survey, including 353 males (41.53%) and 497 females (58.47%). The primary age group was 18–27 years (91.53%), and the educational background was a bachelor's degree (94.7%). The study found that the online behavior of 17.76% of college students was online game behavior. This study did not identify any students who met the criteria for IGA, and 3% met the criteria for indulgent behavior. A dual role of online games was identified; moderate online game activities can improve the emotional state and executive function of college students, while excessive online game behaviors that may not reach the degree of addiction can also harm emotional state and executive function.Conclusions: This study suggests that although IGA has been regarded as a mental disease, online game behavior should be treated differently. Online game activities should not be entirely denied, but mental disorders caused by excessive gaming activities deserve attention. In particular, the emotional state and executive function of students with excessive online game behaviors should be monitored and intervened in advance to avoid game behaviors turning into indulgent behaviors or addiction. As a cognitive control process, executive function may play a key role in regulating IGA and emotional state.
Study of Three-Point Linkage of Power Machine
Authors: Pásztor Judit , Popa-Müller Izolda 
Published: October 2021

Abstract
The three-point linkage serves to interconnect the power machine and the suspended or semi-suspended work machine. It has a role in the operation of the machine group, in towing and in the setup of the machines. Part of the weight of the suspended machine is loaded on the driven wheels, thus increasing the adhesion weight which results in an increase in the tractive force. Understanding the operation of this equipment it is necessary for horticulture, agronomy and landscape architecture future engineers. In this thesis we model the effect of connection points of the three-point linkage on the tractive force in a specific case: that of the suspended plow.
Кримінально-правова характеристика геноциду: світова практика встановлення чисельності жертв
Authors: Герасименко М. , Ховпун О. 
Published: October 2021

Розкриваючи питання кримінально-правової характеристики злочину геноциду української нації у 1932–1933 рр., автор досліджує світову практику встановлення чисельності жертв особливо тяжкого злочину. Цінність даного наукового дослідження полягає в тому, що міжнародний досвід надає можливість криміналістам, слідчим, експертам, історикам та дослідникам використовувати методологію, методи та спеціальні методики у ході проведення судових експертиз, історико-правових досліджень та під час встановлення чисельності жертв від злочину геноциду, вчиненого комуністичним тоталітарним режимом.
Крім того, проаналізовано висновок судової науково-демографічної експертизи Інституту демографії та соціальних досліджень імені М. В. Птухи НАН України від 30 листопада 2009 р
Impacts of terminal molecules on metal-atom diffusion into alkane self-assembled-monolayer films: first-principles study
Authors: Watanabe Shunta , Nakayama Takashi 
Published: October 2021

Abstract
The effects of terminal molecules on metal-atom diffusion into alkane self-assembled-monolayer (SAM) films were studied using first-principles calculations. It was shown that the diffusion of Al and Au atoms easily occurs when the alkane molecules have a CH3 termination, while the diffusion is suppressed by COOK terminal molecules for Au atom and by COOH and COOK molecules for Al atom. This is in good agreement with experiments. We showed that such suppression is caused by the orbital-hybridization-induced interaction between a metal atom and terminal molecules: the ionic bonding between negatively charged Au and surrounding positively charged K atoms, and the covalent-like bonding between Al and neighboring O atoms. We also showed that, once the metal atoms form films on the SAM surface, the metal atoms bond to each other and stabilize, thus also suppressing the diffusion into the SAM substrate.