bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Oncogenic Role of APC/C Activator Protein Cdc20 by an Integrated Pan-Cancer Analysis in Human Tumors
Authors: Wu Fei , Sun Yang , Chen Jie , Li Hongyun , Yao Kang , Liu Yongjun , Liu Qingyong , Lu Jiaju 
Published: September 2021

The landscape of CDC20 gene expression and its biological impacts across different types of cancers remains largely unknown. Here, a pan-cancer analysis was performed to analyze the role of Cdc20 in various human cancers. Our results indicated that the expression levels of the CDC20 gene were significantly elevated in bladder cancer, breast cancer, colon cancer, rectum cancer, stomach cancer, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, and uterine cancer. In addition, the expression of CDC20 was significantly and positively correlated with the increase of clinical stages in multiple cancer types, including breast cancer, kidney cancer, and lung cancer, et al. Among 33 cancer subtypes in the TCGA dataset, the high expression of CDC20 was correlated with poor prognosis in 10 cancer types. Furthermore, the abundance of phosphorylated Cdc20 in the primary tumor was elevated and correlated with increased tumor grade. Next, we sought to elucidate the oncogenic role by analyzing its association with immune infiltration. For most cancer types, the CDC20 expression was positively correlated with the infiltration of cancer-associated fibroblasts and myeloid-derived suppressor cells. To further understand its functional activity, we explored the classic Cdc20 downstream substrates, which were found to be mutually exclusive with the expression of Cdc20. Moreover, the pan-cancer analysis of the molecular function of Cdc20 indicated that BUB1, CCNA2, CCNB1, CDK1, MAD2L1, and PLK1 might play a critical role in interaction with Cdc20. The abundance of Cdc20 was further validated at transcriptional and translational levels with a publicly available dataset and clinical tumor tissues. The knockdown of Cdc20 dramatically inhibited tumor growth both in vivo and in vitro. Therefore, our studies delineated the oncogenic role of CDC20 and its prognostic significance at the pan-cancer level and proved its functional activity in Cdc20 high expression cancer types. Our studies will merits further molecular assays to understand the potential role of Cdc20 in tumorigenesis and provide the rationale for developing novel therapeutic strategies.
Glucose Intolerance and Cancer Risk: A Community-Based Prospective Cohort Study in Shanghai, China
Authors: Ke Juzhong , Lin Tao , Liu Xiaolin , Wu Kang , Ruan Xiaonan , Ding Yibo , Liu Wenbin , Qiu Hua , Tan Xiaojie , Wang Xiaonan , Chen Xi , Li Zhitao , Cao Guangwen 
Published: September 2021

BackgroundCancer becomes the leading cause of premature death in China. Primary objective of this study was to determine the major risk factors especially glucose intolerance for cancer prophylaxis.MethodsA cluster sampling method was applied to enroll 10,657 community-based adults aged 15-92 years in Shanghai, China in 2013. A structured questionnaire and physical examination were applied in baseline survey. Prediabetes was diagnosed using 75-g oral glucose tolerance test. After excluding 1433 subjects including 224 diagnosed with cancer before and 1 year after baseline survey, the remaining 9,224 subjects were followed-up to December 31, 2020.ResultsA total of 502 new cancer cases were diagnosed. The cancer incidence was 10.29, 9.20, and 5.95/1,000 person-years in diabetes patients, those with prediabetes, and healthy participants, respectively (p&lt;0.001). The multivariate Cox regression analysis indicated that age, prediabetes and diabetes, were associated with an increased risk of cancer in those &lt;65 years, the hazard ratios (95% confidence interval) for prediabetes and diabetes were, 1.49(1.09-2.02) and 1.51(1.12-2.02), respectively. Glucose intolerance (prediabetes and diabetes) were associated with increased risks of stomach cancer, colorectal cancer, and kidney cancer in those &lt;65 years. Anti-diabetic medications reduced the risk of cancer caused by diabetes. The multivariate Cox analysis showed that age, male, &lt;9 years of education, and current smoking were associated with increased risks of cancer in those ≥65 years independently.ConclusionsGlucose intolerance is the prominent cancer risk factor in adults &lt;65 years. Lifestyle intervention and medications to treat glucose intolerance help prevent cancer in this population.
Development and Validation of an Esophageal Squamous Cell Carcinoma Risk Prediction Model for Rural Chinese: Multicenter Cohort Study
Authors: Han Junming , Wang Lijie , Zhang Huan , Ma Siqi , Li Yan , Wang Zhongli , Zhu Gaopei , Zhao Deli , Wang Jialin , Xue Fuzhong 
Published: September 2021

BackgroundThere are rare prediction models for esophageal squamous cell carcinoma (ESCC) for rural Chinese population. We aimed to develop and validate a prediction model for ESCC based on a cohort study for the population.MethodsData of 115,686 participants were collected from esophageal cancer (EC) early diagnosis and treatment of cancer program as derivation cohort while data of 54,750 participants were collected as validation cohort. Risk factors considered included age, sex, smoking status, alcohol drinking status, body mass index (BMI), tea drinking status, marital status, annual household income, source of drinking water, education level, and diet habit. Cox proportional hazards model was used to develop ESCC prediction model at 5 years. Calibration ability, discrimination ability, and decision curve analysis were analyzed in both derivation and validation cohort. A score model was developed based on prediction model.ResultsOne hundred eighty-six cases were diagnosed during 556,949.40 person-years follow-up in the derivation cohort while 120 cases from 277,302.70 in the validation cohort. Prediction model included the following variables: age, sex, alcohol drinking status, BMI, tea drinking status, and fresh fruit. The model had good discrimination and calibration performance: R2, D statistic, and Harrell’s C statistic of prediction model were 43.56%, 1.70, and 0.798 in derivation cohort and 45.19%, 1.62, and 0.787 in validation cohort. The calibration analysis showed good coherence between predicted probabilities and observed probabilities while decision curve analysis showed clinical usefulness. The score model was as follows: age (3 for 45–49 years old; 4 for 50–54 years old; 7 for 55–59 years old; 9 for 60–64 years; 10 for 65–69 years), sex (5 for men), BMI (1 for ≤25), alcohol drinking status (2 for alcohol drinkers), tea drinking status (2 for tea drinkers), and fresh fruit (2 for never) and showed good discrimination ability with area under the curve and its 95% confidence interval of 0.792 (0.761,0.822) in the deviation cohort and 0.773 (0.736,0.811) in the validation cohort. The calibration analysis showed great coherence between predicted probabilities and observed probabilities.ConclusionsWe developed and validated an ESCC prediction model using cohort study with good discrimination and calibration capability which can be used for EC screening for rural Chinese population.
An Integrated Radiomics Model Incorporating Diffusion-Weighted Imaging and 18F-FDG PET Imaging Improves the Performance of Differentiating Glioblastoma From Solitary Brain Metastases
Authors: Zhang Liqiang , Yao Rui , Gao Jueni , Tan Duo , Yang Xinyi , Wen Ming , Wang Jie , Xie Xiangxian , Liao Ruikun , Tang Yao , Chen Shanxiong , Li Yongmei 
Published: September 2021

BackgroundThe effectiveness of conventional MRI (cMRI)-based radiomics in differentiating glioblastoma (GBM) from solitary brain metastases (SBM) is not satisfactory enough. Therefore, we aimed to develop an integrated radiomics model to improve the performance of differentiating GBM from SBM.MethodsOne hundred patients with solitary brain tumors (50 with GBM, 50 with SBM) were retrospectively enrolled and randomly assigned to the training set (n = 80) or validation set (n = 20). A total of 4,424 radiomic features were obtained from contrast-enhanced T1-weighted imaging (CE-T1WI) with the contrast-enhancing and peri-enhancing edema region, T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC), and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) images. The partial least squares (PLS) regression with fivefold cross-validation is used to analyze the correlation between different radiomic features and different modalities. The cross-validity analysis was performed to judge whether a new principal component or a new feature dimension can significantly improve the final prediction effect. The principal components with effective interpretation in all radiomic features were projected to a low-dimensional space (2D in this study). The effective features of the new projection mapping were then sent to the random forest classifier to predict the results. The performance of differentiating GBM from SBM was compared between the integrated radiomics model and other radiomics models or nonradiomics methods using the area under the receiver operating characteristics curve (AUC).ResultsThrough the cross-validity analysis of partial least squares, hundreds of radiomic features were projected into a new two-dimensional space to complete the construction of radiomics model. Compared with the combined radiomics model using DWI + 18F-FDG PET (AUC = 0.93, p = 0.014), cMRI + DWI (AUC = 0.89, p = 0.011), cMRI + 8F-FDG PET (AUC = 0.91, p = 0.015), and single radiomics model using cMRI (AUC = 0.85, p = 0.018), DWI (AUC = 0.84, p = 0.017), and 18F-FDG PET (AUC = 0.85, p = 0.421), the integrated radiomics model (AUC = 0.98) showed more efficient diagnostic performance. The integrated radiomics model (AUC = 0.98) also showed significantly better performance than any single ADC, SUV, or TBR parameter (AUC = 0.57–0.71, p &lt; 0.05). The integrated radiomics model showed better performance in the training (AUC = 0.98) and validation (AUC = 0.93) sets than any other models and methods, demonstrating robustness.ConclusionsWe developed an integrated radiomics model incorporating DWI and 18F-FDG PET, which improved the performance of differentiating GBM from SBM greatly.
Identification of Glycolysis-Related lncRNAs and the Novel lncRNA WAC-AS1 Promotes Glycolysis and Tumor Progression in Hepatocellular Carcinoma
Authors: Xia Xigang , Zhang Hao , Xia Peng , Zhu Yimin , Liu Jie , Xu Kequan , Yuan Yufeng 
Published: September 2021

BackgroundHigh glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched.MethodsWe analyzed the co-expression of glycolysis-related genes and lncRNAs in The Cancer Genome Atlas (TCGA) database to screen glycolysis-related lncRNAs. Further prognostic analysis and differential expression analysis were performed. We further analyzed the relationship between lncRNAs and tumor immune infiltration. Since WAC antisense RNA 1 (WAC-AS1) had the greatest effect on the prognosis among all screened lncRNAs and had a larger coefficient in the prognostic model, we chose WAC-AS1 for further verification experiments and investigated the function and mechanism of action of WAC-AS1 in hepatocellular carcinoma.ResultsWe screened 502 lncRNAs that have co-expression relationships with glycolytic genes based on co-expression analysis. Among them, 112 lncRNAs were abnormally expressed in liver cancer, and 40 lncRNAs were related to the prognosis of patients. Eight lncRNAs (WAC-AS1, SNHG3, SNHG12, MSC-AS1, MIR210HG, PTOV1-AS1, AC145207.5 and AL031985.3) were used to established a prognostic model. Independent prognostic analysis (P&lt;0.001), survival analysis (P&lt;0.001), receiver operating characteristic (ROC) curve analysis (AUC=0.779) and clinical correlation analysis (P&lt;0.001) all indicated that the prognostic model has good predictive power and that the risk score can be used as an independent prognostic factor (P&lt;0.001). The risk score and lncRNAs in the model were found to be related to a variety of immune cell infiltration and immune functions. WAC-AS1 was found to affect glycolysis and promote tumor proliferation (P&lt;0.01). WAC-AS1 affected the expression of several glycolysis-related genes (cAMP regulated phosphoprotein 19 (ARPP19), CHST12, MED24 and KIF2A) (P&lt;0.01). Under hypoxic conditions, WAC-AS1 regulated ARPP19 by sponging miR-320d to promote glucose uptake and lactate production (P&lt;0.01).ConclusionWe constructed a model based on glycolysis-related lncRNAs to evaluate the prognostic risk of patients. The risk score and lncRNAs in the model were related to immune cell infiltration. WAC-AS1 can regulate ARPP19 to promote glycolysis and proliferation by sponging miR-320d.
Associations Between Movement Behaviors and Emotional Changes in Toddlers and Preschoolers During Early Stages of the COVID-19 Pandemic in Chile
Authors: Aguilar-Farias Nicolas , Toledo-Vargas Marcelo , Miranda-Marquez Sebastian , Cortinez-O'Ryan Andrea , Martino-Fuentealba Pia , Cristi-Montero Carlos , Rodriguez-Rodriguez Fernando , Guarda-Saavedra Paula , Del Pozo Cruz Borja , Okely Anthony D. 
Published: September 2021

Background: There is limited evidence about emotional and behavioral responses in toddlers and preschoolers during the novel coronavirus (COVID-19) pandemic, particularly in Latin America.Objective: To assess associations between changes in movement behaviors (physical activity, screen time and sleeping) and emotional changes in toddlers and preschoolers during early stages of the pandemic in Chile.Methods: A cross-sectional study conducted from March 30th to April 27th, 2020. Main caregivers of 1- to 5-year-old children living in Chile answered an online survey that included questions about sociodemographic characteristics, changes in the child's emotions and behaviors, movement behaviors and caregivers' stress during the pandemic. Multiple linear regressions were used to assess the association between different factors and emotional changes in toddlers and preschoolers.Results: In total, 1727 caregivers provided complete data on emotional changes for children aged 2.9 ± 1.36 years old, 47.9% girls. A large proportion of toddlers and preschoolers in Chile experienced emotional and behavioral changes. Most caregivers reported that children “were more affectionate” (78.9%), “more restless” (65.1%), and ‘more frustrated' (54.1%) compared with pre-pandemic times. Apart from changes in movement behaviors, factors such as child age, caregivers' age and stress, and residential area (urban/rural) were consistently associated with changes in emotions and behaviors.Conclusion: The pandemic substantially affected the emotions and behaviors of toddlers and preschoolers in Chile. The findings suggest that supportive actions for caregivers may have a positive impact not only on adults but also on children. Mental health promotion programs should consider multilevel approaches in which the promotion of movement behaviors and support for caregivers should be essential pieces for future responses.
Maintenance of Elective Patient Care at Berlin University Children's Hospital During the COVID-19 Pandemic
Authors: Terliesner Nicolas , Rosen Alexander , Kaindl Angela M. , Reuter Uwe , Lippold Kai , Mall Marcus A. , Bernuth Horst von , Gratopp Alexander 
Published: September 2021

Background: In Germany, so far the COVID-19 pandemic evolved in two distinct waves, the first beginning in February and the second in July, 2020. The Berlin University Children's Hospital at Charité (BCH) had to ensure treatment for children not infected and infected with SARS-CoV-2. Prevention of nosocomial SARS-CoV-2 infection of patients and staff was a paramount goal. Pediatric hospitals worldwide discontinued elective treatments and established a centralized admission process.Methods: The response of BCH to the pandemic adapted to emerging evidence. This resulted in centralized admission via one ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatment during the first wave, but maintenance of elective care and decentralized admissions during the second wave. We report numbers of patients treated and of nosocomial SARS-CoV-2 infections during the two waves of the pandemic.Results: During the first wave, weekly numbers of inpatient and outpatient cases declined by 37% (p &lt; 0.001) and 29% (p = 0.003), respectively. During the second wave, however, inpatient case numbers were 7% higher (p = 0.06) and outpatient case numbers only 6% lower (p = 0.25), compared to the previous year. Only a minority of inpatients were tested positive for SARS-CoV-2 by RT-PCR (0.47% during the first, 0.63% during the second wave). No nosocomial infection of pediatric patients by SARS-CoV-2 occurred.Conclusion: In contrast to centralized admission via a ward exclusively dedicated to children with unclear SARS-CoV-2 status and discontinuation of elective treatments, maintenance of elective care and decentralized admission allowed the almost normal use of hospital resources, yet without increased risk of nosocomial infections with SARS-CoV-2. By this approach unwanted sequelae of withheld specialized pediatric non-emergency treatment to child and adolescent health may be avoided.
Association of Maternal Gestational Weight Gain With Left Ventricle Geometry and Function in Offspring at 4 Years of Age: A Prospective Birth Cohort Study
Authors: Wang Jian , Du Bowen , Wu Yujian , Li Zhuoyan , Chen Qian , Zhang Xi , Zhang Lin , Ye Yujiao , Wu Yurong , Chen Sun , Sun Kun 
Published: September 2021

Background: Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change.Methods: Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age.Results: Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [β = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [β = 0.149, (0.015,0.282)], interventricular septal thickness in systole [β = 0.027, (0.011,0.043)], and in diastole [β = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG.Conclusions: This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring.
Clinical Outcomes of Single vs. Two-Strain Probiotic Prophylaxis for Prevention of Necrotizing Enterocolitis in Preterm Infants
Authors: Priyadarshi Archana , Lowe Gemma , Saddi Vishal , Trivedi Amit , Luig Melissa , Tracy Mark 
Published: September 2021

Background: The administration of live microbiota (probiotic) via enteral route to preterm infants facilitates intestinal colonization with beneficial bacteria, resulting in competitive inhibition of the growth of pathogenic bacteria preventing gut microbiome dysbiosis. This dysbiosis is linked to the pathogenesis of necrotizing enterocolitis (NEC), an acquired multi-factorial intestinal disease characterized by microbial invasion of the gut mucosa, particularly affecting preterm infants. Probiotic prophylaxis reduces NEC; however, variations in strain-specific probiotic effects, differences in administration protocols, and synergistic interactions with the use of combination strains have all led to challenges in selecting the optimal probiotic for clinical use.Aim: To compare any differences in NEC rates, feeding outcomes, co-morbidities in preterm infants receiving single or two-strain probiotics over a 4-year period. The two-strain probiotic prophylaxis was sequentially switched over after 2 years to the single strain probiotic within this 4-year study period, in similar cohort of preterm infants.Methods: During two consecutive equal 2-year epochs, preterm infants (&lt;32 weeks and or with birth weight &lt;1,500 g) receiving two-strain (Lactobacillus acidophilus and Bifidobacterium bifidum) and single strain (Bifidobacterium breve M-16 V,) probiotic prophylaxis for prevention of NEC were included in this retrospective, observational study. The primary outcome included rates of NEC; secondary outcomes included prematurity related co-morbidities and feeding outcomes. Time to reach full enteral feeds was identified as the first day of introducing milk feeds at 150 ml/kg/day.Results: There were 180 preterm infants in the two-strain, 196 in the single strain group from the two equal consecutive 2-year epochs. There were no differences in the NEC rates, feeding outcomes, all-cause morbidities except for differences in rates of retinopathy of prematurity.Conclusion: In our intensive-care setting, clinical outcomes of single vs. two—strain probiotic prophylaxis for prevention of NEC were similar. Although our study demonstrates single strain probiotic may be equally effective than two-strain in the prevention of NEC, small sample size and low baseline incidence of NEC in our unit were not sufficiently powered to compare single vs. two-strain probiotic prophylaxis in preventing NEC. Further clustered randomized controlled trials are required to study the effects of single vs. multi-strain probiotic products for NEC prevention in preterm infants.