bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of fat-free mass in a multi-ethnic cohort of infants using bioelectrical impedance: Validation against the PEA POD
Authors: Lyons-Reid Jaz , Ward Leigh C. , Derraik José G. B. , Tint Mya-Thway , Monnard Cathriona R. , Ramos Nieves Jose M. , Albert Benjamin B. , Kenealy Timothy , Godfrey Keith M. , Chan Shiao-Yng , Cutfield Wayne S. 
Published: October 2022

BackgroundBioelectrical impedance analysis (BIA) is widely used to measure body composition but has not been adequately evaluated in infancy. Prior studies have largely been of poor quality, and few included healthy term-born offspring, so it is unclear if BIA can accurately predict body composition at this age.AimThis study evaluated impedance technology to predict fat-free mass (FFM) among a large multi-ethnic cohort of infants from the United Kingdom, Singapore, and New Zealand at ages 6 weeks and 6 months (n = 292 and 212, respectively).Materials and methodsUsing air displacement plethysmography (PEA POD) as the reference, two impedance approaches were evaluated: (1) empirical prediction equations; (2) Cole modeling and mixture theory prediction. Sex-specific equations were developed among ∼70% of the cohort. Equations were validated in the remaining ∼30% and in an independent University of Queensland cohort. Mixture theory estimates of FFM were validated using the entire cohort at both ages.ResultsSex-specific equations based on weight and length explained 75–81% of FFM variance at 6 weeks but only 48–57% at 6 months. At both ages, the margin of error for these equations was 5–6% of mean FFM, as assessed by the root mean squared errors (RMSE). The stepwise addition of clinically-relevant covariates (i.e., gestational age, birthweight SDS, subscapular skinfold thickness, abdominal circumference) improved model accuracy (i.e., lowered RMSE). However, improvements in model accuracy were not consistently observed when impedance parameters (as the impedance index) were incorporated instead of length. The bioimpedance equations had mean absolute percentage errors (MAPE) &lt; 5% when validated. Limits of agreement analyses showed that biases were low (&lt; 100 g) and limits of agreement were narrower for bioimpedance-based than anthropometry-based equations, with no clear benefit following the addition of clinically-relevant variables. Estimates of FFM from BIS mixture theory prediction were inaccurate (MAPE 11–12%).ConclusionThe addition of the impedance index improved the accuracy of empirical FFM predictions. However, improvements were modest, so the benefits of using bioimpedance in the field remain unclear and require further investigation. Mixture theory prediction of FFM from BIS is inaccurate in infancy and cannot be recommended.
Epidemiological trends of female breast and gynecologic cancers in adolescents and young adults in China from 1990 to 2019: Results from the Global Burden of Disease Study 2019
Authors: Zhao Yuting , Qiu Pei , Yan Lutong , Li Shouyu , Yang Zejian , Zhang Huimin , He Jianjun , Zhou Can 
Published: October 2022

BackgroundResearch on the incidence, mortality, and disability-adjusted life years (DALYs) of female breast and gynecologic cancers (FeBGCs) and the relevant risk factors for adolescents and young adults (AYAs) are valuable for policy-making in China. We aimed to estimate the incidence, deaths, and DALYs and predict epidemiological trends of FeBGCs among AYAs in China between 1990 and 2019.MethodsData from the 2019 Global Burden of Disease (GBD) study between 1990 and 2019 in 195 countries and territories were retrieved. Data about the number of FeBGC incident cases, deaths, DALYs, age-standardized rates (ASRs), and estimated annual percentage changes (EAPCs) were extracted. A comparative risk assessment framework was performed to estimate the risk factors attributable to breast cancer deaths and DALYs, and autoregressive integrated moving average (ARIMA) models were fitted for time-series analysis to predict female cancer morbidity and mortality among Chinese AYAs until 2030.ResultsIn 2019, there are 61,038 incidence cases, 8,944 deaths, and 529,380 DALYs of FeBGCs among the AYAs in China, respectively. The estimated annual percentage change (EAPC) values were positive scores (&gt;0) in ASIRs and negative scores (&lt;0) in ASMR and ASDR. Furthermore, in 2030, the incidence rate of FeBGCs would grow to 30.49 per 100,000 in China, while the mortality rate would maintain a steady state. Of the deaths and DALYs, diet high in red meat was the greatest contributor to breast cancer, while a high body mass index (BMI) was the greatest contributor to cervical, ovarian, and uterine cancers.ConclusionThe increasing Chinese FeBGC burden is mainly observed in AYAs and non-red meat diet, and the control of body weight could reduce FeBGC burden in China.
IGF2BP3 promotes progression of gallbladder carcinoma by stabilizing KLK5 mRNA in N6-methyladenosine-dependent binding
Authors: Zhang Junzhe , Yang Kaini , Bu Junfeng , Yan Jiayan , Hu Xiaoqiang , Liu Ke , Gao Si , Tang Shuibin , Gao Lili , Chen Wei 
Published: October 2022

BackgroundRecent studies have reported that IGF2BP3 is linked to the pathogenesis of various malignancies. Since IGF2BP3 is associated with poor outcomes of gallbladder carcinoma (GBC), we aimed to explore the association between its N6-methyladenosine (m6A) RNA methylation and GBC progression.MethodsBioinformatic analysis of GSE136982, GSE104165, and RNA-seq was performed. In vitro and in vivo gain- and loss-of-function assays were done. qPCR, Western blotting, and IHC were conducted in cells or in collected clinical tissue samples. RNA immunoprecipitation, RNA stability measurement, methylated RNA immunoprecipitation, and dual-luciferase reporter assays were performed in this study.ResultsThe expression of IGF2BP3 was higher in GBC tissues than in peritumoral tissues. Functions such as cell proliferation and migration, both in vitro and in vivo, were inhibited by downregulation of IGF2BP3. The analysis of RNA-seq indicated that KLK5 was a downstream target of IGF2BP3. The expression of KLK5 was measured in GBC cells and tumor samples. It was found to be positively correlated with IGF2BP3 level. Upon IGF2BP3 depletion, ectopic expression of KLK5 could rescue cell function in part. Mechanistically, we found that IGF2BP3 directly binds to KLK5 mRNA and regulates its stability in an m6A-dependent manner. As a result, inhibition of KLK5 decreased the expression of PAR2, and deregulated phospho-Akt. Using bioinformatic prediction combined with miRNA microarray analysis, we identified that let-7g-5p is an inhibitor of IGF2BP3, and let-7g-5p expression was negatively correlated with IGF2BP3. Overexpression of let-7g-5p affected the aggressive phenotype of GBC cells by deregulating IGF2BP3, and inhibiting the KLK5/PAR2/AKT axis.ConclusionsOur data showed that IGF2BP3 is associated with the aggressive phenotype of GBC. Mechanistically, IGF2BP3 activated the PAR2/AKT axis by stabilizing KLK5 mRNA in an m6A-dependent manner. The loss of let-7g-5p enhanced the expression of IGF2BP3 and improved GBC progression. Thus, IGF2BP3 plays a crucial role in GBC, and the let-7g-5p/IGF2BP3/KLK5/PAR2 axis may be a therapeutic target for GBC.
The antihyperlipidemic drug potassium piperonate impairs the migration and tumorigenesis of breast cancer cells via the upregulation of miR-31
Authors: Tian Xiaoxia , Lu Junping , Nanding Kathleen , Zhang Linzhe , Liu Yanrong , Mailisu Mailisu , Morigen Morigen , Fan Lifei 
Published: October 2022

BackgroundBreast cancer is the second cause of cancer death in women, and tumor metastasis is the primary cause of mortality. Due to the involvement of many regulatory molecules and signaling pathways, the occurrence and development of metastases needs to be further studied. MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that have been shown to play an important role in the diagnosis and treatment of many diseases, as well as representing an attractive candidate for metastasis control. In this study, we investigated the mechanism of potassium piperonate (GBK) in impairing breast cancer cell invasion and metastasis by targeting miR-31.MethodsBreast cancer cells, either treated with GBK or left untreated, were assessed for migration and invasion capacities using wound healing and transwell assays. GBK-targeted miRNAs were identified and verified using RT-qPCR. Western blotting was used to validate the changes in expression levels of miR-31-targeted genes. Methylation specific PCR was performed to detect the effect of GBK on the methylation levels of the lncRNA LOC554202 host gene. The synergistic effect of GBK and the chemotherapy drug cisplatin (DDP) on breast cancer cells was verified using cell proliferation, colony formation, and RT-qPCR assays in vitro, and the tumor xenograft model in vivo.ResultsWe found that miR-31 was the main target of GBK. GBK treatment affected the epigenetic modification at CpG sites by downregulating DNA methyltransferases. Thus, the CpG-associated methylation levels of lncRNA LOC554202 decreased significantly, and in turn upregulated both miR-31 and its host gene LOC554202 in breast cancer cells. We also observed the significant inhibition of miR-31-targeted genes following GBK treatment, including RHOA, WAVE3, and SATB2, with functions closely related to cancer cell invasion, migration, and proliferation. Furthermore, we revealed that the combination of GBK and DDP had a synergistic effect on inhibiting the proliferation of breast cancer cells in vitro and in vivo, especially in triple negative breast cancer (TNBC).ConclusionsThis study investigated the target of GBK in the inhibition of breast cancer migration and invasion, and the underlying mechanisms involved, providing theoretical support for the development of GBK as an auxiliary drug for clinical treatment.
Prognostic role of pre-treatment serum ALB in Patients with oropharyngeal cancer: A retrospective cohort study
Authors: Zhu Jiajia , Li Liang , Duan Yuansheng , Wu Yansheng , Wang Xudong 
Published: October 2022

BackgroundThe morbidity of oropharyngeal cancer (OPC) is continuing to rise in numerous developed countries. An accurate prognostic assessment is needed to evaluate the malignant degree or risk classification to optimize treatment. Albumin (ALB) as an independent prognostic indicator of cancer survival has been established in previous studies. This study investigated the prognostic value of pre-treatment serum ALB in OPC patients.MethodsThe clinicopathological data of 246 patients diagnosed with OPC from 2010 to 2019 were analyzed retrospectively. Analyze the relationship between ALB and clinicopathological characteristics of patients. The optimal cut-off values for ALB were determined via Cutoff Finder (Method for cutoff determination: Survival: significance (log-rank test)). To determine the independent prognostic factors, the Cox proportional hazards model was used to perform univariate and multivariate analyses of the serum ALB levels related to overall survival (OS) and disease-free survival (DFS).ResultsThe optimal cut-off point for ALB was 39.15 g/L determined via Cutoff Finder. Serum ALB levels were significantly associated with age (P=0.047), Presence of comorbidity (P=0.009), Charlson score index (P=0.007), Hemoglobin (P&lt;0.001), Neutrophil to Lymphocyte Ratio (P=0.002), Albumin-To-Alkaline Phosphatase Ratio (P&lt;0.001), Alkaline phosphatase (P=0.005), T stage (P=0.016), and HPV status (P=0.002). In the univariate and multivariate analyses, ALB was found to be an independent prognostic indicator for DFS (HR =0.39, 95% CI:0.23-0.66, P=0.000) and OS (HR =0.46, 95% CI: 0.25-0.83, P=0.01) in OPC patients.ConclusionsPre-treatment serum ALB could serve as a valuable prognostic biomarker for the prognostic stratification of OPC patients.
Automatic volumetric diagnosis of hepatocellular carcinoma based on four-phase CT scans with minimum extra information
Authors: Ling Yating , Ying Shihong , Xu Lei , Peng Zhiyi , Mao Xiongwei , Chen Zhang , Ni Jing , Liu Qian , Gong Shaolin , Kong Dexing 
Published: October 2022

SummaryWe built a deep-learning based model for diagnosis of HCC with typical images from four-phase CT and MEI, demonstrating high performance and excellent efficiency.ObjectivesThe aim of this study was to develop a deep-learning-based model for the diagnosis of hepatocellular carcinoma.Materials and methodsThis clinical retrospective study uses CT scans of liver tumors over four phases (non-enhanced phase, arterial phase, portal venous phase, and delayed phase). Tumors were diagnosed as hepatocellular carcinoma (HCC) and non-hepatocellular carcinoma (non-HCC) including cyst, hemangioma (HA), and intrahepatic cholangiocarcinoma (ICC). A total of 601 liver lesions from 479 patients (56 years ± 11 [standard deviation]; 350 men) are evaluated between 2014 and 2017 for a total of 315 HCCs and 286 non-HCCs including 64 cysts, 178 HAs, and 44 ICCs. A total of 481 liver lesions were randomly assigned to the training set, and the remaining 120 liver lesions constituted the validation set. A deep learning model using 3D convolutional neural network (CNN) and multilayer perceptron is trained based on CT scans and minimum extra information (MEI) including text input of patient age and gender as well as automatically extracted lesion location and size from image data. Fivefold cross-validations were performed using randomly split datasets. Diagnosis accuracy and efficiency of the trained model were compared with that of the radiologists using a validation set on which the model showed matched performance to the fivefold average. Student’s t-test (T-test) of accuracy between the model and the two radiologists was performed.ResultsThe accuracy for diagnosing HCCs of the proposed model was 94.17% (113 of 120), significantly higher than those of the radiologists, being 90.83% (109 of 120, p-value = 0.018) and 83.33% (100 of 120, p-value = 0.002). The average time analyzing each lesion by our proposed model on one Graphics Processing Unit was 0.13 s, which was about 250 times faster than that of the two radiologists who needed, on average, 30 s and 37.5 s instead.ConclusionThe proposed model trained on a few hundred samples with MEI demonstrates a diagnostic accuracy significantly higher than the two radiologists with a classification runtime about 250 times faster than that of the two radiologists and therefore could be easily incorporated into the clinical workflow to dramatically reduce the workload of radiologists.
Severe pneumonia caused by human adenovirus type 55 in children
Authors: Zhang Dongwei , Chen Yi , Shi Tingting , Fan Huifeng , Tian Xingui , Zhou Rong , Huang Li , Yang Diyuan , Lu Gen 
Published: October 2022

BackgroundEmerging human adenovirus type 55 (HAdV-55) causes fatal pneumonia in adults. There is a lack of studies on severe pneumonia caused by HAdV-55 in children.MethodsWe conducted a retrospective review of pediatric patients hospitalized at Guangzhou Women and Children’s Medical Center with severe pneumonia from 2013 to 2020 who had human adenovirus (HAdV) detected in throat samples or bronchoalveolar lavage fluid using RT-PCR. The presence of HAdV-55 was determined by PCR amplification of the hypervariable regions of the hexon gene. Demographic, clinical, etiological, and outcome data were collected and analyzed.ResultsOver the eight-year period, HAdV-55 was detected in three severe and six critical pediatric pneumonia patients. None of the patients had any underlying diseases, and had a median age of 18 months (range, 6–108 months). The male to female ratio was 2:1. All patients presented with fever and cough, and three patients presented with wheezing and diarrhea. Six patients had coinfections with other respiratory pathogens, such as bacteria, Mycoplasma pneumoniae and fungi. Three critical patients developed plastic bronchitis (PB). The median lengths of invasive mechanical ventilation and hospital stay of the critical patients were 10 (8, 28.75) days and 25 (13, 32.25) days, respectively. Three critical patients died, although two of them received extracorporeal membrane oxygenation (ECMO) and blood purification. Three surviving patients developed post-infectious bronchiolitis obliterans (PIBO) at the follow-up.ConclusionsHAdV-55 can cause fatal pneumonia in children, and shows a high rate of co-infection with other respiratory pathogens and a poorer prognosis combined with PB. Thus, HAdV-55 may be an important subtype in patients with HAdV-induced pneumonia who develop PIBO.
Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation
Authors: Shao Yanfei , Chen Jingxian , Hu Yujie , Wu Yuan , Zeng Hualin , Lin Shuying , Lai Qiying , Fan Xiaodong , Zhou Xueliang , Zheng Minhua , Gao Bizhen , Sun Jing 
Published: October 2022

Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation.Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC.Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs.Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.
Phospholipid-mimicking block, graft, and block-graft copolymers for phase-transition microbubbles as ultrasound contrast agents
Authors: Huang Jianbo , Wang Hong , Huang Lei , Zhou Yuqing 
Published: October 2022

Background: Lipid and polymer microbubbles (MBs) are widely used as ultrasound contrast agents in clinical diagnosis, and possess great potential in ultrasound-mediated therapy due to their drug loading function. However, overcoming the limitations of stability and echo enhancement of MBs are still a considerable challenge.Methods: A series novel block, graft and block-graft copolymers was proposed and prepared in this work, and these copolymers were used as shells to encapsulate perfluoropentane as ultrasound contrast agents. First, block, graft and block-graft copolymers with different topological structures were prepared. Then, these copolymers were prepared into block copolymer phase-transition MBs, graft copolymer phase-transition MBs, and block-graft copolymer phase-transition MBs, respectively. Finally, the dexamethasone was used for drug-loaded phase-transition microbubbles model to explore the potential of theranostic microbubbles.Results: Finally, these three resulting copolymer MBs with average size of 4–5 μm exhibited well enhancement of ultrasound imaging under the influence of different frequencies and mechanical index, and they exhibited a longer contrast-enhanced ultrasound imaging time and higher resistance to mechanical index compared with SonoVue in vitro and in vivo. In vitro drug release results also showed that these copolymer MBs could encapsulate dexamethasone drugs, and the drug release could be enhanced by ultrasonic triggering. These copolymer MBs were therapeutic MBs for targeted triggering drug release.Conclusion: Therefore, the feasibility of block, graft, and block-graft copolymers as ultrasonic contrast agents was verified, and their ultrasonic enhancement performance in vitro and in vivo was compared. The ultrasound contrast agents developed in this work have excellent development potential in comprehensive diagnosis and treatment.
Comparison of different methods to assess tacrolimus concentration intra-patient variability as potential marker of medication non-adherence
Authors: Kostalova Barbora , Mala-Ladova Katerina , Sulkova Sylvie Dusilova , Denhaerynck Kris , De Geest Sabina , Maly Josef 
Published: October 2022

Background and objective: Non-adherence to tacrolimus commonly manifests as low drug concentrations and/or high intra-patient variability (IPV) of concentrations across multiple measurements. We aimed to compare several methods of tacrolimus IPV calculation and evaluate how well each reflects blood concentration variation due to medication non-adherence in kidney transplant recipients.Methods: This Czech single-center retrospective longitudinal study was conducted in 2019. All outpatients ≥18 years of age, ≥3 months post-transplant, and on tacrolimus-based regimens were approached. After collecting seven consecutive tacrolimus concentrations we asked participating patients to self-report adherence to immunosuppressants (BAASIS© scale). The IPV of tacrolimus was calculated as the medication level variability index (MLVI), the coefficient of variation (CV), the time-weighted CV, and via nonlinearly modeled dose-corrected trough levels. These patient-level variables were analyzed using regression analysis. Detected nonlinearities in the dose-response curve were controlled for by adding tacrolimus dosing and its higher-order terms as covariates, along with self-reported medication adherence levels.Results: Of 243 patients using tacrolimus, 42% (n = 102) reported medication non-adherence. Non-adherence was associated with higher CVs, higher time-weighted CVs, and lower dose-corrected nonlinearly modeled trough levels; however, it was not associated with MLVIs. All of the significant operationalizations suggested a weak association that was similar across the applied methods.Discussion and conclusion: Implementation non-adherence was reflected by higher CV or time-weighted CV and by lower blood concentrations of tacrolimus. As an additional tool for identifying patients at risk for non-adherence, simple IPV calculations incorporated into medical records should be considered in everyday clinical practice.