bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cuproptosis-related signature associated with the tumor environment and prognosis of patients with glioma
Authors: Wang Weichen , Lu Zhichao , Wang Maoyu , Liu Zongheng , Wu Bing , Yang Chengkai , Huan He , Gong Peipei 
Published: August 2022

BackgroundCopper ions are essential for cellular physiology. Cuproptosis is a novel method of copper-dependent cell death, and the cuproptosis-based signature for glioma remains less studied.MethodsSeveral glioma datasets with clinicopathological information were collected from TCGA, GEO and CGGA. Robust Multichip Average (RMA) algorithm was used for background correction and normalization, cuproptosis-related genes (CRGs) were then collected. The TCGA-glioma cohort was clustered using ConsensusClusterPlus. Univariate Cox regression analysis and the Random Survival Forest model were performed on the differentially expressed genes to identify prognostic genes. The cuproptosis-signature was constructed by calculating CuproptosisScore using Multivariate Cox regression analysis. Differences in terms of genomic mutation, tumor microenvironment, and enrichment pathways were evaluated between high- or low-CuproptosisScore. Furthermore, drug response prediction was carried out utilizing pRRophetic.ResultsTwo subclusters based on CRGs were identified. Patients in cluster2 had better clinical outcomes. The cuproptosis-signature was constructed based on CuproptosisScore. Patients with higher CuproptosisScore had higher WHO grades and worse prognosis, while patients with lower grades were more likely to develop IDH mutations or MGMT methylation. Univariate and Multivariate Cox regression analysis demonstrated CuproptosisScore was an independent prognostic factor. The accuracy of the signature in prognostic prediction was further confirmed in 11 external validation datasets. In groups with high-CuproptosisScore, PIK3CA, MUC16, NF1, TTN, TP53, PTEN, and EGFR showed high mutation frequency. IDH1, TP53, ATRX, CIC, and FUBP1 demonstrated high mutation frequency in low-CuproptosisScore group. The level of immune infiltration increased as CuproptosisScore increased. SubMap analysis revealed patients with high-CuproptosisScore may respond to anti-PD-1 therapy. The IC50 values of Bexarotene, Bicalutamide, Bortezomib, and Cytarabine were lower in the high-CuproptosisScore group than those in the low-CuproptosisScore group. Finally, the importance of IGFBP2 in TCGA-glioma cohort was confirmed.ConclusionThe current study revealed the novel cuproptosis-based signature might help predict the prognosis, biological features, and appropriate treatment for patients with glioma.
Low protein diet supplemented with ketoacids on muscle wasting in chronic kidney disease: A clinical trial
Authors: Zhang Yueyue , Gu Lijie , Wang Ling , Rong Shu , Yuan Weijie 
Published: August 2022

AimNutrition is an important part of the care of patients with chronic kidney disease (CKD). However, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We carried out this study to find out whether a low-protein diet supplemented with ketoacids (LPD + KA) could improve muscle wasting in patients with CKD.MethodsPatients were enrolled in this non-blind, parallel-group, randomized trial assessing the nutritional status of CKD, randomly assigned to either the LPD + KA group or conventional LPD group. Blood samples such as Hemoglobin, Cystatin C, Creatinine, BUN, Albumin, Pre- Albumin, Glycerin Trilaurate, and Cholesterol were measured at baseline and every 3 months. The parameters of skeletal muscle and other body composition were assessed before and after dietary intervention for 12 months.ResultsA total of 58 patients with CKD completed the study and were available for further analysis. The hemoglobin and albumin were observed to be markedly improved in the LPD + KA group during the follow-up as compared to baseline. Body mass index and total body water index of both groups were increased upon follow-up but the increase in the LPD + KA group was comparatively higher. Moreover, an increase in body fat%, skeletal muscle mass index, and appendicular skeletal muscle mass index was observed in both groups between baseline and follow-up, but it was statistically insignificant.ConclusionThis study did not find a significant improvement of KAs on muscle wasting, and a long time or more indices study may need to find the effects of the LPD + KA diets.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT02568020].
A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing
Authors: Guo Kai , Duan Xinxin , Zhao Jiahui , Sun Boyu , Liu Xiaoming , Zhao Zongmao 
Published: August 2022

Background:Glioma is the most fatal neoplasm among the primary intracranial cancers. Necroptosis, a form of programmed cell death, is correlated with tumor progression and immune response. But, the role of necroptosis-related genes (NRGs) in glioma has not been well-uncovered.Methods:Single-cell and bulk RNA sequencing data, obtained from publicly accessed databases, were used to establish a necroptosis-related gene signature for predicting the prognosis of glioma patients. Multiple bioinformatics algorithms were conducted to evaluate the efficacy of the signature. The relative mRNA level of each signature gene was validated by quantitative real-time reverse transcription PCR (qRT-PCR) in glioma cell lines compared to human astrocytes.Results:In this predicted prognosis model, patients with a high risk score showed a shorter overall survival, which was verified in the testing cohorts. The signature risk score was positively related with immune cell infiltration and some immune check points, such as CD276 (B7-H3), CD152 (CTLA-4), CD223 (LAG-3), and CD274 (PD-L1). Single-cell RNA sequencing analysis confirmed that the glioma microenvironment consists of various immune cells with different markers. The eight NRGs of the signature were detected to be expressed in several immune cells. QRT-PCR results verified that all the eight signature genes were differentially expressed between human astrocytes and glioma cells.Conclusion:The eight NRGs correlate with the immune microenvironment of glioma according to our bioinformatics analysis. This necroptosis-related gene signature may evaluate the precise methodology of predicting prognosis of glioma and provide a novel thought in glioma investigation.
Development and validation of a prognosis prediction model based on 18 endoplasmic reticulum stress-related genes for patients with lung adenocarcinoma
Authors: Shu Long , Liu Shuang , Tao Yongguang 
Published: August 2022

BackgroundEndoplasmic reticulum (ER) stress had a crucial impact on cell survival, proliferation, and metastasis in various cancers. However, the role of ER stress in lung adenocarcinoma remains unclear.MethodGene expression and clinical data of lung adenocarcinoma (LUAD) samples were extracted from The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. ER stress score (ERSS) was constructed based on hub genes selected from 799 ER stress-related genes by least absolute shrinkage and selection operator (LASSO) regression. A Cox regression model, integrating ERSS and the TNM stage, was developed to predict overall survival (OS) in TCGA cohort and was validated in GEO cohorts. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and gene mutation analyses were performed to further understand the molecular features of ERSS. The tumor immune infiltration was evaluated by ESTIMATE, CIBERSORT, and xCell algorithms. The receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the risk model. p&lt; 0.05 was considered statistically significant.ResultsOne hundred fifty-seven differentially expressed genes (DEGs) were identified between tumor and para-carcinoma tissues, and 45 of them significantly correlated with OS. Next, we identified 18 hub genes and constructed ERSS by LASSO regression. Multivariate analysis demonstrated that higher ERSS (p&lt; 0.0001, hazard ratio (HR) = 3.8, 95%CI: 2.8–5.2) and TNM stage (p&lt; 0.0001, HR = 1.55, 95%CI: 1.34–1.8) were independent predictors for worse OS. The prediction model integrating ERSS and TNM stage performed well in TCGA cohort (area under the curve (AUC) at five years = 0.748) and three GEO cohorts (AUC at 5 years = 0.658, 0.717, and 0.739). Pathway enrichment analysis showed that ERSS significantly correlated with unfolded protein response. Meanwhile, pathways associated with the cell cycle, growth, and metabolism were significantly enriched in the high ERSS group. Patients with SMARCA4, TP53, and EGFR mutations showed significantly higher ERSS (p = 4e−04, 0.0027, and 0.035, respectively). Tissues with high ERSS exhibited significantly higher infiltration of M1 macrophages, activated dendritic cells, and lower infiltration of CD8+ T cells and B cells, which indicate an activated tumor antigen-presenting but suppressive immune response status.ConclusionWe developed and validated an ER stress-related risk model that exhibited great predictive value for OS in patients with LUAD. Our work also expanded the understanding of the role of ER stress in LUAD.
Predictive value of NLR and PLR in response to preoperative chemotherapy and prognosis in locally advanced gastric cancer
Authors: Wang Wentao , Tong Yilin , Sun Shulan , Tan Yuen , Shan Zexing , Sun Fan , Jiang Chengyao , Zhu Yanmei , Zhang Jianjun 
Published: August 2022

PurposePretreatment neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios are markers of systemic inflammation. In patients with locally advanced gastric cancer (GC), the utility of these ratios in predicting tumor regression grade (TRG) after neoadjuvant chemotherapy (NCT) remains unclear.MethodsThis retrospective study examined 283 locally advanced GC patients who underwent NCT and radical surgery. The receiver operating characteristic (ROC) curve analysis and the Youden index were applied to identify optimal NLR/PLR cutpoints. The Kaplan–Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Univariate/multivariate analyses were conducted by the logistic regression method.ResultsTRG grade proved significantly worse in patients with high values of both NLR and PLR whether in univariate (OR = 3.457; p = 0.044) or multivariate (OR = 6.876; p = 0.028) analysis. The degree of tumor differentiation was an independent predictive factor for TRG (OR = 2.874; p = 0.037) in multivariate analysis. In the subgroup analyses, NLR predicted OS (p = 0.04) and DFS (p = 0.03) in female patients, whereas PLR was predictive of both OS (p = 0.026) and DFS (p = 0.018) in patients with clinical TNM stage 3 disease and dissected lymph node counts &lt;28. PLR similarly predicted OS in patients &lt;65 years old (p = 0.049), those with positive lymph nodes (p = 0.021), or those with moderate or poorly differentiated tumors (p = 0.049).ConclusionPretreatment NLR and PLR together serve to independently predict TRG after NCT and surgery in patients with locally advanced GC. Screening for patients with high NLR and PLR values may allow them to benefit upfront from alternatives to NCT.
Publication trends and hotspots of drug resistance in colorectal cancer during 2002-2021: A bibliometric and visualized analysis
Authors: Zhao Peng-yue , Jiao Ya-nan , Ma Zhao-fu , Yan Yang , Li Yu-xuan , Hu Shi-dong , Li Song-yan , Du Xiao-hui 
Published: August 2022

BackgroundChemotherapy, radiotherapy, targeted therapy and immunotherapy have demonstrated expected clinical efficacy, while drug resistance remains the predominant limiting factor to therapeutic failure in patients with colorectal cancer (CRC). Although there have been numerous basic and clinical studies on CRC resistance in recent years, few publications utilized the bibliometric method to evaluate this field. The objective of current study was to provide a comprehensive analysis of the current state and changing trends of drug resistance in CRC over the past 20 years.MethodsThe Web of Science Core Collection (WOSCC) was utilized to extracted all studies regarding drug resistance in CRC during 2002-2021. CiteSpace and online platform of bibliometrics were used to evaluate the contributions of various countries/regions, institutions, authors and journals in this field. Moreover, the recent research hotspots and promising future trends were identified through keywords analysis by CiteSpace and VOSviewer.Results1451 related publications from 2002 to 2021 in total were identified and collected. The number of global publications in this field has increased annually. China and the USA occupied the top two places with respect to the number of publications, contributing more than 60% of global publications. Sun Yat-sen University and Oncotarget were the institution and journal which published the most papers, respectively. Bardelli A from Italy was the most prolific writer and had the highest H-index. Keywords burst analysis identified that “Growth factor receptor”, “induced apoptosis” and “panitumumab” were the ones with higher burst strength in the early stage of this field. Analysis of keyword emergence time showed that “oxaliplatin resistance”, “MicroRNA” and “epithelial mesenchymal transition (EMT)” were the keywords with later average appearing year (AAY).ConclusionsThe number of publications and research interest on drug resistance in CRC have been increasing annually. The USA and China were the main driver and professor Bardelli A was the most outstanding researcher in this field. Previous studies have mainly concentrated on growth factor receptor and induced apoptosis. Oxaliplatin resistance, microRNA and EMT as recently appeared frontiers of research that should be closely tracked in the future.
The “chicken-leg anastomosis”: Low-cost tissue-realistic simulation model for esophageal atresia training in pediatric surgery
Authors: Palmisani Francesca , Sezen Patrick , Haag Elisabeth , Metzelder Martin L. , Krois Wilfried 
Published: August 2022

IntroductionShifting the training from the operating room (OR) to simulation models has been proven effective in enhancing patient safety and reducing the learning time to achieve competency and increase the operative efficiency. Currently the field of pediatric surgery only offers few low-cost trainers for specialized training and these feature predominantly artificial and often unrealistic tissue. The aim of this study was to develop an easy access low-cost tissue-realistic simulation model for open training of esophageal atresia and to evaluate the acceptance in trainees and junior pediatric surgeons.Materials and methodsThe model is fashioned using reconfigured chicken skin from a chicken leg. To create a model of esophageal atresia, the chicken skin is dissected off the muscle and reconfigured around a foley catheter balloon to recreate the proximal pouch and a feeding tube to recreate the distal pouch. Surrounding structures such as the tracheo-esophageal fistula and the azygos vein can be easily added, obtaining a realistic esophageal atresia (Type C) prototype. Evaluation of model construction, usage and impact on user were performed by both a self-assessment questionnaire with pre- and post-training questions as well as observer-based variables and a revised Objective Structured Assessment of Technical Skills (OSATS) score.ResultsA total of 10 participants were constructing and using the model at two different timepoints. OSATS score for overall performance was significantly higher (p = 0.005, z = −2.78) during the second observational period [median (MD): 4,95% confidence interval CI: 3.4, 5.1] compared to the first (MD: 3, 95% CI 2.4, 4.1). Self-reported boost in confidence after model usage for performing future esophageal atresia (EA) repair and bowel anastomosis (BA) in general was significantly higher (EA: U = 1, z = −2.3, p = 0.021, BA: U = 1, z = −2.41, p = 0.016) in participants with more years in training/attending status (EA MD:5, BA MD: 5.5) compared to less experienced participants (EA MD: 1.5, BA: 1).ConclusionOur easy access low-cost simulation model represents a feasible and tissue realistic training option to increase surgical performance of pediatric surgical trainees outside the OR.
Development and validation of a nomogram for the early prediction of drug resistance in children with epilepsy
Authors: Geng Hua , Chen Xuqin 
Published: August 2022

Background and purposeThis study aimed to effectively identify children with drug-resistant epilepsy (DRE) in the early stage of epilepsy, and take personalized interventions, to improve patients' prognosis, reduce serious comorbidity, and save social resources. Herein, we developed and validated a nomogram prediction model for children with DRE.MethodsThe training set was patients with epilepsy who visited the Children's Hospital of Soochow University (Suzhou Industrial Park, Jiangsu Province, China) between January 2015 and December 2017. The independent risk factors for DRE were screened by univariate and multivariate logistic regression analyses using SPSS21 software. The nomogram was designed according to the regression coefficient. The nomogram was validated in the training and validation sets. Internal validation was conducted using bootstrapping analyses. We also externally validated this instrument in patients with epilepsy from the Children's Hospital of Soochow University (Gusu District, Jiangsu Province, China) and Yancheng Maternal and Child Health Hospital between January 2018 and December 2018. The nomogram's performance was assessed by concordance (C-index), calibration curves, as well as GiViTI calibration belts.ResultsMultivariate logistic regression analysis of 679 children with epilepsy from the Children's Hospital of Soochow University (Suzhou Industrial Park, Jiangsu Province, China) showed that onset age&lt;1, status epilepticus (SE), focal seizure, &gt; 20 pre-treatment seizures, clear etiology (caused by genetic, structural, metabolic, or infectious), development and epileptic encephalopathy (DEE), and neurological abnormalities were all independent risk factors for DRE. The AUC of 0.92 for the training set compared to that of 0.91 for the validation set suggested a good discrimination ability of the prediction model. The C-index was 0.92 and 0.91 in the training and validation sets. Additionally, both good calibration curves and GiViTI calibration belts (P-value: 0.849 and 0.291, respectively) demonstrated that the predicted risks had strong consistency with the observed outcomes, suggesting that the prediction model in both groups was perfectly calibrated.ConclusionA nomogram prediction model for DRE was developed, with good discrimination and calibration in the training set and the validation set. Furthermore, the model demonstrated great accuracy, consistency, and prediction ability. Therefore, the nomogram prediction model can aid in the timely identification of DRE in children.
Intraoperative Neuromonitoring for Pediatric Pelvic Tumors
Authors: Crocoli Alessandro , Martucci Cristina , Randi Franco , Ponzo Viviana , Trucchi Alessandro , De Pasquale Maria Debora , Marras Carlo Efisio , Inserra Alessandro 
Published: August 2022

BackgroundTumors of the pre-sacral and sacral spaces are a rare occurrence in children. Total tumor excision is required due to the significant risk of relapse in the event of partial surgery, but the surgical procedure may lead to postoperative problems such as urinary, sexual, and anorectal dysfunctions. Intraoperative neuromonitoring (IONM) has gained popularity in recent years as a strategy for preventing the onset of neurologic impairments by combining several neurophysiological techniques. The aim of our study is to describe the experience of Bambino Gesù Children’s Hospital in the use of IONM in pediatric pelvic surgery.Materials and MethodsThe data of patients treated for pelvic malignancies at Bambino Gesù Children’s Hospital from 2015 to 2019 were retrospectively collected. All patients were assessed from a neurologic and neuro-urologic point of view at different time-points (before and immediately after surgery, after 6 months, and 1-year follow-up). They were all monitored during a surgical procedure using multimodal IONM including transcranial motor evoked potentials (TcMEP), triggered-EMG (t-EMG), pudendal somatosensory evoked potentials (PSSEP), and bulbocavernosus reflex (BCR).ResultsDuring the study period, ten children underwent pelvic tumor removal at our Institution. In all cases, intraoperative neurophysiological recordings were stable and feasible. The preservation of neurophysiological response at the same intensity during surgical procedures correlated with no new deficits for all neurophysiological techniques.DiscussionAlthough the impact of the IONM on surgical strategies and clinical follow-up is unknown, this preliminary experience suggests that the appropriate use of several neurophysiological techniques can influence both the radicality of pelvic tumor removal and the neurological and urological outcome at clinical follow-up. Finally, because of the highly complex anatomy and inter-individual variances, this is especially useful in this type of surgery.
Flipped classroom improves student learning outcome in Chinese pharmacy education: A systematic review and meta-analysis
Authors: Peng Wei , Xiong Ying , Wei Jingwen , Chen Xiuping , Huai Wenying , He Sike , Liu Dan , Tian Xiaoping , Tang Songqi , Chen Yunhui 
Published: August 2022

Background: The application of flipped classroom (FC) pedagogy has recently become increasingly popular in Chinese pharmacy education. However, its effectiveness in improving student learning has not yet been assessed. This study aimed to evaluate the effects of teaching with such pedagogical approach by examining studies that compare the FC approach with the traditional lecture-based learning (LBL) module through a systematic review and meta-analysis.Methods: Seven databases, including the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Wanfang database, and China Biomedical Literature Database, were searched from the inception to 30 June 2021, to identify eligible articles of randomized controlled studies. The primary outcomes included the theoretical and experimental test scores, and the secondary outcomes were the results from questionnaires about the number of students who preferred the FC or endorsed its improving effects on their learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency. The quantitative synthesis was conducted with Revman V.5.3 software following the Cochrane Reviewer’s Handbook guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Results: Eleven eligible studies published from 2017 to 2020 enrolling 1,200 students were included in this meta-analysis. The quantitative synthesis demonstrated that the FC module presented an overall more significant effectiveness over traditional LBL approach for Chinese pharmacy education in improving student academic performance as measured by theoretical test scores (SMD = 1.08, 95% CI: 0.60–1.56, p &lt; 0.00001) and experimental test scores (MD = 6.62, 95% CI: 4.42–8.82, p &lt; 0.00001). Further sub-group analysis revealed that the preferable effectiveness of FC was also evident in both theory-oriented (SMD = 0.77, 95% CI: 0.10–1.45, p &lt; 0.00001) and experiments-oriented courses (MD = 6.52, 95% CI: 3.48–9.56, p &lt; 0.00001) for both undergraduate (SMD = 0.84, 95% CI: 0.31–1.37, p &lt; 0.00001) and 3-year junior-college students (MD = 8.17, 95% CI: 6.44–9.89, p &lt; 0.00001). Additionally, analysis on the questionnaire outcomes revealed that more respondents preferred for FC and endorsed its improvement effects on developing students’ learning enthusiasm, self-learning ability, thinking skills, communication skills, and learning efficiency.Conclusion: Current evidence suggests that FC pedagogical approach can effectively improve student learning outcomes and is applicable to Chinese pharmacy education.