bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRIES: A Matlab Toolbox for Mapping the Responses to Intracranial Electrical Stimulation
Authors: Sun Kaijia , Wang Haixiang , Bai Yunxian , Zhou Wenjing , Wang Liang 
Published: June 2021

ProposeDirected cortical responses to intracranial electrical stimulation are a good standard for mapping inter-regional direct connectivity. Cortico-cortical evoked potential (CCEP), elicited by single pulse electrical stimulation (SPES), has been widely used to map the normal and abnormal brain effective network. However, automated processing of CCEP datasets and visualization of connectivity results remain challenging for researchers and clinicians. In this study, we develop a Matlab toolbox named MRIES (Mapping the Responses to Intracranial Electrical Stimulation) to automatically process CCEP data and visualize the connectivity results.MethodThe MRIES integrates the processing pipeline of the CCEP datasets and various methods for connectivity calculation based on low- and high-frequency signals with stimulation artifacts removed. The connectivity matrices are saved in different folders for visualization. Different visualization patterns (connectivity matrix, circle map, surface map, and volume map) are also integrated to the graphical user interface (GUI), which makes it easy to intuitively display and compare different connectivity measurements. Furthermore, one sample CCEP data set collected from eight epilepsy patients is used to validate the MRIES toolbox.ResultWe show the GUI and visualization functions of MRIES using one example CCEP data that has been described in a complete tutorial. We applied this toolbox to the sample CCEP data set to investigate the direct connectivity between the medial temporal lobe and the insular cortex. We find bidirectional connectivity between MTL and insular that are consistent with the findings of previous studies.ConclusionMRIES has a friendly GUI and integrates the full processing pipeline of CCEP data and various visualization methods. The MRIES toolbox, tutorial, and example data can be freely downloaded. As an open-source package, MRIES is expected to improve the reproducibility of CCEP findings and facilitate clinical translation.
Multimodal Simulation of a Novel Device for a Safe and Effective External Ventricular Drain Placement
Authors: Umana Giuseppe Emmanuele , Scalia Gianluca , Yagmurlu Kaan , Mineo Rosalia , Di Bella Simone , Giunta Matteo , Spitaleri Angelo , Maugeri Rosario , Graziano Francesca , Fricia Marco , Nicoletti Giovanni Federico , Tomasi Santino Ottavio , Raudino Giuseppe , Chaurasia Bipin , Bellocchi Gianluca , Salvati Maurizio , Iacopino Domenico Gerardo , Cicero Salvatore , Visocchi Massimiliano , Strigari Lidia 
Published: June 2021

BackgroundExternal ventricular drain (EVD) placement is mandatory for several pathologies. The misplacement rate of the EVD varies widely in literature, ranging from 12.3 to 60%. The purpose of this simulation study is to provide preliminary data about the possibility of increasing the safety of one of the most common life-saving procedures in neurosurgery by testing a new device for EVD placement.MethodsWe used a novel guide for positioning the ventricular catheter (patent RM2014A000376). The trajectory was assessed using 25 anonymized head CT scans. The data sets were used to conduct three-dimensional computer-based and combined navigation and augmented reality-based simulations using plaster models. The data set inclusion criteria were volumetric head CT scan, without midline shift, of patients older than 18. Evans’ index was used to quantify the ventricle’s size. We excluded patients with slit ventricles, midline shift, skull fractures, or complex skull malformations. The proximal end of the device was tested on the cadaver.ResultsThe cadaveric tests proved that a surgeon could use the device without any external help. The multimodal simulation showed Kakarla grade 1 in all cases but one (grade 2) on both sides, after right and left EVD placement. The mean Evans’ index was 0.28. The geometric principles that explain the device’s efficacy can be summarized by studying the properties of circumference and chord. The contact occurs, for each section considered, at the extreme points of the chord. Its axis, perpendicular to the plane tangent to the spherical surface at the entry point, corresponds to the direction of entry of the catheter guided by the instrument.ConclusionAccording to our multimodal simulation on cadavers, 3D computer-based simulation, 3D plaster modeling, 3D neuronavigation, and augmented reality, the device promises to offer safer and effective EVD placement. Further validation in future clinical studies is recommended.
Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
Authors: Zhang Tianqi , Beeharry Maneesh Kumarsing , Zheng Yanan , Wang Zhenqiang , Li Jianfang , Zhu Zhenggang , Li Chen 
Published: June 2021

BackgroundGastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly understood.MethodsBioinformatics and qRT-PCR assays were used to analyze the expression of SNHG12 in GC tissues and cells. In vitro and in vivo experiments were conducted to detect the role of SNHG12 in GC development. qRT-PCR, PCR, western blotting (WB), RNA binding protein immunoprecipitation (RIP), immunoprecipitation (IP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) were performed to investigate the underlying mechanisms by which SNHG12 promotes GC proliferation.ResultsSNHG12 was highly expressed in GC cells and tissues, and predicted poor survival. In vitro and in vivo assays showed that SNHG12 knockdown inhibited GC proliferation, while SNHG12 overexpression promoted GC proliferation. Further experiments confirmed that SNHG12 was mainly located in the cytoplasm and bound to HuR. Bioinformatics analysis predicted that YWHAZ was the common target of SNHG12 and HuR, and that the “SNHG12-HuR” complex enhanced the stability of YWHAZ mRNA. Furthermore, YWHAZ, which was highly expressed in GC, predicted poor survival and promoted GC proliferation by phosphorylating AKT. Rescue assays verified that SNHG12 promoted GC proliferation by activating the AKT/GSK-3β pathway.ConclusionsSNHG12 binds to HuR and stabilizes YWHAZ. SNHG12 promotes GC proliferation via modulation of the YWHAZ/AKT/GSK-3β axis in vitro and in vivo. Thus, SNHG12 could become a novel therapeutic target for anti-tumor therapy.
A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer
Authors: Liu Fen , Yang Zongcheng , Zheng Lixin , Shao Wei , Cui Xiujie , Wang Yue , Jia Jihui , Fu Yue 
Published: June 2021

BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.
Triple Combination Therapy With PD-1/PD-L1, BRAF, and MEK Inhibitor for Stage III–IV Melanoma: A Systematic Review and Meta-Analysis
Authors: Liu Ye , Zhang Xilan , Wang Guoying , Cui Xinchang 
Published: June 2021

Triple combination of anti-PD-1/PD-L1 immunotherapy and anti-BRAF plus anti-MEK targeted therapy is a promising antitumor strategy and is increasingly being used in clinical trials. To evaluate the safety and efficacy of triple combination of PD-1/PD-L1, BRAF, and MEK inhibition in patients diagnosed with stage III-IV melanoma, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, EMBASE, and Cochrane Library were searched for all studies published from inception to January 2021. The progression free survival (PFS), overall survival (OS), overall response rate (ORR), and risk of adverse events (AEs) were extracted by two independent investigators and pooled hazard ratio (HR) or risk ratio (RR) with 95% CI were determined using the random-effects model for data synthesis. Overall, five randomized controlled trials encompassing 1,266 patients with stage III-IV melanoma were selected. Triple combination therapy significantly improved PFS (HR = 0.71; 95% CI = 0.59 to 0.86; P = 0.0005) and 2-year OS (RR = 1.12; 95% CI = 1.03 to 1.23; P = 0.01), but had no impact on ORR (RR = 1.09; 95% CI = 0.91 to 1.30; P = 0.37) when compared with controlled treatment group. In addition, triple combination therapy was associated with increased risks of hypothyroidism, arthralgia, myalgia, ALT increased, AST increased, asthenia, and pyrexia compared with control group. Triple combination therapy of PD-1/PD-L1, BRAF, and MEK inhibition achieved better survival benefits but had higher incidence of some adverse events over two-drug combination or monotherapy. Further randomized controlled clinical trials are needed to verify our results.Systematic Review RegistrationPROSPERO 2021 CRD42021235845 Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235845.
Interferon Regulatory Factor 4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma
Authors: Li Xuanzong , Zhai Shujun , Zhang Jianbo , Zhang Dai , Wang Shijiang , Wang Linlin , Yu Jinming 
Published: June 2021

BackgroundImmune related interferon regulatory factor 4 (IRF4) is a member of the IRF family, whereas the clinical significance and possible role of IRF4 in lung adenocarcinoma (LUAD) remains unclear. We aimed to investigate the role of IRF4 in predicting the prognosis of LUAD patients.MethodsUsing The Cancer Genome Atlas (TCGA) database and our immunohistochemical (IHC) cohort, we analyzed the correlation between IRF4 expression and clinical characteristics, and the prognostic value of IRF4 was also evaluated in LUAD. The potential biological functions of IRF4 in LUAD were analyzed by Gene Set Enrichment Analysis (GSEA). The relationship between IRF4 and immune cell infiltration were evaluated by TISIDB database and our own IHC cohort. In addition, an immune checkpoint inhibitor (ICI) treated cohort from Gene Expression Omnibus database was used to determine the role of IRF4 in LUAD patients with immunotherapy.ResultsWe found that either mRNA or protein expression level of IRF4 was significantly higher in LUAD than in normal tissues (P &lt; 0.001). The elevate in IRF4 expression in LUAD was significantly associated with the earlier clinical stage (P = 0.002). Patients with LUAD and IRF4 high expression correlated with significant longer overall survival in both TCGA database (P &lt; 0.05) and our IHC-cohort (P = 0.001). Our results also demonstrated that IRF4 could serve as an independent favorable prognostic factor in patients with LUAD. GSEA analysis indicated that high IRF4 expression group enriched with several immune-related pathways, such as B cell receptor signaling pathway, T cell receptor signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LUAD, IRF4 positively correlated with several different immune infiltrations including various B cells, CD8+ T cells and CD4+ T cells both in mRNA and protein levels. Additionally, we found that the expression of IRF4 was positively associated with PD-1 and PD-L1 mRNA expression levels, and IRF4 high expression predicted moderate better survival in LUAD with immunotherapy (P = 0.071).ConclusionsOur results suggested that IRF4 was associated with higher B cells and T cells infiltration levels and might be a favorable prognostic biomarker in LUAD patients, whereas the potential prognostic role of IRF4 in ICI-treated patients needed further exploration.
Physical Fitness Plays a Crucial Mediator Role in Relationships Among Personal, Social, and Lifestyle Factors With Adolescents' Cognitive Performance in a Structural Equation Model. The Cogni-Action Project
Authors: Lemes Vanilson , Gaya Anelise R. , Sadarangani Kabir P. , Aguilar-Farias Nicolas , Rodriguez-Rodriguez Fernando , Martins Clarice Maria de Lucena , Fochesatto Camila , Cristi-Montero Carlos 
Published: June 2021

Background: The beneficial relationship between physical fitness and cognitive performance is affected and modulated by a wide diversity of factors that seem to be more sensitive during the development stage, particularly during early adolescence. This study aimed to examine the role of physical fitness considering the multivariate association between age, health-related quality of life (HRQOL), school vulnerability index (SVI), body mass index z-score (BMIz), physical activity, and sleep problems with the cognitive performance in boys and girls.Method: Participants were 1,196 adolescents aged 10–14 years (50.7% of boys) from Chile. Three physical fitness components and eight cognitive tasks were measured. BMIz was determined using growth references by age and sex, whereas questionaries were used to assess sleep problems, physical activity, and HRQOL. SVI was established according to the score given by the Chilean Government to educational establishments. We performed a structural equation model (SEM) to test multivariate associations among study' variables by sex.Results: Fitness was positively associated with boys' and girls' cognitive performance (β = 0.23 and β = 0.17; p = 0.001, respectively). Moreover, fitness presented a significant mediator role in the relationships between BMIz, SVI, and physical activity with cognitive performance (indirect effect). Additionally, SVI showed a negative association both direct and indirect effect in all three fitness components and all cognitive tasks, being this relationship stronger in girls than in boys.Conclusion: Our findings suggest that physical fitness and all its components play a crucial mediator role in the associations between several factors associated with adolescents' cognitive performance. Thereby, educational and health strategies should prioritise improving physical fitness through physical activity. They also should address other factors such as school vulnerability, obesity, and the early gender gap in a comprehensive approach boosting cognitive performance among early adolescents.Trial registration: Research Registry (ID: researchregistry5791).
Development and Validation of a Nomogram for Predicting Drug-Induced Acute Kidney Injury in Hospitalized Patients: A Case-Control Study Based on Propensity-Score Matching
Authors: Yu Chengxuan , Guo Daihong , Yao Chong , Zhu Yu , Liu Siyuan , Kong Xianghao 
Published: June 2021

Background: Drug-induced acute kidney injury (D-AKI) is associated with increased mortality and longer hospital stays. This study aims to establish a nomogram to predict the occurrence of D-AKI in hospitalized patients in a multi-drug environment.Methods: A single center retrospective study among adult hospitalized patients was conducted from July 2019 to September 2019 based on the Adverse Drug Events Active Surveillance and Assessment System-2 developed by our hospital. According to the propensity score matching algorithm, four controls per case were matched to eliminate the confounding bias caused by individual baseline variables. The predictors for D-AKI were obtained by logistic regression equation and used to establish the nomogram.Results: Among 51,772 hospitalized patients, 332 were diagnosed with D-AKI. After matching, 288 pairs and 1,440 patients were included in the study, including 1,005 cases in the development group and 435 cases in the validation group. Six variables were independent predictors for D-AKI: alcohol abuse, the concurrent use of nonsteroidal anti-inflammatory drugs or diuretics, chronic kidney disease, lower baseline red blood cell count and neutrophil count ≥7 × 109/L. The area under the curve (AUC) of the prediction model in the development group and validation group were 0.787 (95%CI, 0.752–0.823) and 0.788 (95%CI, 0.736–0.840), respectively. The GiViTI calibration belts showed that the model had a good prediction accuracy for the occurrence of D-AKI (p &gt; 0.05).Conclusion: This nomogram can help identify patients at high risk of D-AKI, which was useful in preventing the progression of D-AKI and treating it in the early stages.
Norm Values and Psychometric Properties of the 24-Item Demoralization Scale (DS-I) in a Representative Sample of the German General Population
Authors: Quintero Garzón Leonhard , Hinz Andreas , Koranyi Susan , Mehnert-Theuerkauf Anja 
Published: June 2021

Purpose: The Demoralization scale (DS-I) is a validated and frequently used instrument to assess existential distress in patients with cancer and other severe medical illness. The purpose of this study was to provide normative values derived from a representative German general population sample and to analyze the correlational structure of the DS-I.Methods: A representative sample of the adult German general population completed the DS-I (24 Items), the Emotion Thermometers (ET) measuring distress, anxiety, depression, anger, need for help, and the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-fatigue).Results: The sample consists of N = 2,407 adults (mean age = 49.8; range = 18–94 years), 55.7% women). The percentages of participants above the DS-I cutoff (≥30) was 13.5%. The mean scores of the DS-I dimensions were as follows: (1) loss of meaning and purpose: M = 2.78 SD = 4.49; (2) disheartenment: M = 3.19 SD = 4.03; (3) dysphoria M = 4.51 SD = 3.20; (4) sense of failure: M = 6.24 SD = 3.40; and for the DS-I total score: M = 16.72 SD = 12.74. Women reported significantly higher levels of demoralization than men, with effect sizes between d = 0.09 (Loss of Meaning) and d = 0.21 (Dysphoria). Age was not associated with demoralization in our sample. DS-I reliability was excellent (α = 0.94) and DS-I subscales were interrelated (r between 0.31 and 0.87) and significantly correlated with ET, especially depression, anxiety, and need for help and fatigue (r between 0.14 and 0.69).Conclusions: In order to use the DS-I as a screening tool in clinical practice and research the normative values are essential for comparing the symptom burden of groups of patients within the health care system to the general population. Age and sex differences between groups of patients can be accounted for using the presented normative scores of the DS-I.
Knowledge, Attitude and Acceptability of the Human Papilloma Virus Vaccine and Vaccination Among University Students in Indonesia
Authors: Khatiwada Madan , Kartasasmita Cissy , Mediani Henny Suzana , Delprat Christine , Van Hal Guido , Dochez Carine 
Published: June 2021

Introduction: Cervical cancer, a major consequence of persistent HPV infection, is the third most common cancer in women worldwide and has claimed around 311,000 women lives in 2018. The majority of these deaths took place in low- and middle-income countries (LMICs). In LMICs, where cervical cancer screening coverage is low, the HPV vaccine is a promising tool for preventing HPV infections and, thus, averting cervical cancer cases. In Indonesia, cervical cancer is the second most common cancer and HPV vaccination demonstration programs are underway in several provinces, but the HPV vaccine has not yet been introduced nationally. Since students are an important source of information for the community, and medical and nursing students are the future healthcare professionals, this study explored the knowledge, attitude, and acceptability of the HPV vaccine among University students in Indonesia.Methodology: A self-administered online questionnaire was used to assess the knowledge, attitude, and willingness of University students toward HPV vaccination.Result: A total of 433 students from Medical, Nursing, Social Sciences, and other faculties participated in the survey. It was identified that over 90% of the students were aware of cervical cancer and HPV, but only 68% knew about the HPV vaccine before participating in the study. Despite an average knowledge on the HPV vaccine, the students showed a strong willingness to receive the vaccine (95.8% acceptance rate). They believed that the HPV vaccine is safe and effective and that it will protect against HPV infection. The high cost and the lack of adequate information flow on HPV-related topics have been identified as potential barriers to the adoption of the HPV vaccine in Indonesia.Conclusion: Despite a high willingness for HPV vaccine uptake among students, there is a need to provide education on HPV vaccine-related topics to Indonesian students through awareness and training programs and improving the academic curriculum on vaccination for the long-term sustainability of the HPV vaccination program.