bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression
Authors: Bowers Sarah M. , Sundqvist Martina , Dancey Paul , Cabral David A. , Brown Kelly L. 
Published: September 2022

BackgroundAdenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T&gt;A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein.MethodsMammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7.ResultsIn addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2.ConclusionsThe impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2.
VEGF to CITED2 ratio predicts the collateral circulation of acute ischemic stroke
Authors: Lu Minyi , Liu Yuben , Xian Zhiqiang , Yu Xiaoyao , Chen Jian , Tan Sheng , Zhang Peidong , Guo Yang 
Published: September 2022

ObjectiveThe research objective was to evaluate the predicting role of the vascular endothelial growth factor to CBP/P300-interacting transactivator with Glu/Asp-rich C-terminal domain 2 Ratio (VEGF/CITED2) from peripheral blood mononuclear cells (PBMCs) in the collateral circulation of acute ischemic stroke (AIS).MethodsIn an observational study of patients with AIS, the western blot was applied to test the protein expression of VEGF and CITED2. Then, we calculated the VEGF/CITED2 and collected other clinical data. Binary logistic regression analysis between collateral circulation and clinical data was performed. Finally, receiver operating characteristic (ROC) curve analysis was used to explore the predictive value of VEGF/CITED2.ResultsA total of 67 patients with AIS were included in the study. Binary logistic regression analysis indicated the VEGF/CITED2 (OR 165.79, 95%CI 7.25–3,791.54, P = 0.001) was an independent protective factor. The ROC analyses showed an area under the ROC curve of the VEGF/CITED2 was 0.861 (95%CI 0.761–0.961). The optimal cutoff value of 1.013 for VEGF/CITED2 had a sensitivity of 89.1% and a specificity of 85.7%.ConclusionIn patients with AIS, the VEGF/CITED2 was related to the establishment of collateral circulation. The VEGF/CITED2 is a potentially valuable biomarker for predicting collateral circulation.Clinical trial registrationClinicalTrials.gov, identifier: NCT05345366.
The functional connectivity of the basal ganglia subregions changed in mid-aged and young males with chronic prostatitis/chronic pelvic pain syndrome
Authors: Lan Xi , Niu Xuan , Bai Wei-Xian , Li Hai-Ning , Zhu Xin-Yi , Ma Wen-Jun , Li Jian-Long , Dun Wang-Huan , Zhang Ming , He Juan 
Published: September 2022

BackgroundThe Basal ganglia (BG) played a crucial role in the brain-level mechanisms of chronic pain disorders. However, the functional changes of BG in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still poorly understood. This study investigated the BG subregions’ resting-state functional connectivity (rs-FC) in CP/CPPS patients compared with healthy controls.MethodsTwenty eight patients with CP/CPPS and 28 age- and education-matched healthy males underwent clinical measurements and 3T brain MR imaging, including T1-weighted structural images and resting-state functional imaging. The data were analyzed by the seeded-based rs-FC analysis. Then, a machine learning method was applied to assess the feasibility of detecting CP/CPPS patients through the changed rs-FC.ResultsCompared with healthy males, patients presented decreased rs-FC between the BG subregions and right middle cingulate cortex, and correlated with pain (r = 0.51, p-uncorrected = 0.005) and urinary symptoms (r = –0.4, p-uncorrected = 0.034). The left superior temporal gyrus and right supramarginal gyrus showed decreased rs-FC with the BG subregions as well. The area under the receiver operating characteristic curve of 0.943 (accuracy = 80%, F1-score = 80.6%) was achieved for the classification of CP/CPPS patients and healthy males with support vector machine (SVM) based on the changed rs-FC.ConclusionThese findings provide evidence of altered BG subregions’ rs-FC in CP/CPPS, which may contribute to our understanding of the BG’s role in CP/CPPS.
Utility of dual-layer spectral-detector CT imaging for predicting pathological tumor stages and histologic grades of colorectal adenocarcinoma
Authors: Chen Weicui , Ye Yongsong , Zhang Daochun , Mao Liting , Guo Lei , Zhang Hanliang , Du Xiaohua , Deng Weiwei , Liu Bo , Liu Xian 
Published: September 2022

ObjectivesTo assess the utility of Dual-layer spectral-detector CT (DLCT) in predicting the pT stage and histologic grade for colorectal adenocarcinoma (CRAC).MethodsA total of 131 patients (mean 62.7 ± 12.9 years; 72 female, 59 male) with pathologically confirmed CRAC (35 pT1-2, 61 pT3, and 35 pT4; 32 high grade and 99 low grade), who received dual-phase DLCT were enrolled in this retrospective study. Normalized iodine concentration (NIC), slope of the spectral HU curve (λHU), and effective atomic number (Eff-Z) were measured for each lesion by two radiologists independently. Intraobserver reliability and interobserver agreement were assessed. The above values were compared between three pT-stage and two histologic-grade groups. The correlation between the pT stages and above values were assessed. Receiver operating characteristic (ROC) curves were calculated to evaluate the diagnostic efficacy.ResultsIntra-class correlation coefficients were ranged from 0.856 to 0.983 for all measurements. Eff-Z [7.21(0.09) vs 7.31 (0.10) vs 7.35 (0.19)], NICAP [0.11 (0.05) vs 0.15 (0.08) vs 0.15 (0.08)], NICVP [0.27 (0.06) vs 0.34 (0.11) vs 0.35 (0.12)], λHUAP [1.20 (0.45) vs 1.93 (1.18) vs 2.37 (0.91)], and λHUVP [2.07 (0.68) vs 2.35 (0.62) vs 3.09 (1.07)] were significantly different among pT stage groups (all P&lt;0.001) and exhibited a positive correlation with pT stages (r= 0.503, 0.455, 0.394, 0.512, 0.376, respectively, all P&lt;0.001). Eff-Z [7.37 (0.10) vs 7.28 (0.08)], NICAP[0.20 (0.10) vs 0.13 (0.08)], NICVP[0.35 (0.07) vs 0.31 (0.11)], and λHUAP [2.59 (1.11) vs 1.63 (0.75)] in the high-grade group were markedly higher than those in the low-grade group (all P&lt;0.05). For discriminating the advanced- from early-stage CARC, the AUCs of Eff-Z, NICAP, NICVP, λHUAP, and λHUVP were 0.83, 0.80, 0.79, 0.86, and 0.68, respectively (all P&lt;0.001). For discriminating the high- from low-grade CARC, the AUCs of Eff-Z, NICAP, NICVP, and λHUAP were 0.81, 0.81, 0.64, and 0.81, respectively (all P&lt;0.05).ConclusionsThe quantitative parameters derived from DLCT may provide new markers for assessing pT stages and histologic differentiation in patients with CRAC.
Development and validation of a prognostic nomogram for bone metastasis from lung cancer: A large population-based study
Authors: Li Weihua , Guo Zixiang , Zou Zehui , Alswadeh Momen , Wang Heng , Liu Xuqiang , Li Xiaofeng 
Published: September 2022

BackgroundBone is one of the most common metastatic sites of advanced lung cancer, and the median survival time is significantly shorter than that of patients without metastasis. This study aimed to identify prognostic factors associated with survival and construct a practical nomogram to predict overall survival (OS) in lung cancer patients with bone metastasis (BM).MethodsWe extracted the patients with BM from lung cancer between 2011 and 2015 from the Surveillance, Epidemiology, and End Result (SEER) database. Univariate and multivariate Cox regressions were performed to identify independent prognostic factors for OS. The variables screened by multivariate Cox regression analysis were used to construct the prognostic nomogram. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability.ResultsA total of 7861 patients were included in this study and were randomly divided into training (n=5505) and validation (n=2356) cohorts using R software in a ratio of 7:3. Cox regression analysis showed that age, sex, race, grade, tumor size, histological type, T stage, N stage, surgery, brain metastasis, liver metastasis, chemotherapy and radiotherapy were independent prognostic factors for OS. The C-index was 0.723 (95% CI: 0.697-0.749) in the training cohorts and 0.738 (95% CI: 0.698-0.778) in the validation cohorts. The AUC of both the training cohorts and the validation cohorts at 3-month (0.842 vs 0.859), 6-month (0.793 vs 0.814), and 1-year (0.776 vs 0.788) showed good predictive performance, and the calibration curves also demonstrated the reliability and stability of the model.ConclusionsThe nomogram associated with the prognosis of BM from lung cancer was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.
The impact of merkel cell polyomavirus positivity on prognosis of merkel cell carcinoma: A systematic review and meta-analysis
Authors: Yang Aimin , Wijaya Wilson Adrian , Yang Lei , He Yinhai , Cen Ying , Chen Junjie 
Published: September 2022

IntroductionThere are numerous findings over the past decade have indicated that Merkel cell carcinoma (MCC) may have two pathways of pathogenesis: one related to ultraviolet irradiation and the other to the Merkel cell polyomavirus (MCPyV). However, the predictive and clinicopathological value of MCPyV positivity in MCC patients is still debatable. This article aims to examine the most recent data regarding this issue.MethodsThe thorough literature searches were conducted in the Medline Ovid, PubMed, Web of Science, the Cochrane CENTRAL Databases, and Embase Databases until December 31, 2021. The associations between overall survival (OS), Merkel cell carcinoma-specific survival (MSS), recurrence-free survival (RFS), progression-free survival (PFS), clinicopathologic features, and MCPyV positivity were examined in our meta-analysis.ResultsThis meta-analysis included a total of 14 studies involving 1595 patients. Our findings demonstrated a significant correlation between MCPyV positivity and improved OS (HR=0.61, 95%CI:0.39-0.94, P=0.026) and improved PFS (HR=0.61, 95% CI: 0.45-0.83, P=0.002). MCPyV positivity did not, however, appear to be associated with either MSS (HR=0.61, 95%CI: 0.28-1.32, P=0.209) or RFS (HR= 0.93, 95%CI: 0.37-2.34, P=0.873). Pooled results revealed a correlation between MCPyV positivity with gender (male vs. female, OR=0.606, 95%CI: 0.449-0.817, P=0.001), histopathological stage (AJCC I-II vs. III-IV, OR=1.636, 95%CI: 1.126-2.378, P=0.010) and primary site (head and neck vs. other sites, OR=0.409, 95%CI: 0.221-0.757, P=0.004).ConclusionThese results imply that MCPyV positivity may present a promising predictive biomarker for human MCC and call for further study.
Predicting IDH subtype of grade 4 astrocytoma and glioblastoma from tumor radiomic patterns extracted from multiparametric magnetic resonance images using a machine learning approach
Authors: Kandalgaonkar Pashmina , Sahu Arpita , Saju Ann Christy , Joshi Akanksha , Mahajan Abhishek , Thakur Meenakshi , Sahay Ayushi , Epari Sridhar , Sinha Shwetabh , Dasgupta Archya , Chatterjee Abhishek , Shetty Prakash , Moiyadi Aliasgar , Agarwal Jaiprakash , Gupta Tejpal , Goda Jayant S. 
Published: September 2022

Background and purposeSemantic imaging features have been used for molecular subclassification of high-grade gliomas. Radiomics-based prediction of molecular subgroups has the potential to strategize and individualize therapy. Using MRI texture features, we propose to distinguish between IDH wild type and IDH mutant type high grade gliomas.MethodsBetween 2013 and 2020, 100 patients were retrospectively analyzed for the radiomics study. Immunohistochemistry of the pathological specimen was used to initially identify patients for the IDH mutant/wild phenotype and was then confirmed by Sanger’s sequencing. Image texture analysis was performed on contrast-enhanced T1 (T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on MR image slices followed by single-slice multiple sampling image augmentation. Both whole tumor multislice segmentation and single-slice multiple sampling approaches were used to arrive at the best model. Radiomic features were extracted, which included first-order features, second-order (GLCM—Grey level co-occurrence matrix), and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression, followed by radiomic classification using Support Vector Machine (SVM) and a 10-fold cross-validation strategy for model development. The area under the Receiver Operator Characteristic (ROC) curve and predictive accuracy were used as diagnostic metrics to evaluate the model to classify IDH mutant and wild-type subgroups.ResultsMultislice analysis resulted in a better model compared to the single-slice multiple-sampling approach. A total of 164 MR-based texture features were extracted, out of which LASSO regression identified 14 distinctive GLCM features for the endpoint, which were used for further model development. The best model was achieved by using combined T1C and T2W MR images using a Quadratic Support Vector Machine Classifier and a 10-fold internal cross-validation approach, which demonstrated a predictive accuracy of 89% with an AUC of 0.89 for each IDH mutant and IDH wild subgroup.ConclusionA machine learning classifier of radiomic features extracted from multiparametric MRI images (T1C and T2w) provides important diagnostic information for the non-invasive prediction of the IDH mutant or wild-type phenotype of high-grade gliomas and may have potential use in either escalating or de-escalating adjuvant therapy for gliomas or for using targeted agents in the future.
Proteomics and phosphoproteomics of chordoma biopsies reveal alterations in multiple pathways and aberrant kinases activities
Authors: Hang Jing , Ouyang Hanqiang , Wei Feng , Zhong Qihang , Yuan Wanqiong , Jiang Liang , Liu Zhongjun 
Published: September 2022

BackgroundChordoma is a slow-growing but malignant subtype of bone sarcoma with relatively high recurrence rates and high resistance to chemotherapy. It is urgent to understand the underlying regulatory networks to determine more effective potential targets. Phosphorylative regulation is currently regarded as playing a significant role in tumorigenesis, and the use of tyrosine kinase inhibitors in clinical practice has yielded new promise for the treatment of a variety of sarcoma types.Materials and methodsWe performed comprehensive proteomic and phosphoproteomic analyses of chordoma using four-dimensional label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis. The potential aberrantly expressed kinases and their functions were validated using western blotting and CCK-8 assays.ResultsCompared with paired normal muscle tissues, 1,139 differentially expressed proteins (DEPs) and 776 differentially phosphorylated proteins (DPPs) were identified in chordoma tumor tissues. The developmentally significant Wnt-signaling pathway and oxidative phosphorylation were aberrant in chordoma. Moreover, we predicted three kinases (AURA, CDK9, and MOK) with elevated activity by kinase-pathway network analysis (KiPNA) and verified their increased expression levels. The knockdown of these kinases markedly suppressed chordoma cell growth, and this was also the case for cells treated with the CDK9 inhibitor AZD4573. We additionally examined 208 proteins whose expression and phosphorylation levels were synergetically altered.ConclusionsWe herein depicted the collective protein profiles of chordomas, providing insight into chordomagenesis and the potential development of new therapeutic targets.
Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis
Authors: Zhu Zeen , Wang Xueni , Zhang Wunai , Gong Mengyuan , Zhang Simei , Yang Bao , Qu Bolun , Wu Zheng , Ma Qingyong , Wang Zheng , Qian Weikun 
Published: September 2022

PurposeThe anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis.MethodsCCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits.ResultsThe growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH–GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin.ConclusionHuaier can activate ferroptosis by inducing autophagy in PCs.
Radiation-induced sarcomas: A single referral cancer center experience and literature review
Authors: Laurino Simona , Omer Ludmila Carmen , Albano Francesco , Marino Graziella , Bianculli Antonella , Solazzo Angela Pia , Sgambato Alessandro , Falco Geppino , Russi Sabino , Bochicchio Anna Maria 
Published: September 2022

Background and objectiveThe oncogenic effect of ionizing radiation is widely known. Sarcomas developing after radiation therapy (RT), termed “iatrogenic disease of success”, represent a growing problem, since the advancements in cancer management and screening programs have increased the number of long-term cancer survivors. Although many patients have been treated with radiation therapy, only few data are available on radiation-induced sarcomas (RIS).MethodsWe examined the medical and radiological records of 186 patients with histologically proven soft tissue and bone sarcomas, which referred to IRCCS CROB Centro di Riferimento Oncologico della Basilicata from January 2009 to May 2022. Among them, seven patients received a histological diagnosis of secondary RIS, according to Cahan’s criteria. Clinicopathological features and treatment follow-up data of RIS patients were retrospectively analyzed.ResultsAmong these secondary RIS, five arose in irradiated breast cancer (5/2,570, 0.19%) and two in irradiated head and neck cancer (2/1,986, 0.10%) patients, with a mean onset latency time of 7.3 years. The histology of RIS was one desmoid tumor, two angiosarcomas, one chondrosarcoma, two leiomyosarcomas, and one undifferentiated pleomorphic sarcoma. Out of the seven RIS, one received radiotherapy, one received electrochemotherapy (ECT), one received a second-line chemotherapy, three were subjected to three lines of chemotherapy, and one underwent radiofrequency ablation, chemotherapy, and ECT. Median survival time is 36 months. No significant survival differences were found stratifying patients for age at RT, latency time, and age at RIS diagnosis.ConclusionsRIS represents a possible complication for long-survivor cancer patients. Therefore, adherence to a strict follow-up after the radiation treatment is recommended to allow early diagnosis and optimal management of RIS patients. After the planned follow-up period, considering the long-term risk to develop a RIS, a specific multispecialty survivorship care plan could be of benefit for patients.
Visualizing the knowledge domains and research trends of childhood asthma: A scientometric analysis with CiteSpace
Authors: Wu Jinghua , Yu Yi , Yao Xinmeng , Zhang Qinzhun , Zhou Qin , Tang Weihong , Huang Xianglong , Ye Chengyin 
Published: September 2022

BackgroundAsthma is one of the most common chronic diseases in children globally. In recent decades, advances have been made in understanding the mechanism, diagnosis, treatment and management for childhood asthma, but few studies have explored its knowledge structure and future interests comprehensively.ObjectiveThis scientometric study aims to understand the research status and emerging trends of childhood asthma.MethodsCiteSpace (version 5.8.R3) was used to demonstrate national and institutional collaborations in childhood asthma, analyze research subjects and journal distribution, review research keywords and their clusters, as well as detect research bursts.ResultsA total of 14,340 publications related to childhood asthma were extracted from Web of Science (core database) during January 2011 to December 2021. The results showed that academic activities of childhood asthma had increased steadily in the last decade. Most of the research was conducted by developed countries while China, as a developing country, was also actively engaged in this field. In addition to subjects of allergy and immunology, both public health aspects and ecological environmental impacts on the disease were emphasized recently in this research field. Keywords clustering analysis indicated that research on asthma management and atopy was constantly updated and became the two major research focuses recently, as a significant shift in research hotspots from etiology and diagnosis to atopic march and asthma management was identified. Subgroup analysis for childhood asthma management and atopy suggested that caregiver- or physician-based education and interventions were emerging directions for asthma management, and that asthma should be carefully studied in the context of atopy, together with other allergic diseases.ConclusionsThis study presented a comprehensive and systematic overview of the research status of childhood asthma, provided clues to future research directions, and highlighted two significant research trends of asthma management and atopy in this field.