bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does acupuncture therapy affect peripheral inflammatory cytokines of major depressive disorder? A protocol for the systematic review and meta-analysis
Authors: Zhao Ya-Nan , Zhang Shuai , Chen Yu , Wang Yu , Chen Hao , Duan Yu-Ting , Li Shao-Yuan , Zhang Zi-Xuan , Wang Yi-Fei , Xin Chen , Li Liang , Rong Pei-Jing 
Published: November 2022

BackgroundAcupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis.Methods and analysisThis study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD.DiscussionAcupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD.Systematic review registration[PROSPERO], identifier [CRD42021289207 on 04 December 2021].
Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs
Authors: Zhang Yinjiang , Zhang Yashuo , Yao Rongfei , He Xu , Zhao Linyi , Zuo Xiangyu , Lu Binan , Pang Zongran 
Published: November 2022

BackgroundIron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.Materials and methodsGSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.ResultsTwenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.ConclusionOur findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.
Prognostic prediction by a novel integrative inflammatory and nutritional score based on least absolute shrinkage and selection operator in esophageal squamous cell carcinoma
Authors: Feng Jifeng , Wang Liang , Yang Xun , Chen Qixun , Cheng Xiangdong 
Published: November 2022

BackgroundThis study aimed to establish and validate a novel predictive model named integrative inflammatory and nutritional score (IINS) for prognostic prediction in esophageal squamous cell carcinoma (ESCC).Materials and methodsWe retrospectively recruited 494 pathologically confirmed ESCC patients with surgery and randomized them into training (n = 346) or validation group (n = 148). The least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) regression analysis was initially used to construct a novel predictive model of IINS. The clinical features and prognostic factors with hazard ratio (HRs) and 95% confidence intervals (CIs) grouped by IINS were analyzed. Nomogram was also established to verify the prognostic value of IINS.ResultsAccording to the LASSO Cox PH regression analysis, a novel score of IINS was initially constructed based on 10 inflammatory and nutritional indicators with the optimal cut-off level of 2.35. The areas under the curve (AUCs) of IINS regarding prognostic ability in 1-year, 3-years, and 5-years prediction were 0.814 (95% CI: 0.769–0.854), 0.748 (95% CI: 0.698–0.793), and 0.792 (95% CI: 0.745–0.833) in the training cohort and 0.802 (95% CI: 0.733–0.866), 0.702 (95% CI: 0.621–0.774), and 0.748 (95% CI: 0.670–0.816) in the validation cohort, respectively. IINS had the largest AUCs in the two cohorts compared with other prognostic indicators, indicating a higher predictive ability. A better 5-years cancer-specific survival (CSS) was found in patients with IINS ≤ 2.35 compared with those with IINS &gt; 2.35 in both training cohort (54.3% vs. 11.1%, P &lt; 0.001) and validation cohort (53.7% vs. 18.2%, P &lt; 0.001). The IINS was then confirmed as a useful independent factor (training cohort: HR: 3.000, 95% CI: 2.254–3.992, P &lt; 0.001; validation cohort: HR: 2.609, 95% CI: 1.693–4.020, P &lt; 0.001). Finally, an IINS-based predictive nomogram model was established and validated the CSS prediction (training set: C-index = 0.71 and validation set: C-index = 0.69, respectively).ConclusionPreoperative IINS is an independent predictor of CSS in ESCC. The nomogram based on IINS may be used as a potential risk stratification to predict individual CSS and guide treatment in ESCC with radical resection.
A novel approach for eliminating metal artifacts based on MVCBCT and CycleGAN
Authors: Cao Zheng , Gao Xiang , Chang Yankui , Liu Gongfa , Pei Yuanji 
Published: November 2022

PurposeTo develop a metal artifact reduction (MAR) algorithm and eliminate the adverse effects of metal artifacts on imaging diagnosis and radiotherapy dose calculations.MethodsCycle-consistent adversarial network (CycleGAN) was used to generate synthetic CT (sCT) images from megavoltage cone beam CT (MVCBCT) images. In this study, there were 140 head cases with paired CT and MVCBCT images, from which 97 metal-free cases were used for training. Based on the trained model, metal-free sCT (sCT_MF) images and metal-containing sCT (sCT_M) images were generated from the MVCBCT images of 29 metal-free cases and 14 metal cases, respectively. Then, the sCT_MF and sCT_M images were quantitatively evaluated for imaging and dosimetry accuracy.ResultsThe structural similarity (SSIM) index of the sCT_MF and metal-free CT (CT_MF) images were 0.9484, and the peak signal-to-noise ratio (PSNR) was 31.4 dB. Compared with the CT images, the sCT_MF images had similar relative electron density (RED) and dose distribution, and their gamma pass rate (1 mm/1%) reached 97.99% ± 1.14%. The sCT_M images had high tissue resolution with no metal artifacts, and the RED distribution accuracy in the range of 1.003 to 1.056 was improved significantly. The RED and dose corrections were most significant for the planning target volume (PTV), mandible and oral cavity. The maximum correction of Dmean and D50 for the oral cavity reached 90 cGy.ConclusionsAccurate sCT_M images were generated from MVCBCT images based on CycleGAN, which eliminated the metal artifacts in clinical images completely and corrected the RED and dose distributions accurately for clinical application.
Investigation of the impact of machine operating parameters on beam delivery time and its correlation with treatment plan characteristics for synchrotron-based proton pencil beam spot scanning system
Authors: Liang Xiaoying , Beltran Chris , Liu Chunbo , Shen Jiajian , Bues Martin , Furutani Keith M. 
Published: November 2022

PurposeTo investigate the beam delivery time (BDT) reduction due to the improvement of machine parameters for Hitachi synchrotron-based proton PBS system.MethodsBDTs for representative treatment plans were calculated to quantitatively estimate the BDT improvement from our 2015 system at Mayo Clinic in Arizona to our system to be implemented in 2025 at Mayo Clinic in Florida, and to a hypothetical future system. To specifically assess how each incremental improvement in the operating parameters reduced the total BDT, for each plan, we simulated the BDT 10,368 times with various settings of the nine different operating parameters. The effect of each operating parameter on BDT reduction and its correlation with treatment plan characteristics were analyzed. The optimal number of multiple energy extraction (MEE) layers per spill for different systems was also investigated.ResultsThe median (range) decrease in BDT was 60% (56%-70%) from the 2015 to the 2025 system. The following incremental improvement in parameters of the 2015 system for the 2025 system played an important role in this decreased BDT: beam intensity (8 to 20 MU/s), recapture efficiency (50% to 80%), number of MEE layers per spill (4 to 8), scanning magnet preparation and verification time (1.9 to 0.95 msec), and MEE layer switch time (200 to 100 msec). Reducing the total spill change time and scanning magnet preparation and verification time from those of the 2025 system further reduced BDT in the hypothetical future system. 8 MEE layers per spill is optimal for a system with 50% recapture efficiency; 16 MEE layers per spill is optimal for a system with 80% recapture efficiency; and more than 16 MEE layers per spill is beneficial only for a system close to 100% recapture efficiency.ConclusionsWe systematically studied the effect of each machine operating parameter on the reduction in total BDT and its correlation with treatment plan characteristics. Our findings will aid new and existing synchrotron-based proton beam therapy centers to make balanced decisions on BDT benefits vs. costs when considering machine upgrade or new system selection.
Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response
Authors: Zhang Haoyu , Cao Ke , Li Ganbin , Zhai Zhiwei , Wei Guanghui , Qu Hao , Wang Zhenjun , Han Jiagang 
Published: November 2022

AimTo analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT.Materials and methodsThe data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response.ResultsOf 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P &lt; 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P &lt; 0.001). Besides, less patients’ CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P &lt; 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response.ConclusionApproximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.
Applying post-neoadjuvant pathologic stage as prognostic tool in esophageal squamous cell carcinoma
Authors: Han Weiming , Deng Wei , Wang Qifeng , Ni Wenjie , Li Chen , Zhou Zongmei , Liang Jun , Chen Dongfu , Feng Qinfu , Bi Nan , Zhang Tao , Wang Xin , Deng Lei , Wang Wenqing , Liu Wenyang , Wang Jianyang , Xue Qi , Mao Yousheng , Liu Xiangyang , Fang Dekang , Li Jian , Wang Dali , Zhao Jun , Xiao Zefen 
Published: November 2022

BackgroundIt is still uncertain whether the newly released eighth American Joint Committee on Cancer (AJCC) post-neoadjuvant pathologic (yp) tumor-node-metastasis (TNM) stage for esophageal carcinoma can perform well regarding patient stratification. The current study aimed to assess the prognostication ability of the eighth AJCC ypTNM staging system and attempted to explore how to facilitate the staging system for more effective evaluation of prognosis.Materials and methodsA total of 486 patients treated with neoadjuvant radiotherapy/chemoradiotherapy (nRT/CRT) were enrolled. ypN stage was reclassified by recursive partitioning. Prognostic performance, monotonicity, homogeneity, and discriminatory of yp and modified yp (myp) staging systems were assessed by time-dependent receiver operating characteristic (ROC), linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and Akaike information criterion (AIC).ResultsThe ypT stage, ypN stage, and pathologic response were significant prognostic factors of overall survival. Survival was not discriminated well using the eighth AJCC ypN stage and ypTNM stage. Recursive partitioning reclassified mypN0-N2 as metastasis in 0, 1–2, and ≥3 regional lymph nodes. Applying the ypT stage, mypN stage, and pathologic response to construct the myp staging system, the myp stage performed better in time-dependent ROC, linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and AIC.ConclusionsThe eighth AJCC ypTNM staging system performed well in differentiating prognosis to some extent. By reclassifying the ypN stage and enrolling pathologic response as a staging element, the myp staging system holds significant potential for prognostic discrimination.
Specific signature biomarkers highlight the potential mechanisms of circulating neutrophils in aneurysmal subarachnoid hemorrhage
Authors: Weng Weipin , Cheng Fan , Zhang Jie 
Published: November 2022

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating hemorrhagic stroke with high disability and mortality. Neuroinflammation and the immunological response after aSAH are complex pathophysiological processes that have not yet been fully elucidated. Therefore, attention should be paid to exploring the inflammation-related genes involved in the systemic response to the rupture of intracranial aneurysms.Methods: The datasets of gene transcriptomes were downloaded from the Gene Expression Omnibus database. We constructed a gene co-expression network to identify cluster genes associated with aSAH and screened out differentially expressed genes (DEGs). The common gene was subsequently applied to identify hub genes by protein-protein interaction analysis and screen signature genes by machine learning algorithms. CMap analysis was implemented to identify potential small-molecule compounds. Meanwhile, Cibersort and ssGSEA were used to evaluate the immune cell composition, and GSEA reveals signal biological pathways.Results: We identified 602 DEGs from the GSE36791. The neutrophil-related module associated with aSAH was screened by weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis. Several small molecular compounds were predicted based on neutrophil-related genes. MAPK14, ITGAM, TLR4, and FCGR1A have been identified as crucial genes involved in the peripheral immune activation related to neutrophils. Six significant genes (CST7, HSP90AB1, PADI4, PLBD1, RAB32, and SLAMF6) were identified as signature biomarkers by performing the LASSO analysis and SVM algorithms. The constructed machine learning model appears to be robust by receiver-operating characteristic curve analysis. The immune feature analysis demonstrated that neutrophils were upregulated post-aSAH and PADI4 was positively correlated with neutrophils. The NETs pathway was significantly upregulated in aSAH.Conclusion: We identified core regulatory genes influencing the transcription profiles of circulating neutrophils after the rupture of intracranial aneurysms using bioinformatics analysis and machine learning algorithms. This study provides new insight into the mechanism of peripheral immune response and inflammation after aSAH.
Comparative efficacy of various CHIs combined with western medicine for non-small cell lung cancer: A bayesian network meta-analysis of randomized controlled trials
Authors: Peng Ciyan , Chen Jing , Cui Wei , Li Sini , Li Jianhe , Peng Liubao 
Published: November 2022

Background: Given the limitations of Western medicine (WM) for the treatment of non-small cell lung cancer (NSCLC) and the wide exploration of Chinese herbal injections (CHIs), systematically evaluate the efficacy of Various CHIs Combined with WM for Non-small Cell Lung Cancer. In this study, we performed a network meta-analysis to evaluate the comparative efficacy of 16 CHIs combined with WM regimens for the treatment of NSCLC.Methods: Literature databases were searched from their inception to November 2021, and all randomized control trials (RCTs) involving NSCLC patients treated with a combination of Chinese and WM were retrieved. Outcomes, including disease control rate, survival quality score, incidence of gastrointestinal adverse reactions, incidence of leukopenia, and incidence of thrombocytopenia, were analyzed using RevMan (5.3), Stata17, and R software. Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the treatments examined, and clustering analysis was used to compare the effects of CHIs on different outcomes.Results: A total of 389 studies involving 31,263 patients and 16 CHIs were included. The 16 CHIs were: Aidi injection (ADI), Huachansu injection (HCSI), oil of Ophiopogon injection (OOMI), disodium cantharidinate and vitamin B6 injection (DCI), Shenfu injection (SFI), Shenmai injection (SMI), Shenqi Fuzheng injection (SQFZI), Chansu injection (CSI), Delisheng injection (DLSI), Fufang Kushen injection (FFKSI), Huangqi injection (HQI), Kangai injection (KAI), Kanglaite injection (KLTI), Shengmai injection (SI), Xiangguduotang injection (XGDTI), and Xiaoaiping injection (XAPI). The results of the network meta-analysis showed that, with WM treatment as a co-intervention, CSI was most likely to improve the disease control rate (SUCRA = 80.90%), HQI had the highest probability of being the best option for improving the survival quality score (SUCRA = 82.60%), DCI had the highest probability of reducing the incidence of gastrointestinal adverse reactions (SUCRA = 85.50%), HCSI + WM had the highest probability of reducing the incidence of thrombocytopenia (SUCRA = 91.30%), while SMI had the highest probability of reducing the incidence of leukopenia (SUCRA = 79.10%).Conclusion: CHIs combined with WM is proved to be more effective than WM alone, which may be beneficial to NSCLC patients. SMI + WM and DCI + WM are most likely the optimal CHI to improve disease control rates, survival quality score, and reduce adverse effects. This study has limitations; therefore, higher quality RCTs and real-world evidence are required to support our conclusions.
M6A regulator-mediated immune infiltration and methylation modification in hepatocellular carcinoma microenvironment and immunotherapy
Authors: Zhao Kun , Wei Bing , Zhang Yingxuan , Shi Wenkai , Zhang Guokun , Wang Zhengfeng 
Published: November 2022

Introduction: Tremendous evidence indicates that N6-methyladenosine (m6A) epigenetic modification and m6A-related enzymes constitute a complex network, which jointly regulates prevailing pathological processes and various signaling pathways in humankind. Currently, the role of the m6A-mediated molecular regulatory network in hepatocellular carcinoma (HCC) remains elusive.Methods: We recruited expression and pathological files of 368 HCC patients from The Cancer Genome Atlas cohort. Four public datasets serve as external authentication sets for nearest template prediction (NTP) validation. The correlation between 35 regulators and their prognostic value was compared. Gene set variation analysis (GSVA) was used to explore the latent mechanism. Four independent algorithms (ssGSEA, xCell, MCP-counter, and TIMER) were used to calculate the ratio of tumor cells and non-tumor cells to evaluate the tumor immune microenvironment. The m6Ascore model was established by principal component analysis (PCA). Prediction of immunotherapy and potential drugs was performed using TIDE and SubMap.Results: A total of 35 m6A regulators were widely associated, most of which were risk factors for HCC patients. The m6A phenotypic-cluster revealed differences in regulator transcriptional level, gene mutation frequency, functional pathways, and immune cell infiltration abundance under distinct m6A patterns. As expected, the m6A gene cluster confirmed the aforementioned results. The m6Ascore model further found that patients in the high-m6Ascore group were associated with lower tumor purity, higher enrichment of immune and stromal cells, upregulation of metabolic pathways, lower expression of m6A regulators, and favorable outcomes. Low-m6Ascore patients were associated with adverse outcomes. Notably, low-m6Ascore patients might be more sensitive to anti-PD-L1 therapy.Conclusion: This study found that a classification model based on the m6A manner could predict HCC prognosis and response to immunotherapy for HCC patients, which might improve prognosis and contribute to clinical individualized decision-making.