bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening
Authors: Chen Min , Wu Guang-Bo , Xie Zhi-Wen , Shi Dan-Li , Luo Meng 
Published: September 2022

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers with high mortality in the world. HCC screening and diagnostic models are becoming effective strategies to reduce mortality and improve the overall survival (OS) of patients. Here, we expected to establish an effective novel diagnostic model based on new genes and explore potential drugs for HCC therapy.Methods: The gene expression data of HCC and normal samples (GSE14811, GSE60502, GSE84402, GSE101685, GSE102079, GSE113996, and GSE45436) were downloaded from the Gene Expression Omnibus (GEO) dataset. Bioinformatics analysis was performed to distinguish two differentially expressed genes (DEGs), diagnostic candidate genes, and functional enrichment pathways. QRT-PCR was used to validate the expression of diagnostic candidate genes. A diagnostic model based on candidate genes was established by an artificial neural network (ANN). Drug sensitivity analysis was used to explore potential drugs for HCC. CCK-8 assay was used to detect the viability of HepG2 under various presentative chemotherapy drugs.Results: There were 82 DEGs in cancer tissues compared to normal tissue. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and infiltrating immune cell analysis were administered and analyzed. Diagnostic-related genes of MT1M, SPINK1, AKR1B10, and SLCO1B3 were selected from DEGs and used to construct a diagnostic model. The receiver operating characteristic (ROC) curves were 0.910 and 0.953 in the training and testing cohorts, respectively. Potential drugs, including vemurafenib, LOXO-101, dabrafenib, selumetinib, Arry-162, and NMS-E628, were found as well. Vemurafenib, dabrafenib, and selumetinib were observed to significantly affect HepG2 cell viability.Conclusion: The diagnostic model based on the four diagnostic-related genes by the ANN could provide predictive significance for diagnosis of HCC patients, which would be worthy of clinical application. Also, potential chemotherapy drugs might be effective for HCC therapy.
The effect of tai chi intervention on NLRP3 and its related antiviral inflammatory factors in the serum of patients with pre-diabetes
Authors: Hu Shujuan , Hu Yingxing , Long Peilin , Li Peixiong , Chen Ping , Wang Xianwang 
Published: September 2022

BackgroundNLRP3 inflammasome and its related antiviral inflammatory factors have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, but its contribution to pre-diabetes remains poorly understood.ObjectiveTo investigate the effects and the potential mechanism of Tai Chi intervention on NLRP3 inflammasome and its related inflammatory factors in the serum of middle-aged and older people with pre-diabetes mellitus (PDM).Methods40 pre-diabetic subjects were divided into a pre-diabetic control group (PDM-C group, N=20) and a Tai Chi group (PDM-TC group, N=20) by random number table. 10 normoglycemic subjects (NG) were selected as controls. We measured clinical metabolic parameters and collected blood samples before and after the 12 weeks of Tai Chi intervention. Antiviral inflammatory factors in serum were detected by enzyme-linked immunosorbent assay.ResultsThe blood glucose, insulin resistance, and inflammation in PDM groups were higher than those in the NG group (P&lt;0.05 and P&lt;0.01, respectively). The results also suggested that 12 weeks of Tai Chi intervention could reduce body weight, blood pressure, blood glucose, insulin resistance, blood lipid, and the expressions of serum inflammatory factors in the pre-diabetic population.ConclusionTai Chi intervention may improve blood glucose, lipid levels, and insulin resistance in middle-aged and elderly pre-diabetic patients by reducing the level of NLRP3 inflammasome and its related inflammatory factors.
Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis
Authors: Zhang Jindong , Song Liangdong , Zhu Huixuan , Liu Qinyuan , Wang Delin 
Published: September 2022

BackgroundRadical cystectomy and removal of pelvic lymph nodes (RC-PLND) is a recommended treatment for high-risk non-muscle-invasive and muscle-invasive non-metastatic bladder cancer (BC). However, 50% of patients relapse after RC-PLND. This study aimed to evaluate the effect of programmed cell death ligand-1 (PD-L1) on the prognosis of bladder urothelial carcinoma (BUC) after RC-PLND.MethodsWe present this meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Guidelines. The main outcomes were overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) of 3 and 5 years after RC-PLND.ResultsOverall, 11 studies and 1393 BUC cases were included in our meta-analysis. In tumor cells (TCs), the PD-L1 negative group had statistically significant advantage in 5-year OS (risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.74–0.97, P = 0.02), RFS (RR: 0.76, 95% CI: 0.58–0.99, P = 0.04), and CSS (RR: 0.73, 95% CI: 0.58–0.92, P = 0.009) compared with the PD-L1 positive group. But, no statistically significant difference in 5-year OS and RFS was observed between the PD-L1 negative and positive groups in tumor-infiltrating immune cells.ConclusionsOur study found that patients with BUC who tested positive for PD-L1 in TCs had a poor prognosis after RC-PLND. PD-1 or PD-L1 inhibitors could be used as a adjuvant medication for patients with BUC after RC-PLND who exhibit PD-L1 overexpression in TCs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022301424.
Signature construction and molecular subtype identification based on cuproptosis-related genes to predict the prognosis and immune activity of patients with hepatocellular carcinoma
Authors: Peng Xingyu , Zhu Jinfeng , Liu Sicheng , Luo Chen , Wu Xun , Liu Zitao , Li Yanzhen , Yuan Rongfa 
Published: September 2022

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high incidence, high malignancy, and low survival rate. Cuproptosis is a novel form of cell death mediated by lipoylated TCA cycle proteins-mediated novel cell death pathway and is highly associated with mitochondrial metabolism. However, the relationship between the expression level of cuproptosis-related genes (CRGs) and the prognosis of HCC is still unclear.MethodsCombining the HCC transcriptomic data from The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed cuproptosis-related genes (DECRGs) and obtained the prognosis-related DECRGs through univariate regression analysis.LASSO and multivariate COX regression analyses of these DECRGs yielded four genes that were used to construct the signature. Next, we use ROC curves to evaluate the performance of signatures. The tumor microenvironment, immune infiltration, tumor mutation load, half-maximum suppression concentration, and immunotherapy effects were also compared between the low-risk and high-risk groups. Finally, we analyzed the expression level, prognosis, and immune infiltration correlation on the four genes that constructed the model.ResultsFour DECRGs s were used to construct the signature. The ROC curves indicated that signature can better assess the prognosis of HCC patients. Patients were grouped according to the signature risk score. Patients in the low-risk group had a significantly longer survival time than those in the high-risk group. Furthermore, the tumor mutation burden (TMB) values were associated with the risk score and the higher-risk group had a higher proportion of TP53 mutations than the low-risk group.ESTIMATE analysis showed significant differences in stromal scores between the two groups.N6-methyladenosine (m6A) and multiple immune checkpoints were expressed at higher levels in the high-risk group. Then, we found that signature score correlated with chemotherapeutic drug sensitivity and immunotherapy efficacy in HCC patients. Finally, we further confirmed that the four DECRGs genes were associated with the prognosis of HCC through external validation.ConclusionsWe studied from the cuproptosis perspective and developed a new prognostic feature to predict the prognosis of HCC patients. This signature with good performance will help physicians to evaluate the overall prognosis of patients and may provide new ideas for clinical decision-making and treatment strategies.
Comparative anatomical outcomes of high-flow vs. low-flow phacoemulsification cataract surgery: A systematic review and meta-analysis
Authors: Kuo Po-Chin , Hung Jia-Horung , Su Yu-Chen , Fang Ching-Ju , Lee Chaw-Ning , Huang Yi-Hsun , Shao Shih-Chieh , Lai Edward Chia-Cheng 
Published: September 2022

BackgroundPhacoemulsification is an effective and widely performed technique in cataract surgery, but the comparative anatomical outcomes, including endothelial cell loss (ECL), central corneal thickness (CCT), and central macular thickness (CMT), between high-flow and low-flow phacoemulsification cataract surgery remain unclear.MethodsThis study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Random-effects models were applied to measure pooled mean differences (MD) with 95% confidence intervals (CI) of anatomical outcomes between high-flow and low-flow phacoemulsification cataract surgery. We judged overall certainty of evidence (CoE) based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria.ResultsWe included six randomized controlled trials (RCTs) totaling 477 participants. The meta-analysis showed similar changes associated with these two surgery types in both ECL at postoperative days 2–14 (MD: −1.63%; 95% CI: −3.73 to 0.47%; CoE: very low), days 15–42 (MD: −0.65%; 95% CI −2.96 to 1.65%; CoE: very low) and day 43 to month 18 (MD: −0.35%; 95% CI: −1.48 to 0.78%; CoE: very low), and CCT at postoperative day 1 (MD: −16.37 μm; 95% CI: −56.91 to 24.17 μm; CoE: very low), days 2–14 (MD: −10.92 μm; 95% CI: −30.00 to 8.16 μm; CoE: very low) and days 15–42 (MD: −2.76 μm; 95% CI: −5.75 to 0.24 μm; CoE: low). By contrast, low-flow phacoemulsification showed less increase in CMT at postoperative days 15–42 (MD, −4.58 μm; 95% CI: −6.3 to −2.86 μm; CoE: low).ConclusionsWe found similar anatomical outcomes, except in CMT, for both high-flow and low-flow phacoemulsification cataract surgery. Future head-to-head RCTs on visual outcomes should confirm our findings.Systematic review registrationPROSPERO, identifier: CRD42022297036.
Predicting futile recanalization, malignant cerebral edema, and cerebral herniation using intelligible ensemble machine learning following mechanical thrombectomy for acute ischemic stroke
Authors: Zeng Weixiong , Li Wei , Huang Kaibin , Lin Zhenzhou , Dai Hui , He Zilong , Liu Renyi , Zeng Zhaodong , Qin Genggeng , Chen Weiguo , Wu Yongming 
Published: September 2022

PurposeTo establish an ensemble machine learning (ML) model for predicting the risk of futile recanalization, malignant cerebral edema (MCE), and cerebral herniation (CH) in patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and recanalization.MethodsThis prospective study included 110 patients with premorbid mRS ≤ 2 who met the inclusion criteria. Futile recanalization was defined as a 90-day modified Rankin Scale score &gt;2. Clinical and imaging data were used to construct five ML models that were fused into a logistic regression algorithm using the stacking method (LR-Stacking). We added the Shapley Additive Explanation method to display crucial factors and explain the decision process of models for each patient. Prediction performances were compared using area under the receiver operating characteristic curve (AUC), F1-score, and decision curve analysis (DCA).ResultsA total of 61 patients (55.5%) experienced futile recanalization, and 34 (30.9%) and 22 (20.0%) patients developed MCE and CH, respectively. In test set, the AUCs for the LR-Stacking model were 0.949, 0.885, and 0.904 for the three outcomes mentioned above. The F1-scores were 0.882, 0.895, and 0.909, respectively. The DCA showed that the LR-Stacking model provided more net benefits for predicting MCE and CH. The most important factors were the hypodensity volume and proportion in the corresponding vascular supply area.ConclusionUsing the ensemble ML model to analyze the clinical and imaging data of AIS patients with successful recanalization at admission and within 24 h after MT allowed for accurately predicting the risks of futile recanalization, MCE, and CH.
Melatonin: Manager of psychosomatic and metabolic disorders in polymorbid cardiovascular pathology
Authors: Partsernyak Alexander S. , Polyakova Victoria O. , Trufanov Artem G. , Medvedev Dmitriy S. , Trotsyuk Dina V. , Markin Kirill , Kurasov Evgeniy S. , Kuznetsova Evgeniya V. , Krasichkov Alexander S. 
Published: September 2022

ObjectivesTo investigate the relationship between changes in circadian patterns of melatonin and clinical manifestations of polymorbid cardiovascular pathology (PCVP) in young men and to analyze the effectiveness of their complex treatment.Materials and methodsWe made the immunohistochemical (IHC) analysis of epiphysis tissues from autopsies of 25 men aged 32–44 with PCVP and metabolic syndrome (MS) who had died as a result of ischemic cardiomyopathy (IC) and 25 persons after the car accident as a control group. Then, 93 young men aged 35–44 with PCVP, metabolic syndrome, and depressive spectrum disorders (DSD) were divided into three groups: (1) standard therapy; (2) standard therapy and psychotherapy sessions; (3) standard therapy in combination with psychotherapeutic and psychophysiological visual and auditory correction sessions. The control group included 24 conditionally healthy male volunteers. Before and after the treatment, we studied the anthropometric status, lipid and carbohydrate metabolism indicators, the level of urinary 6-hydroxymelatonin sulfate, the degree of nocturnal decrease in blood pressure (BP), and the relationship of these indicators with circadian variations of melatonin excretion.ResultsYoung polymorbid patients who died from IC have a lower expression of melatonin type 1 and 2 receptors. All patients with PCVP showed a decrease in the nocturnal melatonin excretion fraction and a correlation with higher severity of depressive (r = −0.72) and anxiety (r = −0.66) symptoms. Reduced values of the 6-hydroxymelatonin sulfate (6-SM) in the 1st (r = 0.45), 2nd (r = 0.39), and 3rd (r = 0.51) groups before treatment was associated with periods of increased BP. The achievement of melatonin excretion reference values and normalization of biochemical parameters of carbohydrate and lipid metabolism, daily BP profile, and psychophysiological state were noted in all three patients’ groups, with a more pronounced effect in group 3.ConclusionLow nocturnal melatonin excretion levels are associated with greater severity of clinical symptoms and a higher risk of death in patients with PCVP. Therefore, comprehensive therapy may be more effective for correcting this disease.
Effects of probiotic and magnesium co-supplementation on mood, cognition, intestinal barrier function and inflammation in individuals with obesity and depressed mood: A randomized, double-blind placebo-controlled clinical trial
Authors: Mahboobi Sepideh , Ghasvarian Marzieh , Ghaem Haleh , Alipour Hamzeh , Alipour Shohreh , Eftekhari Mohammad Hassan 
Published: September 2022

BackgroundThe co-occurrence of obesity and mood impairments named as “metabolic mood syndrome” (MMS) is often neglected in the obesity management. This study aimed to evaluate effects of Probio-Tec ®BG-VCap-6.5 and magnesium co-supplementation on mood, cognition, intestinal barrier function and serum C reactive protein (CRP) levels in participants with obesity and depressed mood.DesignSeventy-four eligible participants were randomly allocated to either Probio-Tec®BG-VCap-6.5 [containing Lactobacillus rhamnosus (LGG®) and Bifidobacterium animalis subsp. Lactis (BB-12®)] + Magnesium chloride or placebo for 9 weeks. Sociodemographic data were collected in the beginning. Anthropometric, dietary and physical activity (PA) assessments were carried out. Beck Depression Inventory-II (BDI-II) and Montreal Cognitive Assessment (MoCA) scores were assessed through validated questionnaires. Fasting plasma zonulin, lipopolysaccharide (LPS) and (CRP) were measured by ELIZA kits.ResultsOf seventy-four participants (mean age 37.51 ± 8.10), 52 completed the study. Changes in serum LPS and zonulin were not different significantly between groups (−3.04 ± 44.75 ng/dl, 0.11 ± 5.13, ng/dl, p &gt; 0.05 for LPS and 1.40 ± 48.78 ng/dl, −0.17 ± 6.60, p &gt; 0.05 for zonulin, respectively). CRP levels reduced significantly in intervention group compared to placebo [−474.75 (−1,300.00, −125.00) mg/l vs. 175.20 (−957.75, 1,683.25) mg/l, p = 0.016]. Changes in BDI-II and MoCA scores were not significantly different between intervention (−7.13 ± 5.67, 1.20 ± 2.16, respectively) and placebo (−5.42 ± 6.71, 1.94 ± 1.86, respectively) groups (p &gt; 0.05).ConclusionNine weeks of probiotic and magnesium co-supplementation resulted in decreased CRP levels as an indicator of inflammatory state with no significant effects on mood, cognition and intestinal integrity in individuals with obesity and depressed mood.
Maintenance tegafur-plus-uracil after adjuvant concurrent chemoradiotherapy may improve outcome for resected oral cavity squamous cell carcinoma with extranodal extension
Authors: Huang Pei-Wei , Lin Chien-Yu , Lee Li-Yu , Hsieh Chia-Hsun , Hsu Cheng-Lung , Liau Chi-Ting , Fan Kang-Hsing , Huang Shiang-Fu , Liao Chun-Ta , Chang Tung-Chieh , Wang Hung-Ming 
Published: September 2022

ObjectivesTo evaluate whether tegafur-uracil maintenance (UFTm) following postoperation adjuvant cisplatin-based concurrent chemoradiotherapy (CCRT) may reduce distant metastasis in patients with resected oral cavity squamous cell carcinoma (OSCC) with pathologic extranodal extension (pENE+).MethodsA retrospective comparison was conducted between two cohorts of patients with resected pENE+ OSCC who completed adjuvant CCRT between March 2015 and December 2017, including one cohort of a phase II trial using UFTm and a trial-eligible but off-protocol cohort without using UFTm (non-UFTm) after their adjuvant CCRT. The UFTm trial enrolled patients without relapse within 2 months after the end of adjuvant CCRT and administered UFT 400 mg/day for 1 year. Kaplan–Meier methods estimated the actuarial rate of distant metastasis-free (DMF), locoregional control (LRC), event-free survival (EFS), and overall survival (OS).ResultsA total of 103 patients were included in this study, 64 patients in UFTm and 39 patients in non-UFTm. Severe adverse events in UFTm included grade 3 anemia (n = 1, 1.6%) and grade 3 mucositis (n = 1, 1.6%). A total of 40 (62.5%) patients completed the full course of UFTm, while the remaining terminated UFTm earlier due to disease relapse (n = 14, 21.8%), poor compliance (n = 9, 14.1%), and adverse event (n = 1, 1.6%). The median (range) follow-up time of surviving patients was 43 (22–65) months. The outcomes compared between UFTm and non-UFTm were OS (hazard ratio [HR] 0.31 [95% CI: 0.17–0.57], p &lt; 0·001), EFS (0.45 [0.25–0.82], 0.009), LRC (0.45 [0.19–1.05], 0.067), and DMF (0.47 [0.24–0.95], 0.035). Multivariable analysis, adjusted for UFTm, Charlson comorbidity index score 1–3, site of tongue, and number of ENE+ LN ≧4, confirmed better OS (0.29 [0.16–0.54], &lt;0.001) and EFS (0.47 [0.26–0.85], 0.012) in favor of UFTm over non-UFTm. The 2-year DM rate was 25.8% in UFTm and 44.2% in non-UFTm. For relapsed patients in UFTm vs. non-UFTm, the rate of metastasectomy for oligometastasis was 53% vs. 6%, and the OS was 21.0 (95% CI: 17.8–24.1) months vs. 11.0 (9.1–12.8) months (p &lt; 0.001), respectively.ConclusionsUFTm may improve the dismal outcomes of the resected pENE+ OSCC. Further investigations are needed to confirm our observations.
PCDH20 inhibits esophageal squamous cell carcinoma proliferation and migration by suppression of the mitogen-activated protein kinase 9/AKT/β-catenin pathway
Authors: Ning Yijiao , Deng Chaoqun , Li Chunhong , Peng Weiyan , Yan Chun , Ran Jing , Chen Weihong , Liu Yujia , Xia Jiuyi , Ye Lin , Wei Zhengqiang , Xiang Tingxiu 
Published: September 2022

Aberrant protocadherins (PCDHs) expression trigger tumor invasion and metastasis. PCDH20 anti-tumor functions in various tumor have been identified. Tumor suppression is due to Wnt/β-catenin pathway antagonism and may be suppressed caused by PCDH20 downregulation through promotor methylation, whereas PCDH20 effects and regulation mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. We analyzed PCDH20 effects on ESCC and underlying action mechanisms for PCDH20. We test PCDH20 expression in ESCC tissues and cells by semi-quantitative PCR (RT-PCR) and q-PCR (real-time quantitative polymerase chain reaction). MSP (methylation-specific PCR) was carried out to assess the methylation of PCDH20 in ESCC cells and tissues. Anti-tumor effects of PCDH20 in vitro were assessed by clone formation assay, CCK8 assay, Transwell assay, and flow cytometry. Nude mice tumorigenicity was used to assess PCDH20 anti-tumor effect in vivo. Online database, qPCR, and Western blotting were used to identify the downregulation of MAP3K9 by PCDH20, associated with AKT/β-catenin signaling inactivation. We found that PCDH20 expression was dramatically attenuated in esophageal cancer tissues and cells, maybe due to promotor methylation, and ectopic PCDH20 expression suppressed ESCC malignant biological phenotypes. PCDH20 exerted anti-tumor effects by MAP3K9 downregulation, which suppressed AKT/β-catenin signaling in ESCC cells.ConclusionPCDH20 was a tumor suppressor gene, which antagonized AKT/β-catenin signaling pathway in ESCC by decreasing MAP3K9.