bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-machine interface-based training for improving upper extremity function after stroke: A meta-analysis of randomized controlled trials
Authors: Xie Yu-lei , Yang Yu-xuan , Jiang Hong , Duan Xing-Yu , Gu Li-jing , Qing Wu , Zhang Bo , Wang Yin-xu 
Published: August 2022

BackgroundUpper extremity dysfunction after stroke is an urgent clinical problem that greatly affects patients' daily life and reduces their quality of life. As an emerging rehabilitation method, brain-machine interface (BMI)-based training can extract brain signals and provide feedback to form a closed-loop rehabilitation, which is currently being studied for functional restoration after stroke. However, there is no reliable medical evidence to support the effect of BMI-based training on upper extremity function after stroke. This review aimed to evaluate the efficacy and safety of BMI-based training for improving upper extremity function after stroke, as well as potential differences in efficacy of different external devices.MethodsEnglish-language literature published before April 1, 2022, was searched in five electronic databases using search terms including “brain-computer/machine interface”, “stroke” and “upper extremity.” The identified articles were screened, data were extracted, and the methodological quality of the included trials was assessed. Meta-analysis was performed using RevMan 5.4.1 software. The GRADE method was used to assess the quality of the evidence.ResultsA total of 17 studies with 410 post-stroke patients were included. Meta-analysis showed that BMI-based training significantly improved upper extremity motor function [standardized mean difference (SMD) = 0.62; 95% confidence interval (CI) (0.34, 0.90); I2 = 38%; p &lt; 0.0001; n = 385; random-effects model; moderate-quality evidence]. Subgroup meta-analysis indicated that BMI-based training significantly improves upper extremity motor function in both chronic [SMD = 0.68; 95% CI (0.32, 1.03), I2 = 46%; p = 0.0002, random-effects model] and subacute [SMD = 1.11; 95%CI (0.22, 1.99); I2 = 76%; p = 0.01; random-effects model] stroke patients compared with control interventions, and using functional electrical stimulation (FES) [SMD = 1.11; 95% CI (0.67, 1.54); I2 = 11%; p &lt; 0.00001; random-effects model]or visual feedback [SMD = 0.66; 95% CI (0.2, 1.12); I2 = 4%; p = 0.005; random-effects model;] as the feedback devices in BMI training was more effective than using robot. In addition, BMI-based training was more effective in improving patients' activities of daily living (ADL) than control interventions [SMD = 1.12; 95% CI (0.65, 1.60); I2 = 0%; p &lt; 0.00001; n = 80; random-effects model]. There was no statistical difference in the dropout rate and adverse effects between the BMI-based training group and the control group.ConclusionBMI-based training improved upper limb motor function and ADL in post-stroke patients. BMI combined with FES or visual feedback may be a better combination for functional recovery than robot. BMI-based trainings are well-tolerated and associated with mild adverse effects.
Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity
Authors: Jia Yumeng , Shi Sirong , Cheng Bolun , Cheng Shiqiang , Liu Li , Meng Peilin , Yang Xuena , Chu Xiaoge , Wen Yan , Zhang Feng , Guo Xiong 
Published: August 2022

BackgroundT-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown.MethodsIn this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6.ResultsWe identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO.ConclusionsThis study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD.
Hawthorn fruit acid consumption attenuates hyperlipidemia-associated oxidative damage in rats
Authors: Feng Yicheng , Gao Shan , Zhu Ting , Sun Guibo , Zhang Peisen , Huang Yichun , Qu Shuang , Du Xiaomeng , Mou Dehua 
Published: August 2022

ContextHyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage.ObjectiveThe present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism.Materials and methodsSprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR.ResultsThis study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway.ConclusionHFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.
Reduction of inter-observer variability using MRI and CT fusion in delineating of primary tumor for radiotherapy in lung cancer with atelectasis
Authors: Zhang Hongjiao , Fu Chengrui , Fan Min , Lu Liyong , Chen Yiru , Liu Chengxin , Sun Hongfu , Zhao Qian , Han Dan , Li Baosheng , Huang Wei 
Published: August 2022

PurposeTo compare the difference between magnetic resonance imaging (MRI) and computed tomography (CT) in delineating the target area of lung cancer with atelectasis.MethodA retrospective analysis was performed on 15 patients with lung cancer accompanied by atelectasis. All positioning images were transferred to Eclipse treatment planning systems (TPSs). Six MRI sequences (T1WI, T1WI+C, T1WI+C Delay, T1WI+C 10 minutes, T2WI, DWI) were registered with positioning CT. Five radiation oncologists delineated the tumor boundary to obtain the gross tumor volume (GTV). Conformity index (CI) and dice coefficient (DC) were used to measure differences among observers.ResultsThe differences in delineation mean volumes, CI, and DC among CT and MRIs were significant. Multiple comparisons were made between MRI sequences and CT. Among them, DWI, T2WI, and T1WI+C 10 minutes sequences were statistically significant with CT in mean volumes, DC, and CI. The mean volume of DWI, T2WI, and T1WI+C 10 minutes sequence in the target area is significantly smaller than that on the CT sequence, but the consistency is higher than that of CT sequences.ConclusionsThe recognition of atelectasis by MRI was better than that by CT, which could reduce interobserver variability of primary tumor delineation in lung cancer with atelectasis. Among them, DWI, T2WI, T1WI+C 10 minutes may be a better choice to improve the GTV delineation of lung cancer patients with atelectasis.
Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma
Authors: Bi Shui-Qing , Zhang Qing-Mei , Zeng Xia , Liu Chang , Nong Wei-Xia , Xie Huan , Li Feng , Lin Li-Na , Luo Bin , Ge Ying-Ying , Xie Xiao-Xun 
Published: August 2022

ObjectiveThe study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma.MethodsThe expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo.ResultsMAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma.ConclusionMAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.
Preferred place of death and end-of-life care for adult cancer patients in Iran: A cross-sectional study
Authors: Fereidouni Armin , Salesi Mahmood , Rassouli Maryam , Hosseinzadegan Fariba , Javid Mohammad , Karami Maryam , Elahikhah Maryam , Barasteh Salman 
Published: August 2022

BackgroundMore than 50,000 deaths in terms of cancer occur annually in Iranian hospitals. Determining the preferred place of end-of-life care and death for cancer patients in Iran is a quality marker for good end-of-life care and good death. The purpose of this study was to determine the preferred place of end-of-life care and death in cancer patients.MethodIn 2021, the current descriptive cross-sectional investigation was carried out. Using the convenience sample approach, patients were chosen from three Tehran referral hospitals (the capital of Iran). A researcher-made questionnaire with three parts for demographic data, clinical features, and two questions on the choice of the desired location for end-of-life care and the death of cancer patients served as the data collecting instrument. Data were analyzed using SPSS software version 18. The relationship between the two variables preferred place for end-of-life care and death and other variables was investigated using chi-square, Fisher exact test, and multiple logistic regression.ResultThe mean age of patients participating in the study was 50.21 ± 13.91. Three hundred ninety (69.6%) of the patients chose home, and 170 (30.4%) patients chose the hospital as the preferred place of end-of-life care. Choosing the home as a preferred place for end-of-life care had a significant relationship with type of care (OR = .613 [95% CI: 0.383–0.982], P = .042), level of education (OR = 2.61 [95% CI: 1.29–5.24], P = 0.007), type of cancer (OR = 1.70 [1.01–2.89], P = .049), and income level (Mediate: (OR: 3.27 (1.49, 7.14), P = .003) andLow: (OR: 3.38 (1.52–7.52), P = .003). Also, 415 (75.2%) patients chose home and 137 (24.8%) patients chose hospital as their preferred place of death. Choosing the home as a preferred place of death had a significant relationship with marriage (OR = 1.62 [95% CI: 1.02–2.57], P = .039) and time to diagnostic disease less than 6 months (OR = 1.62 [95% CI: 0.265–0.765], P = .002).ConclusionThe findings of the current research indicate that the majority of cancer patients selected their homes as the preferred location for end-of-life care and final disposition. Researchers advise paying more attention to patients’ wishes near the end of life in light of the findings of the current study. This will be achieved by strengthening the home care system using creating appropriate infrastructure, insurance coverage, designing executive instructions, and integration of palliative care in home care services.
High salt intake combined with hypertension elevated the risk of primary liver cancer: a prospective cohort study
Authors: Liu Tong , Zhang Qingsong , Xiao Xiaoli , Wang Yiming , Ma Xiangming , Song Mengmeng , Zhang Qi , Cao Liying , Shi Hanping 
Published: August 2022

BackgroundHypertension and high-salt intake may act synergistically to increase the risk of primary liver cancer (PLC). We prospectively examined the joint effect of hypertension and salt intake on the risk of PLC incidence.MethodsA total of 92,978 participants were included in the final analyses. The study population was divided into 4 groups according to the presence or absence of hypertension and salt intake. Cox proportional hazards regression models were used to evaluate the association of hypertension and/or high-salt intake with the risk of incident cancers. The CAUSALMED procedure was used to perform the mediation analyses.ResultsDuring a median follow-up of 12.69 years, a total of 418 incident cancer cases were identified. Hypertension was a risk factor for PLC in women but not in men. High salt intake was associated with an elevated risk of PLC in men. A significant interaction between salt intake and hypertension was found for the risk of PLC (P for interaction=0.045). Compared with Group 1 (hypertension-, high salt intake-), participants in Group 2 (hypertension-, high salt intake+) and Group 4 (hypertension+, high salt intake+) were associated with an elevated risk of PLC with the corresponding multivariate HRs (95%CIs) of 1.73(0.96,3.10) and 1.96(1.09,3.53) respectively. No significant mediation effect was found for the association between hypertension, salt intake and PLC risk.ConclusionsThe combination of high salt intake and hypertension could significantly increase the risk of PLC. It may be reasonable to recommend a low-salt intake to prevent and control the prevalence of PLC and hypertension.Trial registrationKailuan study, ChiCTR–TNRC–11001489. Registered 24 August, 2011-Retrospectively registered, https://www.chictr.org.cn/showprojen.aspx?proj=8050
Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma
Authors: Zhong Wenting , Liu Hongxia , Li Feng , lin Youyu , Ye Yan , Xu Luyun , Li ShengZhao , Chen Hui , Li Chengcheng , Lin Yuxuan , Zhuang Wei , Lin Yao , Wang Qingshui 
Published: August 2022

BackgroundRenal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.MethodsThe expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database.ResultsThe mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients’ prognosis in different subgroups of ccRCC.ConclusionOur study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.
Investigation of the inhibition effect of 1,2,3,4,6-pentagalloyl-β-D-glucose on gastric cancer cells based on a network pharmacology approach and experimental validation
Authors: Bi Jing-hui , Jiang Yu-han , Ye Shi-jie , Wu Min-rui , Yi Yang , Wang Hong-xun , Wang Li-mei 
Published: August 2022

BackgroundGastric cancer (GC) is ranked as the third leading cause of cancer-related mortality worldwide. 1,2,3,4,6-Pentagalloyl-β-D-glucose (β-PGG) has various pharmacological activities and has been shown to suppress cancer development. However, the mechanism by which β-PGG inhibits gastric cancer has not been elucidated.ObjectiveThis study explored the potential targets and mechanism of β-PGG in GC using the network pharmacology approach combined with in-vitro experiments.MethodsThe PharmMapper software was used to predict the potential targets of β-PGG, and GC-related genes were identified on the GeneCards database. PPI analysis of common genes was performed using the STRING database. The potential regulatory mechanism of β-PGG in GC was explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The binding ability of key genes and target proteins was verified by molecular docking. The effects of β-PGG on genes and proteins were evaluated using the CCK-8 assay, cell cycle analysis, apoptosis assay, real-time fluorescence quantification polymerase chain reaction (qRT-PCR), and Western blotting.ResultsEight hub genes involved in cell cycle progression and apoptosis were identified. Cancer-related signaling pathways were identified using the Cytoscape tool. Some of those genes were significantly enriched in the p53 signaling pathway. The CCK-8 assay showed that β-PGG inhibited the proliferation of GC cells. Cell cycle and apoptosis experiments revealed that β-PGG induced cell cycle arrest and apoptosis of gastric cancer cells. qRT-PCR and Western blot analysis showed that β-PGG inhibited β-PGG cells by modulating the p53 signaling pathway.ConclusionIn the present study, the targets and mechanism of β-PGG in gastric cancer were explored. The results indicate that β-PGG can be used to develop treatments for GC.
Sex-specific differences in immunogenomic features of response to immune checkpoint blockade
Authors: Scott Susan C. , Shao Xiaoshan M. , Niknafs Noushin , Balan Archana , Pereira Gavin , Marrone Kristen A. , Lam Vincent K. , Murray Joseph C. , Feliciano Josephine L. , Levy Benjamin P. , Ettinger David S. , Hann Christine L. , Brahmer Julie R. , Forde Patrick M. , Karchin Rachel , Naidoo Jarushka , Anagnostou Valsamo 
Published: August 2022

IntroductionThe magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower response rates and decreased survival after ICI monotherapy. The mechanisms underlying this sex dimorphism in ICI response are unknown, and may be related to sex-driven differences in the immunogenomic landscape of tumors that shape anti-tumor immune responses in the context of therapy.MethodsTo investigate the association of immunogenic mutations with HLA haplotypes, we leveraged whole exome sequence data and HLA genotypes from 482 non-small cell lung cancer (NSCLC) tumors from The Cancer Genome Atlas (TCGA). To explore sex-specific genomic features linked with ICI response, we analyzed whole exome sequence data from patients with NSCLC treated with ICI. Tumor mutational burden (TMB), HLA class I and II restricted immunogenic missense mutation (IMM) load, and mutational smoking signature were defined for each tumor. IMM load was combined with HLA class I and II haplotypes and correlated with therapeutic response and survival following ICI treatment. We examined rates of durable clinical benefit (DCB) for at least six months from ICI treatment initiation. Findings were validated utilizing whole exome sequence data from an independent cohort of ICI treated NSCLC.ResultsAnalysis of whole exome sequence data from NSCLC tumors of females and males revealed that germline HLA class II diversity (≥9 unique HLA alleles) was associated with higher tumor class II IMM load in females (p=0.01) and not in males (p=0.64). Similarly, in tumors of female patients, somatic HLA class II loss of heterozygosity was associated with increased IMM load (p=0.01) while this association was not observed in tumors in males (p=0.20). In females, TMB (p=0.005), class I IMM load (p=0.005), class II IMM load (p=0.004), and mutational smoking signature (p&lt;0.001) were significantly higher in tumors responding to ICI as compared to non-responding tumors. In contrast, among males, there was no significant association between DCB and any of these features. When IMM was considered in the context of HLA zygosity, high MHC-II restricted IMM load and high HLA class II diversity was significantly associated with overall survival in males (p=0.017).ConclusionsInherent sex-driven differences in immune surveillance affect the immunogenomic determinants of response to ICI and likely mediate the dimorphic outcomes with ICI therapy. Deeper understanding of the selective pressures and mechanisms of immune escape in tumors in males and females can inform patient selection strategies and can be utilized to further hone immunotherapy approaches in cancer.