bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIM37 interacts with PTEN to promote the growth of human T-cell acute lymphocytic leukemia cells through regulating PI3K/AKT pathway
Authors: Qu Honglan , Gao-wa HASEN , Hou Yanyan , Ren Mengwei , Li Jun , Jing Baoshong , Du YanDan 
Published: February 2023

BackgroundTRIM37 has been reported to be associated with the tumorigenesis of cancers. However, the role of TRIM37 in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. This study aimed to characterize the effect of TRIM37 on T-ALL.MethodsTRIM37 expression in T-ALL patients and T-ALL cell lines was determined by qRT-PCR and Western blot. Knockdown or overexpression of TRIM37 was conducted by transferring small-interfering TRIM37 or lentivirus-mediated transducing into T-ALL cells. CCK-8 assay and flow cytometry assay were conducted to analyze the proliferation and apoptosis of T-ALL cells. Co-immunoprecipitation experiments were conducted to investigate the relationship between TRIM37 and PTEN and the ubiquitination of PTEN.ResultsOur results suggested that TRIM37 expression was upregulated in the blood of T-ALL patients and T-ALL cell lines. Knockdown of TRIM37 noticeably inhibited the proliferation and promoted apoptosis of T-ALL cells. Ectopic expression of TRIM37 promoted the proliferation and suppressed the apoptosis rate of MOLT-4 cells and enhanced the phosphorylation of AKT. Moreover, TRIM37 interacted with PTEN and accelerated the degradation of PTEN via TRIM37-mediated ubiquitination in T-ALL cells. Moreover, TRIM37 reduced the sensitivity of T-ALL cells to bortezomib treatment. Additionally, PI3K/AKT signaling pathway was involved in the function of TRIM37 in T-ALL. TRIM37 contributed to the proliferation of T-ALL cells and reduced the susceptibility of T-ALL cells to bortezomib treatment through ubiquitination of PTEN and activating PI3K/AKT signaling pathway.ConclusionsOur study suggested that TRIM37 could be considered as a therapeutic target for T-ALL.
Risk factor analysis and construction of prediction models of gallbladder carcinoma in patients with gallstones
Authors: Zhu Zhencheng , Luo Kunlun , Zhang Bo , Wang Gang , Guo Ke , Huang Pin , Liu Qiuhua 
Published: February 2023

BackgroundGallbladder carcinoma (GBC) is a biliary tract tumor with a high mortality rate. The objectives of this study were to explore the risk factors of GBC in patients with gallstones and to establish effective screening indicators.MethodsA total of 588 patients from medical centers in two different regions of China were included in this study and defined as the internal test samples and the external validation samples, respectively. We retrospectively reviewed the differences in clinicopathologic data of the internal test samples to find the independent risk factors that affect the occurrence of GBC. Then, we constructed three different combined predictive factors (CPFs) through the weighting method, integral system, and nomogram, respectively, and named them CPF-A, CPF-B, and CPF-C sequentially. Furthermore, we evaluated these indicators through calibration and DCA curves. The ROC curve was used to analyze their diagnostic efficiency. Finally, their diagnostic capabilities were validated in the external validation samples.ResultsIn the internal test samples, the results showed that five factors, namely, age (RR = 3.077, 95% CI: 1.731-5.496), size of gallstones (RR = 13.732, 95% CI: 5.937-31.762), course of gallstones (RR = 2.438, 95% CI: 1.350-4.403), CEA (RR = 9.464, 95% CI: 3.394-26.392), and CA199 (RR = 9.605, 95% CI: 4.512-20.446), were independent risk factors for GBC in patients with gallstones. Then, we established three predictive indicators: CPF-A, CPF-B, and CPF-C. These models were further validated using bootstrapping with 1,000 repetitions. Calibration and decision curve analysis showed that the three models fit well. Meanwhile, multivariate analysis showed that CPF-B and CPF-C were independent risk factors for GBC in patients with gallstones. In addition, the validation results of the external validation samples are essentially consistent with the internal test samples.ConclusionAge (≤58.5 vs. &gt;58.5 years), size of gallstones (≤1.95 vs. &gt;1.95cm), course of gallstones (≤10 vs. &gt;10 years), CEA (≤5 vs. &gt;5 ng/ml), and CA199 (≤37 vs. &gt;37 U/ml) are independent risk factors for GBC in patients with gallstones. When positive indicators were ≥2 among the five independent risk factors or the score of the nomogram was &gt;82.64, the risk of GBC was high in gallstone patients.
Zinc finger and SCAN domain containing 1, ZSCAN1, is a novel stemness-related tumor suppressor and transcriptional repressor in breast cancer targeting TAZ
Authors: Chu Jian , Li Yunzhe , He Misi , Zhang Hui , Yang Lingling , Yang Muyao , Liu Jingshu , Cui Chenxi , Hong Liquan , Hu Xingchi , Zhou Lei , Li Tangya , Li Changchun , Fan Huiwen , Jiang Guoqin , Lang Tingyuan 
Published: February 2023

IntroductionCancer stem cells (CSCs) targeted therapy holds the potential for improving cancer management; identification of stemness-related genes in CSCs is necessary for its development.MethodsThe Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were used for survival analysis. ZSCAN1 correlated genes was identified by Spearman correlation analysis. Breast cancer stem-like cells (BCSLCs) were isolated by sorting CD44+CD24- cells from suspension cultured breast cancer (BC) spheroids. The sphere-forming capacity and sphere- and tumor-initiating capacities were determined by sphere formation and limiting dilution assays. The relative gene expression was determined by qRT-PCR, western blot. Lentivirus system was used for gene manipulation. Nuclear run-on assay was employed to examine the levels of nascent mRNAs. DNA pull-down and Chromatin immunoprecipitation (ChIP) assays were used for determining the interaction between protein and target DNA fragments. Luciferase reporter assay was used for evaluating the activity of the promoter.Results and discussionZSCAN1 is aberrantly suppressed in BC, and this suppression indicates a bad prognosis. Ectopic expression of ZSCAN1 inhibited the proliferation, clonogenicity, and tumorigenicity of BC cells. ZSCAN1-overexpressing BCSLCs exhibited weakened stemness properties. Normal human mammary epithelial (HMLE) cells with ZSCAN1 depletion exhibited enhanced stemness properties. Mechanistic studies showed that ZSCAN1 directly binds to -951 ~ -925bp region of WWTR1 (encodes TAZ) promoter, inhibits WWTR1 transcription, thereby inhibiting the stemness of BCSCs. Our work thus revealed ZSCAN1 as a novel stemness-related tumor suppressor and transcriptional repressor in BC.
PARP inhibitor-related haemorrhages: What does the real-world study say?
Authors: Wang Shiyan , Guo Mengran , Zhang Xiang , Fan Ping , Jin Zhaohui 
Published: February 2023

BackgroundPARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event.MethodsA pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS).Results725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib.ConclusionRecognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.
JAG1 is correlated to suppressive immune microenvironment and predicts immunotherapy resistance in lung adenocarcinoma
Authors: He Jing , Li Lu , Lv Lulu , Chen Xiaoyan , Ge Minghui , Ren Yong , Tang Xinyu , Liu Ping , Gao Wen 
Published: February 2023

BackgroundThe current exploration of the tumor immune microenvironment is enthusiastic, but few studies explored the impact of angiogenesis on the immune microenvironment. Immunotherapy combined with anti-angiogenesis therapy has become one of the first-line treatment for lung adenocarcinoma. Our study aimed to explore the reasons for resistance of immunotherapy, and explore markers for immunotherapy combined with anti-angiogenesis therapy.MethodsFirst, by unsupervised clustering of 36 angiogenesis-related genes in lung adenocarcinoma patients from TCGA database, AGS1 and AGS2 groups were distinguished with significantly different clinical outcomes. Secondly, the immune microenvironment and metabolic characteristics were analyzed. Next, we used the GDSC and GEO database to analyze therapeutic responses. Then, through multivariate Cox regression, the hub gene: JAG1, significantly related to prognosis was selected, and further verified by multi-omics data. Finally, we validated that patient with high JAG1 expression had a low immune-infiltrating tumor microenvironment through single-cell transcriptomic data.ResultsCompared with the AGS1 group, AGS2 showed an immune “cold” phenotype with lower lymphocyte infiltration, and was associated with worse prognoses. At the same time, the immunosuppressive TGF-β response was significantly higher in AGS2. Furthermore, the glycolysis ability of the AGS2 was stronger than AGS1. The expression of JAG1 was significantly higher in the AGS2, and was significantly negatively correlated with the degree of immune infiltration, accompanying with higher glycolytic capacity. The above results indicate that patients with high expression of JAG1 may lead to immunosuppressive phenotype due to its strong glycolytic capacity, thus making immunotherapy resistance.ConclusionPatients with high expression of JAG1 enhanced glycolytic capacity was likely to cause suppressed immune microenvironment. JAG1 may be a marker for resistance of immunotherapy. Combining anti-angiogenesis therapy could be considered to improve the prognosis of those patients.
Hepatectomy versus transcatheter arterial chemoembolization for resectable BCLC stage A/B hepatocellular carcinoma beyond Milan criteria: A randomized clinical trial
Authors: Fang Chongkai , Luo Rui , Zhang Ying , Wang Jinan , Feng Kunliang , Liu Silin , Chen Chuyao , Yao Ruiwei , Shi Hanqian , Zhong Chong 
Published: February 2023

BackgroundHepatectomy is the recommended option for radical treatment of BCLC stage A/B hepatocellular carcinoma (HCC) that has progressed beyond the Milan criteria. This study evaluated the efficacy and safety of preoperative neoadjuvant transcatheter arterial chemoembolization (TACE) for these patients.MethodsIn this prospective, randomized, open-label clinical study, BCLC stage A/B HCC patients beyond the Milan criteria were randomly assigned (1:1) to receive either neoadjuvant TACE prior to hepatectomy (NT group) or hepatectomy alone (OP group). The primary outcome was overall survival (OS), while the secondary outcomes were progression-free survival (PFS) and adverse events (AEs).ResultsOf 249 patients screened, 164 meeting the inclusion criteria were randomly assigned to either the NT group (n = 82) or OP group (n = 82) and completed follow-up requirements. Overall survival was significantly greater in the NT group compared to the OP group at 1 year (97.2% vs. 82.4%), two years (88.4% vs. 60.4%), and three years (71.6% vs. 45.7%) (p = 0.0011) post-treatment. Similarly, PFS was significantly longer in the NT group than the OP group at 1 year (60.1% vs. 39.9%), 2 years (53.4% vs. 24.5%), and 3 years (42.2% vs. 24.5%) (p = 0.0003). No patients reported adverse events of grade 3 or above in either group.ConclusionsNeoadjuvant TACE prolongs the survival of BCLC stage A/B HCC patients beyond the Milan criteria without increasing severe adverse events frequency.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200055618.
Comparison of oxygen supplementation in very preterm infants: Variations of oxygen saturation features and their application to hypoxemic episode based risk stratification
Authors: Ramanand Pravitha , Indic Premananda , Travers Colm P. , Ambalavanan Namasivayam 
Published: February 2023

BackgroundOxygen supplementation is commonly used to maintain oxygen saturation (SpO2) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO2 signal features and assess their performance in hypoxemia risk screening during NICU monitoring.Subjects and methodsSpO2 data from 25 infants with gestational age &lt;32 weeks and birthweight &lt;2,000 g who underwent a cross over trial of low-flow nasal cannula (NC) and digitally-set servo-controlled oxygen environment (OE) supplementations was considered in this secondary analysis. Features pertaining to signal distribution, variability and complexity were estimated and analyzed for differences between the supplementations. Univariate and regularized multivariate logistic regression was applied to identify relevant features and develop screening models for infants likely to experience a critically high number of IH per day of observation. Their performance was assessed using area under receiver operating curves (AUROC), accuracy, sensitivity, specificity and F1 scores.ResultsWhile most SpO2 measures remained comparable during both supplementations, signal irregularity and complexity were elevated while on OE, pointing to more volatility in oxygen saturation during this supplementation mode. In addition, SpO2 variability measures exhibited early prognostic value in discriminating infants at higher risk of critically many IH events. Poincare plot variability at lag 1 had AUROC of 0.82, 0.86, 0.89 compared to 0.63, 0.75, 0.81 for the IH number, a clinical parameter at observation times of 30 min, 1 and 2 h, respectively. Multivariate models with two features exhibited validation AUROC &gt; 0.80, F1 score &gt; 0.60 and specificity &gt;0.85 at observation times ≥ 1 h. Finally, we proposed a framework for risk stratification of infants using a cumulative risk score for continuous monitoring.ConclusionAnalysis of oxygen saturation signal routinely collected in the NICU, may have extensive applications in inferring subtle changes to cardiorespiratory dynamics under various conditions as well as in informing clinical decisions about infant care.
Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease
Authors: Jiang Zebin , Wu Zemin , Liu Ruixue , Du Qin , Fu Xian , Li Min , Kuang Yongjun , Lin Shen , Wu Jiaxuan , Xie Weiji , Shi Ganggang , Peng Yanqiang , Zheng Fuchun 
Published: February 2023

Dyslipidemia due to renal insufficiency is a common complication in patients with chronic kidney diseases (CKD), and a major risk factor for the development of cardiovascular events. Atorvastatin (AT) is mainly used in the treatment of dyslipidemia in patients with CKD. However, response to the atorvastatin varies inter-individually in clinical applications. We examined the association between polymorphisms in genes involved in drug metabolism and transport, and plasma concentrations of atorvastatin and its metabolites (2-hydroxy atorvastatin (2-AT), 2-hydroxy atorvastatin lactone (2-ATL), 4-hydroxy atorvastatin (4-AT), 4-hydroxy atorvastatin lactone (4-ATL), atorvastatin lactone (ATL)) in kidney diseases patients. Genotypes were determined using TaqMan real time PCR in 212 CKD patients, treated with 20 mg of atorvastatin daily for 6 weeks. The steady state plasma concentrations of atorvastatin and its metabolites were quantified using ultraperformance liquid chromatography in combination with triple quadrupole mass spectrometry (UPLC−MS/MS). Univariate and multivariate analyses showed the variant in ABCC4 (rs3742106) was associated with decreased concentrations of AT and its metabolites (2-AT+2-ATL: β = -0.162, p = 0.028 in the dominant model; AT+2-AT+4-AT: β = -0.212, p = 0.028 in the genotype model), while patients carrying the variant allele ABCC4-rs868853 (β = 0.177, p = 0.011) or NR1I2-rs6785049 (β = 0.123, p = 0.044) had higher concentrations of 2-AT+2-ATL in plasma compared with homozygous wildtype carriers. Luciferase activity was enhanced in HepG2 cells harboring a construct expressing the rs3742106-T allele or the rs868853-G allele (p &lt; 0.05 for each) compared with a construct expressing the rs3742106G or the rs868853-A allele. These findings suggest that two functional polymorphisms in the ABCC4 gene may affect transcriptional activity, thereby directly or indirectly affecting release of AT and its metabolites from hepatocytes into the circulation.
Efficacy of herbal medicine treatment based on syndrome differentiation for Parkinson’s disease: A systematic review and meta-analysis of randomized placebo-controlled clinical trials
Authors: Jun Purumea , Zhao HuiYan , Jung In Chul , Kwon Ojin , Han Chang-Hyun , Won Jiyoon , Jang Jung-Hee 
Published: February 2023

Background: Parkinson’s disease (PD), the second most common progressive neurodegenerative disease, causes heterogeneous clinical symptoms. Patients experience a range of motor and non-motor symptoms, and personalized diagnosis and treatment are needed. In traditional East Asian medicine, syndrome differentiation (SD) is a diagnostic approach for customized therapy that uses a comprehensive analysis and varies for the same disease. We aimed to evaluate the efficacy of herbal medicine (HM) prescribed according to the SD of PD.Methods: Ten electronic databases were searched from inception to August 2021 without language limitations. All randomized controlled trials (RCTs) involving HM for SD of PD were included. Assessment of Cochrane's risk of bias and meta-analysis and Grading of Recommendations Assessment, Development, and Evaluation was also performed. Effect measurement was summarized using the mean difference (MD) with 95% confidence interval, through a meta-analysis.Results: Thirteen RCTs involving 843 participants were included. The overall risk of bias was either low or unclear. Compared with the placebo, a combined therapy of HM and Western medicine (WM) significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) (MD = −8.03, [−10.27, −5.79], p &lt; 0.00001; I2 = 0%) and was more beneficial, as assessed using the UPDRS (I–III), the Parkinson’s Disease Questionnaire-39, and the Non-Motor Symptoms Scale. Adverse events did not differ between the groups.Conclusion: The findings suggest that the combined treatment of WM and HM based on SD diagnosis has additional benefits in PD treatment. However, the methodological quality of the included RCTs was suboptimal. Nevertheless, this systematic review is the first to investigate the efficacy of HM treatment according to the SD diagnosis in PD. The clinically meaningful improvement in HM according to SD in PD needs to be tested in further studies with rigorous designs and longer follow-up periods.Systematic Review Registration: [https://inplasy.com/inplasy-2021-10-0020/], identifier [INPLASY2021100020].
Teaching the Turkish language to foreigners at higher education level in Northern Cyprus: An evaluation based on self-perceived dominant intelligence types, twenty-first-century skills and learning technologies
Authors: Karakaş Kurt Esra , Güneyli Ahmet 
Published: February 2023

IntroductionThere are many foreign students in higher education in Northern Cyprus. Both the academic and life skills of these students depend on attaching the necessary importance to their Turkish language teaching. The goal of this study is to examine how university students employ learning technology, twenty-first-century abilities, and perceived categories of intelligence in the process of learning a foreign language.MethodsIn line with the quantitative research design, this study utilized a descriptive approach. Purposeful and convenience sampling methods were used to create the study sample. As a result, the institution in Northern Cyprus with the largest international student body was chosen. At this university, one of the authors of this study has been employed, and Turkish is the language of teaching. The study sample consisted of 431 university students who took Turkish as a foreign language in the 2021–2022 academic year at the selected university.ResultsThe results of the study revealed a weak yet statistically significant correlation between twenty-first-century skills and usage of foreign language-learning technologies. Additionally, students' twenty-first-century skill scores differed significantly, whereas their foreign language-learning technology scale scores did not match their self-perceived intelligence types.ConclusionThe research's findings indicate that students in higher education possess twenty-first-century skills. Based on this finding, it is possible to engage students in the courses and accomplish effective foreign language acquisition if foreign language education is carried out in accordance with modern methodologies and based on twenty-first-century abilities. It has been revealed in this study that it is important to include social learning rather than individual and competitive learning in foreign language education classes.