bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Population-Based Study: How to Identify High-Risk T1–2 Esophageal Cancer Patients?
Authors: Qi Yiming , Wu Shuangshuang , Tao Linghui , Xu Guoshu , Chen Jiabin , Feng Zhengquan , Lu Chao , Wan Yanli , Li Jing 
Published: December 2021

BackgroundDue to individualized conditions of lymph node metastasis (LNM) and distant metastasis (DM), the following therapeutic strategy and diagnosis of T1–2 esophageal cancer (ESCA) patients are varied. A prediction model for identifying risk factors for LNM, DM, and overall survival (OS) of high-risk T1–2 ESCA patients is of great significance to clinical practice.MethodsA total of 1,747 T1–2 ESCA patients screened from the surveillance, epidemiology, and end results (SEER) database were retrospectively analyzed for their clinical data. Univariate and multivariate logistic regression models were established to screen out risk factors for LNM and DM of T1-2 ESCA patients, while those of OS were screened out using the Cox regression analysis. The identified risk factors for LNM, DM, and OS were then subjected to the establishment of three nomograms, respectively. The accuracy of the nomograms was evaluated by depicting the calibration curve, and the predictive value and clinical utility were evaluated by depicting the clinical impact curve (CIC) and decision curve analysis (DCA), respectively.ResultsThe age, race, tumor grade, tumor size, and T-stage were significant factors for predicting LNM of T1–2 ESCA patients (p &lt; 0.05). The age, T-stage, tumor grade, and tumor size were significant factors for predicting DM of T1–2 ESCA patients (p &lt; 0.05). The age, race, sex, histology, primary tumor site, tumor size, N-stage, M-stage, and surgery were significant factors for predicting OS of T1–2 ESCA patients (p &lt; 0.05). The C-indexes of the three nomograms constructed by these factors were 0.737, 0.764, and 0.740, respectively, suggesting that they were clinically effective.ConclusionsThe newly constructed nomograms can objectively and accurately predict the LNM, DM, and OS of T1–2 ESCA patients, which contribute to the individualized decision making before clinical management.
Different Glucose Metabolic Features According to Cancer and Immune Cells in the Tumor Microenvironment
Authors: Choi Hongyoon , Na Kwon Joong 
Published: December 2021

BackgroundA close metabolic interaction between cancer and immune cells in the tumor microenvironment (TME) plays a pivotal role in cancer immunity. Herein, we have comprehensively investigated the glucose metabolic features of the TME at the single-cell level to discover feasible metabolic targets for the tumor immune status.MethodsWe examined expression levels of glucose transporters (GLUTs) in various cancer types using The Cancer Genome Atlas (TCGA) data and single-cell RNA-seq (scRNA-seq) datasets of human cancer tissues including melanoma, head and neck, and breast cancer. In addition, scRNA-seq data of immune cells in the TME acquired from human melanoma after immune checkpoint inhibitors were analyzed to investigate the dynamics of glucose metabolic profiles of specific immune cells.ResultsPan-cancer bulk RNA-seq showed that the GLUT3-to-GLUT1 ratio was positively associated with immune cell enrichment score. The scRNA-seq datasets of various human cancer tissues showed that GLUT1 was highly expressed in cancer cells, while GLUT3 was highly expressed in immune cells in TME. The scRNA-seq data obtained from human melanoma tissues pre- and post-immunotherapy showed that glucose metabolism features of myeloid cells, particularly including GLUTs expression, markedly differed according to treatment response.ConclusionsDifferently expressed GLUTs in TME suggest that GLUT could be a good candidate a surrogate of tumor immune metabolic profiles and a target for adjunctive treatments for immunotherapy.
Laparoscopic Versus Open Total Gastrectomy for Advanced Gastric Cancer: A Multicenter, Propensity Score-Matched Cohort Study in China
Authors: Feng Xingyu , Chen Xin , Ye Zaisheng , Xiong Wenjun , Yao Xueqing , Wang Wei , Wang Junjiang , Chen Luchuan , Li Yong 
Published: December 2021

BackgroundGiven the great technical difficulty and procedural complexity of laparoscopic total gastrectomy (LTG), the technical and oncologic safety of LTG versus open total gastrectomy (OTG) in the field of advanced gastric cancer (AGC) is yet undetermined.ObjectiveThis multicenter cohort study aimed to compare the surgical and oncological outcomes of LTG with those of OTG in AGC patients.Patients and MethodsIn total, 588 patients from 3 centers who underwent primary total gastrectomy with D2 lymphadenectomy, by well-trained surgeons with adequate experience, for pathologically confirmed locally AGC (T2N0–3, T3N0–3, or T4N0–3) between January 1, 2011, and December 31, 2015, were identified, and their clinical data were collected from three participating centers. After 1:1 propensity score matching (PSM), 450 cases (LTG, n = 225; OTG, n = 225) were eligible and assessed.ResultsNo significant difference in the number of retrieved lymph nodes, 5-year disease-free survival (DFS) rates, or 5-year overall survival (OS) rates between both surgical groups were observed. Although LTG had significantly longer surgical time (262 vs. 180 min, p &lt; 0.001), LTG was associated with fewer postoperative complications [relative risk (RR) 0.583, 95% CI 0.353–0.960, p = 0.047), less intraoperative bleeding (120 vs. 200 ml, p &lt; 0.001), longer proximal margin resection (3 vs. 2 cm, p &lt; 0.001), and shorter postoperative hospitalization (11 vs. 13 days, p &lt; 0.001). The mortality rate was comparable in both groups.ConclusionsLTG was not inferior to OTG in terms of survival outcomes and was associated with shorter surgical and postoperative hospitalization time and fewer postoperative complications, suggesting LTG with D2 lymphadenectomy as an important alternative to OTG for patients with AGC, but to be carried out in highly experienced centers.
Extracellular Vesicles Induce an Aggressive Phenotype in Luminal Breast Cancer Cells Via PKM2 Phosphorylation
Authors: Kang Seo Young , Lee Eun Ji , Byun Jung Woo , Han Dohyun , Choi Yoori , Hwang Do Won , Lee Dong Soo 
Published: December 2021

BackgroundAerobic glycolysis is a hallmark of glucose metabolism in cancer. Previous studies have suggested that cancer cell–derived extracellular vesicles (EVs) can modulate glucose metabolism in adjacent cells and promote disease progression. We hypothesized that EVs originating from cancer cells can modulate glucose metabolism in recipient cancer cells to induce cell proliferation and an aggressive cancer phenotype.MethodsTwo breast cancer cell lines with different levels of glycolytic activity, MDA-MB-231 cells of the claudin-low subtype and MCF7 cells of the luminal type, were selected and cocultured as the originating and recipient cells, respectively, using an indirect coculture system, such as a Transwell system or a microfluidic system. The [18F]fluorodeoxyglucose (FDG) uptake by the recipient MCF7 cells was assessed before and after coculture with MDA-MB-231 cells. Proteomic and transcriptomic analyses were performed to investigate the changes in gene expression patterns in the recipient MCF7 cells and MDA-MB-231 cell-derived EVs.ResultsFDG uptake by the recipient MCF7 cells significantly increased after coculture with MDA-MB-231 cells. In addition, phosphorylation of PKM2 at tyrosine-105 and serine-37, which is necessary for tumorigenesis and aerobic glycolysis, was highly activated in cocultured MCF7 cells. Proteomic profiling revealed the proliferation and dedifferentiation of MCF7 cells following coculture with MDA-MB-231 cells. Transcriptomic analysis demonstrated an increase in glycolysis in cocultured MCF7 cells, and the component analysis of glycolysis-related genes revealed that the second most abundant component after the cytoplasm was extracellular exosomes. In addition, proteomic analysis of EVs showed that the key proteins capable of phosphorylating PKM2 were present as cargo inside MDA-MB-231 cell-derived EVs.ConclusionsThe phenomena observed in this study suggest that cancer cells can induce a phenotype transition of other subtypes to an aggressive phenotype to consequently activate glucose metabolism via EVs. Therefore, this study could serve as a cornerstone for further research on interactions between cancer cells.
Tumor Immune Microenvironment Related Gene-Based Model to Predict Prognosis and Response to Compounds in Ovarian Cancer
Authors: Yang Jiang , Hong Shasha , Zhang Xiaoyi , Liu Jingchun , Wang Ying , Wang Zhi , Gao Likun , Hong Li 
Published: December 2021

BackgroundThe tumor immune microenvironment (TIME) has been recognized to be an imperative factor facilitating the acquisition of many cancer-related hallmarks and is a critical target for targeted biological therapy. This research intended to construct a risk score model premised on TIME-associated genes for prediction of survival and identification of potential drugs for ovarian cancer (OC) patients.Methods and ResultsThe stromal and immune scores were computed utilizing the ESTIMATE algorithm in OC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network and differentially expressed genes analyses were utilized to detect stromal-and immune-related genes. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was utilized for additional gene selection. The genes that were selected were utilized as the input for a stepwise regression to construct a TIME-related risk score (TIMErisk), which was then validated in Gene Expression Omnibus (GEO) database. For the evaluation of the protein expression levels of TIME regulators, the Human Protein Atlas (HPA) dataset was utilized, and for their biological functions, the TIMER and CIBERSORT algorithm, immunoreactivity, and Immune Cell Abundance Identifier (ImmuCellAI) were used. Possible OC medications were forecasted utilizing the Genomics of Drug Sensitivity in Cancer (GDSC) database and connectivity map (CMap). TIMErisk was developed based on ALPK2, CPA3, PTGER3, CTHRC1, PLA2G2D, CXCL11, and ZNF683. High TIMErisk was recognized as a poor factor for survival in the GEO and TCGA databases; subgroup analysis with FIGO stage, grade, lymphatic and venous invasion, debulking, and tumor site also indicated similar results. Functional immune cells corresponded to more incisive immune reactions, including secretion of chemokines and interleukins, natural killer cell cytotoxicity, TNF signaling pathway, and infiltration of activated NK cells, eosinophils, and neutrophils in patients with low TIMErisk. Several small molecular medications which may enhance the prognosis of patients in the TIMErisk subgroup were identified. Lastly, an enhanced predictive performance nomogram was constructed by compounding TIMErisk with the FIGO stage and debulking.ConclusionThese findings may offer a valuable indicator for clinical stratification management and personalized therapeutic options for OC patients and may be a foundation for future mechanistic research of their association.
A Systematic Review of Economic Evaluations of Active Tuberculosis Treatments
Authors: Byun Joo-Young , Kim Hye-Lin , Lee Eui-Kyung , Kwon Sun-Hong 
Published: December 2021

Background: The disease burden of active tuberculosis (TB) is considerable, but systematic reviews of economic evaluations of active TB treatments are scarce.Methods: PubMed, EMBASE, and the Cochrane Library databases were used to search for articles on cost-effectiveness analysis or cost-utility analysis that economically evaluated active TB treatments, which were then systematically reviewed by two independent reviewers. We extracted vital components of the included studies, such as country, population, intervention/comparator, primary outcome, values of outcomes, thresholds, model type, time horizon, and health states included in the model.Results: Seventeen studies were included in this systematic review. Thirteen dealt with interventions of medications, and the remaining four compared care strategies. The Markov model was the most commonly used tool to compare medications, whereas studies on care plans mainly used decision trees. The most commonly used primary outcome was disability-adjusted life years, followed by quality-adjusted life years. For treatment-naïve TB, the 4-month regimen was more cost-effective than the 6-month regimen mainly in low- and middle-income countries. For multidrug-resistant TB, a bedaquiline-based regimen was cost-effective. For multidrug-resistant TB, decentralized care that employed the use of home or mobile devices was more cost-effective than hospital-based centralized care in low- and middle-income countries.Conclusion: New treatment strategies to improve therapeutic outcomes by enhancing treatment adherence, such as regimens with shorter durations (2 or 4 months) and decentralized care, or new anti-TB agents (e.g., bedaquiline) have been suggested as cost-effective interventions for active TB. This review provides information on the economic evaluation of active TB from good-quality studies, thus aiding the future economic evaluation of active TB.
Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats
Authors: Ji Chunlan , Li Yin , Mo Yenan , Lu Zhaoyu , Lu Fuhua , Lin Qizhan , Liu Xusheng , Zou Chuan , Wu Yuchi 
Published: December 2021

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats.Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman’s correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO.Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.
Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4
Authors: Shi Jing , Li Yuanyuan , Zhang Yi , Chen Jie , Gao Jianqing , Zhang Tianyuan , Shang Xiaoguang , Zhang Xiangnan 
Published: December 2021

Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.
The Impact of Reimbursement Practices on the Pharmaceutical Market for Off-Patent Medicines in Slovakia
Authors: Tesar Tomas , Golias Peter , Masarykova Lucia , Kawalec Paweł , Inotai András 
Published: December 2021

Background: The aim of this study was to investigate the impact of selected legislative initiatives and their implementation for off-patent medicinal products in Slovakia compared with the rest of the Visegrád Group (V4 countries).Methods: We analyzed the development of applications for the reimbursement of generic and biosimilar drugs. Particular emphasis was placed on a) the availability and penetration of biosimilars from 2006 to 2020 in Slovakia, b) a comparative analysis of biosimilars in V4 countries based on the national reimbursement lists of medicinal products for August 2021. Data relating to the sales of generic and biosimilar medicines in Czechia, Hungary, Poland, and Slovakia were based on the IQVIA MIDAS MAT July 2021.Results: The number of applications for the reimbursement of generic drugs decreased from 296 in 2016 to 165 in 2020. In financial terms, the sales of generic medicines in Slovakia increased from 21.7% in 2015 to 22.3% in 2020. Over the same period, the sales of generic drugs in Poland fell from 40.4% in 2015 to 35.0% in 2020, from 26.2 to 22.1% in Hungary, and from 29.6 to 20.4% in Czechia. When considering the 66 biosimilars registered by the European Medicines Agency 38 drugs (58%) were available on the Slovak market as of August 1, 2021; this compared to 32 drugs (48%) in Poland, 38 drugs (58%) in Hungary, and 40 drugs (61%) in Czechia. In financial terms, the sales of biosimilars in Slovakia increased from 0.94% in 2015 to 2.00% in 2020. Over the same period, the sales of biosimilars in Poland increased from 0.59% in 2015 to 1.29% in 2020, from 0.72 to 2.23% in Hungary, and from 0.76 to 2.15% in Czechia.Conclusion: To intensify the use of generic and biosimilar medicines, we suggest the comprehensive re-evaluation of combinations of the three-threshold entry, the amount of mandatory price reductions, and external reference pricing requirements (as the average of the three lowest prices among the official prices of a medicinal product in other Member States) for generic and biosimilar drugs. We also suggest cancellation of the exception from the fixed co-payment of the insured.
Can Trait Mindfulness Improve Job Satisfaction? The Relationship Between Trait Mindfulness and Job Satisfaction of Preschool Teachers: The Sequential Mediating Effect of Basic Psychological Needs and Positive Emotions
Authors: Song Zhanmei , Pan Baocheng , Wang Youli 
Published: December 2021

Objective: This study aims to explore the relationship between basic psychological needs and positive emotions of preschool teachers between trait mindfulness and job satisfaction.Methods: Three hundred and ninety-eight preschool teachers were tested with mindfulness attention awareness scale, basic psychological needs scale, positive emotion scale, and job satisfaction scale.Results: Preschool teachers trait mindfulness can predict job satisfaction (β = 0.265, p &lt; 0. 001). Preschool teachers trait mindfulness has an indirect impact on job satisfaction through basic psychological needs (β = 0.059, p = 0.002), and preschool teachers trait mindfulness has an indirect impact on job satisfaction through positive emotions (β = 0.123, p &lt; 0. 001). In addition, basic psychological needs and positive emotions play a sequential intermediary role between preschool teachers trait mindfulness and job satisfaction (β = 0.017, p &lt; 0. 001).Conclusion: Basic psychological needs and positive emotions play a sequential mediating role between preschool teachers trait mindfulness and job satisfaction, and this sequential mediating effect accounts for a high proportion of the total effect.
Differential Dynamical Pattern of Regional Homogeneity in Bipolar and Unipolar Depression: A Preliminary Resting-State fMRI Study
Authors: Sun Fuping , Liu Zhening , Yang Jun , Fan Zebin , Yang Jie 
Published: December 2021

Background: Bipolar depression (BD) and unipolar depression (UD) are both characterized by depressive moods, which are difficult to distinguish in clinical practice. Human brain activity is time-varying and dynamic. Investigating dynamical pattern alterations of depressed brains can provide deep insights into the pathophysiological features of depression. This study aimed to explore similar and different abnormal dynamic patterns between BD and UD.Methods: Brain resting-state functional magnetic resonance imaging data were acquired from 36 patients with BD type I (BD-I), 38 patients with UD, and 42 healthy controls (HCs). Analysis of covariance was adopted to examine the differential pattern of the dynamical regional homogeneity (dReHo) temporal variability across 3 groups, with gender, age, and education level as covariates. Post-hoc analyses were employed to obtain the different dynamic characteristics between any 2 groups. We further applied the machine-learning methods to classify BD-I from UD by using the detected distinct dReHo pattern.Results: Compared with patients with UD, patients with BD-I demonstrated decreased dReHo variability in the right postcentral gyrus and right parahippocampal gyrus. By using the dReHo variability pattern of these two regions as features, we achieved the 91.89% accuracy and 0.92 area under curve in classifying BD-I from UD. Relative to HCs, patients with UD showed increased dReHo variability in the right postcentral gyrus, while there were no dReHo variability differences in patients with BD-I.Conclusions: The results of this study mainly report the differential dynamic pattern of the regional activity between BD-I and UD, particular in the mesolimbic system, and show its promising potential in assisting the diagnosis of these two depression groups.