bluuebunny/crossref_metadata_2025 huggingface dataset:
Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1
Authors: Zhao Chen , Li Yingwei , Qiu Chunping , Chen Jingying , Wu Huan , Wang Qiuman , Ma Xinyue , Song Kun , Kong Beihua
Published: December 2021

Ovarian carcinoma remains the most lethal gynecological carcinoma. Abnormal expression of splicing factors is closely related to the occurrence and development of tumors. The DEAD-box RNA helicases are important members of the splicing factor family. However, their role in the occurrence and progression of ovarian cancer is still unclear. In this study, we identified DEAD-box helicase 23 (DDX23) as a key DEAD-box RNA helicase in ovarian cancer using bioinformatics methods. We determined that DDX23 was upregulated in ovarian cancer and its high expression predicted poor prognosis. Functional assays indicated that DDX23 silencing significantly impeded cell proliferation/invasion in vitro and tumor growth in vivo. Mechanistically, transcriptomic analysis showed that DDX23 was involved in mRNA processing in ovarian cancer cells. Specifically, DDX23 regulated the mRNA processing of FOXM1. DDX23 silencing reduced the production of FOXM1C, the major oncogenic transcript of FOXM1 in ovarian cancer, thereby decreasing the FOXM1 protein expression and attenuating the malignant progression of ovarian cancer. Rescue assays indicated that FOXM1 was a key executor in DDX23-induced malignant phenotype of ovarian cancer. Furthermore, we confirmed that DDX23 was transcriptionally activated by the transcription factor (TF) E2F1 in ovarian cancer using luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. In conclusion, our study demonstrates that high DDX23 expression is involved in malignant behavior of ovarian cancer and DDX23 may become a potential target for precision therapy of ovarian cancer.
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

Background

Due 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.

Methods

A 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.

Results

The age, race, tumor grade, tumor size, and T-stage were significant factors for predicting LNM of T1–2 ESCA patients (p < 0.05). The age, T-stage, tumor grade, and tumor size were significant factors for predicting DM of T1–2 ESCA patients (p < 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 < 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.

Conclusions

The 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

Background

A 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.

Methods

We 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.

Results

Pan-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.

Conclusions

Differently 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.
Ischemic-Free Liver Transplantation Reduces the Recurrence of Hepatocellular Carcinoma After Liver Transplantation
Authors: Tang Yunhua , Wang Tielong , Ju Weiqiang , Li Fangcong , Zhang Qi , Chen Zhitao , Gong Jinlong , Zhao Qiang , Wang Dongping , Chen Maogen , Guo Zhiyong , He Xiaoshun
Published: December 2021

Ischemia reperfusion injury (IRI) is an adverse factor for hepatocellular carcinoma (HCC) recurrence after liver transplantation. Ischemic-free liver transplantation (IFLT) is a novel transplant procedure that can largely reduce or even prevent IRI, but the clinical relevance of IFLT and the recurrence of HCC after liver transplantation are still unknown. This retrospective study compared survival outcomes, HCC recurrence, perioperative data and IRI severity following liver transplantation (LT). 30 patients received IFLT and 196 patients received conventional liver transplantation (CLT) were chosen for the entire cohort between June 2017 and August 2020. A 1:3 propensity score matching was performed, 30 IFLT recipients and 85 matched CLT patients were enrolled in propensity-matched cohorts. An univariate and multivariate Cox regression analysis was performed, and showed surgical procedure (CLT vs IFLT) was an independent prognostic factor (HR 3.728, 95% CI 1.172-11.861, P=0.026) for recurrence free survival (RFS) in HCC patients following liver transplantation. In the Kaplan–Meier analysis, the RFS rates at 1 and 3 years after LT in recipients with HCC in the IFLT group were significantly higher than those in the CLT group both in the entire cohort and propensity-matched cohort (P=0.006 and P=0.048, respectively). In addition, patients in the IFLT group had a lower serum lactate level, lower serum ALT level and serum AST level on postoperative Day 1. LT recipients with HCC in the IFLT group had a lower incidence of early allograft dysfunction than LT recipients with HCC in the CLT group. Histological analysis showed no obvious hepatocyte necrosis or apoptosis in IFLT group. In conclusion, IFLT can significantly reduce IRI damage and has the potential to be a useful strategy to reduce HCC recurrence after liver transplantation.
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

Background

Given 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.

Objective

This multicenter cohort study aimed to compare the surgical and oncological outcomes of LTG with those of OTG in AGC patients.

Patients and Methods

In 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.

Results

No 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 < 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 < 0.001), longer proximal margin resection (3 vs. 2 cm, p < 0.001), and shorter postoperative hospitalization (11 vs. 13 days, p < 0.001). The mortality rate was comparable in both groups.

Conclusions

LTG 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

Background

Aerobic 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.

Methods

Two 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.

Results

FDG 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.

Conclusions

The 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

Background

The 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 Results

The 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.

Conclusion

These 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.
Morphine Exacerbates Experimental Colitis-Induced Depression of Nesting in Mice
Authors: Cheatham Stanley M. , Muchhala Karan H. , Koseli Eda , Jacob Joanna C. , Komla Essie , Negus S. Stevens , Akbarali Hamid I.
Published: December 2021

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are excellent analgesics, but recent clinical evidence suggests that these drugs might worsen disease severity in Crohn's disease patients, limiting their clinical utility for treating Inflammatory Bowel Disease (IBD). One indicator of change in well-being from conditions such as IBD is behavioral depression and disruption to activities of daily living. Preclinical measures of behavioral depression can provide an indicator of changes in quality of life and subsequent modification by candidate analgesics. In mice, nesting is an adaptive unconditioned behavior that is susceptible to disruption by noxious stimuli, and some types of pain related nesting depression are responsive to opioid and NSAID analgesics. Here we show that a 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) model of experimental colitis depresses nesting behavior in mice, and we evaluated effects of morphine, an opioid, and ketoprofen, a NSAID, on TNBS-induced nesting depression. In Swiss Webster mice, TNBS significantly reduced nesting that peaked on Day 3 and recovered in a time-dependent manner with complete recovery by Day 7. In the absence of colonic inflammation, daily treatment with morphine (1–10 mg/kg) did not decrease nesting except at 10mg/kg/day. However, in TNBS-treated mice 3.2 mg/kg/day morphine significantly exacerbated TNBS-induced nesting depression and delayed recovery. While 3.2 mg/kg/day morphine alone did not alter locomotor activity and TNBS-induced depression of locomotion recovered, the combination of TNBS and 3.2 mg/kg/day morphine significantly attenuated locomotion and prevented recovery. Daily treatment with 3.2 or 10 mg/kg ketoprofen in TNBS-treated mice did not prevent depression of nesting. These data suggest that opioid analgesics but not NSAIDS worsen colonic inflammation-induced behavioral depression. Furthermore, these findings highlight the importance of evaluating analgesic effects in models of colonic inflammation induced depression of behavior.
Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets
Authors: Alles Sascha R. A. , Smith Peter A.
Published: December 2021

The persistence of increased excitability and spontaneous activity in injured peripheral neurons is imperative for the development and persistence of many forms of neuropathic pain. This aberrant activity involves increased activity and/or expression of voltage-gated Na+ and Ca2+ channels and hyperpolarization activated cyclic nucleotide gated (HCN) channels as well as decreased function of K+ channels. Because they display limited central side effects, peripherally restricted Na+ and Ca2+ channel blockers and K+ channel activators offer potential therapeutic approaches to pain management. This review outlines the current status and future therapeutic promise of peripherally acting channel modulators. Selective blockers of Nav1.3, Nav1.7, Nav1.8, Cav3.2, and HCN2 and activators of Kv7.2 abrogate signs of neuropathic pain in animal models. Unfortunately, their performance in the clinic has been disappointing; some substances fail to meet therapeutic end points whereas others produce dose-limiting side effects. Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K+ channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na+ channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca2+ channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing “pain” as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a histone methyltransferase inhibitor used in the management of T-cell lymphoma, or cercosporamide a MNK 1/2 inhibitor used in treatment of rheumatoid arthritis; (vi) combination therapy using drugs that are selective for different channel types or regulatory processes; (vii) directing preclinical validation work toward the use of human or human-derived tissue samples; and (viii) application of molecular biological approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) technology.
Respiratory Tract Microecology and Bronchopulmonary Dysplasia in Preterm Infants
Authors: Sun Tong , Yu Haiyang , Fu Jianhua
Published: December 2021

Bronchopulmonary dysplasia (BPD) is a severe respiratory complication in preterm infants. Although the etiology and pathogenesis of BPD are complex and remain to be clarified, recent studies have reported a certain correlation between the microecological environment of the respiratory tract and BPD. Changes in respiratory tract microecology, such as abnormal microbial diversity and altered evolutional patterns, are observed prior to the development of BPD in premature infants. Therefore, research on the colonization and evolution of neonatal respiratory tract microecology and its relationship with BPD is expected to provide new ideas for its prevention and treatment. In this paper, we review microecological changes in the respiratory tract and the mechanisms by which they can lead to BPD in preterm infants.
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.
Assessment of Alveolar Bone and Periodontal Status in Peritoneal Dialysis Patients
Authors: Sun Kristine , Shen Hui , Liu Yingli , Deng Hai , Chen Huiwen , Song Zhongchen
Published: December 2021

Chronic kidney disease (CKD) affects 8–13% of the global population and has become one of the largest burdens on healthcare systems around the world. Peritoneal dialysis is one of the ultimate treatments for patients with severe CKD. Recently, increasing severe periodontal problems have been found in CKD patients. Periodontitis has been identified as a new variable risk factor for CKD. The aim of this study was to investigate the periodontal status and severity of alveolar bone loss in CKD patients with peritoneal dialysis (PD). One hundred and six patients undergoing PD (PD group) and 97 systemically healthy periodontitis patients (control group) were enrolled. The differences in the dimensions of the alveolar bone between two groups were compared, and the distribution of alveolar bone defects was analyzed by cone-beam computed tomography (CBCT). Gingival index (GI), plaque index (PLI), periodontal probing depth (PPD), and attachment loss (AL) were recorded. The levels of inflammatory factors in gingival crevicular fluid were assessed by ELISA. Compared to control group, there was a higher degree of alveolar bone loss in maxillary premolars, maxillary 2nd molar and mandibular 1st molar in patients with PD (p < 0.05). A comparison of bone loss in different sites revealed that the area with the highest degree of bone loss were on the mesial-buccal, mid-buccal, distal-buccal, and mesial-lingual site in PD patients. The expression levels of inflammatory factors were higher in PD group (p < 0.01). In conclusion, PD patients presented more severe periodontal and inflammatory status than systemically healthy periodontitis patients. The loss of the alveolar bone differed between the two groups. Different sites and teeth exhibited a diverse degree of bone loss. This study highlights that clinicians should pay close attention to periodontal status of peritoneal dialysis patients and provides a new thinking to improve healthcare for CKD.
Understanding G × E Interaction for Nutritional and Antinutritional Factors in a Diverse Panel of Vigna stipulacea (Lam.) Kuntz Germplasm Tested Over the Locations
Authors: Gore Padmavati G. , Das Arpita , Bhardwaj Rakesh , Tripathi Kuldeep , Pratap Aditya , Dikshit Harsh K. , Bhattacharya Sudip , Nair Ramakrishnan M. , Gupta Veena
Published: December 2021

Micronutrient malnutrition or hidden hunger is a serious challenge toward societal well-being. Vigna stipulacea (Lam.) Kuntz (known locally as Minni payaru), is an underutilized legume that has the potential to be a global food legume due to its rich nutrient profile. In the present study, 99 accessions of V. stipulacea were tested for iron (Fe), zinc (Zn), calcium (Ca), protein, and phytate concentrations over two locations for appraisal of stable nutrient-rich sources. Analysis of variance revealed significant effects of genotype for all the traits over both locations. Fe concentration ranged from 29.35–130.96 mg kg–1 whereas Zn concentration ranged from 19.44 to 74.20 mg kg–1 across both locations. The highest grain Ca concentration was 251.50 mg kg–1 whereas the highest grain protein concentration was recorded as 25.73%. In the case of grain phytate concentration, a genotype with the lowest value is desirable. IC622867 (G-99) was the lowest phytate containing accession at both locations. All the studied traits revealed highly significant genotypic variances and highly significant genotype × location interaction though less in magnitude than the genotypic variance. GGE Biplot analysis detected that, for grain Fe, Zn, and Ca concentration the ‘ideal’ genotypes were IC331457 (G-75), IC331610 (G-76), and IC553564 (G-60), respectively, whereas for grain protein concentration IC553521 (G-27) was the most “ideal type.” For phytate concentration, IC351407 (G-95) and IC550523 (G-99) were considered as ‘ideal’ and ‘desirable,’ respectively. Based on the desirability index, Location 1 (Kanpur) was identified as ideal for Fe, Zn, Ca, and phytate, and for grain protein concentration, Location 2 (New Delhi) was the ideal type. A significant positive correlation was detected between grain Fe as well as grain Zn and protein concentration considering the pooled analysis over both the locations where as a significant negative association was observed between phytate and protein concentration over the locations. This study has identified useful donors and enhanced our knowledge toward the development of biofortified Vigna cultivars. Promoting domestication of this nutrient-rich semi-domesticated, underutilized species will boost sustainable agriculture and will contribute toward alleviating hidden hunger.
An Overview of the Genetics and Genomics of the Urochloa Species Most Commonly Used in Pastures
Authors: Ferreira Rebecca Caroline Ulbricht , Costa Lima Moraes Aline da , Chiari Lucimara , Simeão Rosangela Maria , Vigna Bianca Baccili Zanotto , de Souza Anete Pereira
Published: December 2021

Pastures based on perennial monocotyledonous plants are the principal source of nutrition for ruminant livestock in tropical and subtropical areas across the globe. TheUrochloagenus comprises important species used in pastures, and these mainly includeUrochloa brizantha,Urochloa decumbens,Urochloa humidicola, andUrochloa ruziziensis. Despite their economic relevance, there is an absence of genomic-level information for these species, and this lack is mainly due to genomic complexity, including polyploidy, high heterozygosity, and genomes with a high repeat content, which hinders advances in molecular approaches to genetic improvement. Next-generation sequencing techniques have enabled the recent release of reference genomes, genetic linkage maps, and transcriptome sequences, and this information helps improve our understanding of the genetic architecture and molecular mechanisms involved in relevant traits, such as the apomictic reproductive mode. However, more concerted research efforts are still needed to characterize germplasm resources and identify molecular markers and genes associated with target traits. In addition, the implementation of genomic selection and gene editing is needed to reduce the breeding time and expenditure. In this review, we highlight the importance and characteristics of the four main species ofUrochloaused in pastures and discuss the current findings from genetic and genomic studies and research gaps that should be addressed in future research.
Multi-Threshold Image Segmentation of Maize Diseases Based on Elite Comprehensive Particle Swarm Optimization and Otsu
Authors: Chen Chengcheng , Wang Xianchang , Heidari Ali Asghar , Yu Helong , Chen Huiling
Published: December 2021

Maize is a major global food crop and as one of the most productive grain crops, it can be eaten; it is also a good feed for the development of animal husbandry and essential raw material for light industry, chemical industry, medicine, and health. Diseases are the main factor limiting the high and stable yield of maize. Scientific and practical identification is a vital link to reduce the damage of diseases and accurate segmentation of disease spots is one of the fundamental techniques for disease identification. However, one single method cannot achieve a good segmentation effect to meet the diversity and complexity of disease spots. In order to solve the shortcomings of noise interference and oversegmentation in the Otsu segmentation method, a non-local mean filtered two-dimensional histogram was used to remove the noise in disease images and a new elite strategy improved comprehensive particle swarm optimization (PSO) method was used to find the optimal segmentation threshold of the objective function in this study. The experimental results of segmenting three kinds of maize foliar disease images show that the segmentation effect of this method is better than other similar algorithms and it has better convergence and stability.
Employee Social Network Strategies: Implications for Firm Strategies and Performance in Future Organizations
Authors: Thiel Monica
Published: December 2021

Employee social network strategies play a key role in firm strategies and organizational performance. Currently, scholars underestimate the contributions of employee social strategies in firm strategies. Little is known how informal employee social networks, group entitativity and competition could shape and direct firm strategies and organizational performance. The article examines social network theory and strategic management’s content, process and open schools of thought to propose a new interpretation for managing firm strategies. More specifically, the author examines alternate causal paths, underlying processes and structures as mechanisms in employee social network strategies within a theoretical framework. The article proposes 4 theoretically driven propositions and makes two contributions. First, the article contributes to organizational behavior literature by focusing on the literature gap in network dynamics and competitive actions through employee social networks. Second, although there is immense literature on positive and negative employee competition in business, the article makes a contribution to the strategic management literature by moving beyond formalized structures and roles within an organization to focus on the multilevel informal workplace social interactions and processes that impact strategizing activities. Overall, the article extends strategy research in relation to how employee social networks operate through competition and group entitativity in firm strategies.
Components of Unrealistic Optimism of College Students: The Case of the COVID-19 Pandemic
Authors: Eshel Yohanan , Kimhi Shaul , Marciano Hadas , Adini Bruria
Published: December 2021

College students are among the most strongly affected populations by the coronavirus disease-2019 (COVID-19) pandemic because of uncertainty regarding academic success, future careers, and social life during their study period. Their mental health and behavior may dramatically be impacted. The study examined an unrealistic optimism of Israeli college students in assessing the health, security, and economic risks during the pandemic, and the contributions of these perceived risks to the prediction of psychological coping responses, such as well-being, and coping suppressing response of anxiety, expressed during this pandemic. Using social networks, a questionnaire was disseminated to students during the third lockdown that was implemented in Israel because of the pandemic. Depressive and anxiety symptoms, perceived threats, resilience, well-being, hope, and morale were measured using a structured quantitative questionnaire. First, we hypothesized that the three perceived risks would be inversely rated, so perceived health risk would be rated lowest, and perceived economic risk would be rated highest. The second and third hypotheses claimed that psychological coping responses articulated along this pandemic would be predicted by all these perceived risks, as well as the observance of pandemic precaution rules. The fourth hypothesis suggested that the three investigated perceived risks will positively and significantly correlate with each other. The results generally supported the hypotheses and indicated that the unrealistic optimism process was employed quite consistently by the participating students.
Universality and Cultural Diversity in Moral Reasoning and Judgment
Authors: Bentahila Lina , Fontaine Roger , Pennequin Valérie
Published: December 2021

Many theories have shaped the concept of morality and its development by anchoring it in the realm of the social systems and values of each culture. This review discusses the current formulation of moral theories that attempt to explain cultural factors affecting moral judgment and reasoning. It aims to survey key criticisms that emerged in the past decades. In both cases, we highlight examples of cultural differences in morality, to show that there are cultural patterns of moral cognition in Westerners’ individualistic culture and Easterners’ collectivist culture. It suggests a paradigmatic change in this field by proposing pluralist “moralities” thought to be universal and rooted in the human evolutionary past. Notwithstanding, cultures vary substantially in their promotion and transmission of a multitude of moral reasonings and judgments. Depending on history, religious beliefs, social ecology, and institutional regulations (e.g., kinship structure and economic markets), each society develops a moral system emphasizing several moral orientations. This variability raises questions for normative theories of morality from a cross-cultural perspective. Consequently, we shed light on future descriptive work on morality to identify the cultural characteristics likely to impact the expression or development of reasoning, justification, argumentation, and moral judgment in Westerners’ individualistic culture and Easterners’ collectivist culture.
The Effect of Place Attachment on Overseas Students’ Tourism Ambassador Behavior: A Mediation Role of Life Satisfactionrdrd
Authors: Wang Xin , Lai Ivan Ka Wai , Liu Xinyu
Published: December 2021

Life satisfaction is a research hotspot in positive psychology in recent years. This study uses overseas students as subjects and attempts to examine the effect of place attachment and student life satisfaction on Mainland Chinese students’ word-of-mouth (WOM) recommendations and their Ambassador Behavioral (AB) intention. A survey was systematically conducted in six institutions in Macao. The results of 312 valid data indicate that place dependence has a positive influence on place identity; place identity and place dependence have a positive influence on student life satisfaction; student life satisfaction mediates the influence of the two dimensions of place attachment on WOM and AB intention. Recommendations are provided to improve overseas students’ life satisfaction in the study places. It helps to improve their sense of ownership and actively participate in the construction of the study places.
The Effect of Malicious Envy on Schadenfreude When Schadenfreude Is Elicited Through Social Comparisons
Authors: Lin Huiyan , Liang Jiafeng
Published: December 2021

Previous studies have investigated whether envy, particularly malicious envy, increases feelings of schadenfreude and whether this effect is evident in both gain and loss frames. However, as a social-comparison-based emotion, schadenfreude was not investigated through social comparisons in these previous studies. Thus, the present study aimed to investigate whether malicious envy influences schadenfreude when schadenfreude is elicited in the context of precise and ambiguous social comparisons. To address this issue, participants in the present study were asked to play a monetary game with several other players. In the experimental condition, participants gained less or lost more than the other player; in the control condition, both the participants and the player gained little or lost much. Subsequently, the participants observed that the player encountered a misfortune, that is, gained less or lost more money than the participant. The results showed that when participants knew the exact amount of monetary gained and lost by themselves and the other player (i.e., precise social comparisons), malicious envy increased feelings of schadenfreude only in the loss frame rather than in the gain frame. More importantly, malicious envy turned out to reduce feelings of schadenfreude in both gain and loss frames, when participants did not know the exact amount (i.e., ambiguous social comparisons). The findings provide novel evidence that malicious envy does not always increase schadenfreude particularly when schadenfreude is elicited through social comparisons.
Cross-Cultural Applicability of Organizational Stressor Indicator for Sport Performers Questionnaire in Ghana Using Structural Equation Modeling Approach
Authors: Srem-Sai Medina , Quansah Frank , Frimpong James Boadu , Hagan John Elvis , Schack Thomas
Published: December 2021

The purpose of this study was to examine the cross-cultural validity of the Organizational Stressor Indicator for Sport Performers (OSI-SP) scale by investigating its psychometric properties with Ghanaian footballers. The study particularly sought to assess in the Ghanaian context, 1, the convergence validity and reliability of the OSI-SP scale, 2, the discriminant validity of the OSI-SP scale to understand the applicability of its factor structure, and 3, whether the OSI-SP hypothesized model fits the data collected within the study context. The intensity aspect of the OSI-SP questionnaire was administered to 424 Ghana Premier League (GPL) male footballers who took part in the 2020/2021 season. Quality control strategies were put in place to ensure consistency across interpreters and as well improve the validity of the data. The results from a multi-factor first-order confirmatory factor analysis showed some level of convergence validity of the OSI-SP scale in the Ghanaian context using football players. Out of the 23 items on the original scale, 20 met the factor loadings criterion. In assessing the discriminant validity of the OSI-SP scale using Heterotrait-monotrait (HTMT), 50% of the correlation ratios met the criterion for the original 23-item instrument. Comparing the new model (with the 20-items) with the original model (with 23-items) using the Akaike Information Criterion (AIC) value, the model fit indices for the modified model (20-items) appeared better than the original model with 23-items. Generally, there was minimal support for the applicability of the OSI-SP instrument across the sample of Ghanaian footballers. The implications of these findings are discussed in detail.