bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia-Induced LncRNA-MIR210HG Promotes Cancer Progression By Inhibiting HIF-1α Degradation in Ovarian Cancer
Authors: Liu Ping , Huang Huiqiong , Qi Xiaorong , Bian Ce , Cheng Meng , Liu Lili , Xue Luqi , Zhao Xia , Yi Tao , Quan Yi
Published: November 2021

LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.
Identification of Hypoxia-Related Molecular Classification and Associated Gene Signature in Oral Squamous Cell Carcinoma
Authors: Li Chen , Chen Xin , Ren Xiaolin , Chen Jia-lin , Chen Hao , Yu Jing-jia , Ran Qiu-chi , Kang Shuang , Chen Xi-meng , Zhao Zhen-jin
Published: November 2021

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.
Norcholic Acid Promotes Tumor Progression and Immune Escape by Regulating Farnesoid X Receptor in Hepatocellular Carcinoma
Authors: Gong Yihang , Li Kun , Qin Yunfei , Zeng Kaining , Liu Jianrong , Huang Shaozhuo , Chen Yewu , Yu Haoyuan , Liu Wei , Ye Linsen , Yang Yang
Published: November 2021

Accumulating evidence shows a close association between various types of bile acids (BAs) and hepatocellular carcinoma (HCC), and they have been revealed to affect tumor immune response and progression mainly by regulating Farnesoid X receptor (FXR). Nevertheless, the roles of Norcholic acid(NorCA) in HCC progression remain unknown yet. In this study, herein we demonstrate that NorCA can promote HCC cell proliferation, migration and invasion through negatively regulating FXR. Additionally, NorCA can increase PD-L1 level on the surfaces of HCC cells and their exosomes, and NorCA-induced exosomes dramatically dampen the function of CD4+T cells, thereby inducing an immunosuppressive microenvironment. Meanwhile, a negative correlation between PD-L1 and FXR expression in human HCC specimens was identified, and HCC patients with FXRlowPD-L1highexpression exhibit a rather dismal survival outcome. Importantly, FXR agonist (GW4064) can synergize with anti-PD-1 antibody (Ab) to inhibit HCC growth in tumor-bearing models. Taken together, NorCA can promote HCC progression and immune invasion by inhibiting FXR signaling, implying a superiority of the combination of FXR agonist and anti‐PD‐1 Ab to the monotherapy of immune checkpoint inhibitor in combating HCC. However, more well-designed animal experiments and clinical trials are warranted to further confirm our findings in future due to the limitations in our study.
An Abnormal Host/Microbiomes Signature of Plasma-Derived Extracellular Vesicles Is Associated to Polycythemia Vera
Authors: Barone Monica , Barone Martina , Ricci Francesca , Auteri Giuseppe , Corradi Giulia , Fabbri Francesco , Papa Valentina , Bandini Erika , Cenacchi Giovanna , Tazzari Pier Luigi , Vianelli Nicola , Turroni Silvia , Cavo Michele , Palandri Francesca , Candela Marco , Catani Lucia
Published: November 2021

Polycythemia Vera (PV) is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. Chronic inflammation is commonly observed in myeloproliferative neoplasms including PV. The inflammatory network includes the extracellular vesicles (EVs), which play a role in cell-cell communication. Recent evidence points to circulating microbial components/microbes as potential players in hemopoiesis regulation. To address the role of EVs in PV, here we investigated phenotype and microbial DNA cargo of circulating EVs through multidimensional analysis. Peripheral blood and feces were collected from PV patients (n=38) and healthy donors (n=30). Circulating megakaryocyte (MK)- and platelet (PLT)-derived EVs were analyzed by flow cytometry. After microbial DNA extraction from feces and isolated EVs, the 16S rDNA V3-V4 region was sequenced. We found that the proportion of circulating MK-derived EVs was significantly decreased in PV patients as compared with the healthy donors. By contrast, the proportion of the PLT-derived EVs was increased. Interestingly, PV was also associated with a microbial DNA signature of the isolated EVs with higher diversity and distinct microbial composition than the healthy counterparts. Of note, increased proportion of isolated lipopolysaccharide-associated EVs has been demonstrated in PV patients. Conversely, the gut microbiome profile failed to identify a distinct layout between PV patients and healthy donors. In conclusion, PV is associated with circulating EVs harbouring abnormal phenotype and dysbiosis signature with a potential role in the (inflammatory) pathogenesis of the disease.
Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation
Authors: Tian Tian , Yu Min , Li Juan , Jiang Maoqiong , Ma Daiyuan , Tang Shubin , Lin Zhiyu , Chen Lin , Gong Youling , Zhu Jiang , Zhou Qiang , Huang Meijuan , Lu You
Published: November 2021

Background

Data on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.

Materials and Methods

Relevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.

Results

A total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).

Conclusions

Taken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.
A Pan-Cancer Analysis of the Oncogenic and Immunogenic Role of m6Am Methyltransferase PCIF1
Authors: Jin Ming-Zhu , Zhang Yi-Gan , Jin Wei-Lin , Wang Xi-Peng
Published: November 2021

Background

Phosphorylated CTD-interacting factor 1 (PCIF1) is identified as the only known methyltransferase of N6,2′-O-dimethyladenosine (m6Am) in mRNA. However, its oncogenic and immunogenic role in cancer research is at an initial stage.

Methods

Herein, we carried out a pan-cancer analysis of PCIF1, with a series of datasets (e.g., TIMER2.0, GEPIA2, cBioPortal).

Results

PCIF1 expression was higher in most cancers than normal tissues and was discrepant across pathological stages. Highly expressed PCIF1 was positively correlated with overall survival (OS) or disease-free survival (DFS) of some tumors. PCIF1 expression had a positive correlation with CD4+ T-cell infiltration in kidney renal clear cell carcinoma (KIRC), CD8+ T cells, macrophages, and B cells in thyroid carcinoma (THCA), and immune checkpoint genes (ICGs) in LIHC but a negative correlation with CD4+ T cells, neutrophils, myeloid dendritic cells, and ICGs in THCA. It also affected tumor mutational burden (TMB) and microsatellite instability (MSI) of most tumors.

Conclusion

PCIF1 expression was correlated with cancer prognosis and immune infiltration, suggesting it to be a potential target for cancer therapy.
Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China
Authors: Xiong Anwen , Wang Jiali , Zhou Caicun
Published: November 2021

Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%–85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.
Cerebellar Liponeurocytoma Mimicking Medulloblastoma: Case Report of a Childhood and Literature Review
Authors: Dong Changhui , Jiang Yining , Zhao Liyan , Wang Yubo , Bai Yang , Sun Ying , Li Yunqian
Published: November 2021

Background

Cerebellar liponeurocytoma is a rare benign neoplasm of the central nervous system, which arises mainly in adult patients with only 3 cases reported in children. Due to its rarity, the diagnosis and treatment strategies for cerebellar liponeurocytoma remain unclear. The purpose of this study was to explore the epidemiology, clinical features, imaging findings, pathological characteristics, different diagnoses, treatment, and prognosis of cerebellar liponeurocytoma in juveniles.

Case Description

A 5-year-old boy was admitted to the department of neurosurgery due to a 5-month history of headaches, nausea, vomiting, dizziness, dysphoria, as well as visual blurring associated with the peak of the headache. Magnetic resonance imaging showed a 4.9×5.4×6.2 cm mass located in the fourth ventricle and cerebellar vermis combined with hydrocephalus and periventricular edema. The mass was completely removed, and pathological examination indicated a cerebellar liponeurocytoma of the World Health Organization Grade II classification.

Conclusion

The present study was the first to report a cerebellar liponeurocytoma with total tumor resection and adjuvant radiotherapy in a pediatric patient. Total tumor resection and postoperative radiotherapy together with close and long-term follow-up seem to be the optimal treatment strategy for juvenile patients. However, the side-effect of radiation needs to be considered.
Progress in the Application of Immune Checkpoint Inhibitor-Based Immunotherapy for Targeting Different Types of Colorectal Cancer
Authors: He Rui , Lao Yefang , Yu Wenyan , Zhang Xiaohui , Jiang Min , Zhu Chunrong
Published: November 2021

Colorectal cancer (CRC), a common malignant disease, has the second highest mortality rate among all cancer types. Due to the diversity and heterogeneity of CRC, few effective treatment strategies have been developed in recent years, except for surgical resection. As immunotherapy has become a revolutionary treatment after surgery, along with chemoradiotherapy and targeted therapy, numerous basic research studies and clinical trials have been conducted on CRC. Therefore, immune checkpoint inhibitor (ICI) therapy has become the main anti-CRC immunotherapy method used at present. With the rapid development of biotechnology and cell research, an increasing number of monotherapy or combination therapy strategies using ICIs for CRC have been designed in recent years. Methods to classify and review ICI strategies for different types of CRC to better guide treatment are continuously investigated. However, the identification of why the ICIs would be more effective in targeting particular subtypes of CRC such as high microsatellite instability (MSI-H) is more important because of the different immune backgrounds in patients. This review intends to classify different subtypes of CRC and summarizes the basic and clinical studies on ICIs for each subtype of CRC currently available. In addition, we also attempt to briefly discuss the progress in immunotherapy methods other than ICI therapy, such as chemoimmunotherapy strategy, chimeric antigen receptor-modified T (CAR-T) cells, or immunotherapy based on oncolytic viruses. Finally, we provide a perspective on the development of immunotherapy in the treatment of CRC and attempt to propose a new systematic classification of CRC based on immunological strategies, which may improve guidance for the selection of immunotherapy strategies for different subtypes of CRC in the future.
Are the Derived Indexes of Peripheral Whole Blood Cell Counts (NLR, PLR, LMR/MLR) Clinically Significant Prognostic Biomarkers in Multiple Myeloma? A Systematic Review And Meta-Analysis
Authors: Zhang Xinwen , Duan Jialin , Wen Zhenyu , Xiong Hao , Chen Xiaomin , Liu Yang , Liao Kunyu , Huang Chunlan
Published: November 2021

Background

Multiple myeloma (MM) is an incurable malignant plasma cell tumor. Whole blood cell count (WBCC) derived indexes are widely used as a predictive biomarker for various types of solid and hematological malignant tumors. Our study is to evaluate its effectiveness in MM by meta-analysis.

Methods

Relevant literatures were retrieved from PubMed, Embase and Web of Science databases according to PRISMA guideline. All relevant parameters were extracted and combined for statistical analysis.

Results

Nineteen studies incorporating 3818 MM patients were eventually included in this meta-analysis. 13 studies evaluated that elevated NLR was significantly associated with poor survival outcomes (OS: HR=2.04, P<0.001; PFS: HR=1.96, P=0.003). Elevated NLR was revealed to correlate with ISS stage (ISS III VS I-II, OR=2.23, P=0.003). A total of 7 studies have shown that elevated LMR predicts a better prognosis in MM patients (OS: HR=0.57, P<0.001; PFS: HR=0.49, P<0.05), and two other studies demonstrated that increased MLR was related to poor OS/PFS (OS: HR=1.58, P<0.05; PFS: HR=1.60, P<0.05). However, in the other 6 studies including 1560 patients, the prognostic value of PLR had not been confirmed (OS: HR=0.89, P>0.05; PFS: HR=0.87, P>0.05).

Conclusions

The indexes NLR and LMR/MLR derived from WBCC were validated to be useful biomarkers to predict the prognosis in MM patients, but the evidence of PLR was insufficient.
Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis
Authors: Wang Hongmei , Wu Meng , Liu Haonan , Zhou Hang , Zhao Yang , Geng Yifan , Jiang Bo , Zhang Kai , Zhang Bo , Han Zhengxiang , Du Xiuping
Published: November 2021

Background

The present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated.

Methods

Numerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve.

Results

The analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo.

Conclusions

Overall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic.

Systematic Review Registration

https://inplasy.com/inplasy-2021-6-0033/.
Language Screening in 3-Year-Olds: Development and Validation of a Feasible and Effective Instrument for Pediatric Primary Care
Authors: Holzinger Daniel , Weber Christoph , Barbaresi William , Beitel Christoph , Fellinger Johannes
Published: November 2021

Objective:The study was aimed at evaluating the validity and feasibility of SPES-3 (Sprachentwicklungsscreening), a language screening in 3-year-old children within the constraints of regular preventive medical check-ups.

Methods:A four-component screening measure including parental reports on the child's expressive vocabulary and grammar based on the MacArthur Communicative Development Inventory and pediatrician-administered standardized assessments of noun plurals and sentence comprehension was used in a sample of 2,044 consecutively seen children in 30 pediatric offices. One-hundred forty-four children (70 who failed and 74 who passed the screener) comprised the validation sample and also underwent follow-up gold standard assessment. To avoid verification and spectrum bias multiple imputation of missing diagnosis for children who did not undergo gold standard assessment was used. Independent diagnoses by two experts blinded to the screening results were considered gold standard for diagnosing language disorder. Screening accuracy of each of the four subscales was analyzed using receiver operator characteristic (ROC) curves. Feasibility was assessed by use of a questionnaire completed by the pediatricians.

Results:The two parental screening subscales demonstrated excellent accuracy with area under the curve (AUC) scores of 0.910 and 0.908 whereas AUC scores were significantly lower for the subscales directly administered by the pediatricians (0.816 and 0.705). A composite score based on both parental screening scales (AUC = 0.946) outperformed single subscales. A cut off of 41.69 on aT-scale resulted in about 20% positive screens and showed good sensitivity (0.878) and specificity (0.876). Practicability, acceptability and sustainability of the screening measure were mostly rated as high.

Conclusion:The parent-reported subscales of the SPES-3 language screener are a promising screening tool for use in primary pediatric care settings.
The Role of Gut Microbiota and Microbiota-Related Serum Metabolites in the Progression of Diabetic Kidney Disease
Authors: Zhang Qing , Zhang Yanmei , Zeng Lu , Chen Guowei , Zhang La , Liu Meifang , Sheng Hongqin , Hu Xiaoxuan , Su Jingxu , Zhang Duo , Lu Fuhua , Liu Xusheng , Zhang Lei
Published: November 2021

Objective: Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study.

Methods: Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m2) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m2) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap.

Results: Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(−)-3-phenylactic acid, trans-3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora g_Abiotrophia and g_norank_f_Peptococcaceae were positively correlated with the increase in renal function indicators and serum metabolite HA. G_Lachnospiraceae_NC2004_Group was negatively correlated with the increase in renal function indicators and serum metabolites [L-(−)-3-phenyllactic acid and IAA].

Conclusions: This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.
Emission of Solitons From an Obstacle Moving in the Bose-Einstein Condensate
Authors: Song Yu , Mo Yu , Feng Shiping , Yang Shi-Jie
Published: November 2021

Dark solitons dynamically generated from a potential moving in a one-dimensional Bose-Einstein condensate are displayed. Based on numerical simulations of the Gross-Pitaevskii equation, we find that the moving obstacle successively emits a series of solitons which propagate at constant speeds. The dependence of soliton emission on the system parameters is examined. The formation mechanism of solitons is interpreted as interference between a diffusing wavepacket and the condensate background, enhanced by the nonlinear interactions.

PACS numbers: 03.75.Mn, 03.75.Lm, 05.30.Jp
Transmural Distribution of Coronary Perfusion and Myocardial Work Density Due to Alterations in Ventricular Loading, Geometry and Contractility
Authors: Fan Lei , Namani Ravi , Choy Jenny S. , Kassab Ghassan S. , Lee Lik Chuan
Published: November 2021

Myocardial supply changes to accommodate the variation of myocardial demand across the heart wall to maintain normal cardiac function. A computational framework that couples the systemic circulation of a left ventricular (LV) finite element model and coronary perfusion in a closed loop is developed to investigate the transmural distribution of the myocardial demand (work density) and supply (perfusion) ratio. Calibrated and validated against measurements of LV mechanics and coronary perfusion, the model is applied to investigate changes in the transmural distribution of passive coronary perfusion, myocardial work density, and their ratio in response to changes in LV contractility, preload, afterload, wall thickness, and cavity volume. The model predicts the following: (1) Total passive coronary flow varies from a minimum value at the endocardium to a maximum value at the epicardium transmurally that is consistent with the transmural distribution of IMP; (2) Total passive coronary flow at different transmural locations is increased with an increase in either contractility, afterload, or preload of the LV, whereas is reduced with an increase in wall thickness or cavity volume; (3) Myocardial work density at different transmural locations is increased transmurally with an increase in either contractility, afterload, preload or cavity volume of the LV, but is reduced with an increase in wall thickness; (4) Myocardial work density-perfusion mismatch ratio at different transmural locations is increased with an increase in contractility, preload, wall thickness or cavity volume of the LV, and the ratio is higher at the endocardium than the epicardium. These results suggest that an increase in either contractility, preload, wall thickness, or cavity volume of the LV can increase the vulnerability of the subendocardial region to ischemia.
Impact of and Reasons for Not Performing Exercise Training After an Acute Coronary Syndrome in the Setting of an Interdisciplinary Cardiac Rehabilitation Program: Results From a Risk-Op- Acute Coronary Syndrome Ambispective Registry
Authors: Cabrera-Aguilera Ignacio , Ivern Consolació , Badosa Neus , Marco Ester , Salas-Medina Luís , Mojón Diana , Vicente Miren , Llagostera Marc , Farré Nuria , Ruiz-Bustillo Sonia
Published: November 2021

Background and Aims: Exercise training (ET) is a critical component of cardiac rehabilitation (CR), but it remains underused. The aim of this study was to compare clinical outcomes between patients who completed ET (A-T), those who accepted ET but did not complete it (A-NT), and those who did not accept to undergo it (R-NT), and to analyze reasons for rejecting or not completing ET.

Methods and Results: A unicenter ambispective observational registry study of 497 patients with acute coronary syndrome (ACS) was carried out in Barcelona, Spain, from 2016 to 2019. The primary endpoint was a composite of all-cause mortality, hospitalization for ACS, or need for revascularization during follow-up. Multivariable analysis was carried out to identify variables independently associated with the primary outcome. Initially, 70% of patients accepted participating in the ET, but only 50.5% completed it. The A-T group were younger and had fewer comorbidities. Baseline characteristics in A-NT and R-NT groups were very similar. The main reason for not undergoing or completing ET was rejection (reason unknown) or work/schedule incompatibility. The median follow-up period was 31 months. Both the composite primary endpoint and mortality were significantly lower in the A-T group compared to the A-NT and R-NT (primary endpoint: 3.6% vs. 23.2% vs. 20.4%, p < 0.001, respectively; mortality: 0.8% vs. 9.1% vs. 8.2%, p < 0.001; respectively). During multivariable analysis, the only variables that remained statistically significant with the composite endpoint were ET completion, previous ACS, and anemia.

Conclusion: Completion of ET after ACS was associated with improved prognosis. Only half of the patients completed the ET program, with the leading reasons for not completing it being refusal (reason unknown) and work/schedule incompatibility. These results highlight the need to focus on the needs of patients in order to guarantee that structural barriers to ET no longer exist.
Authentication of Zingiber Species Based on Analysis of Metabolite Profiles
Authors: Wang Chenxi , Zhang Yue , Ding Hui , Song Meifang , Yin Jiaxin , Yu Heshui , Li Zheng , Han Lifeng , Zhang Zhonglian
Published: November 2021

Zingiber corallinum and Zingiber montanum, which belong to the Zingiberaceae family, are traditional Chinese folk medicinal herbs in Guizhou and Yunnan Province of China. They share great similarities in morphology, chemical constituent, and DNA barcoding sequence. The taxonomy of the two Zingiber species is controversial and discrimination of traditional Chinese medicines directly affects the pharmacological and clinical effects. In the present study, we performed a systemic analysis of “super-barcode” and untargeted metabolomics between Z. corallinum and Z. montanum using chloroplast (cp) genome sequencing and gas chromatography-mass spectrometry (GC-MS) analysis. Comparison and phylogenetic analysis of cp genomes of the two Zingiber species showed that the cp genome could not guarantee the accuracy of identification. An untargeted metabolomics strategy combining GC-MS with chemometric methods was proposed to distinguish the Zingiber samples of known variety. A total of 51 volatile compounds extracted from Z. corallinum and Z. montanum were identified, and nine compounds were selected as candidate metabolic markers to reveal the significant difference between Z. corallinum and Z. montanum. The performance of the untargeted metabolomic approach was verified with unknown Zingiber samples. Although the cp genomes could not be used to identify Zingiber species in this study, it will still provide a valuable genomics resource for population studies in the Zingiberaceae family, and the GC-MS based metabolic fingerprint is more promising for species identification and safe application of Z. corallinum and Z. montanum.
Integration of Metabolome and Transcriptome Reveals the Relationship of Benzenoid–Phenylpropanoid Pigment and Aroma in Purple Tea Flowers
Authors: Mei Xin , Wan Shihua , Lin Chuyuan , Zhou Caibi , Hu Liuhong , Deng Chan , Zhang Lingyun
Published: November 2021

Tea (Camellia sinensis) flowers are normally white, even though the leaves could be purple. We previously discovered a specific variety with purple leaves and flowers. In the face of such a phenomenon, researchers usually focus on the mechanism of color formation but ignore the change of aroma. The purple tea flowers contain more anthocyanins, which belong to flavonoids. Meanwhile, phenylalanine (Phe), derived from the shikimate pathway, is a precursor for both flavonoids and volatile benzenoid–phenylpropanoids (BPs). Thus, it is not clear whether the BP aroma was attenuated for the appearance of purple color. In this study, we integrated metabolome and transcriptome of petals of two tea varieties, namely, Zijuan (ZJ) with white flowers and Baitang (BT) with purple flowers, to reveal the relationship between color (anthocyanins) and aroma (volatile BPs). The results indicated that in purple petals, the upstream shikimate pathway promoted for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) was elevated. Among the increased anthocyanins, delphinidin-3-O-glucoside (DpG) was extremely higher; volatile BPs, including benzyl aldehyde, benzyl alcohol, acetophenone (AP), 1-phenylethanol, and 2-phenylethanol, were also enhanced, and AP was largely elevated. The structural genes related to the biosynthesis of volatile BPs were induced, while the whole flavonoid biosynthesis pathway was downregulated, except for the genes flavonoid 3′-hydroxylase (F3′H) and flavonoid 3′,5′-hydroxylase (F3′5′H), which were highly expressed to shift the carbon flux to delphinidin, which was then conjugated to glucoside by increased bronze-1 (BZ1) (UDP-glucose: flavonoid 3-O-glucosyltransferase) to form DpG. Transcription factors (TFs) highly related to AP and DpG were selected to investigate their correlation with the differentially expressed structural genes. TFs, such as MYB, AP2/ERF, bZIP, TCP, and GATA, were dramatically expressed and focused on the regulation of genes in the upstream synthesis of Phe (DAHPS; arogenate dehydratase/prephenatedehydratase) and the synthesis of AP (phenylacetaldehyde reductase; short-chain dehydrogenase/reductase), Dp (F3′H; F3′5′H), and DpG (BZ1), but inhibited the formation of flavones (flavonol synthase) and catechins (leucoanthocyanidin reductase). These results discovered an unexpected promotion of volatile BPs in purple tea flowers and extended our understanding of the relationship between the BP-type color and aroma in the tea plant.
Training Set Construction for Genomic Prediction in Auto-Tetraploids: An Example in Potato
Authors: Wilson Stefan , Malosetti Marcos , Maliepaard Chris , Mulder Han A. , Visser Richard G. F. , van Eeuwijk Fred
Published: November 2021

Training set construction is an important prerequisite to Genomic Prediction (GP), and while this has been studied in diploids, polyploids have not received the same attention. Polyploidy is a common feature in many crop plants, like for example banana and blueberry, but also potato which is the third most important crop in the world in terms of food consumption, after rice and wheat. The aim of this study was to investigate the impact of different training set construction methods using a publicly available diversity panel of tetraploid potatoes. Four methods of training set construction were compared: simple random sampling, stratified random sampling, genetic distance sampling and sampling based on the coefficient of determination (CDmean). For stratified random sampling, population structure analyses were carried out in order to define sub-populations, but since sub-populations accounted for only 16.6% of genetic variation, there were negligible differences between stratified and simple random sampling. For genetic distance sampling, four genetic distance measures were compared and though they performed similarly, Euclidean distance was the most consistent. In the majority of cases the CDmean method was the best sampling method, and compared to simple random sampling gave improvements of 4–14% in cross-validation scenarios, and 2–8% in scenarios with an independent test set, while genetic distance sampling gave improvements of 5.5–10.5% and 0.4–4.5%. No interaction was found between sampling method and the statistical model for the traits analyzed.
One Function One Tool? A Review on Mutual Exclusivity in Tool Use Learning in Human and Non-human Species
Authors: Tran Thuy Tuong Uyen , Esseily Rana , Bovet Dalila , Király Ildikó
Published: November 2021

The goal of this review is twofold: first to explore whether mutual exclusivity and functional fixedness overlap and what might be their respective specificities and second, to investigate whether mutual exclusivity as an inferential principle could be applied in other domains than language and whether it can be found in non-human species. In order to do that, we first give an overview of the representative studies of each phenomenon. We then analyze papers on tool use learning in children that studied or observed one of these phenomena. We argue that, despite their common principle -one tool one function- mutual exclusivity and functional fixedness are two distinct phenomena and need to be addressed separately in order to fully understand the mechanisms underlying social learning and cognition. In addition, mutual exclusivity appears to be applicable in other domains than language learning, namely tool use learning and is also found in non-human species when learning symbols and tools.
Remote Working in a Public Bureaucracy: Redeveloping Practices of Managerial Control When Out of Sight
Authors: Hartner-Tiefenthaler Martina , Goisauf Melanie , Gerdenitsch Cornelia , Koeszegi Sabine T.
Published: November 2021

This article examines managerial control practices in a public bureaucracy at the moment of introducing remote work as part with a new ways of working (NWW) project. The qualitative study builds on 38 interviews with supervisors and subordinates conducted before the advent of COVID-19. By interpreting interviewees’ conversations about current and anticipated future work practices in the changing work setting, we reveal tacit and hidden practices of managerial control that are currently prevalent in many organizations introducing remote working. Three constitutive moments of the organization’s transformation to NWW are analytically distinguished: (i) how implicit becomes explicit, (ii) how collective becomes self, and (iii) how personal becomes impersonal. Our findings emphasize that the transition to NWW must take into account prevailing institutional logics and must reconnect to a fundamental and often neglected question: What does doing work mean within the particular organization? Negotiating this fundamental question might help to overcome supervisors’ uncertainties about managerial control and provide clarity to subordinates about what is expected from them while working remotely. Finally, we discuss how the transition to NWW may serve as both an opportunity and a potential threat to established organizational practices while highlighting the challenge supervisors face when the institutional logics conflict with remote working.
Validation of the Committed Action Questionnaire-8 and Its Mediating Role Between Experiential Avoidance and Life Satisfaction Among Chinese University Students
Authors: Li Ya , Yang Fei-long , Pan Chen , Chu Qian-qian , Tang Qiu-ping
Published: November 2021

Background: Committed action is one of the core processes of psychological flexibility derived from acceptance and commitment therapy. It has not been widely investigated in mainland China as appropriate measures are lacking. The current study aimed to validate a Chinese (Mandarin) version of the Committed Action Questionnaire (CAQ-8) in a non-clinical college sample and to explore whether committed action would have a mediating effect in the association between experiential avoidance (EA) and life satisfaction.

Methods: We translated the CAQ-8 into Chinese (Mandarin). A total of 913 Chinese undergraduates completed a set of questionnaires measuring committed action, EA, mindful awareness, anxiety, depression, stress, and life satisfaction. For test–retest reliability, 167 respondents completed the CAQ-8 again 4 weeks later.

Results: The entire scale of CAQ-8 (Mandarin) and two subscales showed adequate internal consistency and acceptable test–retest reliability. Confirmatory factor analyses confirmed the two-factor structure and the convergent and criterion validity were acceptable. Committed action was correlated with less EA, more mindful awareness, less depressive symptoms, less anxiety, less stress, and more life satisfaction. In bootstrap mediation analyses, committed action partially mediated the association between EA and life satisfaction.

Conclusion: The results suggest that the CAQ-8 (Mandarin) is a brief, psychometrically sound instrument to investigate committed action in Chinese populations, and the relationship between EA and life satisfaction was partially explained by committed action. This study provides new information about the usefulness of CAQ-8 and supports the assumption that committed action may be considered a promising factors for improving life satisfaction who have involved in EA among an educated non-clinical population.
Mediators and Moderators of Reinforced Self-Affirmation as a Method for Reducing the Memory Misinformation Effect
Authors: Szpitalak Malwina , Polczyk Romuald
Published: November 2021

The misinformation effect occurs when an eyewitness includes information in his or her account that is incongruent with the event he or she witnessed, and stems from being exposed to incorrect external sources. This is a serious threat to the quality of witness testimony and to the correctness of decisions reached by courts. However, few methods have been developed to reduce the vulnerability of witnesses to misinformation. This article presents such a method, namely, reinforced self-affirmation (RSA), which, by increasing memory confidence of witnesses, makes them less inclined to rely on external sources of information and more on their own memory. The effectiveness of this method was confirmed in three experiments. It was also found that memory confidence, but not general self-confidence, is a mediator of the impact of RSA on misinformation effect (ME), and that contingent self-esteem and feedback acceptance, but not sense of self-efficacy or general self-esteem, are moderators of this impact. It is concluded that RSA may be a promising basis for constructing methods, which can be used by forensic psychologists in real forensic settings.
Adapting to Uncertainty: A Mixed-Method Study on the Effects of the COVID-19 Pandemic on Expectant and Postpartum Women and Men
Authors: Tavares Inês M. , Fernandes Joana , Moura Catarina V. , Nobre Pedro J. , Carrito Mariana L.
Published: November 2021

Detrimental biopsychosocial effects of the COVID-19 pandemic on populations have been established worldwide. Despite research indicating that the transition to parenthood is a vulnerable period for maternal and paternal health, an in-depth examination of the specific challenges the pandemic poses for new mothers and fathers is still lacking. Using a mixed-method design, we investigated individual and relational well-being of women and men who were expecting their first child during the first months of the COVID-19 pandemic in Portugal and its associations with contextual, individual, and relational factors. Adults older than 18 (n = 316, 198 women) from early pregnancy to 6-months postpartum completed a cross-sectional online survey assessing sociodemographic, individual (depression, anxiety, perceived stress), and relational (dyadic adjustment, perceived social support) self-report measures. From those, 99 participants (64 women) responded to an open-ended question and reported perceived changes in their couple’s relationship due to the pandemic. Men responding during strict lockdown measures reported significantly higher levels of perceived stress relative to those men who were not under lockdown. Overall, women reported higher levels of depression and greater social support than men. Qualitative analyses resulted in two main themes: Individual Changes and Relational Changes. These themes aggregate personal concerns and experiences (e.g., worsening of mental health, uncertainty about the future, lack of freedom) interrelated with relational issues (e.g., increased togetherness, avoidance of physical contact, and increased availability for parenthood during lockdown). The prevalence of negative effects (58.6%) exceeded the described positive effects (28.3%), and 13.1% described both positive and negative effects of the pandemic. Current findings offer grounds for important evidence-based strategies to mitigate the potential adverse effects of the current pandemic on new mothers’ and fathers’ individual and relational well-being.
Translation and Validation of the Short Form of the Fear of Dental Pain Questionnaire in China
Authors: Wu Lei , Buchanan Heather , van Wijk Arjen J.
Published: November 2021

The short form of the Fear of Dental Pain Questionnaire (s-FDPQ) is a validated measure developed to screen patients for their fear of pain associated with dental procedures. As there is a high prevalence of dental fear/anxiety in Chinese adults, the primary aim of our study was to translate the s-FDPQ into standard Mandarin and explore its reliability and validity with Chinese adults. The second aim of our study was to explore fear of dental pain (FDP) scores in relation to dental attendance, anxiety and gender. We translated the s-FDPQ using the forward-backward method. It was completed by 480 Chinese adults alongside the Modified Dental Anxiety Scale (MDAS; Chinese version) to test convergent validity. 109 participants completed the s-FDPQ again 14 days later to evaluate test-retest reliability. The Chinese s-FDPQ (s-CFDPQ) was internally consistent (alpha = 0.87) and demonstrated convergent validity (r = 0.73 when correlated with the MDAS). Test-retest reliability was good (ICC = 0.86). Individuals who had never attended the dentist (22%) had higher FDP scores than those that had, even if they were not dentally anxious. Also, females reported higher FDP scores (p < 0.001). These findings suggest that the s-CFDPQ is a reliable and valid measure for assessing fear of dental pain in Chinese adults. The s-CFDPQ could allow quick identification of individuals who are fearful of dental pain who may require specialist attention.