bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Transcriptional Profiling Analysis and Immune-Related Risk Model Construction for Intracranial Aneurysm Rupture
Authors: Shan Dezhi , Guo Xing , Yang Guozheng , He Zheng , Zhao Rongrong , Xue Hao , Li Gang
Published: April 2021

Intracranial aneurysms (IAs) may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms are poorly understood. The aims of this study were to analyze the transcriptional profiles to explore the functions and regulatory networks of differentially expressed genes (DEGs) in IA rupture by bioinformatics methods and to identify the underlying mechanisms. In this study, 1,471 DEGs were obtained, of which 619 were upregulated and 852 were downregulated. Gene enrichment analysis showed that the DEGs were mainly enriched in the inflammatory response, immune response, neutrophil chemotaxis, and macrophage differentiation. Related pathways include the regulation of actin cytoskeleton, leukocyte transendothelial migration, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and chemokine signaling pathway. The enrichment analysis of 20 hub genes, subnetworks, and significant enrichment modules of weighted gene coexpression network analysis showed that the inflammatory response and immune response had a causal relationship with the rupture of unruptured IAs (UIAs). Next, the CIBERSORT method was used to analyze immune cell infiltration into ruptured IAs (RIAs) and UIAs. Macrophage infiltration into RIAs increased significantly compared with that into UIAs. The result of principal component analysis revealed that there was a difference between RIAs and UIAs in immune cell infiltration. A 4-gene immune-related risk model for IA rupture (IRMIR), containing CXCR4, CXCL3, CX3CL1, and CXCL16, was established using the glmnet package in R software. The receiver operating characteristic value revealed that the model represented an excellent clinical situation for potential application. Enzyme-linked immunosorbent assay was performed and showed that the concentrations of CXCR4 and CXCL3 in serum from RIA patients were significantly higher than those in serum from UIA patients. Finally, a competing endogenous RNA network was constructed to provide a potential explanation for the mechanism of immune cell infiltration into IAs. Our findings highlighted the importance of immune cell infiltration into RIAs, providing a direction for further research.
Deep Brain Stimulation in Treatment-Resistant Depression: A Systematic Review and Meta-Analysis on Efficacy and Safety
Authors: Wu Youliang , Mo Jiajie , Sui Lisen , Zhang Jianguo , Hu Wenhan , Zhang Chao , Wang Yao , Liu Chang , Zhao Baotian , Wang Xiu , Zhang Kai , Xie Xuemin
Published: April 2021

Objective: Deep brain stimulation (DBS) has shown promising outcomes as new therapeutic opportunities for patients with treatment-resistant depression (TRD) who do not respond adequately to several consecutive treatments. This study aims to systematically review and conduct a meta-analysis on the efficacy and safety of DBS for TRD.

Method: The literature was comprehensively reviewed using Medline, Google scholar, Cochrane library, Embase, and World Health Organization International Clinical Trials Registry Platform until January 2019. The studied outcomes included response, remission, recurrence, and adverse events (AEs) rates, and were reported as the rate ratio (RR) or pooled estimate with a 95% confidence interval (95% CI). Heterogeneity was measured by an I-square test and a sensitive analysis.

Results: A total of 17 studies involving 7 DBS targets were included. For efficacy, DBS treatment was statistically beneficial for TRD, and the response, remission, and recurrence rates were 56% (ranging from 43 to 69%), 35% (ranging from 27 to 44%), and 14% (ranging from 4 to 25%), respectively. However, only two randomized-controlled trials (RCTs) considered the invalidity of DBS (RR = 1.45, 95% CI = 0.50–4.21). For safety, the AEs rate was 67% (ranging from 54 to 80%). The AEs were common and moderate, but the problems related to suicide and suicidal ideation should not be underestimated.

Conclusion: These findings suggest that DBS for TRD is considered promising, which should be confirmed by well-designed and large sample studies. Future basic research and comprehensive clinical trials are needed to reach better understanding on the mechanisms of action and optimal targeted structure.
Effect of Vitamin D Supplementation on Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Li Ziyi , Wu Liangzhi , Zhang Junguo , Huang Xin , Thabane Lehana , Li Guowei
Published: April 2021

Objective: Laboratory findings indicated that vitamin D might have a potent protective effect on breast cancer, but epidemiology studies reported conflicting results. The aim of the study was to conduct a systematic review and meta-analysis to clarify the efficacy of vitamin D supplementation on risk of breast cancer.

Methods: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and abstracts of three major conferences were searched (up to December 8, 2020). Parallel randomized controlled trials (RCTs) examining the efficacy of vitamin D supplementation on risk of breast cancer or change of mammography compared with placebo in females were included. Data were meta-analyzed using a random-effects model. Bayesian meta-analysis was conducted to synthesize the results using data from observational studies as priors.

Results: Seven RCTs were identified for effect of vitamin D on risk of breast cancer, with 19,137 females included for meta-analysis. No statistically significant effect of vitamin D on risk of breast cancer was found in classical random-effects meta-analysis (risk ratio = 1.04, 95% confidence interval: 0.84–1.28, p = 0.71). When Bayesian meta-analyses were conducted, results remained non-significant. There was no statistically significant effect of vitamin D on mammography density observed: mean difference = 0.46, 95% confidence interval: −2.06 to 2.98, p = 0.72.

Conclusion: There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density. The protective effect of vitamin D on risk of breast cancer from previous observational studies may be overestimated.

Systematic Review Registration: PROSPERO, identifier CRD42019138718.
Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma
Authors: Sun Rui , Li Simin , Zhao Ke , Diao Mei , Li Long
Published: April 2021

Background

This study aimed to systematically investigate gene signatures for hepatoblastoma (HB) and identify potential biomarkers for its diagnosis and treatment.

Materials and Methods

GSE131329 and GSE81928 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between hepatoblastoma and normal samples were identified using the Limma package in R. Then, the similarity of network traits between two sets of genes was analyzed by weighted gene correlation network analysis (WGCNA). Cytoscape was used to visualize and select hub genes. PPI network of hub genes was construed by Cytoscape. GO enrichment and KEGG pathway analyses of hub genes were carried out using ClueGO. The random forest classifier was constructed based on the hub genes using the GSE131329 dataset as the training set, and its reliability was validated using the GSE81928 dataset. The resulting core hub genes were combined with the InnateDB database to identify the innate core genes.

Results

A total of 4244 DEGs in HB were identified. WGCNA identified four modules that were significantly correlated with the disease status. A total of 114 hub genes were obtained within the top 20 genes of each node rank. 6982 relation pairs and 3700 nodes were contained in the PPI network of 114 hub genes. GO enrichment and KEGG pathway analyses of hub genes were focused on MAPK, cell cycle, p53, and other crucial pathways involved in HB. A random forest classifier was constructed using the 114 hub genes as feature genes, resulting in a 95.5% true positive rate when classifying HB and normal samples. A total of 35 core hub genes were obtained through the mean decrease in accuracy and mean decrease Gini of the random forest model. The classification efficiency of the random forest model was 81.4%. Finally, CDK1, TOP2A, ADRA1A, FANCI, XRCC1, TPX2, CCNB2, CDK4, GLYATL1, and CFHR3 were identified by cross-comparison with the InnateDB database.

Conclusion

Our study established a random forest classifier that identified 10 core genes in HB. These findings may be beneficial for the diagnosis, prediction, and targeted therapy of HB.
A Nomogram Combining a Four-Gene Biomarker and Clinical Factors for Predicting Survival of Melanoma
Authors: Zhang Chuan , Dang Dan , Wang Yuqian , Cong Xianling
Published: April 2021

Background

Currently there is no effective prognostic indicator for melanoma, the deadliest skin cancer. Thus, we aimed to develop and validate a nomogram predictive model for predicting survival of melanoma.

Methods

Four hundred forty-nine melanoma cases with RNA sequencing (RNA-seq) data from TCGA were randomly divided into the training set I (n = 224) and validation set I (n = 225), 210 melanoma cases with RNA-seq data from Lund cohort of Lund University (available in GSE65904) were used as an external test set. The prognostic gene biomarker was developed and validated based on the above three sets. The developed gene biomarker combined with clinical characteristics was used as variables to develop and validate a nomogram predictive model based on 379 patients with complete clinical data from TCGA (Among 470 cases, 91 cases with missing clinical data were excluded from the study), which were randomly divided into the training set II (n = 189) and validation set II (n = 190). Area under the curve (AUC), concordance index (C-index), calibration curve, and Kaplan-Meier estimate were used to assess predictive performance of the nomogram model.

Results

Four genes, i.e., CLEC7A, CLEC10A, HAPLN3, and HCP5 comprise an immune-related prognostic biomarker. The predictive performance of the biomarker was validated using tROC and log-rank test in the training set I (n = 224, 5-year AUC of 0.683), validation set I (n = 225, 5-year AUC of 0.644), and test set I (n = 210, 5-year AUC of 0.645). The biomarker was also significantly associated with improved survival in the training set (P < 0.01), validation set (P < 0.05), and test set (P < 0.001), respectively. In addition, a nomogram combing the four-gene biomarker and six clinical factors for predicting survival in melanoma was developed in the training set II (n = 189), and validated in the validation set II (n = 190), with a concordance index of 0.736 ± 0.041 and an AUC of 0.832 ± 0.071.

Conclusion

We developed and validated a nomogram predictive model combining a four-gene biomarker and six clinical factors for melanoma patients, which could facilitate risk stratification and treatment planning.
Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy
Authors: Du Qing-Hua , Gan Yi-Xiu , Wang Ren-Sheng , Liu Wen-Qi , Li Jian , Liang Fei-Fei , Li Xiang-De , Zhu Hui-Jun , Ou Xue , Zhong Qiu-Lu , Luo Dan-Jing , Zhu Zhi-Peng , Zhu Shang-Yong
Published: April 2021

Purpose

To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).

Methods and Materials

A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model.

Results

CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an “increase-maximum-decline” behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc.

Conclusion

Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70–73Gy could be considered when the high dose is inevitable.
Safety and Activity of Programmed Cell Death 1 Versus Programmed Cell Death Ligand 1 Inhibitors for Platinum-Resistant Urothelial Cancer: A Meta-Analysis of Published Clinical Trials
Authors: Li Zaishang , Li Xueying , Lam Wayne , Cao Yabing , Han Hui , Zhang Xueqi , Fang Jiequn , Xiao Kefeng , Zhou Fangjian
Published: April 2021

Background

Programmed death 1/ligand 1 (PD-1/L1) inhibitors have acceptable antitumor activity in patients with platinum-resistant urothelial cancer (UC). However, the reliability and comparability of the antitumor activity, safety profiles and survival outcomes of different immune checkpoint inhibitors are unknown. Our objective was to compare the clinical efficacy and safety of anti–PD-1/PD-L1 therapies in platinum-resistant UC patients.

Methods

We reviewed the published trials from the PubMed, Embase and Cochrane Library databases up to August 2020. A well-designed mirror principle strategy to screen and pair trial characteristics was used to justify indirect comparisons. The primary end point was the objective response rate (ORR). The safety profile and survival outcomes were also evaluated. The restricted mean survival time (RMST) up to 12 months was calculated.

Results

Eight studies including 1,666 advanced or metastatic UC patients (1,021 patients with anti–PD-L1 treatment and 645 patients with anti–PD-1 treatment) met the study criteria. The ORRs of anti–PD-1 and PD-L1 therapy were 22% (95% CI, 18%–25%) and 15% (95% CI, 13%–17%) with all studies combined. The proportions of the treated population with a confirmed objective response (I2 = 0; P = 0.966; HR, 1.60; 95% CI, 1.23–2.07; P < 0.001) and disease control (I2 = 30.6%; P = 0.229; HR, 1.35; 95% CI, 1.10–1.66; P = 0.004) were higher with anti–PD-1 therapy than with anti–PD-L1 therapy. The treatment-related adverse events (AEs) (I2 = 78.3%; P = 0.003; OR, 1.09; 95% CI, 0.65–1.84; P = 0.741) and grade 3–5 treatment-related AEs (I2 = 68.5%; P = 0.023; OR, 1.69; 95% CI, 0.95–3.01; P = 0.074) of anti–PD-1 therapy were comparable to those of anti–PD-L1 therapy. The RMST values at the 12-month follow-up were 9.4 months (95% CI,: 8.8–10.0) for anti–PD-1 therapy and 9.3 months (95% CI, 8.8–9.7) for anti–PD-L1 therapy (z = 0.26, P = 0.794). There was no significant difference between patients in the anti–PD-1 and anti–PD-L1 groups (12-month overall survival (OS): 43% versus 42%, P = 0.765. I2 = 0; P = 0.999; HR, 0.95; 95% CI, 0.83–1.09; P = 0.474).

Conclusions

The results of our systematic comparison suggest that anti–PD-1 therapy exhibits better antitumor activity than anti–PD-L1 therapy, with comparable safety profiles and survival outcomes. These findings may contribute to enhanced treatment awareness in patients with platinum-resistant UC.
Vascular Acrosyndromes Associated With Prolonged Tumor Response in Advanced Lung Cancer Patients During Treatment With Antimetabolites: A Report of Two Cases
Authors: Geier Margaux , Babey Hélène , Monceau-Baroux Lucie , Quéré Gilles , Descourt Renaud , Cornec Divi , Robinet Gilles
Published: April 2021

Background

Pemetrexed and gemcitabine are both antimetabolites drugs approved in advanced non-small cell lung cancer (NSCLC). Their toxicity profile is well known. However, rare vascular side effects can occur such as vascular acrosyndromes and especially digital ischemia. The cause of this disfiguring and painful event is still controversial. Amputation is frequently required and has been described as a predictor of poor survival outcomes.

Case Presentation

This report presents two cases of vascular acrosyndrome in NSCLC patients during treatment with antimetabolites (pemetrexed and gemcitabine). Patients presented severe digital ischemia having required prostacyclin analog and chemotherapy discontinuation. In one case, symptoms improved while in the other case symptoms persisted. Both patients experienced prolonged tumor response. These findings suggest a multifactorial mechanism behind digital necrosis including an autoimmune process, which could lead to prolonged tumor control as described with immune checkpoint inhibitors.

Conclusion

Severe vascular acrosyndrome such as digital ischemia can occur in lung cancer patients treated with antimetabolites. Awareness needs to be raised when using these drugs in patients with predisposing factors. Whether occurrence of chemotherapy-induced immune vascular side effects might explain prolonged tumor response deserves further investigations.
Autophagy-Related Long Non-coding RNA Is a Prognostic Indicator for Bladder Cancer
Authors: Wan Jiaming , Guo Cheng , Fang Hongpeng , Xu Zhongye , Hu Yongwei , Luo Yun
Published: April 2021

Bladder cancer (BC) is one of the most common malignant urinary system tumors, and its prognosis is poor. In recent years, autophagy has been closely linked to the development of BC. Therefore, we investigated the potential prognostic role of autophagy-related long non-coding RNA (lncRNA) in patients with BC. We obtained the lncRNA information and autophagy genes, respectively, from The Cancer Genome Atlas (TCGA) data set and the human autophagy database (HADb) and performed a co-expression analysis to identify autophagy gene-associated lncRNAs. Then, we divided the data into training group and testing group. In the training group, 15 autophagy-related lncRNAs were found to have a prognostic value (AC026369.3, USP30-as1, AC007991.2, AC104785.1, AC010503.4, AC037198.1, AC010331.1, AF131215.6, AC084357.2, THUMPD3-AS1, U62317.4, MAN1B1-DTt, AC024060.1, AL662844.4, and AC005229.4). The patients were divided into low-risk group and high-risk group based on the prognostic lncRNAs. The overall survival (OS) time for the high-risk group was shorter than that for the low-risk group [risk ratio (hazard ratio, HR) = 1.08, 95% CI: 1.06–1.10; p < 0.0001]. Using our model, the defined risk value can predict the prognosis of a patient. Next, the model was assessed in the TCGA testing group to further validate these results. A total of 203 patients with BC were recruited to verify the lncRNA characteristics. We divided these patients into high-risk group and low-risk group. The results of testing data set show that the survival time of high-risk patients is shorter than that of low-risk patients. In the training group, the area under the curve (AUC) was more than 0.7, indicating a high level of accuracy. The AUC for a risk model was greater than that for each clinical feature alone, indicating that the risk value of a model was the best indicator for predicting the prognosis. Further training data analysis showed that the gene set was significantly enriched in cancer-related pathways, including actin cytoskeleton regulation and gap junctions. In conclusion, our 15 autophagy-related lncRNAs have a prognostic potential for BC, and may play key roles in the biology of BC.
External Validation of the Extraprostatic Extension Grade on MRI and Its Incremental Value to Clinical Models for Assessing Extraprostatic Cancer
Authors: Xu Lili , Zhang Gumuyang , Zhang Xiaoxiao , Bai Xin , Yan Weigang , Xiao Yu , Sun Hao , Jin Zhengyu
Published: April 2021

Objectives

To externally validate the extraprostatic extension (EPE) grade criteria on MRI and analyze the incremental value of EPE grade to clinical models of prostate cancer.

Methods

A consecutive 130 patients who underwent preoperative prostate MRI followed by radical prostatectomy between January 2015 to January 2020 in our institution were retrospectively enrolled. The EPE grade, Cancer of the Prostate Risk Assessment (CAPRA), and Memorial Sloan Kettering Cancer Center nomogram (MSKCCn) score for each patient were assigned. Significant clinicopathological factors in univariate and multivariate analyses were combined with EPE grade to build the Clinical + EPE grade model, and the CAPRA and MSKCCn score were also combined with EPE grade to build the CAPRA + EPE grade and MSKCCn + EPE grade model, respectively. The area under the curve (AUC), sensitivity and specificity of these models were calculated to evaluate their diagnostic performance. Calibration and decision curve analyses were used to analyze their calibration performance and clinical utility.

Results

The AUC for predicting EPE was 0.767–0.778 for EPE grade, 0.704 for CAPRA, and 0.723 for MSKCCn. After combination with EPE grade, the AUCs of these clinical models increased significantly than using clinical models along (P < 0.05), but was comparable with using EPE grade alone (P > 0.05). The calibration curves of EPE grade, clinical models and combined models showed that these models are well-calibrated for EPE. In the decision curve analysis, EPE grade showed slightly higher net benefit than MSKCCn and CAPRA.

Conclusion

The EPE grade showed good performance for evaluating EPE in our cohort and possessed well clinical utility. Further combinations with the EPE grade could improve the diagnostic performance of clinical models.
Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment—A Cardio-Oncology Study
Authors: Wilk Michał , Waśko-Grabowska Anna , Skoneczna Iwona , Szmit Sebastian
Published: April 2021

Background

Abiraterone acetate (ABI) therapy improves overall survival in metastatic prostate cancer (PC) patients; however, this effect may be diminished by concurrent comorbidities. We aimed to evaluate the influence of pre-existing chronic diseases and concomitant medications on the course of ABI treatment among post-chemotherapy patients with metastatic castration-resistant prostate cancer patients (mCRPC).

Methods

From the Polish National Health Fund database, we identified 93 post-chemotherapy, mCRPC patients, who were qualified for ABI treatment in our oncology center between 2014 and 2018. Survival curves and Cox proportional hazard models (univariate and multivariate) were used to determine the predictors for longer time to treatment failure (TTF) of ABI therapy.

Results

Median TTF was 9,8 months (IQR: 0,6–56,5) Factors associated with longer TTF were: well controlled hypertension (HR, 0.59; 95% CI. 0.38–0.90; p = 0.02), stable coronary artery disease (HR, 0.56; 95% CI, 0.33–0.95; p=0.03), the use of angiotensin system inhibitor (ASi) (HR, 0.61; 95% CI 0.4–0.94; p = 0,02). Patients who were receiving ASi had median TTF of 12.2 months versus 5.8 months in men who did not receive ASi before ABI initiation. At the start of ABI therapy, the aforementioned groups did not differ in terms of well-known prognostic factors: Gleason score, PSA level, or the number of patients with visceral metastases. In a multivariate analysis, the use of ASi remained statistically significant, even after adjustment for well-known oncological factors (HR, 0.57; 95% CI, 0.34–0.98; p = 0.04).

Conclusions

The use of ASi may enhance and prolong ABI therapy in post-docetaxel mCRPC patients and may potentially be considered a new, non-oncological, predictive factor for longer TTF. This association requires a prospective validation.
Programmable Supercontinuum Laser Spectrum Generator Based on a Liquid-Crystal on Silicon Spatial Light Modulator
Authors: García-Martínez Pascuala , Moreno Ignacio , Sánchez-López María del Mar , Gomis Jordi , Martínez Pedro , Cofré Aarón
Published: April 2021

Supercontinuum (SC) lasers combine a broadband light spectrum with the unique properties of single-mode lasers. In this work we present an optical system to spectrally filter a SC laser source using liquid-crystal on silicon (LCoS) spatial light modulators (SLM). The proposed optical system disperses the input laser and the spectrally separated components are projected onto the LCoS-SLM, where the state of polarization of each wavelength is separately modulated. Finally, recombining the modulated spectral components results in an output laser source where the spectrum can be controlled dynamically from a computer. The system incorporates two branches to independently control the visible (VIS) and the near infrared (NIR) spectral content, thus providing a SC laser source from 450 to 1,600 nm with programmable spectrum. This new ability for controlling at will the wide spectra of the SC laser sources can be extremely useful for biological imaging applications.
Seed-Specific Expression of Arabidopsis AtCYP85A2 Produces Biologically Active Brassinosteroids Such as Castasterone and Brassinolide to Improve Grain Yield and Quality in Seeds of Brachypodium Distachyon
Authors: Roh Jeehee , Moon Jinyoung , Lee Ye Eun , Park Chan Ho , Kim Seong-Ki
Published: April 2021

Brachypodium distachyon is a monocotyledonous model plant that contains castasterone (CS) but no brassinolide (BL) as the end product of brassinosteroids (BR) biosynthesis, indicating dysfunction of BL synthase, which catalyzes the conversion of CS to BL. To increase BR activity, Arabidopsis cytochrome P450 85A2 (AtCYP85A2) encoding BR 6-oxidase/BL synthase was introduced into B. distachyon with the seed-specific promoters pBSU1, pAt5g10120, and pAt5g54000. RT-PCR analysis and GUS activity revealed that AtCYP85A2 was only expressed in the seeds of the transgenic plants pBSU1-AtCYP85A2::Bd21-3, pAt5g10120-AtCYP85A2::Bd21-3, and pAt5g54000-AtCYP85A2::Bd21-3. The crude enzyme prepared from the seeds of these three transgenic plants catalyzed the conversion of 6-deoxoCS to CS. The transgenic plants showed greater specific enzyme activity than the wild-type plant for the conversion of 6-deoxoCS to CS, indicating enhanced BR 6-oxidase activity in the transgenic plants. The enzyme solution also catalyzed the conversion of CS into BL. Additionally, BL was identified from the seeds of transgenic plants, verifying that seed-specific AtCYP85A2 encodes a functional BL synthase to increase BR activity in the seeds of transgenic Brachypodium. In comparison with wild-type Brachypodium, the transgenic plants showed better growth and development during the vegetative growing stage. The flowers of the transgenic plants were remarkably larger, resulting in increments in the number, size, and height of seeds. The total starch, protein, and lipid contents in transgenic plants were higher than those in wild-type plants, indicating that seed-specific expression of AtCYP85A2 improves both grain yield and quality in B. distachyon.
Warning Messages in Crisis Communication: Risk Appraisal and Warning Compliance in Severe Weather, Violent Acts, and the COVID-19 Pandemic
Authors: Rahn Maxi , Tomczyk Samuel , Schopp Nathalie , Schmidt Silke
Published: April 2021

Background

In crisis communication, warning messages are key to informing and galvanizing the public to prevent or mitigate damage. Therefore, this study examines how risk appraisal and individual characteristics influence the intention to comply with behavioral recommendations of a warning message regarding three hazard types: the COVID-19 pandemic, violent acts, and severe weather.

Methods

A cross-sectional survey examined 403 German participants from 18 to 89 years (M = 29.24; 72% female). Participants were allocated to one of three hazard types (COVID-19 pandemic, violent acts, severe weather) and presented with warning messages that were previously issued via an official warning app. Four components of risk appraisal—perceived severity (PS), anticipated negative emotions (AE), anticipatory worry (AW), and risk perception (RP)—were assessed before and after presenting the warning message. Path models were calculated to predict the intention to comply with the warning message, controlling for age, gender, and previous hazard experience.

Results

For the COVID-19 pandemic, higher age (β = 0.18) predicted warning compliance (R2 = 0.05). AE (β = 0.20) predicted compliance in the case of violent acts (R2 = 0.09). For severe weather, PS (β = 0.28), age (β = 0.29), and female gender (β = 0.34) lead to higher compliance (R2 = 0.27). Changes across risk appraisal components were not consistent, as some facets decreased after the receipt of a warning message.

Discussion

Risk appraisal has shown a marginal yet differential influence on warning message compliance in different types of hazards. Regarding the COVID-19 pandemic, the impact of sociodemographic factors on compliance should be studied more intensively. Moreover, integrating intermediary variables, such as self-efficacy, is necessary.
Humor in Times of COVID-19 in Spain: Viewing Coronavirus Through Memes Disseminated via WhatsApp
Authors: Cancelas-Ouviña Lucía-Pilar
Published: April 2021

The COVID-19 crisis, and its ensuing periods of confinement, has generated high levels of social stress on a global scale. In Spain, citizens were isolated in their homes and were not able to interact physically with family members, friends or co-workers. Different resources were employed to face this new stressful and unexpected situation (fitness, reading, painting, meditation, mindfulness, dancing, listening to music, playing instruments, cooking, etc.). Humor was one of the most frequent and widely used strategies in an attempt to keep perspective, deal with the seriousness of the situation and make the day-to-day more bearable. Humor is cultural: it varies from one country to the next and is part of the idiosyncrasies of a culture. It is deemed a particularly important feature of the Spanish personality. During the COVID-19 crisis, the main means or channels of communication were social networks. Throughout the confinement period, there was an excessive flow of humorous memes concerning Coronavirus and related shared experiences during the National State of Emergency decreed by the Spanish Government. The memes draw on irony, ingenuity and creativity to make a difficult and stressful experience more bearable. In this paper, a qualitative methodology based on ethnography research is used and ethnographic fieldwork is carried out on the memes disseminated through WhatsApp during the lockdown period experienced in Spain (14 March to 21 June 2020). The memes are considered to be an example of Netlore, digital contemporary folklore, and a theoretical framework on memes and humor is presented that discusses its different functions in order to channel grief, fear and suffering or to play down specific situations. A corpus of 644 memes that have flooded social networks are categorized and analyzed to witness how the Spanish have managed to bring out their humorous and creative side in difficult times even as they have criticized political decisions, let out their frustrations, described their new “normal” lives, interacted with others and anticipated the future.
Influence of Entrepreneurial Orientation on Venture Capitalists' Initial Trust
Authors: Yang Hongtao , Zhang Lei , Wu Yenchun Jim , Shi Hangyu , Xie Shuting
Published: April 2021

The effectiveness of trust has been extensively investigated in entrepreneurship studies. However, compared to the outcomes of trust, we still lack knowledge about the mechanisms underlying venture capitalists' initial trust in entrepreneurs. Drawing from signal theory and impression management theory, this study explores an impression management motivational explanation for the influencing factors of venture capitalists' initial trust. An empirical test is based on 202 valid questionnaires from venture capitalists, and the results indicate that the signal of five dimensions of entrepreneurial orientation has a significant impact on the initial trust of venture capitalists and that a signal of entrepreneurial orientation of perseverance or passion positively influences venture capitalists' initial trust through acquired impression management strategies, while a signal of entrepreneurial orientation of risk-taking, innovation, or proactivity positively affects the initial trust of venture capitalists through defensive impression management strategies. The perceptions of entrepreneurs' hypocrisy by venture capitalists negatively moderate the relationship between acquired impression management strategies and the initial trust of venture capitalists and negatively moderate the relationship between defensive impression management strategies and the initial trust of venture capitalists.
Save for Safe: Effect of COVID-19 Pandemic on Consumers' Saving and Spending Behavior in China
Authors: Jin Xiaotong , Zhao Yurou , Song Wei , Zhao Taiyang
Published: April 2021

In public health emergencies, people are more willing to save money rather than spending it, which is not conductive to economic development and recovery. Due to the absence of relevant research, the internal logic of this phenomenon is not clear. In the context of the COVID-19 pandemic, this study systematically explored whether and why public health emergencies stimulate consumers' preference for saving (vs. spending). We conducted two online surveys and used methods including stepwise regression analysis and bootstrapping to test the hypotheses. The first survey, with 1,511 participants from China in February 2020, indicates that the severity of emergencies has a significant positive impact on the populations' willingness to save (vs. spend). Risk perception plays a mediating role between the severity of emergencies and consumers' saving (vs. spending) willingness. Materialism plays a moderating role between risk perception and an individual's saving (vs. spending) willingness, individuals who are more materialistic have a lower saving (vs. spending) willingness when they perceive the risks of the pandemic. To verify the duration of the above effects, we conducted a follow-up survey consisted of 466 instances in August 2020. It is noteworthy that the above effects are not significant during the post-pandemic period. Thus, spending behavior in public health emergencies can be motived by reducing risk perception and increasing materialism. These findings can provide a valuable inspiration for public health, crisis management, and economic recovery during public health emergencies.
The Effect of Persuasive Messages in Promoting Home-Based Physical Activity During COVID-19 Pandemic
Authors: Carfora Valentina , Catellani Patrizia
Published: April 2021

We tested the plausibility of a persuasion model to understand the effects of messages framed in terms of gain, non-loss, loss, and non-gain, and related to the physical, mental and social consequences of doing physical activity at home during the lockdown restrictions. 272 Italian participants responded to a questionnaire on their attitude and intention at Time 1, frequency of past behavior, and self-efficacy related to exercising at home. Then, participants were randomly assigned to four different message conditions: (a) gain messages focused on the positive outcomes associated with doing physical activity at home; (b) non-loss messages focused on the avoided negative outcomes associated with doing physical activity at home; (d) loss messages focused on the negative outcomes associated with not doing physical activity at home; (c) non-gain messages focused on the missed positive outcomes associated with not doing physical activity at home. After reading the messages, participants answered a series of questions regarding their perception of threat and fear, their evaluation of the messages, and their attitude and intention toward exercising at home at Time 2. Using multigroup structural equation modeling, we compared message conditions, and tested whether the effects of the messages on attitude and intention at Time 2 were mediated by message-induced threat, message-induced fear, and message evaluation. Results showed that the perception of the messages as not threatening was the key point to activate a positive evaluation of the recommendation. The highest persuasive effect was observed in the case of the non-loss frame, which did not threaten the receivers, triggered a moderated fear and, in turn, activated a positive evaluation of the recommendation, as well as higher attitude and intention to do home-based physical activity at Time 2. Overall, these results advance our comprehension of the effects of message framing on receivers' attitudes and intentions toward home-based physical activity.
Investigating Everyday Musical Interaction During COVID-19: An Experimental Procedure for Exploring Collaborative Playlist Engagement
Authors: Harris Ilana , Cross Ian
Published: April 2021

Musical Group Interaction (MGI) has been found to promote prosocial tendencies, including empathy, across various populations. However, experimental study is lacking in respect of effects of everyday forms of musical engagement on prosocial tendencies, as well as whether key aspects—such as physical co-presence of MGI participants—are necessary to enhance prosocial tendencies. We developed an experimental procedure in order to study online engagement with collaborative playlists and to investigate socio-cognitive components of prosocial tendencies expected to increase as a consequence of engagement. We aimed to determine whether mereperceivedpresence of a partner during playlist-making could elicit observable correlates of social processing implicated in both MGI and prosocial behaviors more generally and identify the potential roles of demographic, musical, and inter-individual differences. Preliminary results suggest that for younger individuals, some of the social processes involved in joint music-making and implicated in empathic processes are likely to be elicited even by an assumption of virtual co-presence. In addition, individual differences in styles of listening behavior may mediate the effects of mere perceived partner presence on recognition memory.
The Severity of Dependence Scale (SDS) for Codeine: Preliminary Investigation of the Psychometric Properties of the SDS in an Online Sample of Codeine Users From the UK
Authors: Deluca Paolo , Foley Michelle , Dunne Jacklyn , Kimergård Andreas
Published: April 2021

Objective: Investigate the psychometric properties of the Severity of Dependence Scale (SDS) for codeine and its association with aberrant codeine related behaviors.

Design: A voluntary and uncompensated cross-sectional online survey.

Setting: Online population (≥18 years).

Respondents: Two hundred and eighty-six respondents (66% women) who had used codeine containing medicines in the last 3 months and were living in the UK.

Results: Of the respondents (mean age = 35.4 years, SD = 12.5), more than half were employed. Only 3.5% respondents reported no income. The majority of respondents (45.1%) primarily obtained prescription-only codeine from a consultation with a health professional, whilst 40.9% mainly purchased “over-the-counter” codeine containing medicines in a pharmacy without a medical prescription. Principal component analysis indicated a single factor solution accounting for 75% of the variance. Factor loadings ranged from 0.83 to 0.89. Cronbach's Alpha was high (α = 0.92). Several behaviors relating to codeine use were found to significantly predict probable codeine dependence. These included: daily codeine use in the last 3 months (OR = 66.89, 95% CI = 15.8–283.18); tolerance to codeine (OR = 32.14, 95% CI = 13.82–74.75); problems with role responsibility due to intoxication (OR = 9.89, 95% CI = 4.95–19.78); having sought advice on the internet to manage codeine use (OR = 9.56, 95% CI = 4.5–20.31); history of alcohol or drug treatment (OR = 3.73, 95% CI = 1.88–7.43).

Conclusions: The SDS was acceptable and feasible to use to assess probable psychological codeine dependence in an online sample of people using codeine containing medicines. SDS scores were associated with behaviors known to be indicators of codeine dependence. Studies are needed in well-defined populations of people who use codeine to test the different aspects of psychometry of the scale compared against “gold standard” criterion [a diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)].
Cognitive Empathy as Imagination: Evidence From Reading the Mind in the Eyes in Autism and Schizotypy
Authors: Nahal Priya , Hurd Peter L. , Read Silven , Crespi Bernard
Published: April 2021

How is cognitive empathy related to sociality, imagination, and other psychological constructs? How is it altered in disorders of human social cognition? We leveraged a large data set (1,168 students, 62% female) on the Reading the Mind in the Eyes test (RMET), the Autism Quotient (AQ), and the Schizotypal Personality Questionnaire (SPQ-BR) to test the hypotheses that the RMET, as a metric of cognitive empathy, reflects mainly social abilities, imagination, or both. RMET showed the expected female bias in performance, though only for eyes that expressed emotions and not for neutral expressions. RMET performance was significantly, and more strongly, associated with the AQ and SPQ subscales that reflect aspects of imagination (AQ-Imagination and SPQ-Magical Ideation) than aspects of social abilities (AQ-Social, AQ-Communication, and SPQ-Interpersonal subscales). These results were confirmed with multiple regression analysis, which also implicated increased attention (AQ-Attention Switching and, marginally non-significantly, AQ-Attention to Detail) in RMET performance. The two imagination-related correlates of RMET performance also show the strongest sex biases for the AQ and SPQ: male biased in AQ-Imagination, and female biased in SPQ-Magical Ideation, with small to medium effect sizes. Taken together, these findings suggest that cognitive empathy, as quantified by the RMET, centrally involves imagination, which is underdeveloped (with a male bias) on the autism spectrum and overdeveloped (with a female bias) on the schizotypy spectrum, with optimal emotion-recognition performance intermediate between the two. The results, in conjunction with previous studies, implicate a combination of optimal imagination and focused attention in enhanced RMET performance.
Improved Continuum Joint Configuration Estimation Using a Linear Combination of Length Measurements and Optimization of Sensor Placement
Authors: Rupert Levi , Duggan Timothy , Killpack Marc D.
Published: April 2021

This paper presents methods for placing length sensors on a soft continuum robot joint as well as a novel configuration estimation method that drastically minimizes configuration estimation error. The methods utilized for placing sensors along the length of the joint include a single joint length sensor, sensors lined end-to-end, sensors that overlap according to a heuristic, and sensors that are placed by an optimization that we describe in this paper. The methods of configuration estimation include directly relating sensor length to a segment of the joint's angle, using an equal weighting of overlapping sensors that cover a joint segment, and using a weighted linear combination of all sensors on the continuum joint. The weights for the linear combination method are determined using robust linear regression. Using a kinematic simulation we show that placing three or more overlapping sensors and estimating the configuration with a linear combination of sensors resulted in a median error of 0.026% of the max range of motion or less. This is over a 500 times improvement as compared to using a single sensor to estimate the joint configuration. This error was computed across 80 simulated robots of different lengths and ranges of motion. We also found that the fully optimized sensor placement performed only marginally better than the placement of sensors according to the heuristic. This suggests that the use of a linear combination of sensors, with weights found using linear regression is more important than the placement of the overlapping sensors. Further, using the heuristic significantly simplifies the application of these techniques when designing for hardware.
LncRNA LINC-PINT Inhibits Malignant Behaviors of Laryngeal Squamous Cell Carcinoma Cells via Inhibiting ZEB1
Authors: Yang Xianguang , Miao Susheng , Mao Xionghui , Xiu Cheng , Sun Ji , Pei Rong , Jia Shenshan
Published: April 2021

Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment.

Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened.

Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition.

Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.