bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Pathogenic and Beneficial Microbes for Roselle Wilt Disease
Authors: Wang Chih-Wei , Yu Yu-Hsiang , Wu Chun-Yao , Feng Ru-Ying , Tandon Kshitij , Chen Ying-Lien , Tang Sen-Lin
Published: November 2021

Wilt disease of roselle (Hibiscus sabdariffa L.) is common in Taiwan; however, the causative agent remains unknown. The stems of wilted roselle are browned, slightly constricted, and covered by white aerial hyphae, suggesting that potential pathogens may originate from soil. To identify the potential pathogens, we conducted a rhizosphere microbiota survey in phenotypically healthy and diseased plants through fungal internal transcribed spacer (ITS) and bacterial 16S rRNA amplicon sequencing for uncovering the microbial compositions in the roselle rhizosphere. The fungal family Nectriaceae exhibited significantly higher abundance in diseased rhizospheres than in healthy rhizospheres, and this bacterial community was more specific to geography (i.e., plot-dependent) than to rhizosphere disease status. However, a few bacterial groups such as Bacilli were associated with the healthy rhizosphere. Fusarium species were the most dominant species of Nectriaceae in the survey and became the main target for potential pathogen isolation. We successfully isolated 119 strains from diseased plants in roselle fields. Koch’s postulates were used to evaluate the pathogenicity of these strains; our results indicated that Fusarium solani K1 (FsK1) can cause wilting and a rotted pith in roselles, which was consistent with observations in the fields. This is the first demonstration that F. solani can cause roselle wilt in Taiwan. Furthermore, these newly isolated strains are the most dominant operational taxonomic units detected in ITS amplicon sequencing in diseased rhizospheres, which serves as further evidence that F. solani is the main pathogen causing the roselle wilt disease. Administration of Bacillus velezensis SOI-3374, a strain isolated from a healthy roselle rhizosphere, caused considerable anti-FsK1 activity, and it can serve as a potential biocontrol agent against roselle wilt disease.
Complement Component C1q as an Emerging Biomarker for the Diagnosis of Tuberculous Pleural Effusion
Authors: Qiao Xin , Shao Ming-Ming , Yi Feng-Shuang , Shi Huan-Zhong
Published: November 2021

Background and Objective:The accurate differential diagnosis of tuberculous pleural effusion (TPE) from other exudative pleural effusions is often challenging. We aimed to validate the accuracy of complement component C1q in pleural fluid (PF) in diagnosing TPE.

Methods:The level of C1q protein in the PF from 49 patients with TPE and 61 patients with non-tuberculous pleural effusion (non-TPE) was quantified by enzyme-linked immunosorbent assay, and the diagnostic performance was assessed by receiver operating characteristic (ROC) curves based on the age and gender of the patients.

Results:The statistics showed that C1q could accurately diagnose TPE. Regardless of age and gender, with a cutoff of 6,883.9 ng/mL, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C1q for discriminating TPE were 0.898 (95% confidence interval: 0.825–0.947), 91.8 (80.4–97.7), 80.3 (68.2–89.4), 78.9 (69.2–86.2), and 92.5 (82.6–96.9), respectively. In subgroup analysis, the greatest diagnostic accuracy was achieved in the younger group (≤ 50 years of age) with an AUC of 0.981 (95% confidence interval: 0.899–0.999) at the cutoff of 6,098.0 ng/mL. The sensitivity, specificity, PLR, NLR, PPV, and NPV of C1q were 95.0 (83.1–99.4), 92.3 (64.0–99.8), 97.4 (85.2–99.6), and 85.7 (60.6–95.9), respectively.

Conclusion:Complement component C1q protein was validated by this study to be a promising biomarker for diagnosing TPE with high diagnostic accuracy, especially among younger patients.
Characterization of the Immune Cell Infiltration Landscape of Thyroid Cancer for Improved Immunotherapy
Authors: Gong Jing , Jin Bo , Shang Liang , Liu Ning
Published: November 2021

Within the endocrine system, thyroid cancer (THCA) is the most typical malignant tumor. Tumor-infiltrating immune cells play vital roles in tumor progression, recurrence, metastasis as well as response to immunotherapy. However, THCA’s immune infiltrative landscape is still not clarified. Therefore, we utilized two statistical algorithms to investigate the immune cell infiltration (ICI) landscape of 505 THCA samples and defined three ICI immune subtypes. The ICI scores were calculated using principal-component analysis. Increased tumor mutation burden (TMB) and immune-related signaling pathways were associated to a high ICI score. The high ICI score group indicated a relatively longer overall survival (OS) than the low ICI score group. Most immune checkpoint-related and immune activation-related genes were considerably upregulated in the ICI high group, which indicates stronger immunogenicity and a greater likelihood of benefiting from immunotherapy. In two cohort studies of patients receiving immunotherapy, high-ICI-score group showed notable therapeutic effects and clinical advantages compared to those with lower ICI scores. These results demonstrate that ICI score acts as an effective prognostic indicator and predictor of response to immunotherapy.
Modified Rhodopsins From Aureobasidium pullulans Excel With Very High Proton-Transport Rates
Authors: Panzer Sabine , Zhang Chong , Konte Tilen , Bräuer Celine , Diemar Anne , Yogendran Parathy , Yu-Strzelczyk Jing , Nagel Georg , Gao Shiqiang , Terpitz Ulrich
Published: November 2021

Aureobasidium pullulans is a black fungus that can adapt to various stressful conditions like hypersaline, acidic, and alkaline environments. The genome of A. pullulans exhibits three genes coding for putative opsins ApOps1, ApOps2, and ApOps3. We heterologously expressed these genes in mammalian cells and Xenopus oocytes. Localization in the plasma membrane was greatly improved by introducing additional membrane trafficking signals at the N-terminus and the C-terminus. In patch-clamp and two-electrode-voltage clamp experiments, all three proteins showed proton pump activity with maximal activity in green light. Among them, ApOps2 exhibited the most pronounced proton pump activity with current amplitudes occasionally extending 10 pA/pF at 0 mV. Proton pump activity was further supported in the presence of extracellular weak organic acids. Furthermore, we used site-directed mutagenesis to reshape protein functions and thereby implemented light-gated proton channels. We discuss the difference to other well-known proton pumps and the potential of these rhodopsins for optogenetic applications.
Human Cytomegalovirus Immediate Early Protein 2 Protein Causes Cognitive Disorder by Damaging Synaptic Plasticity in Human Cytomegalovirus-UL122-Tg Mice
Authors: Wang Zhifei , Yu Wenwen , Liu Lili , Niu Junyun , Zhang Xianjuan , Nan Fulong , Xu Lili , Jiang Bin , Ke Dingxin , Zhu Wenhua , Tian Zibin , Wang Yashuo , Wang Bin
Published: November 2021

Human cytomegalovirus (HCMV) infection is very common in the human population all around the world. Although the majority of HCMV infections are asymptomatic, they can cause neurologic deficits. Previous studies have shown that immediate early protein 2 (IE2, also known as UL122) of HCMV is related with the cognitive disorder mechanism. Due to species isolation, a HCMV-infected animal model could not be established which meant a study into the long-term effects of IE2 on neural development could not be carried out. By establishing HCMV-UL122-Tg mice (UL122 mice), we explored the cognitive behavior and complexity of neuron changes in this transgenic UL122 mice that could consistently express IE2 protein at different ages (confirmed in both 6- and 12-month-old UL122 mice). In the Morris water maze, cognitive impairment was more pronounced in 12-month-old UL122 mice than in 6-month-old ones. At the same time, a decrease of the density of dendritic spines and branches in the hippocampal neurons of 12-month-old mice was observed. Moreover, long-term potentiation was showed to be impaired in 12-month-old UL122 mice. The expressions of several synaptic plasticity-regulated molecules were reduced in 12-month-old UL122 mice, including scaffold proteins postsynaptic density protein 95 (PSD95) and microtubule-associated protein 2 (MAP2). Binding the expression of IE2 was increased in 12-month-old mice compared with 6-month-old mice, and results of statistical analysis suggested that the cognitive damage was not caused by natural animal aging, which might exclude the effect of natural aging on cognitive impairment. All these results suggested that IE2 acted as a pathogenic regulator in damaging synaptic plasticity by downregulating the expression of plasticity-related proteins (PRPs), and this damage increased with aging.
MMDD-Ensemble: A Multimodal Data–Driven Ensemble Approach for Parkinson's Disease Detection
Authors: Ali Liaqat , He Zhiquan , Cao Wenming , Rauf Hafiz Tayyab , Imrana Yakubu , Bin Heyat Md Belal
Published: November 2021

Parkinson's disease (PD) is the second most common neurological disease having no specific medical test for its diagnosis. In this study, we consider PD detection based on multimodal voice data that was collected through two channels, i.e., Smart Phone (SP) and Acoustic Cardioid (AC). Four types of data modalities were collected through each channel, namely sustained phonation (P), speech (S), voiced (V), and unvoiced (U) modality. The contributions of this paper are twofold. First, it explores optimal data modality and features having better information about PD. Second, it proposes a MultiModal Data–Driven Ensemble (MMDD-Ensemble) approach for PD detection. The MMDD-Ensemble has two levels. At the first level, different base classifiers are developed that are driven by multimodal voice data. At the second level, the predictions of the base classifiers are fused using blending and voting methods. In order to validate the robustness of the propose method, six evaluation measures, namely accuracy, sensitivity, specificity, Matthews correlation coefficient (MCC), and area under the curve (AUC), are adopted. The proposed method outperformed the best results produced by optimal unimodal framework from both the key evaluation aspects, i.e., accuracy and AUC. Furthermore, the proposed method also outperformed other state-of-the-art ensemble models. Experimental results show that the proposed multimodal approach yields 96% accuracy, 100% sensitivity, 88.88% specificity, 0.914 of MCC, and 0.986 of AUC. These results are promising compared to the recently reported results for PD detection based on multimodal voice data.
Transcriptome in Combination Proteome Unveils the Phenylpropane Pathway Involved in Garlic (Allium sativum) Greening
Authors: Wu Jinxiang , Niu Zhonglu , Lu Xiaoming , Tang Xiaozhen , Qiao Xuguang , Ma Longchuan , Liu Chao , Li Ningyang
Published: November 2021

Garlic (Allium sativum) is an important vegetable crop that is widely used in cooking and medicine. The greening phenomenon of garlic severely decreases the quality of garlic and hinders garlic processing. To study the mechanism of garlic greening, comprehensive full-length transcript sets were constructed. We detected the differences in greening between Pizhou (PZ) garlic and Laiwu (LW) garlic that were both stored at −2.5°C and protected from light at the same time. The results showed that 60,087 unigenes were respectively annotated to the NR, KEGG, GO, Pfam, eggNOG and Swiss Prot databases, and a total of 30,082 unigenes were annotated. The analysis of differential genes and differential proteins showed that PZ garlic and LW garlic had 923 differentially expressed genes (DEGs), of which 529 genes were up regulated and 394 genes were downregulated. Through KEGG and GO enrichment analysis, it was found that the most significant way of enriching DEGs was the phenylpropane metabolic pathway. Proteomics analysis found that there were 188 differentially expressed proteins (DAPs), 162 up-regulated proteins, and 26 down-regulated proteins between PZ garlic and LW garlic. The content of 10 proteins related to phenylpropanoid biosynthesis in PZ garlic was significantly higher than that of LW garlic. This study explored the mechanisms of garlic greening at a molecular level and further discovered that the formation of garlic green pigment was affected significantly by the phenylpropanoid metabolic pathway. This work provided a theoretical basis for the maintenance of garlic quality during garlic processing and the future development of the garlic processing industries.
Development and Validation of the Individualized Prognostic Nomograms in Patients With Right- and Left-Sided Colon Cancer
Authors: Luo Zai , Fu Zhongmao , Li Tengfei , Zhang Yuan , Zhang Jianming , Yang Yan , Yang Zhengfeng , Li Qi , Qiu Zhengjun , Huang Chen
Published: November 2021

Background

The overall survival (OS) of patients diagnosed with colon cancer (CC) varied greatly, so did the patients with the same tumor stage. We aimed to design a nomogram that is capable of predicting OS in resected left-sided colon cancers (LSCC) and right-sided colon cancers (RSCC), and thus to stratify patients into different risk groups, respectively.

Methods

Records from a retrospective cohort of 577 patients with complete information were used to construct the nomogram. Univariate and multivariate analyses screened risk factors associated with overall survival. The performance of the nomogram was evaluated with concordance index (c-index), calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits, respectively, which was further compared with the American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification. Risk stratification based on nomogram scores was performed with recursive partitioning analysis.

Results

The LSCC nomogram incorporated carbohydrate antigen 12-5 (CA12-5), age and log odds of positive lymph nodes (LODDS), and RSCC nomogram enrolled tumor stroma percentage (TSP), age and LODDS. Compared with the TNM classification, the LSCC and RSCC nomograms both had a statistically higher C-index (0.837, 95% CI: 0.827–0.846 and 0.780, 95% CI 0.773–0.787, respectively) and more clinical net benefits, respectively. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort.

Conclusions

An original predictive nomogram was constructed and validated for OS in patients with CC after surgery, which had facilitated physicians to appraise the individual survival of postoperative patients accurately and to identify high-risk patients who were in need of more aggressive treatment and follow-up strategies.
Augmented Reality and Intraoperative Navigation in Sinonasal Malignancies: A Preclinical Study
Authors: Sahovaler Axel , Chan Harley H. L. , Gualtieri Tommaso , Daly Michael , Ferrari Marco , Vannelli Claire , Eu Donovan , Manojlovic-Kolarski Mirko , Orzell Susannah , Taboni Stefano , de Almeida John R. , Goldstein David P. , Deganello Alberto , Nicolai Piero , Gilbert Ralph W. , Irish Jonathan C.
Published: November 2021

Objective

To report the first use of a novel projected augmented reality (AR) system in open sinonasal tumor resections in preclinical models and to compare the AR approach with an advanced intraoperative navigation (IN) system.

Methods

Four tumor models were created. Five head and neck surgeons participated in the study performing virtual osteotomies. Unguided, AR, IN, and AR + IN simulations were performed. Statistical comparisons between approaches were obtained. Intratumoral cut rate was the main outcome. The groups were also compared in terms of percentage of intratumoral, close, adequate, and excessive distances from the tumor. Information on a wearable gaze tracker headset and NASA Task Load Index questionnaire results were analyzed as well.

Results

A total of 335 cuts were simulated. Intratumoral cuts were observed in 20.7%, 9.4%, 1.2,% and 0% of the unguided, AR, IN, and AR + IN simulations, respectively (p < 0.0001). The AR was superior than the unguided approach in univariate and multivariate models. The percentage of time looking at the screen during the procedures was 55.5% for the unguided approaches and 0%, 78.5%, and 61.8% in AR, IN, and AR + IN, respectively (p < 0.001). The combined approach significantly reduced the screen time compared with the IN procedure alone.

Conclusion

We reported the use of a novel AR system for oncological resections in open sinonasal approaches, with improved margin delineation compared with unguided techniques. AR improved the gaze-toggling drawback of IN. Further refinements of the AR system are needed before translating our experience to clinical practice.
Application Value of Magnetic Resonance Radiomics and Clinical Nomograms in Evaluating the Sensitivity of Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma
Authors: Hu Chunmiao , Zheng Dechun , Cao Xisheng , Pang Peipei , Fang Yanhong , Lu Tao , Chen Yunbin
Published: November 2021

Objective

To predict the sensitivity of nasopharyngeal carcinoma (NPC) to neoadjuvant chemotherapy (NACT) based on magnetic resonance (MR) radiomics and clinical nomograms prior to NACT.

Materials and Methods

From January 2014 to July 2015, 284 consecutive patients with pathologically confirmed NPC underwent 3.0 T MR imaging (MRI) before initiating NACT. The patients’ data were randomly assigned to a training set (n = 200) or a test set (n = 84) at a ratio of 7:3. The clinical data included sex, tumor (T) stage, lymph node (N) stage, American Joint Committee on Cancer (AJCC) stage, and the plasma concentration of Epstein–Barr virus (EBV) DNA. The regions of interest (ROI) were manually segmented on the axial T2-weighted imaging (T2WI) and enhanced T1-weighted imaging (T1WI) sequences using ITK-SNAP software. The radiomics data were post-processed using AK software. Moreover, the Maximum Relevance Minimum Redundancy (mRMR) algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for dimensionality reduction to screen for the features that best predicted the treatment efficacy, and clinical risk factors were used in combination with radiomics scores (Rad-scores) to construct the clinical radiomics-based nomogram. DeLong’s test was utilized to compare the area under the curve (AUC) values of the clinical radiomics-based nomogram, radiomics model, and clinical nomogram. Decision curve analysis (DCA) was employed to evaluate each model’s net benefit.

Results

The clinical nomogram was constructed based on data from patients who were randomly assigned according to T2WI and enhanced T1WI sequences. In the training set, the T2WI sequence-based clinical radiomics nomogram and the radiomics model outperformed the clinical nomogram in predicting the NACT efficacy (AUC, 0.81 vs. 0.60, p = 0.001279 and 0.76 vs. 0.60, p = 0.03026). These findings were well-verified in the test set. The enhanced T1WI sequence-based clinical radiomics nomogram exhibited better performance in predicting treatment efficacy than the clinical nomogram (AUC, 0.79 vs. 0.62, respectively; p = 0.0000834). The DCA revealed that the T2WI and clinical radiomics-based nomograms resulted in a net benefit in predicting the NACT efficacy.

Conclusion

The clinical radiomics-based nomogram improved the prediction of NACT efficacy, with the T2WI sequence-based clinical radiomics achieving the best effect.
Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer
Authors: Pan Weijie , Wang Kaijing , Li Jiayong , Li Hanhua , Cai Yuchan , Zhang Min , Wang Aili , Wu Yazhou , Gao Wei , Weng Wenhao
Published: November 2021

Emerging evidence suggests that hypermethylation of HOXD10 plays an important role in human cancers. However, the biological and clinical impacts of HOXD10 overmethylation and its downstream targets in colorectal cancer remain unknown. We evaluated the methylation level of HOXD10 in paired cancer and normal tissues (n = 42) by using pyrosequencing, followed by validation of the methylation status of HOXD10 from The Cancer Genome Atlas (TCGA) datasets with 302 cancer tissues and 38 normal tissues. The biological function of HOXD10 was characterized in cell lines. We further evaluated the effects of HOXD10 and its targets on chemoresistance in our established resistant cell lines and clinical cohort (n = 66). HOXD10 was found frequently methylated in colorectal cancer, and its hypermethylation correlates with its low expression level, advanced disease, and lymph node metastasis. Functionally, HOXD10 acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10 regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. Restoration of the expression of HOXD10 in 5-fluorouracil (5-FU)-resistant cells significantly upregulates the expressions of miR-7 and IGFBP3 and enhances chemosensitivity to 5-FU. In conclusion, we provide novel evidence that HOXD10 is frequently methylated, silenced, and contributes to the development of colorectal cancers. Restoration of HOXD10 activates the expressions of miR-7 and IGFBP3 and results in an inhibited phenotype biologically, suggesting its potential therapeutic relevance in colorectal cancer (CRC).
Cardiotoxicity of Epidermal Growth Factor Receptor 2-Targeted Drugs for Breast Cancer
Authors: Yang ZiYan , Wang Wei , Wang Xiaojia , Qin ZhiQuan
Published: November 2021

Breast cancer is the most common form of cancer in women and its incidence has been increasing over the years. Human epidermal growth factor receptor 2 (HER2 or ErbB2) overexpression is responsible for 20 to 25% of invasive breast cancers, and is associated with poor prognosis. HER2-targeted therapy has significantly improved overall survival rates in patients with HER2-positive breast cancer. However, despite the benefits of this therapy, its cardiotoxicity is a major concern, especially when HER2-targeted therapy is used in conjunction with anthracyclines. At present, the mechanism of this cardiotoxicity is not fully understood. It is thought that HER2-targeting drugs inhibit HER2/NRG 1 dimer formation, causing an increase in ROS in the mitochondria of cardiomyocytes and inhibiting the PI3K/Akt and Ras/MAPK pathways, resulting in cell apoptosis. Antioxidants, ACE inhibitors, angiotensin II receptor blockers, β-blockers, statins and other drugs may have a cardioprotective effect when used with ErbB2-targeting drugs. NT-proBNP can be used to monitor trastuzumab-induced cardiotoxicity during HER2-targeted treatment and may serve as a biological marker for clinical prediction of cardiotoxicity. Measuring NT-proBNP is non-invasive, inexpensive and reproducible, therefore is worthy of the attention of clinicians. The aim of this review is to discuss the potential mechanisms, clinical features, diagnostic strategies, and intervention strategies related to cardiotoxicity of ErbB2-targeting drugs.
Prescription Pattern and Off-Label Use of Antipsychotics in a Middle Eastern Population
Authors: Bastaki Kholoud , El Anbari Mohammed , Ghuloum Suhaila , Jithesh Puthen Veettil
Published: November 2021

Background: Understanding the prescription pattern of medications in a population can help reveal the potential usage scenarios, including off-label prescriptions, and the need for precision medicine implementation. Therefore, the aim of this study was to assess the prescription pattern and off-label use of antipsychotics in the Qatari population.

Methods: We performed a cross-sectional study of Qatari patients who received antipsychotic prescriptions from the major healthcare providers in the country during the 2-year period between June 2018 and May 2020. The number of patients, prescriptions dispensed, and clinical indications were collected and statistical analysis using chi-square test was conducted.

Results: Among the 9,349 Qatari patients prescribed with antipsychotics during the study period, the majority were female (57%; p < 0.001) and were in the age categories 20–39 and 30–39 years (both 22%; p < 0.001). Among the 35,938 antipsychotic prescriptions dispensed, second-generation antipsychotics were the most highly prescribed (59%), specifically, quetiapine (16%) and olanzapine (12%), but the first-generation antipsychotic prochlorperazine (13%) was also highly prescribed. Most of the indications of antipsychotics (69%) were for off-label use such as for controlling chronic diseases, sleeping disorders, benign paroxysmal positional vertigo and irritable bowel syndrome.

Conclusion: Non-mental health and off-label prescriptions of several antipsychotics were observed. Integration of this data with pharmacogenomic and clinical outcome data will help in determining the course of action for implementing personalized and precision medicine in the country and beyond.
Plasmodium falciparum Multidrug Resistance Proteins (pfMRPs)
Authors: Gil José Pedro , Fançony Cláudia
Published: November 2021

The capacity of the lethal Plasmodium falciparum parasite to develop resistance against anti-malarial drugs represents a central challenge in the global control and elimination of malaria. Historically, the action of drug transporters is known to play a pivotal role in the capacity of the parasite to evade drug action. MRPs (Multidrug Resistance Protein) are known in many phylogenetically diverse groups to be related to drug resistance by being able to handle a large range of substrates, including important endogenous substances as glutathione and its conjugates. P. falciparum MRPs are associated with in vivo and in vitro altered drug response, and might be important factors for the development of multi-drug resistance phenotypes, a latent possibility in the present, and future, combination therapy environment. Information on P. falciparum MRPs is scattered in the literature, with no specialized review available. We herein address this issue by reviewing the present state of knowledge.
Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis
Authors: Zhou Yang , Yan Hui , Zhou Qiang , Feng Ruiling , Wang Penggao , Yang Fang , Zhang Yaodong , Yuan Ziqiao , Zhai Bo
Published: November 2021

The inflammatory factor IL6 secreted by bone marrow mesenchymal stem cells (BMSCs) in the tumor microenvironment (TME) facilitates the survival and therapeutic resistance of neuroblastoma (NB). Here, we found that IL6 expression in primary tumor tissues or bone marrow (BM) metastases was closely associated with the disease risk and prognosis of NB patients. IL6 secretion from immortalized BMSC (iBMSC) was directly regulated by NB cells and is involved in promoting the proliferation and metastasis of NB cells. Beta-Lapachone (ARQ-501, LPC), an ortho-naphthoquinone natural product, significantly prevented the iBMSC-induced malignant transformation effect on NB cells through suppressing the expression and secretion of IL6 from iBMSC in vitro and in vivo. Mechanistically, LPC disrupted the crosstalk between NB cells and iBMSC in an NQO1-dependent manner through blocking the Gal-3/Gal-3BP/IL6 axis. Our results reveal the effect of iBMSC-derived IL6 on TME-induced malignant transformation of NB cells, and provide theoretical basis for the clinical application of LPC as a potential IL6 inhibitor in high-risk refractory NB patients.
The Emergence of Employees’ Change Readiness for Energy-Conservation Behavior During Guided Group Discussions
Authors: Güntner Amelie Verena , Endrejat Paul Constantin , Kauffeld Simone
Published: November 2021

Studies of energy conservation efforts to reduce CO2 emissions in the residential sector are abundant; however similar efforts in organizations have not received as much attention as they deserve. In this study, we focus on methods for increasing employees’ readiness to change their behaviors in favor of energy conservation, specifically examining the use of guided group discussions (GGDs). We use observational research methods to examine the micro-level of behavioral dynamics and understand the emergence of change readiness. We describe how facilitators (“change agents”) can conduct GGDs and foster employees’ change readiness using the established communication approach of Motivational Interviewing (MI). We also explore how employees can increase each other’s change readiness regarding energy conservation behavior. Based on our sample of eight videotaped GGDs (5430 behavioral events), interaction analysis reveals that solution-focused communication elicits change readiness in employees, whereas problem-focused communication prompts resistance to change. We further show that employees can motivate their co-workers to express “green” intentions: when employees verbalized statements in favor of energy saving, this increased other employees’ change readiness, while verbalized statements against energy saving had the opposite effect. This demonstrates that GGD participants are active individuals who can spark behavior change in their co-workers. Finally, based on our findings we propose several communication guidelines for working with groups and discuss the importance of solution-focused energy management practices to facilitate change readiness for energy saving in the workplace.
What Time Alone Offers: Narratives of Solitude From Adolescence to Older Adulthood
Authors: Weinstein Netta , Nguyen Thuy-vy , Hansen Heather
Published: November 2021

Solitude – the state of being alone and not physically with another – can be rewarding. The present research explored the potential benefits of solitude from a pragmatist approach: a ground-up, top-down perspective that is receptive to new knowledge but informed by theory. Participant recruitment was stratified by age and gender, and the sample involved 2,035 individuals including adolescents (13–16 years), adults (35–55 years), or older adults (65+ years). Data were analyzed with a mixed-methods approach. Coded themes from brief narratives about solitude were extracted, and their frequencies (i.e., their salience to participants) were compared across the lifespan. Themes were then correlated with two indicators of well-being in solitude: self-determined motivation for solitude and peaceful mood. Several prominent themes emerged when talking about time spent in solitude. With the exception of feeling competent in solitude, which was described frequently but consistently unrelated to self-reported well-being regardless of age, benefits of solitude tended to shift over the lifespan. Some qualities, such as a sense of autonomy (self-connection and reliance; absence of pressure), were salient and consequential for everyone, but increasingly so from adolescence to older adulthood. Older adults also reported feeling most peaceful in solitude and described their social connection and alienation less frequently, suggesting they see solitude and social time as more distinct states. Findings are discussed in light of existing work on solitude across the lifespan, and theoretical frameworks that spoke well to the data (e.g., self-determination theory).
Scientific Literacy in Communicating Science and Socio-Scientific Issues: Prospects and Challenges
Authors: Li Yanyan , Guo Mengmeng
Published: November 2021

A holistic view of scientific literacy-related literature was generated based on bibliometric analysis. The purpose was to provide insight into and knowledge on evolving knowledge fronts and to highlight the turning points in the existing literature between 1980 and 2019. Scientific literacy in society can potentially help to answer unsolved riddles of socio-scientific issues (SSI) to enable people to become smart and responsible global citizens. Specifically, two decades before and after the year 2000 was taken into account as it comprised the most noticeable revolutionary developments in terms of economics, technology, culture, and society. Interestingly, the attention paid to scientific literacy significantly increased after the financial crisis of 2008. International Journal of Science Education and the Journal of Research in Science Teaching were observed to be the top-cited and top publishing journals, respectively. Similarly, Jonathan Osborne, Rosalind Driver, and Norman G. Lederman were recorded as the most cited and most published authors, respectively, during the study period. Alarmingly, most of the literature evolved in and was dominated by the Western region, indicating the need to understand the regional-cultural complexities of the East and the rest of the world. The recent evolving clusters, with titles of literacy (as a concept), learning progression, and informal reasoning, were observed to be currently active knowledge areas in the evolution of the intellectual structure of scientific literacy-related literature. However, no recent trend or emerging research direction was noticed in the last decade, even though new and digital media (including immersive media) have revolutionized the communication channels and public understanding of science and socio-scientific issues.
Pathways to Financial Success: An Empirical Examination of Perceived Financial Well-Being Based on Financial Coping Behaviors
Authors: Shi Junguo , Ullah Saif , Zhu Xun , Dou Shanshan , Siddiqui Faiza
Published: November 2021

The current study empirically tests a financial well-being (FWB) model built on financial socialization (FS) and early childhood consumer experience (ECCE). The current study was conducted based on primary data obtained through structured questionnaires. By using a convenient sampling technique, data were collected from 1,500 respondents from Pakistan. Results advocated that childhood experiences directly affect the FWB in adults. In addition, FS agents, such as parents, have direct and indirect effects on the FWB in adults. Findings revealed that financial coping behaviors mediate the relationship among FS agents, such as parents, students, and the FWB. Surprisingly, FS agent peers do not impact adult FWBs. The study concluded that FWB could be improved by socializing with parents and teachers and using childhood experiences. Considering the importance of the role of parents and teachers, they should discuss financial issues with children. Policymakers should work to provide some opportunities for children so that they can practice and gain experience.
Autonomous Exploration of Small Bodies Toward Greater Autonomy for Deep Space Missions
Authors: Nesnas Issa A. D. , Hockman Benjamin J. , Bandopadhyay Saptarshi , Morrell Benjamin J. , Lubey Daniel P. , Villa Jacopo , Bayard David S. , Osmundson Alan , Jarvis Benjamin , Bersani Michele , Bhaskaran Shyam
Published: November 2021

Autonomy is becoming increasingly important for the robotic exploration of unpredictable environments. One such example is the approach, proximity operation, and surface exploration of small bodies. In this article, we present an overview of an estimation framework to approach and land on small bodies as a key functional capability for an autonomous small-body explorer. We use a multi-phase perception/estimation pipeline with interconnected and overlapping measurements and algorithms to characterize and reach the body, from millions of kilometers down to its surface. We consider a notional spacecraft design that operates across all phases from approach to landing and to maneuvering on the surface of the microgravity body. This SmallSat design makes accommodations to simplify autonomous surface operations. The estimation pipeline combines state-of-the-art techniques with new approaches to estimating the target’s unknown properties across all phases. Centroid and light-curve algorithms estimate the body–spacecraft relative trajectory and rotation, respectively, using a priori knowledge of the initial relative orbit. A new shape-from-silhouette algorithm estimates the pole (i.e., rotation axis) and the initial visual hull that seeds subsequent feature tracking as the body gets more resolved in the narrow field-of-view imager. Feature tracking refines the pole orientation and shape of the body for estimating initial gravity to enable safe close approach. A coarse-shape reconstruction algorithm is used to identify initial landable regions whose hazardous nature would subsequently be assessed by dense 3D reconstruction. Slope stability, thermal, occlusion, and terra-mechanical hazards would be assessed on densely reconstructed regions and continually refined prior to landing. We simulated a mission scenario for approaching a hypothetical small body whose motion and shape were unknown a priori, starting from thousands of kilometers down to 20 km. Results indicate the feasibility of recovering the relative body motion and shape solely relying on onboard measurements and estimates with their associated uncertainties and without human input. Current work continues to mature and characterize the algorithms for the last phases of the estimation framework to land on the surface.
Development of a Modular Tensegrity Robot Arm Capable of Continuous Bending
Authors: Ikemoto Shuhei , Tsukamoto Kenta , Yoshimitsu Yuhei
Published: November 2021

In this study, we present a tensegrity robot arm that can reproduce the features of complex musculoskeletal structures, and can bend like a continuum manipulator. In particular, we propose a design method for an arm-type tensegrity robot that has a long shape in one direction, and can be deformed like a continuum manipulator. This method is based on the idea of utilizing simple and flexible strict tensegrity modules, and connecting them recursively so that they remain strict tensegrity even after being connected. The tensegrity obtained by this method strongly resists compressive forces in the longitudinal direction, but is flexible in the bending direction. Therefore, the changes in stiffness owing to internal forces, such as in musculoskeletal robots, appear more in the bending direction. First, this study describes this design method, then describes a developed pneumatically driven tensegrity robot arm with 20 actuators. Next, the range of motion and stiffness under various driving patterns are presented as evaluations of the robot performance.
Performance Modeling and Simulation for Water Distribution Networks
Authors: Ganjidoost Amin , Knight Mark A. , Unger Andre J. A. , Haas Carl T.
Published: November 2021

This study develops an implementation framework for asset management strategic planning of water distribution networks to meet sustainable infrastructure, socio-political, and financial targets over the life cycle of the infrastructure. The proposed framework is comprised of three decision-making layers: (1) Visions and Values, (2) Function, and (3) Performance. The asset management strategy framework is implemented and validated by demonstrating functionality and value by using data from three water utilities in Canada. The Visions and Values layer is set to meet the needs of the water utilities' stakeholders. The Function layer uses an advanced system dynamics model to simulate and forecast the system's future behavior. The Performance layer benchmarks, compares, and graphically illustrates the situation and performance of water utilities against each other regardless of their size. Benchmarking results indicate that all three water utilities can sustainably meet the strategic targets established in the Visions and Values layer of the asset management strategy over the benchmarking period. The impact of the desired cash reserve on infrastructure and financial benchmarking performance indicators is also investigated to explore the “optimal” combination of allowable fee-hike and rehabilitation rates using the contour plots developed over the benchmarking period. The results indicate that the optimal combinations of allowable fee-hike of ~8% per year and rehabilitation rate of 1.3% per year along with a 1–4% cash reserve, depends on the network condition, will allow water utilities to have sufficient funds to meet their strategic targets. The performance modeling and simulation approach presented in this study represents a powerful tool for other utilities to develop optimal strategic and operational plans for their networks and thus better service to their stakeholders.
Resilience and Adaptive Capacity of the Swan Coastal Plain Wetlands
Authors: Nanda Amar V. V. , Beesley Leah , Locatelli Luca , Gersonius Berry , Hipsey Matthew R. , Ghadouani Anas
Published: November 2021

An estimated 90% of the Swan Coastal Plain (SCP) wetlands, located in southwestern Australia, have been lost because of infilling or drainage. This loss continues despite the well-known causes, which include nutrient enrichment; the invasion of exotic flora and fauna; loss of fringing vegetation; and altered hydrological regimes caused by groundwater abstraction; urbanization; and a drying climate. Further loss is expected with climate change exacerbating the undesirable ecosystem changes of remaining wetlands. In this study, we consider these wetlands as examples of social-ecological systems (SES) which are characterized by a close interaction of the ecosystem with the social system. We take the theory of resilient SES as a starting point to identify the adaptive capacity and resilience of the wetlands. We argue that resilience provides a useful framework to analyze adaptation processes and to identify appropriate policy responses. We explore incremental adjustments and transformative action and demonstrate that policy responses arise across multiple scales and levels of jurisdiction and institution. By applying the theoretical framework of resilience to the SCP wetlands, we identified (un)desired ecosystem states of wetlands (hydrology and ecology) through different set of policy actions. Our results show that current wetland management is inadequate to maintain the ecosystem's functioning. We recommend cross-jurisdictional collaboration and the use of conceptual eco-hydrological models to depict gradual ecological change and types of regime shifts (thresholds, hysteresis, and irreversible changes). The different adaption options inform decision-makers to adequately adapt wetland management practices when uncertainty in ecosystem responses exist. Empirical data on how multiple jurisdictions operate and decide could help to further support decision-making. With this research we aim to narrow the science-policy interface which depends on corresponding cross-jurisdictional and institutional responses to coordinate wetland management policies and actions.
Meta-Analysis of Risk Factors for Bile Leakage After Hepatectomy Without Biliary Reconstruction
Authors: Tan Ling , Liu Fei , Liu Zi-lin , Xiao Jiang-wei
Published: November 2021

Background and Aim: The risk factors for bile leakage after hepatectomy without biliary reconstruction are controversial. This study investigated the risk factors for bile leakage after hepatectomy without biliary reconstruction.

Methods: We searched databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between January 1, 2000, and May 1, 2021, to evaluate the risk factors for bile leakage after hepatectomy without biliary reconstruction.

Results: A total of 16 articles were included in this study, and the overall results showed that sex (OR: 1.21, 95% CI: 1.04–1.42), diabetes (OR: 1.21, 95% CI: 1.05–1.38), left trisectionectomy (OR: 3.53, 95% CI: 2.32–5.36), central hepatectomy (OR: 3.28, 95% CI: 2.63–4.08), extended hemihepatectomy (OR: 2.56, 95% CI: 1.55–4.22), segment I hepatectomy (OR: 2.56, 95% CI: 1.50–4.40), intraoperative blood transfusion (OR:2.40 95%CI:1.79–3.22), anatomical hepatectomy (OR: 1.70, 95% CI: 1.19–2.44) and intraoperative bleeding ≥1,000 ml (OR: 2.46, 95% CI: 2.12–2.85) were risk factors for biliary leakage. Age >75 years, cirrhosis, underlying liver disease, left hepatectomy, right hepatectomy, benign disease, Child–Pugh class A/B, and pre-operative albumin <3.5 g/dL were not risk factors for bile leakage after hepatectomy without biliary reconstruction.

Conclusion: Comprehensive research in the literature revealed that sex, diabetes, left trisectionectomy, central hepatectomy, extended hemihepatectomy, segment I hepatectomy, intraoperative blood transfusion, anatomical hepatectomy and intraoperative bleeding ≥1,000 ml were risk factors for biliary leakage.
A Controlled Trial of Polyglytone 6211 versus Poliglecaprone 25 for Use in Intradermal Suturing in Dogs
Authors: Gouletsou Pagona , Prassinos Nikitas , Papazoglou Lysimachos , Kostoulas Polychronis , Galatos Apostolos
Published: November 2021

The objective of this work was the comparative evaluation of the healing process after employing 4/0 poliglecaprone 25 and 4/0 polyglytone 6211 in a continuous intradermal suture pattern. Ten Beagle dogs were used, in which skin incisions were created surgically and subsequently were sutured by means of continuous intradermal pattern using polyglytone 6211 or poliglecaprone 25 suture. Cosmetic, clinical, and histologic scores were evaluated. The cosmetic appearance of the wounds was blindly evaluated on days 7, 14, 28, 180, 360, 730, and 1095. On the same days, tissue biopsy was performed for histological evaluation. Clinical evaluation was performed initially daily, then weekly, monthly, and finally yearly, till day 1095. The clinical appearance of the intradermal pattern with both sutures was initially very good, deteriorated in the second post-operative month and thereafter improved. The cosmetic, clinical, and histological differences between the two suture materials were minimal and statistically insignificant. Polyglytone 6211 is sufficient for use in intradermal suturing in dogs. However, its earlier absorption compared to poliglecaprone 25 did not have any beneficial effect on cutaneous wound healing and scar appearance in the experimental animals.
Oxytocin Receptor Gene Polymorphism in Lactating Dogs
Authors: Ogi Asahi , Naef Valentina , Santorelli Filippo Maria , Mariti Chiara , Gazzano Angelo
Published: November 2021

Genetic variations in the oxytocinergic system, known to regulate social behavior throughout the evolution of mammals, are believed to account for differences in mammalian social behavior. Particularly, polymorphic variants of the oxytocin receptor (OXTR) gene have been associated with behavioral variations in both humans and dogs. In this study, we offered evidence of the correlation between levels of salivary oxytocin (sOXT), maternal behavior and a single-nucleotide gene variant in OXTR (rs8679684) in nineteen lactating Labrador Retriever dogs. Carriers of at least one copy of the minor A allele showed higher levels of sOXT and maternal care in comparison with the homozygous T allele carriers. Considering the relevance of mother care in newborn development, these findings could help us to better understand the possible impact of variants in the OXTR gene in selecting dams.