bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying New Hybrid Insulin Peptides (HIPs) in Type 1 Diabetes
Authors: Mannering Stuart I. , Rubin Alan F. , Wang Ruike , Bhattacharjee Pushpak
Published: April 2021

In 2016 Delong et al. discovered a new type of neoepitope formed by the fusion of two unrelated peptide fragments. Remarkably these neoepitopes, called hybrid insulin peptides, or HIPs, are recognized by pathogenic CD4+ T cells in the NOD mouse and human pancreatic islet-infiltrating T cells in people with type 1 diabetes. Current data implicates CD4+ T-cell responses to HIPs in the immune pathogenesis of human T1D. Because of their role in the immune pathogenesis of human T1D it is important to identify new HIPs that are recognized by CD4+ T cells in people at risk of, or with, T1D. A detailed knowledge of T1D-associated HIPs will allow HIPs to be used in assays to monitor changes in T cell mediated beta-cell autoimmunity. They will also provide new targets for antigen-specific therapies for T1D. However, because HIPs are formed by the fusion of two unrelated peptides there are an enormous number of potential HIPs which makes it technically challenging to identify them. Here we review the discovery of HIPs, how they form and discuss approaches to identifying new HIPs relevant to the immune pathogenesis of human type 1 diabetes.
Distinguishing Coronavirus Disease 2019 Patients From General Surgery Emergency Patients With the CIAAD Scale: Development and Validation of a Prediction Model Based on 822 Cases in China
Authors: Zhao Bangbo , Wei Yingxin , Sun Wenwu , Qin Cheng , Zhou Xingtong , Wang Zihao , Li Tianhao , Cao Hongtao , Wang Yujun , Wang Weibin
Published: April 2021

Background: During the epidemic, surgeons cannot identify infectious acute abdomen patients with suspected coronavirus disease 2019 (COVID-19) immediately using the current widely applied methods, such as double nucleic acid detection. We aimed to develop and validate a prediction model, presented as a nomogram and scale, to identify infectious acute abdomen patients with suspected COVID-19 more effectively and efficiently.

Methods: A total of 584 COVID-19 patients and 238 infectious acute abdomen patients were enrolled. The least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses were conducted to develop the prediction model. The performance of the nomogram was evaluated through calibration curves, Receiver Operating Characteristic (ROC) curves, decision curve analysis (DCA), and clinical impact curves in the training and validation cohorts. A simplified screening scale and a management algorithm were generated based on the nomogram.

Results: Five potential COVID-19 prediction variables, fever, chest CT, WBC, CRP, and PCT, were selected, all independent predictors of multivariable logistic regression analysis, and the nomogram, named the COVID-19 Infectious Acute Abdomen Distinguishment (CIAAD) nomogram, was generated. The CIAAD nomogram showed good discrimination and calibration, and it was validated in the validation cohort. Decision curve analysis revealed that the CIAAD nomogram was clinically useful. The nomogram was further simplified as the CIAAD scale.

Conclusion: We established an easy and effective screening model and scale for surgeons in the emergency department to use to distinguish COVID-19 patients. The algorithm based on the CIAAD scale will help surgeons more efficiently manage infectious acute abdomen patients suspected of having COVID-19.
Metagenomic Insights Into Functional and Taxonomic Compositions of an Activated Sludge Microbial Community Treating Leachate of a Completed Landfill: A Pathway-Based Analysis
Authors: Yasuda Shohei , Suenaga Toshikazu , Orschler Laura , Agrawal Shelesh , Lackner Susanne , Terada Akihiko
Published: April 2021

Upcycling wastes into valuable products by mixed microbial communities has recently received considerable attention. Sustainable production of high-value substances from one-carbon (C1) compounds, e.g., methanol supplemented as an external electron donor in bioreactors for wastewater treatment, is a promising application of upcycling. This study undertook a gene-centric approach to screen valuable production potentials from mixed culture biomass, removing organic carbon and nitrogen from landfill leachate. To this end, the microbial community of the activated sludge from a landfill leachate treatment plant and its metabolic potential for the production of seven valuable products were investigated. The DNA extracted from the activated sludge was subjected to shotgun metagenome sequencing to analyze the microbial taxonomy and functions associated with producing the seven products. The functional analysis confirmed that the activated sludge could produce six of the valuable products, ectoine, polyhydroxybutyrate (PHB), zeaxanthin, astaxanthin, acetoin, and 2,3-butanediol. Quantification of the detected functional gene hit numbers for these valuable products as a primary trial identified a potential rate-limiting metabolic pathway, e.g., conversion of L-2,4-diaminobutyrate into N-γ-acetyl-L2,4,-diaminobutyrate during the ectoine biosynthesis. Overall, this study demonstrated that primary screening by the proposed gene-centric approach can be used to evaluate the potential for the production of valuable products using mixed culture or single microbe in engineered systems. The proposed approach can be expanded to sites where water purification is highly required, but resource recovery, or upcycling has not been implemented.
Trained Immunity in Anopheles gambiae: Antibacterial Immunity Is Enhanced by Priming via Sugar Meal Supplemented With a Single Gut Symbiotic Bacterial Strain
Authors: Kulkarni Aditi , Pandey Ashmita , Trainor Patrick , Carlisle Samantha , Chhilar Jainder S. , Yu Wanqin , Moon Alex , Xu Jiannong
Published: April 2021

Mosquitoes have evolved an effective innate immune system. The mosquito gut accommodates various microbes, which play a crucial role in shaping the mosquito immune system during evolution. The resident bacteria in the gut microbiota play an essential role in priming basal immunity. In this study, we show that antibacterial immunity in Anopheles gambiae can be enhanced by priming via a sugar meal supplemented with bacteria. Serratia fonticola S1 and Enterobacter sp. Ag1 are gut bacteria in mosquitoes. The intrathoracic injection of the two bacteria can result in an acute hemocoelic infection in the naïve mosquitoes with mortality of ∼40% at 24 h post-infection. However, the Enterobacter orSerratia primed mosquitoes showed a better 24 h survival upon the bacterial challenge. The priming confers the protection with a certain degree of specificity, the Enterobacter primed mosquitoes had a better survival upon the Enterobacter but not Serratia challenge, and the Serratia primed mosquitoes had a better survival upon the Serratia but not Enterobacter challenge. To understand the priming-mediated immune enhancement, the transcriptomes were characterized in the mosquitoes of priming as well as priming plus challenges. The RNA-seq was conducted to profile 10 transcriptomes including three samples of priming conditions (native microbiota, Serratia priming, and Enterobacter priming), six samples of priming plus challenges with the two bacteria, and one sample of injury control. The three priming regimes resulted in distinctive transcriptomic profiles with about 60% of genes affected by both bacteria. Upon challenges, different primed mosquitoes displayed different transcriptomic patterns in response to different bacteria. When a primed cohort was challenged with a heterogenous bacterium, more responsive genes were observed than when challenged with a homogenous bacterium. As expected, many canonical immune genes were responsive to the priming and challenge, but much more non-immune genes with various functions were also responsive in the contexts, which implies that the prior priming triggers a delicately coordinated systemic regulation that results in an enhanced immunity against the subsequent challenge. Besides the participation of typical immune pathways, the transcriptome data suggest the involvement of lysosome and metabolism in the context. Overall, this study demonstrated a trained immunity via priming with bacteria in diet.
Increasing Incidences and Clonal Diversity of Methicillin-Resistant Staphylococcus aureus in the Nordic Countries - Results From the Nordic MRSA Surveillance
Authors: Petersen Andreas , Larssen Kjersti W. , Gran Frode W. , Enger Hege , Hæggman Sara , Mäkitalo Barbro , Haraldsson Gunnsteinn , Lindholm Laura , Vuopio Jaana , Henius Anna Emilie , Nielsen Jens , Larsen Anders R.
Published: April 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is notifiable in Denmark, Finland, Iceland, Norway and Sweden. The prevalence of MRSA in this region has been low for many years, but all five countries experience increasing numbers of new cases. The aim of the study was to describe the molecular epidemiology in the Nordic countries 2009-2016. Numbers of new cases of MRSA from 1997 to 2016 were compared, and a database containing information on spa-type and place of residence or acquisition, for all new MRSA isolates from 2009 to 2016 was established. A website was developed to visualize the geographic distribution of the spa-types. The incidence of new MRSA cases increased in all Nordic countries with Denmark having 61.8 new cases per 100,000 inhabitants in 2016 as the highest. The number of new cases 2009 to 2016 was 60,984. spa-typing revealed a high genetic diversity, with a total of 2,344 different spa-types identified. The majority of these spa-types (N = 2,017) were found in 1-10 cases. The most common spa-types t127/CC1, t223/CC22, and t304/CC6:8 increased significantly in all Nordic countries during the study period, except for Iceland, while spa-type t002/CC5 decreased in the same four countries. The trends of other common spa-types were different in each of the Nordic countries. The Nordic countries were shown to share similar trends but also to have country-specific characteristics in their MRSA populations. A continued increasing numbers of MRSA will challenge the surveillance economically. A more selected molecular surveillance will probably have to be employed in the future.
The Protein Quality Control Network in Caulobacter crescentus
Authors: Schroeder Kristen , Jonas Kristina
Published: April 2021

The asymmetric life cycle of Caulobacter crescentus has provided a model in which to study how protein quality control (PQC) networks interface with cell cycle and developmental processes, and how the functions of these systems change during exposure to stress. As in most bacteria, the PQC network of Caulobacter contains highly conserved ATP-dependent chaperones and proteases as well as more specialized holdases. During growth in optimal conditions, these systems support a regulated circuit of protein synthesis and degradation that drives cell differentiation and cell cycle progression. When stress conditions threaten the proteome, most components of the Caulobacter proteostasis network are upregulated and switch to survival functions that prevent, revert, and remove protein damage, while simultaneously pausing the cell cycle in order to regain protein homeostasis. The specialized physiology of Caulobacter influences how it copes with proteotoxic stress, such as in the global management of damaged proteins during recovery as well as in cell type-specific stress responses. Our mini-review highlights the discoveries that have been made in how Caulobacter utilizes its PQC network for regulating its life cycle under optimal and proteotoxic stress conditions, and discusses open research questions in this model.
Comparison of Prior Bridging Intravenous Thrombolysis With Direct Endovascular Thrombectomy for Anterior Circulation Large Vessel Occlusion: Systematic Review and Meta-Analysis
Authors: Chen Zhao-Ji , Li Xiao-Fang , Liang Cheng-Yu , Cui Lei , Yang Li-Qing , Xia Yan-Min , Cao Wei , Gao Bu-Lang
Published: April 2021

Background: Whether bridging treatment combining intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) is superior to direct EVT alone for emergent large vessel occlusion (LVO) in the anterior circulation is unknown. A systematic review and a meta-analysis were performed to investigate and assess the effect and safety of bridging treatment vs. direct EVT in patients with LVO in the anterior circulation.

Methods: PubMed, EMBASE, and the Cochrane library were searched to assess the effect and safety of bridging treatment and direct EVT in LVO. Functional independence, mortality, asymptomatic and symptomatic intracranial hemorrhage (aICH and sICH, respectively), and successful recanalization were evaluated. The risk ratio and the 95% CI were analyzed.

Results: Among the eight studies included, there was no significant difference in the long-term functional independence (OR = 1.008, 95% CI = 0.845–1.204, P = 0.926), mortality (OR = 1.060, 95% CI = 0.840–1.336, P = 0.624), recanalization rate (OR = 1.015, 95% CI = 0.793–1.300, P = 0.905), and the incidence of sICH (OR = 1.320, 95% CI = 0.931–1.870, P = 0.119) between bridging therapy and direct EVT. After adjusting for confounding factors, bridging therapy showed a lower recanalization rate (effect size or ES = −0.377, 95% CI = −0.684 to −0.070, P = 0.016), but there was no significant difference in the long-term functional independence (ES = 0.057, 95% CI = −0.177 to 0.291, P = 0.634), mortality (ES = 0.693, 95% CI = −0.133 to 1.519, P = 0.100), and incidence of sICH (ES = −0.051, 95% CI = −0.687 to 0.585, P = 0.875) compared with direct EVT. Meanwhile, in the subgroup analysis of RCT, no significant difference was found in the long-term functional independence (OR = 0.927, 95% CI = 0.727–1.182, P = 0.539), recanalization rate (OR = 1.331, 95% CI = 0.948–1.867, P = 0.099), mortality (OR = 1.072, 95% CI = 0.776–1.481, P = 0.673), and sICH incidence (OR = 1.383, 95% CI = 0.806–2.374, P = 0.977) between patients receiving bridging therapy and those receiving direct DVT.

Conclusion: For stroke patients with acute anterior circulation occlusion and who are eligible for intravenous thrombolysis, there is no significant difference in the clinical effect between direct EVT and bridging therapy, which needs to be verified by more randomized controlled trials.
Thrombectomy for Acute Ischemic Stroke With a New Device-Skyflow: Study Protocol for a Prospective, Multicenter, Stratified Randomized, Single-Blinded, Parallel, Positive Controlled, Non-inferiority Clinical Trial
Authors: Liu Huan , Li Zhaoshuo , Zhu Liangfu , Zhou Tengfei , Wu Qiaowei , He Yanyan , Song Xintong , He Yingkun , Li Tianxiao
Published: April 2021

Background: Stent retriever thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in anterior circulation. The aim of the trial is to evaluate whether the new thrombectomy device-Skyflow can achieve the same safety and efficacy as Solitaire FR in the treatment.

Method: This study is a prospective, multicenter, stratified randomized, single blind, paralleled, positive controlled, non-inferiority clinical trial. The safety and efficacy of vascular recanalization in AIS patients who are treated with either a new thrombectomy device-Skyflow or with Solitaire FR and within 8 h of symptom onset will be compared. A total of 192 patients will be enrolled, each group with 96 patients. The primary endpoint is successful recanalization rate after the operation. The secondary efficacy endpoints are the time from artery puncture to successful recanalization (mTICI 2b-3), NIHSS scores of 24 h (18–36 h), and 7 ± 2 days after the operation, mRS scores, and the rate of patients with mRS 0–2 scores 90 ± 14 days after the operation, and the success rate of instrument operation. The safety endpoints are the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage at 24 h (18–36 h) post-operation, incidence of adverse events (AE) and serious adverse events (SAE), all-cause mortality, and incidence of device defects.

Discussion: This trial will provide information on the safety and efficacy of Sky-flow stent retriever in the treatment of AIS patients with anterior circulation LVO. The success of this trial will be the basis for the product to be finally officially listed and applied in China.

Trial registration: Registered on 11 March 2018 with Chinese clinical trial registry. Registration number is ChiCTR1800015166.
Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?
Authors: Carboni Ezio , Carta Anna R. , Carboni Elena , Novelli Antonello
Published: April 2021

Repurposing ketamine in the therapy of depression could well represent a breakthrough in understanding the etiology of depression. Ketamine was originally used as an anesthetic drug and later its use was extended to other therapeutic applications such as analgesia and the treatment of addiction. At the same time, the abuse of ketamine as a recreational drug has generated a concern for its psychotropic and potential long-term effects; nevertheless, its use as a fast acting antidepressant in treatment-resistant patients has boosted the interest in the mechanism of action both in psychiatry and in the wider area of neuroscience. This article provides a comprehensive overview of the actions of ketamine and intends to cover: (i) the evaluation of its clinical use in the treatment of depression and suicidal behavior; (ii) the potential use of ketamine in pediatrics; (iii) a description of its mechanism of action; (iv) the involvement of specific brain areas in producing antidepressant effects; (v) the potential interaction of ketamine with the hypothalamic-pituitary-adrenal axis; (vi) the effect of ketamine on neuronal transmission in the bed nucleus of stria terminalis and on its output; (vii) the evaluation of any gender-dependent effects of ketamine; (viii) the interaction of ketamine with the inflammatory processes involved in depression; (ix) the evaluation of the effects observed with single or repeated administration; (x) a description of any adverse or cognitive effects and its abuse potential. Finally, this review attempts to assess whether ketamine’s use in depression can improve our knowledge of the etiopathology of depression and whether its therapeutic effect can be considered an actual cure for depression rather than a therapy merely aimed to control the symptoms of depression.
Specific Immune Response and Cytokine Production in CD70 Deficiency
Authors: Abolhassani Hassan
Published: April 2021

Collective clinical and immunologic findings of defects in the CD27–CD70 axis indicate a primary immunodeficiency associated with terminal B-cell development defect and immune dysregulation leading to autoimmunity, uncontrolled viral infection, and lymphoma. Since the molecular mechanism underlying this entity of primary immunodeficiency has been recently described, more insight regarding the function and profile of immunity is required. Therefore, this study aimed to investigate stimulated antibody production, polyclonal vs. virus-specific T-cell response, and cytokine production of a CD70-deficient patient reported previously with early-onset antibody deficiency suffering from chronic viral infections and B-cell lymphoma. The patient and her family members were subjected to clinical evaluation, immunological assays, and functional analyses. The findings of this study indicate an impaired ability of B cells to produce immunoglobulins, and a poor effector function of T cells was also associated with the severity of clinical phenotype. Reduced proportions of cells expressing the memory marker CD45RO, as well as T-bet and Eomes, were observed in CD70-deficient T cells. The proportion of 2B4+and PD-1+virus-specific CD8+T cells was also reduced in the patient. Although theCD70-mutated individuals presented with early-onset clinical manifestations that were well-controlled by using conventional immunological and anticancer chemotherapies, with better prognosis as compared with CD27-deficient patients, targeted treatment toward specific disturbed immune profile may improve the management and even prevent secondary complications.
Pharmacological Benefits of Triphala: A Perspective for Allergic Rhinitis
Authors: Jantrapirom Salinee , Hirunsatitpron Pannaphak , Potikanond Saranyapin , Nimlamool Wutigri , Hanprasertpong Nutthiya
Published: April 2021

Allergic rhinitis (AR) is considered a major nasal condition impacting a large number of people around the world, and it is now becoming a global health problem. Because the underlying mechanisms of AR are complex, the development of single-drug treatment might not be enough to treat a wide spectrum of the disease. Although the standard guidelines classify and provide suitable diagnosis and treatment, the vast majority of people with AR are still without any means of controlling it. Moreover, the benefits of AR drugs are sometimes accompanied by undesirable side effects. Thus, it is becoming a significant challenge to find effective therapies with limited undesirable side effects for a majority of patients suffering from uncontrolled AR. Aller-7/NR-A2, a polyherbal formulation, has revealed promising results in patients by reducing nasal symptoms and eosinophil counts without serious adverse effects. Interestingly, three out of seven of the herbals in the Aller-7/NR-A2 formulation are also found in an Ayurvedic polyherbal formulation known as “Triphala,” which is a potential candidate for the treatment of AR. However, there are no current studies that have examined the effects of Triphala on the disease. This review aims to describe the complexity of AR pathophysiology, currently available treatments, and the effects of Triphala on AR in order to help develop it as a promising alternative treatment in the future.
The Comparison of Plasma and Cerebrospinal Fluid R(−)- and S(+)-Flurbiprofen Concentration After Intravenous Injection of Flurbiprofen Axetil in Human Subjects
Authors: Yao Han , Luo Xingxian , Zhang Hong , An Haiyan , Feng Wanyu , Feng Yi
Published: April 2021

Background: Flurbiprofen axetil is a prodrug that releases the active substance through enzymatic removal of the ester moiety. It is formulated through encapsulation in a lipid microsphere carrier, and widely used to treat perioperative pain. Here, we studied the distribution of R (−)- and S (+)-flurbiprofen in human plasma and cerebrospinal fluid (CSF) after intravenous injection of flurbiprofen axetil.

Methods: A total of 70 adult patients undergoing elective lower limb surgery under spinal anesthesia were given a single intravenous injection of 100-mg flurbiprofen axetil. The patients were randomly assigned to 10 groups for plasma and CSF sampling at 10 time points (5–50 min) after subarachnoid puncture and before actual spinal anesthesia. R (−)- and S (+)-flurbiprofen and CSF/plasma ratio were determined by liquid chromatography–tandem mass spectrometry.

Results: R (−)-flurbiprofen concentration ranged from 2.01 to 10.9 μg/mL in plasma and 1.46–34.4 ng/mL in CSF. S (+)-flurbiprofen concentration ranged from 1.18 to 10.8 μg/mL in plasma and from 2.53 to 47 ng/mL in CSF. In comparison to S (+)-flurbiprofen, R (−)-flurbiprofen concentration was significantly higher in plasma at all time points (p < 0.05) except at 30 or 40 min, and lower in CSF at all time points (p < 0.05) except at 10, 15 and 40 min. Analysis after correcting drug concentration for body mass index also revealed higher plasma and lower CSF R (−)-flurbiprofen concentration. In comparison to S (+)-flurbiprofen, AUC0–50 for R (−)-flurbiprofen was larger in plasma and smaller in CSF (p < 0.05 for both), and accordingly smaller CSF/plasma AUC0–50 ratio (p < 0.05). There was a positive correlation between R (−)-flurbiprofen concentration and S (+)-flurbiprofen concentration in plasma (r = 0.725, p < 0.001) as well as in CSF (r = 0.718, p < 0.001), and a negative correlation between plasma and CSF concentration of S (+)-flurbiprofen (r = −0.250, p = 0.037), but not R (−)-flurbiprofen.

Conclusion: Distribution of R (−)- and S (+)-flurbiprofen in plasma and CSF differed significantly. Penetration of R (−)-flurbiprofen into the CNS was lower than S (+)-flurbiprofen.
Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology
Authors: Goričar Katja , Dolžan Vita , Lenassi Metka
Published: April 2021

Biomarkers that can guide cancer therapy based on patients’ individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.
Resibufogenin Suppresses Triple-Negative Breast Cancer Angiogenesis by Blocking VEGFR2-Mediated Signaling Pathway
Authors: Yang Ting , Jiang Yi-Xin , Wu Ye , Lu Dong , Huang Rui , Wang Long-Ling , Wang Shi-Qi , Guan Ying-Yun , Zhang Hong , Luan Xin
Published: April 2021

Resibufogenin (RBF), an active compound from Bufo bufonis, has been used for the treatment of multiple malignant cancers, including pancreatic cancer, colorectal cancer, and breast cancer. However, whether RBF could exert its antitumor effect by inhibiting angiogenesis remains unknown. Here, we aimed to explore the antiangiogenic activity of RBF and its underlying mechanism on human umbilical vein endothelial cell (HUVEC), and the therapeutic efficacy with regard to antiangiogenesis in vivo using two triple-negative breast cancer (TNBC) models. Our results demonstrated that RBF can inhibit the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Spheroid sprouts were thinner and shorter after RBF treatment in vitro 3D spheroid sprouting assay. RBF also significantly suppressed VEGF-mediated vascular network formation in vivo Matrigel plug assay. In addition, Western blot analysis was used to reveal that RBF inhibited the phosphorylation of VEGFR2 and its downstream protein kinases FAK and Src in endothelial cells (ECs). Molecular docking simulations showed that RBF affected the phosphorylation of VEGFR2 by competitively binding to the ATP-bound VEGFR2 kinase domain, thus preventing ATP from providing phosphate groups. Finally, we found that RBF exhibited promising antitumor effect through antiangiogenesis in vivo without obvious toxicity. The present study first revealed the high antiangiogenic activity and the underlying molecular basis of RBF, suggesting that RBF could be a potential antiangiogenic agent for angiogenesis-related diseases.
Advanced Electromagnetic Metamaterials for Temperature Sensing Applications
Authors: Ma Liang , Chen Dexu , Zheng Wenxian , Li Jian , Zahra Sidrish , Liu Yifeng , Zhou Yuedan , Huang Yongjun , Wen Guangjun
Published: April 2021

Metamaterials with novel properties have excited much research attention in the past several decades. Many applications have been proposed and developed for the reported metamaterials in various engineering areas. Specifically, for the resonant-type metamaterials with narrow resonance line width and strong resonance strength, the resonant frequency and strength are highly depended on the changings of meta-atom structure and/or substrate media properties induced by the environment physical or chemistry parameters varying. Therefore, physical or chemistry sensing applications for the resonant-type metamaterial units or arrays are developed in recent years. In this mini review, to help the researchers in those fields to catch up with the newly research advances, we would like to summarize the recently reported high-performance metamaterial-inspired sensing applications, especially the temperature sensing applications, based on different kinds of metamaterials. Importantly, by analyzing the advantages and disadvantages of several conventional metamaterial units, the newly proposed high quality-factor metamaterial units are discussed for high-precision sensing applications, in terms of the sensitivity and resolution. This mini review can guide researchers in the area of metamaterial-inspired sensors to find some new design routes for high-precision sensing.
Electrocardiographic Imaging for Atrial Fibrillation: A Perspective From Computer Models and Animal Experiments to Clinical Value
Authors: Salinet João , Molero Rubén , Schlindwein Fernando S. , Karel Joël , Rodrigo Miguel , Rojo-Álvarez José Luis , Berenfeld Omer , Climent Andreu M. , Zenger Brian , Vanheusden Frederique , Paredes Jimena Gabriela Siles , MacLeod Rob , Atienza Felipe , Guillem María S. , Cluitmans Matthijs , Bonizzi Pietro
Published: April 2021

Electrocardiographic imaging (ECGI) is a technique to reconstruct non-invasively the electrical activity on the heart surface from body-surface potential recordings and geometric information of the torso and the heart. ECGI has shown scientific and clinical value when used to characterize and treat both atrial and ventricular arrhythmias. Regarding atrial fibrillation (AF), the characterization of the electrical propagation and the underlying substrate favoring AF is inherently more challenging than for ventricular arrhythmias, due to the progressive and heterogeneous nature of the disease and its manifestation, the small volume and wall thickness of the atria, and the relatively large role of microstructural abnormalities in AF. At the same time, ECGI has the advantage over other mapping technologies of allowing a global characterization of atrial electrical activity at every atrial beat and non-invasively. However, since ECGI is time-consuming and costly and the use of electrical mapping to guide AF ablation is still not fully established, the clinical value of ECGI for AF is still under assessment. Nonetheless, AF is known to be the manifestation of a complex interaction between electrical and structural abnormalities and therefore, true electro-anatomical-structural imaging may elucidate important key factors of AF development, progression, and treatment. Therefore, it is paramount to identify which clinical questions could be successfully addressed by ECGI when it comes to AF characterization and treatment, and which questions may be beyond its technical limitations. In this manuscript we review the questions that researchers have tried to address on the use of ECGI for AF characterization and treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI for AF understanding and management. We pay attention to existing techniques and clinical application, to computer models and (animal or human) experiments, to challenges of methodological and clinical validation. The overall objective of the study is to provide a consensus on valuable directions that ECGI research may take to provide future improvements in AF characterization and treatment guidance.
Cycad-Weevil Pollination Symbiosis Is Characterized by Rapidly Evolving and Highly Specific Plant-Insect Chemical Communication
Authors: Salzman Shayla , Crook Damon , Calonje Michael , Stevenson Dennis W. , Pierce Naomi E. , Hopkins Robin
Published: April 2021

Coevolution between plants and insects is thought to be responsible for generating biodiversity. Extensive research has focused largely on antagonistic herbivorous relationships, but mutualistic pollination systems also likely contribute to diversification. Here we describe an example of chemically-mediated mutualistic species interactions affecting trait evolution and lineage diversification. We show that volatile compounds produced by closely related species of Zamia cycads are more strikingly different from each other than are other phenotypic characters, and that two distantly related pollinating weevil species have specialized responses only to volatiles from their specific host Zamia species. Plant transcriptomes show that approximately a fifth of genes related to volatile production are evolving under positive selection, but we find no differences in the relative proportion of genes under positive selection in different categories. The importance of phenotypic divergence coupled with chemical communication for the maintenance of this obligate mutualism highlights chemical signaling as a key mechanism of coevolution between cycads and their weevil pollinators.
The Plant Nuclear Envelope and Its Role in Gene Transcription
Authors: Bishop Jade , Swan Hetty , Valente Francesco , Nützmann Hans-Wilhelm
Published: April 2021

Chromosomes are dynamic entities in the eukaryotic nucleus. During cell development and in response to biotic and abiotic change, individual sections as well as entire chromosomes re-organise and reposition within the nuclear space. A focal point for these processes is the nuclear envelope (NE) providing both barrier and anchor for chromosomal movement. In plants, positioning of chromosome regions and individual genes at the nuclear envelope has been shown to be associated with distinct transcriptional patterns. Here, we will review recent findings on the interplay between transcriptional activity and gene positioning at the nuclear periphery (NP). We will discuss potential mechanisms of transcriptional regulation at the nuclear envelope and outline future perspectives in this research area.
Doing Contrariness: Therapeutic Talk-In-Interaction in a Single Therapy Session With a Traumatized Child
Authors: Buchholz Michael B. , Buchholz Timo , Wülfing Barbara
Published: April 2021

Conversation analysis (CA) of children-adult—interaction in various contexts has become an established field of research. However,child therapyhas received limited attention in CA. In child therapy, the general psychotherapeutic practice of achieving empathy faces particular challenges. In relation to this, our contribution sets out three issues for investigation and analysis: the first one is that practices of achieving empathy must be preceded by efforts aiming to establish which kind of individualized conversation works with this child (Midgley,2006). Psychotherapy process researchers in adult therapy (Stiles et al.,2015) have found that therapists “invent” a new therapy for each patient (Norcross and Wampold,2018). The second issue is that it can be difficult for adults to understand the ways in which children express their conflicts and issues. In particular, play activities in therapy, e.g., with dolls, can open up additional scenarios of interaction. The play scenario can be used to disclose unformulated problems masked in everyday and family interactions. The third issue is how to respect the child's higher degree of vulnerability, compared with adult patients. How is it communicated and dealt with in therapy? We present an interaction analysis of a single case study of the first 20 min of a child therapy session with an adopted girl aged 4 years brought to treatment because of “unexplainable rage.” The session was videotaped; parents granted permission. We analyze this session using an applied version of CA. In our analysis, we describe “doing contrariness,” as a conversational practice producing epistemic and affiliative disruptions, while “avoiding doing contrariness” and “remedying contrariness” are strategies for preserving or restoring the affiliative dimension of a relationship (in child therapy). We show how these practices operate in various modes and how they are used by both parties in our case study to variously aid and impedethe achievement of empathy and understanding.
Appraisal of the Fairness Moral Foundation Predicts the Language Use Involving Moral Issues on Twitter Among Japanese
Authors: Matsuo Akiko , Du Baofa , Sasahara Kazutoshi
Published: April 2021

Moral appraisals are found to be associated with a person’s individual differences (e.g., political ideology), and the effects of individual differences on language use have been studied within the framework of the Moral Foundations Theory (MFT). However, the relationship between one’s moral concern and the use of language involving morality on social media is not self-evident. The present exploratory study investigated that relationship using the MFT. Participants’ tweets and self-reported responses to the questionnaire were collected to measure the degree of their appraisals according to the five foundations of the MFT. The Japanese version of the Moral Foundations Dictionary (J-MFD) was used to quantify the number of words in tweets relevant to the MFT’s five moral foundations. The results showed that endorsement of the Fairness and Authority foundations predicted the word frequency in the J-MFD across all five foundations. The findings suggest that the trade-off relationship between the Fairness and Authority foundations plays a key role in online language communication. The implications and future directions to scrutinize that foundation are discussed.
Default Inheritance in Modified Statements: Bias or Inference?
Authors: Strößner Corina
Published: April 2021

It is a fact that human subjects rate sentences about typical properties such as “Ravens are black” as very likely to be true. In comparison, modified sentences such as “Feathered ravens are black” receive lower ratings, especially if the modifier is atypical for the noun, as in “Jungle ravens are black”. This is called themodifier effect. However, the likelihood of the unmodified statement influences the perceived likelihood of the modified statement: the higher the rated likelihood of the unmodified sentence, the higher the rated likelihood of the modified one. That means the modifier effect does not fully blockdefault inheritanceof typical properties from nouns to modified nouns. This paper discusses this inheritance effect. In particular, I ask whether it is the direct result of composing concepts from nouns, that is, a bias toward “black” when processing “raven”. I report a series of experiments in which I find no evidence for a direct inheritance from composition. This supports the view that default inheritance is rather an inference than a bias.
Association of Stress-Related Factors With Anxiety Among Chinese Pregnant Participants in an Online Crisis Intervention During COVID-19 Epidemic
Authors: Shangguan Fangfang , Wang Ruoxi , Quan Xiao , Zhou Chenhao , Zhang Chen , Qian Wei , Zhou Yongjie , Liu Zhengkui , Zhang Xiang Yang
Published: April 2021

Background: Previous systematic review indicated the prevalence of prenatal anxiety as 14–54%. Pregnant women are a high-risk population for COVID-19. However, the prevalence of anxiety symptoms and related factors is unknown in Chinese pregnant women during COVID-19 outbreak.

Objective: To investigate the prevalence of anxiety symptoms and the related factors in Chinese pregnant women who were attending crisis intervention during the COVID-19 pandemic.

Methods: The data of this cross-sectional study were collected in about 2 months (February 28 to April 26, 2020). Data analysis was performed from April to May 2020. Participants completed a set of questionnaires via the Wechat Mini-program before starting the online self-help crisis intervention for COVID-19 epidemic. A total of 2,120 Chinese pregnant women who were attending a self-help crisis intervention participated in this study. A survey was developed to address possible stress-related factors in pregnant women during the COVID-19 outbreak, including demographic, socioeconomic, and pregnancy-related factors, as well as COVID-19 related factors. Generalized Anxiety Disorder-7 (GAD-7) scale and the 10-item perceived stress scale were, respectively, employed to measure anxiety and stress-related factors.

Results: A total of 21.7% (459) of pregnant women reported at least mild anxiety (≥5 on the GAD-7 scale), and only 82 women reported moderate to severe anxiety (≥10 on the GAD-7 scale). Factors associated with at least mild anxiety included living in Hubei province (OR = 1.68, 95% CI = 1.32–2.13), nobody providing everyday life support (OR = 1.81, 95% CI = 1.18–2.77), pelvic pain or vaginal bleeding (OR = 1.67, 95% CI = 1.32–2.09), and higher perceived stress (OR = 6.87, 95% CI = 5.42–9.02). Having relatives or neighbors with a diagnosis of COVID-19 was not associated with anxiety (p > 0.05).

Conclusions and Relevance: Our findings indicate that evaluation and intervention for maternal and infant health are necessary in pregnant women with anxiety during COVID-19 epidemic, especially those with higher perceived stress, less everyday life support, or vaginal bleeding. Interactions among these related medical, social and psychological factors need to be investigated in future studies.
Dancing in Your Head: An Interdisciplinary Review
Authors: Zardi Andrea , Carlotti Edoardo Giovanni , Pontremoli Alessandro , Morese Rosalba
Published: April 2021

The aim of this review is to highlight the most relevant contributions on dance in neuroscientific research. Neuroscience has analyzed the mirror system through neuroimaging techniques, testing its role in imitative learning, in the recognition of other people's emotions and especially in the understanding of the motor behavior of others. This review analyses the literature related to five general areas: (I) breakthrough studies on the mirror system, and subsequent studies on its involvement in the prediction, the execution, the control of movement, and in the process of “embodied simulation” within the intersubjective relationship; (II) research focused on investigating the neural networks in action observation, and the neural correlates ofmotor expertisehighlighted by comparative studies on different dance styles; (III) studies dealing with the viewer's experience of dance according to specific dance repertoires, which revealed the relevance of choreographic choices for aesthetic appreciation; (IV) studies focused on dance as an aesthetic experience, where both the emotional and the cultural dimension play a significant role, and whose investigation paves the way to further progress both in empirical and in phenomenological research methodologies; (V) collaboration-based experiments, in which neuroscientists and choreographers developed expertise-related questions, especially focusing on the multiple phenomena that underlie motor imagery.
How to Keep Sustainable Development Between Enterprises and Employees? Evaluating the Impact of Person–Organization Fit and Person–Job Fit on Innovative Behavior
Authors: Tang Yuan , Shao Yun-Fei , Chen Yi-Jun , Ma Yin
Published: April 2021

High-tech industries often regard workers as their main source of value creation. In order to stimulate their employees' willingness to innovate and their innovative behavior and reduce the turnover intention, companies are now seeking to establish employer–employee relationships in which their employee's willingness to stay is not simply driven by extrinsic motivations. Therefore, it is an important topic in human resources for companies to implement measures that encourage employees to willingly devote themselves to their jobs and consider organizational growth as a component of their career development. This study aimed to investigate the effect of person–organization fit and person–job fit on employees' innovative behavior and turnover intention via the mediators including job satisfaction and organizational commitment. Six hundred ninety-seven employees from China's eight major high-tech industries were examined in this study, and the empirical results were analyzed using partial least squares. Based on the results, it is suggested that the person–organization fit and person–job fit are both crucial factors affecting employees' job satisfaction and organizational commitment, which, in turn, increase employees' willingness to innovate in their jobs and reduce their turnover intentions. Furthermore, this study could serve as a reference for companies in selecting employees, promoting job satisfaction, and developing strategies for sustainable development.
The Relative Reinforcing Value of Cookies Is Higher Among Head Start Preschoolers With Obesity
Authors: Eagleton Sally G. , Temple Jennifer L. , Keller Kathleen L. , Marini Michele E. , Savage Jennifer S.
Published: April 2021

The relative reinforcing value (RRV) of food measures how hard someone will work for a high-energy-dense (HED) food when an alternative reward is concurrently available. Higher RRV for HED food has been linked to obesity, yet this association has not been examined in low-income preschool-age children. Further, the development of individual differences in the RRV of food in early childhood is poorly understood. This cross-sectional study tested the hypothesis that the RRV of HED (cookies) to low-energy-dense (LED; fruit) food would be greater in children with obesity compared to children without obesity in a sample of 130 low-income 3- to 5-year-olds enrolled in Head Start classrooms in Central Pennsylvania. In addition, we examined individual differences in the RRV of food by child characteristics (i.e., age, sex, and reward sensitivity) and food security status. The RRV of food was measured on concurrent progressive-ratio schedules of reinforcement. RRV outcomes included the last schedule reached (breakpoint) for cookies (cookie Pmax) and fruit (fruit Pmax), the breakpoint for cookies in proportion to the total breakpoint for cookies and fruit combined (RRV cookie), and response rates (responses per minute). Parents completed the 18-item food security module to assess household food security status and the Behavioral Activation System scale to assess reward sensitivity. Pearson’s correlations and mixed models assessed associations between continuous and discrete child characteristics with RRV outcomes, respectively. Two-way mixed effects interaction models examined age and sex as moderators of the association between RRV and Body Mass Index z-scores (BMIZ). Statistical significance was defined as p < 0.05. Children with obesity (17%) had a greater cookie Pmax [F (1, 121) = 4.95, p = 0.03], higher RRV cookie [F (1, 121) = 4.28, p = 0.04], and responded at a faster rate for cookies [F (1, 121) = 17.27, p < 0.001] compared to children without obesity. Children with higher cookie response rates had higher BMIZ (r = 0.26, p < 0.01); and RRV cookie was positively associated with BMIZ for older children (5-year-olds: t = 2.40, p = 0.02) and boys (t = 2.55, p = 0.01), but not younger children or girls. The RRV of food did not differ by household food security status. Low-income children with obesity showed greater motivation to work for cookies than fruit compared to their peers without obesity. The RRV of HED food may be an important contributor to increased weight status in boys and future research is needed to better understand developmental trajectories of the RRV of food across childhood.