bluuebunny/crossref_metadata_2025 huggingface dataset:
The Time Course of Event-Related Brain Potentials in Athletes’ Mental Rotation With Different Spatial Transformations
Authors: Feng Tian , Li Yawei
Published: June 2021

Studies have found that athletes outperformed non-athletes in mental rotation tasks with both object-based and egocentric transformations (ET), but the effect of sport expertise on the processing stages (i.e., perceptual stage, rotation stage, and decision stage) remains conflicted. Bearing the view that the stages occur sequentially and the high temporal resolution of event-related brain potentials, this study focused on brain processing during mental rotation and was designed to determine the time course of electrophysiological changes in athletes and non-athletes. A total of 42 divers and non-athletes were recruited for the study. A mental body rotation task with object-based and egocentric transformation conditions was conducted, and the reaction time (RT), accuracy, performance stages, N2 latency, amplitude, and the amplitude of rotation-related negativity (RRN) were recorded. Behavioral results demonstrated higher accuracy for athletes at 120° and 180°. Moreover, as compared to non-athletes, the enlarged amplitude of N2 and RRN were confirmed in both transformations for athletes and were correlated with the performance stages and athletes’ professional training years. The present study provided a deeper insight into the relationship between sports training, behavior performance, and brain activity.
Dynamics Analysis of Firing Patterns in Pre-Bötzinger Complex Neurons Model
Authors: Yuan Quan , Xu Jieqiong , Chen Huiying
Published: June 2021

Pre-Bötzinger complex (PBC) neurons located in mammalian brain are the necessary conditions to produce respiratory rhythm, which has been widely verified experimentally and numerically. At present, one of the two different types of bursting mechanisms found in PBC mainly depends on the calcium-activated of non-specific cation current (ICaN). In order to study the influence of ICaN and stimulus current Iexc in PBC inspiratory neurons, a single compartment model was simplified, and firing patterns of the model was discussed by using stability theory, bifurcation analysis, fast, and slow decomposition technology combined with numerical simulation. Under the stimulation of different somatic applied currents, the firing behavior of neurons are studied and exhibit multiple mix bursting patterns, which is helpful to further understand the mechanism of respiratory rhythms of PBC neurons.
A Network Architecture for Bidirectional Neurovascular Coupling in Rat Whisker Barrel Cortex
Authors: Kumar Bhadra S. , Khot Aditi , Chakravarthy V. Srinivasa , Pushpavanam S.
Published: June 2021

Neurovascular coupling is typically considered as a master-slave relationship between the neurons and the cerebral vessels: the neurons demand energy which the vessels supply in the form of glucose and oxygen. In the recent past, both theoretical and experimental studies have suggested that the neurovascular coupling is a bidirectional system, a loop that includes a feedback signal from the vessels influencing neural firing and plasticity. An integrated model of bidirectionally connected neural network and the vascular network is hence required to understand the relationship between the informational and metabolic aspects of neural dynamics. In this study, we present a computational model of the bidirectional neurovascular system in the whisker barrel cortex and study the effect of such coupling on neural activity and plasticity as manifest in the whisker barrel map formation. In this model, a biologically plausible self-organizing network model of rate coded, dynamic neurons is nourished by a network of vessels modeled using the biophysical properties of blood vessels. The neural layer which is designed to simulate the whisker barrel cortex of rat transmits vasodilatory signals to the vessels. The feedback from the vessels is in the form of available oxygen for oxidative metabolism whose end result is the adenosine triphosphate (ATP) necessary to fuel neural firing. The model captures the effect of the feedback from the vascular network on the neuronal map formation in the whisker barrel model under normal and pathological (Hypoxia and Hypoxia-Ischemia) conditions.
Gene Dosage- and Age-Dependent Differential Transcriptomic Changes in the Prefrontal Cortex of Shank2-Mutant Mice
Authors: Lee Seungjoon , Kang Hyojin , Jung Hwajin , Kim Eunjoon , Lee Eunee
Published: June 2021

Shank2 is an abundant postsynaptic scaffolding protein that is known to regulate excitatory synapse assembly and synaptic transmission and has been implicated in various neurodevelopmental disorders, including autism spectrum disorders (ASD). Previous studies on Shank2-mutant mice provided mechanistic insights into their autistic-like phenotypes, but it remains unclear how transcriptomic patterns are changed in brain regions of the mutant mice in age- and gene dosage-dependent manners. To this end, we performed RNA-Seq analyses of the transcripts from the prefrontal cortex (PFC) of heterozygous and homozygous Shank2-mutant mice lacking exons 6 and 7 at juvenile (week 3) and adult (week 12) stages. Juvenile heterozygous Shank2-mutant mice showed upregulation of glutamate synapse-related genes, downregulation of ribosomal and mitochondrial genes, and transcriptomic changes that are opposite to those observed in ASD (anti-ASD) such as upregulation of ASD_down (downregulated in ASD), GABA neuron-related, and oligodendrocyte-related genes. Juvenile homozygous Shank2 mice showed upregulation of chromatin-related genes and transcriptomic changes that are in line with those occurring in ASD (pro-ASD) such as downregulation of ASD_down, GABA neuron-related, and oligodendrocyte-related genes. Adult heterozygous and homozygous Shank2-mutant mice both exhibited downregulation of ribosomal and mitochondrial genes and pro-ASD transcriptomic changes. Therefore, the gene dosage- and age-dependent effects of Shank2 deletions in mice include differential transcriptomic changes across distinct functional contexts, including synapses, chromatin, ribosomes, mitochondria, GABA neurons, and oligodendrocytes.
Long Distance From Microvessel to Cancer Cell Predicts Poor Prognosis in Non-Small Cell Lung Cancer Patients
Authors: Ding Haiying , Sun Jiao , Song Yu , Xin Wenxiu , Zhu Junfeng , Zhong Like , Chen Yinbo , Zhang Yiwen , Tong Yinghui , Fang Luo
Published: June 2021

Background

Blood supply, which is crucial for nutrition and drug delivery, was determined by microvessel density as well as the diffusion distance between vessels and cancer cells. Therefore, we evaluated the distance from microvessels to cancer cells (Dmvcc) and its role in the prognosis of non-small cell lung cancer (NSCLC) patients.

Methods

Patients with primary NSCLC were retrospectively analyzed. The tumor samples were immunochemically stained with CD31 to visualize the microvessels. The Dmvcc was defined as the mean distance from each microvessel to its nearest cancer cell in the “hot-spot” of an individual patient. The patients were stratified into short- and long-distance groups using five strategies, including dichotomy by the median value, optimal cutoff, trichotomy, quartation and per-10 µm increase. The correlation between the Dmvcc and survival was evaluated by using univariate and multivariate analyses with various Dmvcc strategies.

Results

In total, 100 patients were analyzed. The median value of Dmvcc was 13.1 μm (ranged, 1.6 to 269.7 μm; mean value, 24.4 ± 33.5 μm). The optimal cutoff value of Dmvcc for predicting survival outcome was 20 μm. Dmvcc was significantly related to overall survival (OS) with all the five categories (p = 0.001–0.000004) and progression-free survival (PFS) categorized by optimal cutoff value (p = 0.024), trichotomy (p = 0.041) and per-10 µm increase (p = 0.040) after adjusting for other factors. Patients with longer Dmvcc (≥20 μm) were observed to have poor survival outcomes (OS: HR = 13.5, 95CI: 4.42–41.18, p = 0.000005; PFS: 3.26, 95CI: 1.56–6.81, p = 0.002). A high Dmvcc per-10 µm was associated with a significantly increased risk of cancer-related death and progression by 98% (p = 0.0001) and 30% (p = 0.044), respectively.

Conclusion

The NSCLC tissues had varying distances from microvessels to cancer cells, and long distances were strongly associated with poor survival.
Deep Learning on Enhanced CT Images Can Predict the Muscular Invasiveness of Bladder Cancer
Authors: Zhang Gumuyang , Wu Zhe , Xu Lili , Zhang Xiaoxiao , Zhang Daming , Mao Li , Li Xiuli , Xiao Yu , Guo Jun , Ji Zhigang , Sun Hao , Jin Zhengyu
Published: June 2021

Background

Clinical treatment decision making of bladder cancer (BCa) relies on the absence or presence of muscle invasion and tumor staging. Deep learning (DL) is a novel technique in image analysis, but its potential for evaluating the muscular invasiveness of bladder cancer remains unclear. The purpose of this study was to develop and validate a DL model based on computed tomography (CT) images for prediction of muscle-invasive status of BCa.

Methods

A total of 441 BCa patients were retrospectively enrolled from two centers and were divided into development (n=183), tuning (n=110), internal validation (n=73) and external validation (n=75) cohorts. The model was built based on nephrographic phase images of preoperative CT urography. Receiver operating characteristic (ROC) curves were performed and the area under the ROC curve (AUC) for discrimination between muscle-invasive BCa and non-muscle-invasive BCa was calculated. The performance of the model was evaluated and compared with that of the subjective assessment by two radiologists.

Results

The DL model exhibited relatively good performance in all cohorts [AUC: 0.861 in the internal validation cohort, 0.791 in the external validation cohort] and outperformed the two radiologists. The model yielded a sensitivity of 0.733, a specificity of 0.810 in the internal validation cohort and a sensitivity of 0.710 and a specificity of 0.773 in the external validation cohort.

Conclusion

The proposed DL model based on CT images exhibited relatively good prediction ability of muscle-invasive status of BCa preoperatively, which may improve individual treatment of BCa.
Treatment of Advanced-Stage Large Cell Neuroendocrine Cancer (LCNEC) of the Lung: A Tale of Two Diseases
Authors: Atieh Tahani , Huang Chao H.
Published: June 2021

LCNEC of the lung comprises a small proportion of pulmonary malignancies. Traditionally, they have been classified based on histologic and immunohistochemistry characteristics with features of small cell and non-small cell lung cancer. The treatment outcome of advanced-stage LCNEC of the lung is poor with response rates ranging from 34 to 46% with platinum doublets, median progression-free survival (mPFS) ranging between 4.4 and 5.8 m, and median overall survival (mOS) ranging from 8 to 12.6 m. The optimal treatment strategy for LCNEC is debated given limited data and different outcomes based on chemotherapy type reported in the available literature. Recently, genomic profiling with Next Generation Sequencing (NGS) has been able to sub-classify LCNEC as SCLC-like or NSCLC-like. Treatment based on this sub-classification has improved outcomes by using SCLC and NSCLC regimens based on their genomic profile in retrospective analysis. Future studies in LCNEC of the lung should incorporate this new molecular sub-classification as stratification and possibly include SCLC-like LCNEC into SCLC studies and NSCLC-like into NSCLC studies.
G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Mantle Cell Lymphoma Growth in Preclinical Models
Authors: Zhou Lixia , Yu Tenghua , Yang Fei , Han Jingjing , Zuo Bin , Huang Lulu , Bai Xia , Jiang Miao , Wu Depei , Chen Suning , Xia Lijun , Ruan Jia , Ruan Changgeng
Published: June 2021

Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin’s B-cell lymphoma with poor prognosis. Despite recent advances, resistance to therapy and relapse remain significant clinical problems. G-protein-coupled estrogen receptor (GPER)-mediated estrogenic rapid signaling is implicated in the development of many cancers. However, its role in MCL is unknown. Here we report that GPER activation with selective agonist G-1 induced cell cycle arrest, DNA damage, mitochondria membrane potential abnormality, and eventually apoptosis of MCL cell lines. We found that G-1 induced DNA damage and apoptosis of MCL cells by promoting the expression of nicotinamide adenine dinucleotide phosphate oxidase and the generation of reactive oxygen species. In addition, G-1 inhibited MCL cell proliferation by inactivation of NF-κB signaling and exhibited anti-tumor functions in MCL xenografted mice. Most significantly, G-1 showed synergistic effect with ibrutinib making it a potential candidate for chemotherapy-free therapies against MCL.
Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression
Authors: Quagliariello Vincenzo , Berretta Massimiliano , Buccolo Simona , Iovine Martina , Paccone Andrea , Cavalcanti Ernesta , Taibi Rosaria , Montopoli Monica , Botti Gerardo , Maurea Nicola
Published: June 2021

Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4’,5-trihydroxystilbene-3-β-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib. We investigated on the effects of polydatin on the oxidative stress, NLRP3 inflammasome and Myd88 expression, highlighting on the production of cytokines and chemokines (IL-1β, IL-6, IL-8, CXCL-12 and TGF-β) during treatment with sunitinib. Exposure of cardiomyocytes and cardiomyoblasts (AC-16 and H9C2 cell lines) and human renal adenocarcinoma cells (769‐P and A498) to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly iROS, MDA and LTB4 compared to only sunitinib-treated cells (P<0.001). In renal cancer cells and cardiomyocytes polydatin reduces expression of pro-inflammatory cytokines and chemokines involved in myocardial damages and chemoresistance and down-regulates the signaling pathway of NLRP3 inflammasome, MyD88 and NF-κB. Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, reduces key chemokines involved in cancer cell survival, chemoresistance and cardiac damages of sunitinib through downregulation of NLRP3-MyD88 pathway, applying as a potential nutraceutical agent in preclinical studies of preventive cardio-oncology.
Regulatory Network Analysis of Mutated Genes Based on Multi-Omics Data Reveals the Exclusive Features in Tumor Immune Microenvironment Between Left-Sided and Right-Sided Colon Cancer
Authors: Yi Tianfei , Zhang Yuwei , Ng Derry Minyao , Xi Yang , Ye Meng , Cen Lvjun , Li Jianjiong , Fan Xiaoxiang , Li Yanguo , Hu Shiyun , Rong Hao , Xie Yangyang , Zhao Guofang , Chen Leyi , Chen Chen , Ni Shujing , Mi Jiaying , Dai Xiaoyu , Liao Qi
Published: June 2021

Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Besides, a stronger association between gene mutations and TIME was observed in RCC. Specifically, using multi-omics data, we demonstrated the mutations of most top mutated genes (TMGs) including BRAF, PCLO, MUC16, LRP2, ANK3, KMT2D, RYR2 made great contributions to elevated fraction of immune cells by up-regulating immune-related genes directly or indirectly through miRNA and DNA methylation, whereas the effects of APC, TP53 and KRAS mutations on TIME were reversed in RCC. Remarkably, we found the expression levels of several immune checkpoint molecules such as PD-1 and LAG3 were correlated with corresponding DNA methylation levels, which were associated with the mutations of TMGs in RCC. In contrast, the associations between gene mutations and TIME were less significant in LCC. Besides, survival analyses showed APC mutation had adverse impact on immunotherapy while patients with BRAF mutation were more suitable for immunotherapy in colon cancer. We hope that our results will provide a deeper insight into the sophisticated mechanism underlying the regulation between mutations and TIME, and thus boost the discovery of differential immunotherapeutic strategies for RCC and LCC.
Ex Vivo Liver Resection and Autotransplantation as Surgical Option for Zone II–III Leiomyosarcoma of IVC: A Case Report and Literature Review
Authors: Tuxun Tuerhongjiang , Li Tao , Apaer Shadike , He Yi-Biao , Bai Lei , Gu Shen-Sen , Wang Zhi-Peng , Huo Qiang , Wang Jiang , Zhao Jin-Ming
Published: June 2021

We report the first documented case of leiomyosarcoma at zone II-III of inferior vena cava with thrombi in three hepatic veins undergoing ex vivo liver resection and autotransplantation (ELRA) and hepatic veins thrombectomy. A 33-year-old female patient presented with abdominal distention and lower extremities edema. Abdominal wall varicosis and shifting dullness were positive on physical examination. Her liver function was classified as Child-Pugh B and a solid tumor at retro-hepatic vena cava extending to right atrium with thrombi in three hepatic veins were confirmed. The diagnosis of leiomyosarcoma with Budd-Chiari syndrome was highly suspected with preoperative ultrasound, echocardiogram, CT scan, and three-dimensional reconstruction. A zone II-III leiomyosarcoma of IVC origin was confirmed at surgery and ex vivo liver resection and autotransplantation, and hepatic vein thrombectomy with atrial reconstruction were performed under cardiopulmonary bypass (CPB). Operative time, anhepatic time, and CPB time were 12 h, 128 min, and 84 min, respectively. The patients experienced post-operative liver dysfunction and was cured with conservative therapy. Hepatic recurrence two years after surgery was managed with radiofrequency. The patient was alive with liver metastasis three years after surgery. Despite being regarded as an extremely aggressive procedure, ELRA could be considered in the treatment of advanced leiomyosarcoma with Budd-Chiari syndrome and hepatic vein thrombi.
Acute Kidney Injury in Pediatric Diabetic Kidney Disease
Authors: Piani Federica , Reinicke Trenton , Borghi Claudio , Tommerdahl Kalie L. , Cara-Fuentes Gabriel , Johnson Richard J. , Bjornstad Petter
Published: June 2021

Diabetic kidney disease (DKD) is a common complication of type 1 and 2 diabetes and often presents during adolescence and young adulthood. Given the growing incidence of both type 1 and type 2 diabetes in children and adolescents, DKD represents a significant public health problem. Acute kidney injury (AKI) in youth with diabetes is strongly associated with risk of DKD development. This review will summarize the epidemiology and pathophysiology of AKI in children with diabetes, the relationship between AKI and DKD, and the potential therapeutic interventions. Finally, we will appraise the impact of the recent COVID-19 infection pandemic on AKI in children with diabetes.
Clinical Outcomes of Tanezumab With Different Dosages for Patient With Osteoarthritis: Network Meta-Analysis
Authors: Hu Rui , Song Ya-Feng , Yang Zhi-Yan , Zhang Chao , Tan Bo
Published: June 2021

Background: Osteoarthritis (OA) high disability rate will increase as people getting older, and is the most prevalent form of arthritis in the future. This study identified the clinical effects of optimum doses of tanezumab for patients with OA.

Method: Three electronic databases were searched up until January 15, 2021. The mean difference (MD) or odds ratio (OR) was considered an effect measure. The design-by-treatment interaction model was adopted for network meta-analyses. Analyses were conducted using WinBUGS 1.4.3 and R 4.0.5 software.

Results: nine publications with 10 studies were included. Compared with placebo in network meta-analysis, except the outcomes of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. However, there was no statistical difference among all different doses of tanezumab. Compared with placebo, except the outcomes of adverse events (AEs) and AEs of abnormal peripheral sensation, all different dosages of tanezumab weren’t superior to placebo in the other effectiveness outcome, and the difference was statistically significant. The 10 mg of tanezumab with highest SUCRA had the best effect, but it was associated with a higher safety event. Compared with placebo, except the outcomes of WOMAC stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Compared with placebo, except for the outcomes of AEs and AEs of abnormal peripheral sensation, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Other direct comparisons showed no statistical difference.

Conclusion: This study recommended that clinicians should give priority to the treatment of OA patients with a low dose of 2.5 mg according to the patient’s condition and actual situation. If the effect using tanezumab with 2.5 mg is not satisfactory, the increase up to 10 mg should be carefully pondered, because of a more unbalanced risk/benefit ratio.
1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship
Authors: Liang Ting , Sun Xiangyang , Li Wenhong , Hou Guihua , Gao Feng
Published: June 2021

Lung cancer is the most common malignancy and leads to around one-quarter of all cancer deaths. Great advances have been achieved in the treatment of lung cancer with novel anticancer agents and improved technology. However, morbidity and mortality rates remain extremely high, calling for an urgent need to develop novel anti–lung cancer agents. 1,2,3-Triazole could be readily interact with diverse enzymes and receptors in organisms through weak interaction. 1,2,3-Triazole can not only be acted as a linker to tether different pharmacophores but also serve as a pharmacophore. This review aims to summarize the recent advances in 1,2,3-triazole–containing compounds with anti–lung cancer potential, and their structure–activity relationship (SAR) together with mechanisms of action is also discussed to pave the way for the further rational development of novel anti–lung cancer candidates.
AGR3 Regulates Airway Epithelial Junctions in Patients with Frequent Exacerbations of COPD
Authors: Ye Rui , Wang Cuihong , Sun Pengbo , Bai Shuang , Zhao Li
Published: June 2021

Background: The mechanisms underlying differences in the susceptibility to chronic obstructive pulmonary disease (COPD) exacerbations between patients are not well understood. Recent studies have shown that the patients with frequent COPD exacerbations is related to specific protein expression in lung tissue. Anterior gradient 3 (AGR3) is expressed in airway epithelial cells in the lung and proteomic analysis revealed that its expression is decreased in patients with frequent COPD exacerbations. Moreover, the loss of epithelial integrity might facilitate trans-epithelial permeability of pathogens in such patients. This study was performed to determine that AGR3 protein play a role in COPD frequency exacerbators.

Methods: Human lung tissues were collected from current-smoking patients (Control; n = 15) as well as patients with infrequent COPD exacerbations (IFCOPD; n = 18) and frequent COPD exacerbations (FCOPD; n = 8). While AGR3 protein expression was measured by immunohistochemistry and western blotting, AGR mRNA expression was determined by real time quantitative polymerase chain reaction (RT-qPCR). Furthermore, adherent junctions (AJs) and tight junctions (TJs) protein expression in human lung tissues were measured by immunohistochemistry. The effects of cigarette smoke extract (CSE) on AJ and TJ protein and mRNA expression in BEAS-2B cells were assessed by western blotting and RT-qPCR. In addition, the effect of AGR3 overexpression and knockdown on AJ and TJ protein expression was determined.

Results: AGR3 was mainly expressed in the airway epithelium and AGR3-positive products were localized in the cytoplasm. Western blotting and RT-qPCR results showed that AGR3 protein (p = 0.009) and mRNA (p = 0.04) expression in the FCOPD group was significantly lower than that in the IFCOPD group. Moreover, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression was lower in the FCOPD group than in the IFCOPD group. The protein and mRNA expression of E-cadherin, occludin, and ZO-1 was decreased within 24 h post-CSE exposure. AGR3 overexpression rescued CSE-induced downregulation of E-cadherin, occludin, and ZO-1.

Conclusion: Difference in AGR3 expression in the lung tissue might be correlated with increased susceptibility to COPD exacerbation. AGR3 can prevent CSE-induced downregulation of E-cadherin, occludin, and ZO-1 in airway epithelial cells. Loss of AGR3 might promote viral and bacterial infection and induce immune inflammation to increase COPD exacerbation.
A Dual-Route Perspective of SARS-CoV-2 Infection: Lung- vs. Gut-specific Effects of ACE-2 Deficiency
Authors: Sajdel-Sulkowska Elizabeth M.
Published: June 2021

SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.
The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers
Authors: Coskun Hande , Elbahi Fatima Azzahra , Al-Karagholi Mohammad Al-Mahdi , Ghanizada Hashmat , Sheykhzade Majid , Ashina Messoud
Published: June 2021

Background

Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (KATP) channels. Here, we investigated the effect of the KATP channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.

Methods

In a randomized, double-blind, placebo-controlled, cross-over study, 20 healthy volunteers aged 18–27 years were randomly allocated to receive an intravenous infusion of 1.5 μg/min CGRP after oral pretreatment with glibenclamide (glibenclamide-CGRP day) or placebo (placebo-CGRP day). The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0–14 h) between glibenclamide and placebo. The secondary endpoints were the difference in AUC for middle cerebral artery blood flow velocity (VMCA), superficial temporal artery (STA) and radial artery (RA) diameter, facial flushing, heart rate (HR) and mean arterial blood pressure (MAP) (0–4 h) between glibenclamide and placebo.

Results

We found no significant difference in the incidence of headache between glibenclamide-CGRP day (14/20, 70%) and placebo-CGRP day (19/20, 95%) (P = 0.06). The AUC for headache intensity, VMCA, STA, RA, facial skin blood flow, HR, and MAP did not differ between glibenclamide-CGRP day compared to placebo-CGRP day (P > 0.05).

Conclusion

Pretreatment with a non-selective KATP channel inhibitor glibenclamide did not attenuate CGRP-induced headache and hemodynamic changes in healthy volunteers. We suggest that CGRP-induced responses could be mediated via activation of specific isoforms of sulfonylurea receptor subunits of KATP channel.
Role of Protein Kinase A-Mediated Phosphorylation in CFTR Channel Activity Regulation
Authors: Della Sala Angela , Prono Giulia , Hirsch Emilio , Ghigo Alessandra
Published: June 2021

Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed on the apical membrane of epithelial cells, where it plays a pivotal role in chloride transport and overall tissue homeostasis. CFTR constitutes a unique member of the ATP-binding cassette transporter superfamily, due to its distinctive cytosolic regulatory (R) domain carrying multiple phosphorylation sites that allow the tight regulation of channel activity and gating. Mutations in the CFTR gene cause cystic fibrosis, the most common lethal autosomal genetic disease in the Caucasian population. In recent years, major efforts have led to the development of CFTR modulators, small molecules targeting the underlying genetic defect of CF and ultimately rescuing the function of the mutant channel. Recent evidence has highlighted that this class of drugs could also impact on the phosphorylation of the R domain of the channel by protein kinase A (PKA), a key regulatory mechanism that is altered in various CFTR mutants. Therefore, the aim of this review is to summarize the current knowledge on the regulation of the CFTR by PKA-mediated phosphorylation and to provide insights into the different factors that modulate this essential CFTR modification. Finally, the discussion will focus on the impact of CF mutations on PKA-mediated CFTR regulation, as well as on how small molecule CFTR regulators and PKA interact to rescue dysfunctional channels.
The Resistance of Oilseed Rape Microspore-Derived Embryos to Osmotic Stress Is Associated With the Accumulation of Energy Metabolism Proteins, Redox Homeostasis, Higher Abscisic Acid, and Cytokinin Contents
Authors: Urban Milan O. , Planchon Sébastien , Hoštičková Irena , Vanková Radomira , Dobrev Peter , Renaut Jenny , Klíma Miroslav , Vítámvás Pavel
Published: June 2021

The present study aims to investigate the response of rapeseed microspore-derived embryos (MDE) to osmotic stress at the proteome level. The PEG-induced osmotic stress was studied in the cotyledonary stage of MDE of two genotypes: Cadeli (D) and Viking (V), previously reported to exhibit contrasting leaf proteome responses under drought. Two-dimensional difference gel electrophoresis (2D-DIGE) revealed 156 representative protein spots that have been selected for MALDI-TOF/TOF analysis. Sixty-three proteins have been successfully identified and divided into eight functional groups. Data are available via ProteomeXchange with identifier PXD024552. Eight selected protein accumulation trends were compared with real-time quantitative PCR (RT-qPCR). Biomass accumulation in treated D was significantly higher (3-fold) than in V, which indicates D is resistant to osmotic stress. Cultivar D displayed resistance strategy by the accumulation of proteins in energy metabolism, redox homeostasis, protein destination, and signaling functional groups, high ABA, and active cytokinins (CKs) contents. In contrast, the V protein profile displayed high requirements of energy and nutrients with a significant number of stress-related proteins and cell structure changes accompanied by quick downregulation of active CKs, as well as salicylic and jasmonic acids. Genes that were suitable for gene-targeting showed significantly higher expression in treated samples and were identified as phospholipase D alpha, peroxiredoxin antioxidant, and lactoylglutathione lyase. The MDE proteome profile has been compared with the leaf proteome evaluated in our previous study. Different mechanisms to cope with osmotic stress were revealed between the genotypes studied. This proteomic study is the first step to validate MDE as a suitable model for follow-up research on the characterization of new crossings and can be used for preselection of resistant genotypes.
The Impact of Demographics, Life and Work Circumstances on College and University Instructors’ Well-Being During Quaranteaching
Authors: Jelińska Magdalena , Paradowski Michał B.
Published: June 2021

In response to the outbreak of the COVID-19 pandemic, educational institutions around the world were forced into lockdown in order to contain the spread of the virus. To ensure continuous provision of education, most transitioned to emergency remote instruction. This has been particularly the case in higher education (HE) institutions. The circumstances of the pandemic have brought unprecedented psychological pressure on the population, in the case of educators and students exacerbated by the transition to a mode of instruction that was completely novel to the majority. The present study examines how college and university instructors dealt with teaching online in these unparalleled circumstances, with a focus on how factors connected with their daily lives and livelihoods influenced their well-being. Between April and September 2020, a comprehensive online survey was filled out by 804 HE instructors from 92 countries. We explore how sociodemographic variables such as gender, age, relationship status, living conditions, and length of professional experience non-trivially affect situational anxiety, work-life synergy, coping, and productivity. The results contribute to a better understanding of the impact of the pandemic and emergency remote instruction on college and university instructors’ well-being by explaining the mechanisms mediating the relationship between individual, contextual, and affective variables. It may provide helpful guidelines for college and university administrators as well as teachers themselves as to how help alleviate the adverse effects of the continuing pandemic and possible similar disruptions leading to school closures on coping and well-being.
Extrinsic and Existential Mortality Risk in Reproductive Decision-Making: Examining the Effects of COVID-19 Experience and Climate Change Beliefs
Authors: Gordon David S.
Published: June 2021

While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater—although less immediate—threat to our species’ survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual’s life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.
The Structure of Children’s Subjective Well-being
Authors: Savahl Shazly , Casas Ferran , Adams Sabirah
Published: June 2021

Research on children’s quality of life and subjective well-being has advanced over the past decade largely as a result of developments in childhood theory, children’s rights legislation, and the shift toward positive social science. However, in line with the uncertainty regarding the conceptualization of subjective well-being, the structural configuration of children’s subjective well-being has not been considered in the literature. In the current study, we present and test a model of children’s subjective well-being, which includes global (context-free items assessing overall and general well-being, without reference to a specific aspect of life) and specific (domain-based items assessing a specific aspect of life) cognitive components, and positive and negative affect. We further test the fit structure of a hierarchical structural (second-order) model of children’s subjective well-being. Finally, we test the measurement invariance of the hierarchical model across age and gender. We use data from the third Wave of the Children’s Worlds Survey. The data source includes a sample of 92,782 participants selected from 35 countries (girls = 49.7%) in two age groups (10- and 12-years-old). We found a good fit for the four-factor confirmatory factor model of children’s subjective well-being. Correlations between the various latent factors were as anticipated—with positive correlations between the life satisfaction components and positive affect, and negative correlations with negative affect. We further found a good fit for the hierarchical structural model of children’s subjective well-being. Finally, we found the tenability of measurement invariance across age and gender. The study extends the generalizability of the hierarchical structural configuration of the subjective well-being to child samples, and provides a viable model to explore correlates and predictors of children’s subjective well-being using the full conceptual model. Finally, we propound the tenability of a quadripartite hierarchical conceptual model of children’s subjective well-being.
Psychological Reactance to Mobility Restrictions Due to the COVID-19 Pandemic: A Japanese Population Study
Authors: Sakai Hiroyuki , Shimizu Mariko , Yoshimura Takayoshi , Hato Eiji
Published: June 2021

In Japan, mobility restrictions were enforced by the government to abate the spread of COVID-19. The current study examined whether experiences of such mobility restrictions affected motivation for future going-out activities. To this end, we conducted a one-time online survey of 1,000 adults in Tokyo to measure going-out activities in four different time periods at once: before the spread of infection, during and after the emergency declaration, and after the end of the pandemic (future desire). In addition, to examine the impact of preferences for online services that make it easier to stay home, we measured the usage history of online services to obtain food during the mobility restriction period. Results indicated that desire for going-out activities after the end of the pandemic increased compared with those before the pandemic, particularly for leisure-related purposes. In addition, the use of online services to obtain food tended to suppress the increased desire for future going-out activities, although this effect was not significant. In conclusion, mobility restrictions resulted in motivational arousal for going-out activities after the end of the pandemic. Our findings indicate that psychological reactance plays a role in determining going-out activities in the future.
A Novel Network Approach to Capture Cognition and Affect: COVID-19 Experiences in Canada and Germany
Authors: Mansell Jordan , Reuter Lisa , Rhea Carter , Kiesel Andrea
Published: June 2021

We tested a novel method for studying human experience (thoughts and affect). We utilized Cognitive-Affective Maps (CAMs)–an approach to visually represent thoughts and their affective connotations as networks of concepts that individuals associate with a given event. Using an innovative software tool, we recruited a comparative sample of (n = 93) Canadians and (n = 100) Germans to draw a CAM of their experience (events, thoughts, feelings) with the Covid-19 pandemic. We treated these CAM networks as a series of directed graphs and examined the extent to which their structural properties (latent and emotional) are predictive for the perceived coronavirus threat (PCT). Across multiple models, we found consistent and significant relationships between these network variables and the PCT in both the Canadian and German sample. Our results provide unique insights into individuals' thinking and perceptions of the viral outbreak. Our results also demonstrate that a network analysis of CAMs' properties is a promising method to study the relationship between human thought and affective connotation. We suggest that CAMs can bridge several gaps between qualitative and quantitative methods. Unlike when using quantitative tools (e.g., questionnaires), participants' answers are not restricted by response items as participants are free to incorporate any thoughts and feelings on the given topic. Furthermore, as compared to traditional qualitative measures, such as structured interviews, the CAM technique may better enable researchers to objectively assess and integrate the substance of a shared experience for large samples of participants.
Elites Do Not Deplete – No Effect of Prior Mental Exertion on Subsequent Shooting Performance in Elite Shooters
Authors: Englert Chris , Dziuba Anna , Giboin Louis-Solal , Wolff Wanja
Published: June 2021

In order to perform at the highest level, elite shooters have to remain focused during the whole course of a tournament, which regularly lasts multiple hours. Investing self-control over extended time periods is often associated with lower levels of perceived self-control strength (i.e., the subjective estimation of how much mental effort one is capable of investing in a given task) and impaired performance in several sports-related domains. However, previous findings on the effects of prior self-control efforts on shooting performance have been mixed, as elite shooters seem to be less affected by preceding self-control demanding tasks than sub-elite athletes. Therefore, the aim of the present study was to investigate the effects of self-control on shooting performance in elite shooters. Hence, we randomly assigned elite shooters to an experimental (n= 12) or a control condition (n= 11) and asked them to perform a series of 40 shots at baseline (T1) and again after a task which either did or did not require self-control (T2). Additionally, we continuously measured the shooters’ level of perceived self-control strength. We assumed that in elite athletes, shooting accuracy as well as the perceived level of self-control strength would not be significantly affected over time from T1 to T2 in both conditions. In line with our assumptions, Bayesian linear mixed effect models revealed that shooting performance remained relatively stable in both conditions over time and the conditions also did not differ significantly in their perceived levels of self-control strength. Contrary to resource-based theories of self-control, these results speak against the idea of a limited self-control resource as previous acts of self-control did not impair subsequent shooting performance in elite athletes.
Validating Biobehavioral Technologies for Use in Clinical Psychiatry
Authors: Cohen Alex S. , Cox Christopher R. , Tucker Raymond P. , Mitchell Kyle R. , Schwartz Elana K. , Le Thanh P. , Foltz Peter W. , Holmlund Terje B. , Elvevåg Brita
Published: June 2021

The last decade has witnessed the development of sophisticated biobehavioral and genetic, ambulatory, and other measures that promise unprecedented insight into psychiatric disorders. As yet, clinical sciences have struggled with implementing these objective measures and they have yet to move beyond “proof of concept.” In part, this struggle reflects a traditional, and conceptually flawed, application of traditional psychometrics (i.e., reliability and validity) for evaluating them. This paper focuses on “resolution,” concerning the degree to which changes in a signal can be detected and quantified, which is central to measurement evaluation in informatics, engineering, computational and biomedical sciences. We define and discuss resolution in terms of traditional reliability and validity evaluation for psychiatric measures, then highlight its importance in a study using acoustic features to predict self-injurious thoughts/behaviors (SITB). This study involved tracking natural language and self-reported symptoms in 124 psychiatric patients: (a) over 5–14 recording sessions, collected using a smart phone application, and (b) during a clinical interview. Importantly, the scope of these measures varied as a function of time (minutes, weeks) and spatial setting (i.e., smart phone vs. interview). Regarding reliability, acoustic features were temporally unstable until we specified the level of temporal/spatial resolution. Regarding validity, accuracy based on machine learning of acoustic features predicting SITB varied as a function of resolution. High accuracy was achieved (i.e., ~87%), but only when the acoustic and SITB measures were “temporally-matched” in resolution was the model generalizable to new data. Unlocking the potential of biobehavioral technologies for clinical psychiatry will require careful consideration of resolution.