bluuebunny/crossref_metadata_2025 huggingface dataset:
EEG-Based Intersubject Correlations Reflect Selective Attention in a Competing Speaker Scenario
Authors: Rosenkranz Marc , Holtze Björn , Jaeger Manuela , Debener Stefan
Published: June 2021

Several solutions have been proposed to study the relationship between ongoing brain activity and natural sensory stimuli, such as running speech. Computing the intersubject correlation (ISC) has been proposed as one possible approach. Previous evidence suggests that ISCs between the participants’ electroencephalogram (EEG) may be modulated by attention. The current study addressed this question in a competing-speaker paradigm, where participants (N = 41) had to attend to one of two concurrently presented speech streams. ISCs between participants’ EEG were higher for participants attending to the same story compared to participants attending to different stories. Furthermore, we found that ISCs between individual and group data predicted whether an individual attended to the left or right speech stream. Interestingly, the magnitude of the shared neural response with others attending to the same story was related to the individual neural representation of the attended and ignored speech envelope. Overall, our findings indicate that ISC differences reflect the magnitude of selective attentional engagement to speech.
Multimodal Simulation of a Novel Device for a Safe and Effective External Ventricular Drain Placement
Authors: Umana Giuseppe Emmanuele , Scalia Gianluca , Yagmurlu Kaan , Mineo Rosalia , Di Bella Simone , Giunta Matteo , Spitaleri Angelo , Maugeri Rosario , Graziano Francesca , Fricia Marco , Nicoletti Giovanni Federico , Tomasi Santino Ottavio , Raudino Giuseppe , Chaurasia Bipin , Bellocchi Gianluca , Salvati Maurizio , Iacopino Domenico Gerardo , Cicero Salvatore , Visocchi Massimiliano , Strigari Lidia
Published: June 2021

Background

External ventricular drain (EVD) placement is mandatory for several pathologies. The misplacement rate of the EVD varies widely in literature, ranging from 12.3 to 60%. The purpose of this simulation study is to provide preliminary data about the possibility of increasing the safety of one of the most common life-saving procedures in neurosurgery by testing a new device for EVD placement.

Methods

We used a novel guide for positioning the ventricular catheter (patent RM2014A000376). The trajectory was assessed using 25 anonymized head CT scans. The data sets were used to conduct three-dimensional computer-based and combined navigation and augmented reality-based simulations using plaster models. The data set inclusion criteria were volumetric head CT scan, without midline shift, of patients older than 18. Evans’ index was used to quantify the ventricle’s size. We excluded patients with slit ventricles, midline shift, skull fractures, or complex skull malformations. The proximal end of the device was tested on the cadaver.

Results

The cadaveric tests proved that a surgeon could use the device without any external help. The multimodal simulation showed Kakarla grade 1 in all cases but one (grade 2) on both sides, after right and left EVD placement. The mean Evans’ index was 0.28. The geometric principles that explain the device’s efficacy can be summarized by studying the properties of circumference and chord. The contact occurs, for each section considered, at the extreme points of the chord. Its axis, perpendicular to the plane tangent to the spherical surface at the entry point, corresponds to the direction of entry of the catheter guided by the instrument.

Conclusion

According to our multimodal simulation on cadavers, 3D computer-based simulation, 3D plaster modeling, 3D neuronavigation, and augmented reality, the device promises to offer safer and effective EVD placement. Further validation in future clinical studies is recommended.
Axonal Transport and Local Translation of mRNA in Neurodegenerative Diseases
Authors: Nagano Seiichi , Araki Toshiyuki
Published: June 2021

Since neurons have long neurites including axons, it is crucial for the axons to transport many intracellular substances such as proteins and mitochondria in order to maintain their morphology and function. In addition, mRNAs have also been shown to be transported within axons. RNA-binding proteins form complexes with mRNAs, and regulate transport of the mRNAs to axons, as well as locally translate them into proteins. Local translation of mRNAs actively occurs during the development and damage of neurons, and plays an important role in axon elongation, regeneration, and synapse formation. In recent years, it has been reported that impaired axonal transport and local translation of mRNAs may be involved in the pathogenesis of some neurodegenerative diseases. In this review, we discuss the significance of mRNA axonal transport and their local translation in amyotrophic lateral sclerosis/frontotemporal dementia, spinal muscular atrophy, Alzheimer’s disease, and fragile X syndrome.
Effects of Cold-Pressing and Hydrodistillation on the Active Non-volatile Components in Lemon Essential Oil and the Effects of the Resulting Oils on Aging-Related Oxidative Stress in Mice
Authors: Li Guijie , Xiang Sha , Pan Yanni , Long Xingyao , Cheng Yujiao , Han Leng , Zhao Xin
Published: June 2021

The aim of this study was to analyze the non-volatile composition and antioxidant differences of lemon essential oils (LEOs) obtained by cold-pressing vs. hydrodistillation. Pathological observations showed that LEO effectively inhibited liver injury caused by oxidative stress, and CPLEO was more effective than HDLEO. CPLEO increased serum T-AOC, SOD, GSH, and GSH-Px levels while decreasing NO, COX-2, IL-6, IL-1β, IFN-γ, and TNF-α levels in mice with oxidative damage. The effects of CPLEO were stronger than those of HDLEO and similar to those of vitamin C. CPLEO upregulated mRNA and protein expressions of Cu/Zn-SOD, Mn-SOD, CAT, HO-1, Nrf2, and NQO1 while downregulating nNOS, iNOS, IL-1β, COX-2, TNF-α, and NF-κB mRNA expression and nNOS, eNOS, iNOS, and COX-2 protein expression in mice with oxidative damage. The results demonstrate that LEO has good antioxidant effects and that CPLEO has a better antioxidant effect than HDLEO as it retains more active non-volatile substances.
Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3β Pathway
Authors: Zhang Tianqi , Beeharry Maneesh Kumarsing , Zheng Yanan , Wang Zhenqiang , Li Jianfang , Zhu Zhenggang , Li Chen
Published: June 2021

Background

Gastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly understood.

Methods

Bioinformatics and qRT-PCR assays were used to analyze the expression of SNHG12 in GC tissues and cells. In vitro and in vivo experiments were conducted to detect the role of SNHG12 in GC development. qRT-PCR, PCR, western blotting (WB), RNA binding protein immunoprecipitation (RIP), immunoprecipitation (IP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) were performed to investigate the underlying mechanisms by which SNHG12 promotes GC proliferation.

Results

SNHG12 was highly expressed in GC cells and tissues, and predicted poor survival. In vitro and in vivo assays showed that SNHG12 knockdown inhibited GC proliferation, while SNHG12 overexpression promoted GC proliferation. Further experiments confirmed that SNHG12 was mainly located in the cytoplasm and bound to HuR. Bioinformatics analysis predicted that YWHAZ was the common target of SNHG12 and HuR, and that the “SNHG12-HuR” complex enhanced the stability of YWHAZ mRNA. Furthermore, YWHAZ, which was highly expressed in GC, predicted poor survival and promoted GC proliferation by phosphorylating AKT. Rescue assays verified that SNHG12 promoted GC proliferation by activating the AKT/GSK-3β pathway.

Conclusions

SNHG12 binds to HuR and stabilizes YWHAZ. SNHG12 promotes GC proliferation via modulation of the YWHAZ/AKT/GSK-3β axis in vitro and in vivo. Thus, SNHG12 could become a novel therapeutic target for anti-tumor therapy.
The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward From Synthetic Lethality
Authors: Turinetto Margherita , Scotto Giulia , Tuninetti Valentina , Giannone Gaia , Valabrega Giorgio
Published: June 2021

PARP inhibitors (PARPi) have shown promising clinical results and have revolutionized the landscape of ovarian cancer management in the last few years. While the core mechanism of action of these drugs has been largely analyzed, the interaction between PARP inhibitors and the microenvironment has been scarcely researched so far. Recent data shows a variety of mechanism through which PARPi might influence the tumor microenvironment and especially the immune system response, that might even partly be the reason behind PARPi efficacy. One of many pathways that are affected is the cGAS-cGAMP-STING; the upregulation of STING (stimulator of interferon genes), produces more Interferon ϒ and pro inflammatory cytokines, thus increasing intratumoral CD4+ and CD8+ T cells. Upregulation of immune checkpoints such as PD1-PDL1 has also been observed. Another interesting mechanism of interaction between PARPi and microenvironment is the ability of PARPi to kill hypoxic cells, as these cells show an intrinsic reduction in the expression and function of the proteins involved in HR. This process has been defined “contextual synthetic lethality”. Despite ovarian cancer having always been considered a poor responder to immune therapy, data is now shedding a new light on the matter. First, OC is much more heterogenous than previously thought, therefore it is fundamental to select predictive biomarkers for target therapies. While single agent therapies have not yielded significant results on the long term, influencing the immune system and the tumor microenvironment via the concomitant use of PARPi and other target therapies might be a more successful approach.
A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer
Authors: Liu Fen , Yang Zongcheng , Zheng Lixin , Shao Wei , Cui Xiujie , Wang Yue , Jia Jihui , Fu Yue
Published: June 2021

Background

Gastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.

Methods

Weighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.

Results

WGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.

Conclusions

Our results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.
Triple Combination Therapy With PD-1/PD-L1, BRAF, and MEK Inhibitor for Stage III–IV Melanoma: A Systematic Review and Meta-Analysis
Authors: Liu Ye , Zhang Xilan , Wang Guoying , Cui Xinchang
Published: June 2021

Triple combination of anti-PD-1/PD-L1 immunotherapy and anti-BRAF plus anti-MEK targeted therapy is a promising antitumor strategy and is increasingly being used in clinical trials. To evaluate the safety and efficacy of triple combination of PD-1/PD-L1, BRAF, and MEK inhibition in patients diagnosed with stage III-IV melanoma, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, EMBASE, and Cochrane Library were searched for all studies published from inception to January 2021. The progression free survival (PFS), overall survival (OS), overall response rate (ORR), and risk of adverse events (AEs) were extracted by two independent investigators and pooled hazard ratio (HR) or risk ratio (RR) with 95% CI were determined using the random-effects model for data synthesis. Overall, five randomized controlled trials encompassing 1,266 patients with stage III-IV melanoma were selected. Triple combination therapy significantly improved PFS (HR = 0.71; 95% CI = 0.59 to 0.86; P = 0.0005) and 2-year OS (RR = 1.12; 95% CI = 1.03 to 1.23; P = 0.01), but had no impact on ORR (RR = 1.09; 95% CI = 0.91 to 1.30; P = 0.37) when compared with controlled treatment group. In addition, triple combination therapy was associated with increased risks of hypothyroidism, arthralgia, myalgia, ALT increased, AST increased, asthenia, and pyrexia compared with control group. Triple combination therapy of PD-1/PD-L1, BRAF, and MEK inhibition achieved better survival benefits but had higher incidence of some adverse events over two-drug combination or monotherapy. Further randomized controlled clinical trials are needed to verify our results.

Systematic Review Registration

PROSPERO 2021 CRD42021235845 Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235845.
Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead
Authors: Shrestha Sumana , Morcavallo Alaide , Gorrini Chiara , Chesler Louis
Published: June 2021

The constitutive and dysregulated expression of the transcription factor MYCN has a central role in the pathogenesis of the paediatric brain tumour medulloblastoma, with an increased expression of this oncogene correlating with a worse prognosis. Consequently, the genomic and functional alterations of MYCN represent a major therapeutic target to attenuate tumour growth in medulloblastoma. This review will provide a comprehensive synopsis of the biological role of MYCN and its family components, their interaction with distinct signalling pathways, and the implications of this network in medulloblastoma development. We will then summarise the current toolbox for targeting MYCN and highlight novel therapeutic avenues that have the potential to results in better-tailored clinical treatments.
Interferon Regulatory Factor 4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma
Authors: Li Xuanzong , Zhai Shujun , Zhang Jianbo , Zhang Dai , Wang Shijiang , Wang Linlin , Yu Jinming
Published: June 2021

Background

Immune related interferon regulatory factor 4 (IRF4) is a member of the IRF family, whereas the clinical significance and possible role of IRF4 in lung adenocarcinoma (LUAD) remains unclear. We aimed to investigate the role of IRF4 in predicting the prognosis of LUAD patients.

Methods

Using The Cancer Genome Atlas (TCGA) database and our immunohistochemical (IHC) cohort, we analyzed the correlation between IRF4 expression and clinical characteristics, and the prognostic value of IRF4 was also evaluated in LUAD. The potential biological functions of IRF4 in LUAD were analyzed by Gene Set Enrichment Analysis (GSEA). The relationship between IRF4 and immune cell infiltration were evaluated by TISIDB database and our own IHC cohort. In addition, an immune checkpoint inhibitor (ICI) treated cohort from Gene Expression Omnibus database was used to determine the role of IRF4 in LUAD patients with immunotherapy.

Results

We found that either mRNA or protein expression level of IRF4 was significantly higher in LUAD than in normal tissues (P < 0.001). The elevate in IRF4 expression in LUAD was significantly associated with the earlier clinical stage (P = 0.002). Patients with LUAD and IRF4 high expression correlated with significant longer overall survival in both TCGA database (P < 0.05) and our IHC-cohort (P = 0.001). Our results also demonstrated that IRF4 could serve as an independent favorable prognostic factor in patients with LUAD. GSEA analysis indicated that high IRF4 expression group enriched with several immune-related pathways, such as B cell receptor signaling pathway, T cell receptor signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LUAD, IRF4 positively correlated with several different immune infiltrations including various B cells, CD8+ T cells and CD4+ T cells both in mRNA and protein levels. Additionally, we found that the expression of IRF4 was positively associated with PD-1 and PD-L1 mRNA expression levels, and IRF4 high expression predicted moderate better survival in LUAD with immunotherapy (P = 0.071).

Conclusions

Our results suggested that IRF4 was associated with higher B cells and T cells infiltration levels and might be a favorable prognostic biomarker in LUAD patients, whereas the potential prognostic role of IRF4 in ICI-treated patients needed further exploration.
Role of Exosomal Non-coding RNAs in Gastric Cancer: Biological Functions and Potential Clinical Applications
Authors: Hu Feng , Liu Jixuan , Liu Huibo , Li Fan , Wan Minjie , Zhang Manli , Jiang Yanfang , Rao Min
Published: June 2021

Gastric cancer (GC) is one of the most common fatal cancers worldwide. The communication between GC and other cells in the GC microenvironment directly affects GC progression. Recently, exosomes have been revealed as new players in intercellular communication. They play an important role in human health and diseases, including cancer, owing to their ability to carry various bioactive molecules, including non-coding RNAs (ncRNAs). NcRNAs, including micro RNAs, long non-coding RNAs, and circular RNAs, play a significant role in various pathophysiological processes, especially cancer. Increasing evidence has shown that exosomal ncRNAs are involved in the regulation of tumor proliferation, invasion, metastasis, angiogenesis, immune regulation, and treatment resistance in GC. In addition, exosomal ncRNAs have promising potential as diagnostic and prognostic markers for GC. Considering the biocompatibility of exosomes, they can also be used as biological carriers for targeted therapy. This review summarizes the current research progress on exosomal ncRNAs in gastric cancer, focusing on their biological role in GC and their potential as new biomarkers for GC and therapeutics. Our review provides insight into the mechanisms involved in GC progression, which may provide a new point cut for the discovery of new diagnostic markers and therapeutic strategies.
Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion
Authors: Venegas-Montoya Edna , Staines-Boone Aidé Tamara , Sánchez-Sánchez Luz María , García-Campos Jorge Alberto , Córdova-Gurrola Rubén Antonio , Salazar-Galvez Yuridia , Múzquiz-Zermeño David , González-Serrano María Edith , Lugo Reyes Saul O.
Published: June 2021

Autosomal recessive (AR) DOCK8 deficiency is a well-known actinopathy, a combined primary immune deficiency with impaired actin polymerization that results in altered cell mobility and immune synapse. DOCK8-deficient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia, and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic etiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favor of genetic defects. We describe a school-age male patient with a clinical picture suggestive of DOCK8 deficiency, except for high serum IgE or a family history: early onset, failure to thrive, eczema, warts, condyloma, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leukocytosis, eosinophilia, high IgA, low IgG, and low CD4+ T cells. We were able to confirm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-deficient patients; at least 4 other patients have had no elevated IgE, and about 40% do not have Hyper-IgE (above 1,000 IU/mL). Despite this, the constellation of signs, symptoms, and findings allow the suspicion of DOCK8 deficiency and other actinopathies.
Physical Fitness Plays a Crucial Mediator Role in Relationships Among Personal, Social, and Lifestyle Factors With Adolescents' Cognitive Performance in a Structural Equation Model. The Cogni-Action Project
Authors: Lemes Vanilson , Gaya Anelise R. , Sadarangani Kabir P. , Aguilar-Farias Nicolas , Rodriguez-Rodriguez Fernando , Martins Clarice Maria de Lucena , Fochesatto Camila , Cristi-Montero Carlos
Published: June 2021

Background: The beneficial relationship between physical fitness and cognitive performance is affected and modulated by a wide diversity of factors that seem to be more sensitive during the development stage, particularly during early adolescence. This study aimed to examine the role of physical fitness considering the multivariate association between age, health-related quality of life (HRQOL), school vulnerability index (SVI), body mass index z-score (BMIz), physical activity, and sleep problems with the cognitive performance in boys and girls.

Method: Participants were 1,196 adolescents aged 10–14 years (50.7% of boys) from Chile. Three physical fitness components and eight cognitive tasks were measured. BMIz was determined using growth references by age and sex, whereas questionaries were used to assess sleep problems, physical activity, and HRQOL. SVI was established according to the score given by the Chilean Government to educational establishments. We performed a structural equation model (SEM) to test multivariate associations among study' variables by sex.

Results: Fitness was positively associated with boys' and girls' cognitive performance (β = 0.23 and β = 0.17; p = 0.001, respectively). Moreover, fitness presented a significant mediator role in the relationships between BMIz, SVI, and physical activity with cognitive performance (indirect effect). Additionally, SVI showed a negative association both direct and indirect effect in all three fitness components and all cognitive tasks, being this relationship stronger in girls than in boys.

Conclusion: Our findings suggest that physical fitness and all its components play a crucial mediator role in the associations between several factors associated with adolescents' cognitive performance. Thereby, educational and health strategies should prioritise improving physical fitness through physical activity. They also should address other factors such as school vulnerability, obesity, and the early gender gap in a comprehensive approach boosting cognitive performance among early adolescents.

Trial registration: Research Registry (ID: researchregistry5791).
Development and Validation of a Nomogram for Predicting Drug-Induced Acute Kidney Injury in Hospitalized Patients: A Case-Control Study Based on Propensity-Score Matching
Authors: Yu Chengxuan , Guo Daihong , Yao Chong , Zhu Yu , Liu Siyuan , Kong Xianghao
Published: June 2021

Background: Drug-induced acute kidney injury (D-AKI) is associated with increased mortality and longer hospital stays. This study aims to establish a nomogram to predict the occurrence of D-AKI in hospitalized patients in a multi-drug environment.

Methods: A single center retrospective study among adult hospitalized patients was conducted from July 2019 to September 2019 based on the Adverse Drug Events Active Surveillance and Assessment System-2 developed by our hospital. According to the propensity score matching algorithm, four controls per case were matched to eliminate the confounding bias caused by individual baseline variables. The predictors for D-AKI were obtained by logistic regression equation and used to establish the nomogram.

Results: Among 51,772 hospitalized patients, 332 were diagnosed with D-AKI. After matching, 288 pairs and 1,440 patients were included in the study, including 1,005 cases in the development group and 435 cases in the validation group. Six variables were independent predictors for D-AKI: alcohol abuse, the concurrent use of nonsteroidal anti-inflammatory drugs or diuretics, chronic kidney disease, lower baseline red blood cell count and neutrophil count ≥7 × 109/L. The area under the curve (AUC) of the prediction model in the development group and validation group were 0.787 (95%CI, 0.752–0.823) and 0.788 (95%CI, 0.736–0.840), respectively. The GiViTI calibration belts showed that the model had a good prediction accuracy for the occurrence of D-AKI (p > 0.05).

Conclusion: This nomogram can help identify patients at high risk of D-AKI, which was useful in preventing the progression of D-AKI and treating it in the early stages.
Therapeutic Effectiveness and Safety of Repurposing Drugs for the Treatment of COVID-19: Position Standing in 2021
Authors: Alam Safaet , Kamal Taslima Binte , Sarker Md. Moklesur Rahman , Zhou Jin-Rong , Rahman S. M. Abdur , Mohamed Isa Naina
Published: June 2021

COVID-19, transmitted by SARS-CoV-2, is one of the most serious pandemic situations in the history of mankind, and has already infected a huge population across the globe. This horrendously contagious viral outbreak was first identified in China and within a very short time it affected the world's health, transport, economic, and academic sectors. Despite the recent approval of a few anti-COVID-19 vaccines, their unavailability and insufficiency along with the lack of other potential therapeutic options are continuing to worsen the situation, with valuable lives continuing to be lost. In this situation, researchers across the globe are focusing on repurposing prospective drugs and prophylaxis such as favipiravir, remdesivir, chloroquine, hydroxychloroquine, ivermectin, lopinavir-ritonavir, azithromycin, doxycycline, ACEIs/ARBs, rivaroxaban, and protease inhibitors, which were preliminarily based on in vitro and in vivo pharmacological and toxicological study reports followed by clinical applications. Based on available preliminary data derived from limited clinical trials, the US National Institute of Health (NIH) and USFDA also recommended a few drugs to be repurposed i.e., hydroxychloroquine, remdesivir, and favipiravir. However, World Health Organization later recommended against the use of chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir in the treatment of COVID-19 infections. Combining basic knowledge of viral pathogenesis and pharmacodynamics of drug molecules as well as in silico approaches, many drug candidates have been investigated in clinical trials, some of which have been proven to be partially effective against COVID-19, and many of the other drugs are currently under extensive screening. The repurposing of prospective drug candidates from different stages of evaluation can be a handy wellspring in COVID-19 management and treatment along with approved anti-COVID-19 vaccines. This review article combined the information from completed clinical trials, case series, cohort studies, meta-analyses, and retrospective studies to focus on the current status of repurposing drugs in 2021.
Goals and Limitations of Modeling Collective Behavior in Biological Systems
Authors: Ouellette Nicholas T. , Gordon Deborah M.
Published: June 2021

Local social interactions among individuals in animal groups generate collective behavior, allowing groups to adjust to changing conditions. Historically, scientists from different disciplines have taken different approaches to modeling collective behavior. We describe how each can contribute to the goal of understanding natural systems. Simple bottom-up models that describe individuals and their interactions directly have demonstrated that local interactions far from equilibrium can generate collective states. However, such simple models are not likely to describe accurately the actual mechanisms and interactions in play in any real biological system. Other classes of top-down models that describe group-level behavior directly have been proposed for groups where the function of the collective behavior is understood. Such models cannot necessarily explain why or how such functions emerge from first principles. Because modeling approaches have different strengths and weaknesses and no single approach will always be best, we argue that models of collective behavior that are aimed at understanding real biological systems should be formulated to address specific questions and to allow for validation. As examples, we discuss four forms of collective behavior that differ both in the interactions that produce the collective behavior and in ecological context, and thus require very different modeling frameworks. 1) Harvester ants use local interactions consisting of brief antennal contact, in which one ant assesses the cuticular hydrocarbon profile of another, to regulate foraging activity, which can be modeled as a closed-loop excitable system. 2) Arboreal turtle ants form trail networks in the canopy of the tropical forest, using trail pheromone; one ant detects the volatile chemical that another has recently deposited. The process that maintains and repairs the trail, which can be modeled as a distributed algorithm, is constrained by the physical configuration of the network of vegetation in which they travel. 3) Swarms of midges interact acoustically and non-locally, and can be well described as agents moving in an emergent potential well that is representative of the swarm as a whole rather than individuals. 4) Flocks of jackdaws change their effective interactions depending on ecological context, using topological distance when traveling but metric distance when mobbing. We discuss how different research questions about these systems have led to different modeling approaches.
The First Female Dry Immersion (NAIAD-2020): Design and Specifics of a 3-Day Study
Authors: Tomilovskaya Elena , Amirova Liubov , Nosikova Inna , Rukavishnikov Ilya , Chernogorov Roman , Lebedeva Svetlana , Saveko Alina , Ermakov Ivan , Ponomarev Ivan , Zelenskaya Inna , Shigueva Tatiana , Shishkin Nikita , Kitov Vladimir , Riabova Alexandra , Brykov Vitaly , Abu Sheli Nelly , Vassilieva Galina , Orlov Oleg
Published: June 2021

This article describes procedures and some results of the first study of females undergoing 3-day Dry Immersion. The experiment “NAIAD-2020” was carried out at the Institute of Biomedical Problems (Moscow, Russia) with the participation of six healthy women volunteers (age 30.17 ± 5.5 years, height 1.66 ± 0.1 m, weight 62.05 ± 8.4 kg, BMI 22.39 ± 2.2 kg/m2) with a natural menstrual cycle. During the study, a standard protocol was used, the same as for men, with a minimum period of time spent outside the immersion bath. Before, during and after Immersion, 22 experiments were carried out aimed at studying the neurophysiological, functional, metabolic and psychophysiological functions of the body, the results of which will be presented in future publications. The total time outside the bath for women did not exceed that for men. Systolic and diastolic pressure did not significantly change during the immersion. In the first 24 h after the end of the immersion, heart rate was significantly higher than the background values [F(4,20) = 14.67; P < 0.0001]. Changes in body temperature and water balance were consistent with the patterns found in men. No significant changes in height and weight were found during immersion. All women reported general discomfort and pain in the abdomen and back. The results of this study did not find significant risks to women’s health and showed the feasibility of using this model of the effects of space flight in women of reproductive age.
LncRNAs Participate in Post-Resuscitation Myocardial Dysfunction Through the PI3K/Akt Signaling Pathway in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Hou Jingying , Zeng Chaotao , Zheng Guanghui , Liang Lian , Jiang Longyuan , Yang Zhengfei
Published: June 2021

In this study, we aimed to explore the role of lncRNAs in post-resuscitation myocardial dysfunction in a rat model of CA-CPR. A rat model of CA-CPR was constructed using a VF method. Myocardial functions, including cardiac output (CO), ejection fraction (EF), and myocardial performance index (MPI), were evaluated at the baseline, and 1, 2, 3, 4, and 6 h after resuscitation. A high throughput sequencing method was used to screen the differentially expressed lncRNAs, miRNAs, and mRNAs, which were further analyzed with bioinformatics. In addition, relationships between the molecules involved in the PI3K/Akt signaling pathway were explored with ceRNA network. Compared with the sham group, EF was significantly reduced and MPI was increased at the five consecutive time points in the CA-CPR group. 68 lncRNAs were upregulated and 40 lncRNAs were downregulated in the CA-CPR group, while 30 miRNAs were downregulated and 19 miRNAs were upregulated. Moreover, mRNAs were also differentially expressed, with 676 upregulated and 588 downregulated. GO analysis suggested that genes associated with cell proliferation, cell death and programmed cell death were significantly enriched. KEGG analysis showed that the PI3K/Akt, MAPK and Ras signaling pathways were the three most-enriched pathways. Construction of a ceRNA regulatory network indicated that LOC102549506, LOC103689920, and LOC103690137 might play important roles in the regulation of the PI3K/Akt signaling pathway in the CA-CPR treated rat. Taken together, LncRNAs, including LOC102549506, LOC103689920 and LOC103690137, might participate in post-resuscitation myocardial dysfunction by functioning as ceRNAs and regulating the PI3K/Akt signaling pathway.
The Cowpea Kinome: Genomic and Transcriptomic Analysis Under Biotic and Abiotic Stresses
Authors: Ferreira-Neto José Ribamar Costa , Borges Artemisa Nazaré da Costa , da Silva Manassés Daniel , Morais David Anderson de Lima , Bezerra-Neto João Pacífico , Bourque Guillaume , Kido Ederson Akio , Benko-Iseppon Ana Maria
Published: June 2021

The present work represents a pioneering effort, being the first to analyze genomic and transcriptomic data from Vigna unguiculata (cowpea) kinases. We evaluated the cowpea kinome considering its genome-wide distribution and structural characteristics (at the gene and protein levels), sequence evolution, conservation among Viridiplantae species, and gene expression in three cowpea genotypes under different stress situations, including biotic (injury followed by virus inoculation—CABMV or CPSMV) and abiotic (root dehydration). The structural features of cowpea kinases (VuPKs) indicated that 1,293 bona fide VuPKs covered 20 groups and 118 different families. The RLK-Pelle was the largest group, with 908 members. Insights on the mechanisms of VuPK genomic expansion and conservation among Viridiplantae species indicated dispersed and tandem duplications as major forces for VuPKs’ distribution pattern and high orthology indexes and synteny with other legume species, respectively. Ka/Ks ratios showed that almost all (91%) of the tandem duplication events were under purifying selection. Candidate cis-regulatory elements were associated with different transcription factors (TFs) in the promoter regions of the RLK-Pelle group. C2H2 TFs were closely associated with the promoter regions of almost all scrutinized families for the mentioned group. At the transcriptional level, it was suggested that VuPK up-regulation was stress, genotype, or tissue dependent (or a combination of them). The most prominent families in responding (up-regulation) to all the analyzed stresses were RLK-Pelle_DLSV and CAMK_CAMKL-CHK1. Concerning root dehydration, it was suggested that the up-regulated VuPKs are associated with ABA hormone signaling, auxin hormone transport, and potassium ion metabolism. Additionally, up-regulated VuPKs under root dehydration potentially assist in a critical physiological strategy of the studied cowpea genotype in this assay, with activation of defense mechanisms against biotic stress while responding to root dehydration. This study provides the foundation for further studies on the evolution and molecular function of VuPKs.
Improving Plant Health Through Nutrient Remineralization in Aquaponic Systems
Authors: Lobanov Victor P. , Combot Doriane , Pelissier Pablo , Labbé Laurent , Joyce Alyssa
Published: June 2021

The exploitation of readily bioavailable fish excreta as a source of plant nutrients lies at the cornerstone of aquaponics farming. Research on nutrient cycling in aquaponic systems has devoted considerable attention to the plant uptake of dissolved nutrients in fish excreta, however, the integration of particulate-bound nutrients into downstream hydroponic farming has remained elusive. The high amount of organic carbon present in fish sludge may lead to biofouling if directly incorporated into hydroponic circulation systems, reducing the utility of incorporating fish solids on a large scale. In this study, we implemented a novel treatment system capable of reducing the carbon and nitrogen load of fish solids to produce a liquid fertilizer for a downstream hydroponics unit. Lettuce (Lactuca sativa) fertilized with exclusively a commercial nutrient solution, the biofilter effluent (coupled aquaponic system), effluent from the solids treatment system, or the latter two combined were grown in nutrient flow technique gutters downstream of a recirculating aquaculture system stocked with rainbow trout (Oncorhynchus mykiss). While crop yields were lower for the aquaponic treatments compared to lettuce grown in a commercial nutrient solution, plant sap analysis demonstrated a contrasting picture with respect to internal nutrient concentrations. Lettuce grown in the commercial hydroponic solution were deficient in several mineral nutrients (Mg, Ca, Na, and Si) nor did they have higher iron concentrations despite the significantly higher EDTA-chelated aqueous iron (460 × greater than other treatments) in the nutrient solution. Nutrient uptake in the rhizosphere was not investigated on a molecular level, although stunted rhizosphere growth in the commercial nutrient solution control suggests a weakened capacity for nutrient uptake in comparison to other treatments. Alongside the remineralization of micronutrients, the solids treatment system addressed the common issue of excess carbon leading to biofouling via a total suspended solids reduction of 87.27% ± 9.95 during the coupled aquaponics cultivation period. Ultimately, these data lead to two important conclusions. Firstly, optimizing nutrient bioavailability is not synonymous to increasing the presence of a nutrient in the water column. Secondly, estimating ideal nutrient solution concentrations involves both preventing nutrient blocking and improving bioavailability.
Assessing the Suitability of Elite Lines for Hybrid Seed Production and as Testers in Wide Crosses With Wheat Genetic Resources
Authors: Schneider Johannes , Berkner Marcel O. , Philipp Norman , Schulthess Albert W. , Reif Jochen C.
Published: June 2021

The use of genetic resources in breeding is considered critical to ensure future selection gain, but the absence of important adaptation genes often masks the breeding value of genetic resources for grain yield. Testing genetic resources in a hybrid background has been proposed as a solution to obtain unbiased estimates of breeding values for grain yield. In our study, we evaluated the suitability of European wheat elite lines for implementing this hybrid strategy, focusing on maximizing seed yield in hybrid production and reducing masking effects due to susceptibility to lodging, yellow rust, and leaf rust of genetic resources. Over a 3-year period, 63 wheat elite female lines were crossed with eight male plant genetic resources in a multi-environment field experiment to evaluate seed yield on the female side. Then, the resulting hybrids and their parents were tested for plant height, lodging, and susceptibility to yellow rust and leaf rust in a further field experiment at multiple locations. We found that seed yield was strongly influenced by the elite wheat line choice in addition to environment and observed substantial differences among elite tester lines in their ability to reduce susceptibility to lodging, yellow rust, and leaf rust when the hybrid strategy was implemented. Consequently, breeders can significantly increase the amount of hybrid seed produced in wide crosses through appropriate tester choice and adapt genetic resources of wheat with the hybrid strategy to the modern cropping system.
Complete Chloroplast Genomes of Acanthochlamys bracteata (China) and Xerophyta (Africa) (Velloziaceae): Comparative Genomics and Phylogenomic Placement
Authors: Wanga Vincent Okelo , Dong Xiang , Oulo Millicent Akinyi , Mkala Elijah Mbandi , Yang Jia-Xin , Onjalalaina Guy Eric , Gichua Moses Kirega , Kirika Paul Muigai , Gituru Robert Wahiti , Hu Guang-Wan , Wang Qing-Feng
Published: June 2021

Acanthochlamys P.C. Kao is a Chinese endemic monotypic genus, whereas XerophytaJuss. is a genus endemic to Africa mainland, Arabian Peninsula and Madagascar with ca.70 species. In this recent study, the complete chloroplast genome of Acanthochlamys bracteata was sequenced and its genome structure compared with two African Xerophyta species (Xerophyta spekei and Xerophyta viscosa) present in the NCBI database. The genomes showed a quadripartite structure with their sizes ranging from 153,843 bp to 155,498 bp, having large single-copy (LSC) and small single-copy (SSC) regions divided by a pair of inverted repeats (IR regions). The total number of genes found in A. bracteata, X. spekei and X. viscosa cp genomes are 129, 130, and 132, respectively. About 50, 29, 28 palindromic, forward and reverse repeats and 90, 59, 53 simple sequence repeats (SSRs) were found in the A. bracteata, X. spekei, and X. viscosa cp genome, respectively. Nucleotide diversity analysis in all species was 0.03501, Ka/Ks ratio average score was calculated to be 0.26, and intergeneric K2P value within the Order Pandanales was averaged to be 0.0831. Genomic characterization was undertaken by comparing the genomes of the three species of Velloziaceae and it revealed that the coding regions were more conserved than the non-coding regions. However, key variations were noted mostly at the junctions of IRs/SSC regions. Phylogenetic analysis suggests that A. bracteata species has a closer genetic relationship to the genus Xerophyta. The present study reveals the complete chloroplast genome of A. bracteata and gives a genomic comparative analysis with the African species of Xerophyta. Thus, can be useful in developing DNA markers for use in the study of genetic variabilities and evolutionary studies in Velloziaceae.
Personality and Motives for Social Media Use When Physically Distanced: A Uses and Gratifications Approach
Authors: Bowden-Green Thomas , Hinds Joanne , Joinson Adam
Published: June 2021

This paper explores individuals’ motives for using social media when living under ‘social distancing’ conditions imposed during the COVID-19 pandemic, where they were instructed to physically distance from other people. Adopting a ‘uses and gratifications’ approach, and using a previously established five-factor scale, we examine the relationship between individuals’ motives for using social media and their personality traits. Hundred and eighty-nine social media users living in the United Kingdom completed surveys assessing their motives for using social media and their personality. Our findings demonstrate that participants were generally motivated to use social media to ‘pass time’ and to ‘maintain relationships.’ Further, we find that those high in extraversion in particular use social media to ‘maintain relationships.’ By comparing our findings to previous studies where face-to-face interaction was not restricted, our findings indicate that individuals’ motives for using social media change when they are placed under physical distancing restrictions. We reflect on the potential application of our findings for others experiencing similar conditions, such as those working in remote locations, as well as the potential implications for living in a post-pandemic world with increased virtual ‘meetings’ using social media.
I Only Want Passionate Relationships: Are You Ready for That?
Authors: Joanpere Mar , Redondo-Sama Gisela , Aubert Adriana , Flecha Ramon
Published: June 2021

Research shows the existence of a coercive dominant discourse that associates attraction with violence and influences the socialization processes of many girls and women. According to previous studies, the coercive dominant discourse constitutes a risk factor for gender violence, as men with violent attitudes and behaviors are socially presented as attractive and exciting while egalitarian and non-aggressive men are considered “not sexy.” Yet fewer evidences indicate that men acting from the New Alternative Masculinities (NAM) model overcome this double standard through verbal and non-verbal communicative acts, which tell that they do not choose women acting under the coercive dominant discourse for a relationship because they are not “jumping for joy” when meeting them. Drawing from communicative daily life stories conducted to men and women from diverse sociocultural backgrounds and ages, this article presents how language is used in concrete heterosexual sexual-affective relationships. The analysis resulting from the fieldwork focus on how NAM men’s communicative acts with women set conditions of desire. This article shows evidence on how communicative acts of NAM empowerment incorporate “language of desire,” taking a clear position for egalitarian and passionate relationships. Implications for gender violence prevention are presented.