bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preclinical Model of Computerized Cognitive Training: Touchscreen Cognitive Testing Enhances Cognition and Hippocampal Cellular Plasticity in Wildtype and Alzheimer’s Disease Mice
Authors: Shepherd Amy , Zhang Tracy , Hoffmann Lucas B. , Zeleznikow-Johnston Ariel M. , Churilov Leonid , Hannan Anthony J. , Burrows Emma L.
Published: December 2021

With the growing popularity of touchscreen cognitive testing in rodents, it is imperative to understand the fundamental effects exposure to this paradigm can have on the animals involved. In this study, we set out to assess hippocampal-dependant learning in the APP/PS1 mouse model of Alzheimer’s disease (AD) on two highly translatable touchscreen tasks – the Paired Associate Learning (PAL) task and the Trial Unique Non-Matching to Location (TUNL) task. Both of these tests are based on human tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and are sensitive to deficits in both mild cognitive impairment (MCI) and AD. Mice were assessed for deficits in PAL at 9–12 months of age, then on TUNL at 8–11 and 13–16 months. No cognitive deficits were evident in APP/PS1 mice at any age, contrary to previous reports using maze-based learning and memory tasks. We hypothesized that daily and long-term touchscreen training may have inadvertently acted as a cognitive enhancer. When touchscreen-tested mice were assessed on the Morris water maze, they showed improved task acquisition compared to naïve APP/PS1 mice and wild-type (WT) littermate controls. In addition, we show that touchscreen-trained WT and APP/PS1 mice show increased cell proliferation and immature neuron numbers in the dentate gyrus compared to behaviorally naïve WT and APP/PS1 mice. This result indicates that the touchscreen testing paradigm could improve cognitive performance, and/or mask an impairment, in experimental mouse models. This touchscreen-induced cognitive enhancement may involve increased neurogenesis, and possibly other forms of cellular plasticity. This is the first study to show increased numbers of proliferating cells and immature neurons in the hippocampus following touchscreen testing, and that touchscreen training can improve cognitive performance in maze-based spatial navigation tasks. This potential for touchscreen testing to induce cognitive enhancement, or other phenotypic shifts, in preclinical models should be considered in study design. Furthermore, touchscreen-mediated cognitive enhancement could have therapeutic implications for cognitive disorders.
The Opioid Receptor Antagonist Naloxone Enhances First-Order Fear Conditioning, Second-Order Fear Conditioning and Sensory Preconditioning in Rats
Authors: Michalscheck Robine M. L. , Leidl Dana M. , Westbrook R. Frederick , Holmes Nathan M.
Published: December 2021

The opioid receptor antagonist naloxone enhances Pavlovian fear conditioning when rats are exposed to pairings of an initially neutral stimulus, such as a tone, and a painful foot shock unconditioned stimulus (US; so-called first-order fear conditioning;Pavlov, 1927). The present series of experiments examined whether naloxone has the same effect when conditioning occurs in the absence of US exposure. In Experiments 1a and 1b, rats were exposed to tone-shock pairings in stage 1 (one trial per day for 4 days) and then to pairings of an initially neutral light with the already conditioned tone in stage 2 (one trial per day for 4 days). Experiment 1a confirmed that this training results in second-order fear of the light; and Experiment 1b showed that naloxone enhances this conditioning: rats injected with naloxone in stage 2 froze more than vehicle-injected controls when tested with the light alone (drug-free). In Experiments 2a and 2b, rats were exposed to light-tone pairings in stage 1 (one trial per day for 4 days) and then to tone-shock pairings in stage 2 (one trial per day for 2 days). Experiment 2a confirmed that this training results in sensory preconditioned fear of the light; and Experiment 2b showed that naloxone enhances sensory preconditioning when injected prior to each of the light-tone pairings: rats injected with naloxone in stage 1 froze more than vehicle-injected controls when tested with the light alone (drug-free). These results were taken to mean that naloxone enhances fear conditioning independently of its effect on US processing; and more generally, that opioids regulate the error-correction mechanisms that underlie associative formation.
Environmental and Molecular Modulation of Motor Individuality in Larval Zebrafish
Authors: Hageter John , Waalkes Matthew , Starkey Jacob , Copeland Haylee , Price Heather , Bays Logan , Showman Casey , Laverty Sean , Bergeron Sadie A. , Horstick Eric J.
Published: December 2021

Innate behavioral biases such as human handedness are a ubiquitous form of inter-individual variation that are not strictly hardwired into the genome and are influenced by diverse internal and external cues. Yet, genetic and environmental factors modulating behavioral variation remain poorly understood, especially in vertebrates. To identify genetic and environmental factors that influence behavioral variation, we take advantage of larval zebrafish light-search behavior. During light-search, individuals preferentially turn in leftward or rightward loops, in which directional bias is sustained and non-heritable. Our previous work has shown that bias is maintained by a habenula-rostral PT circuit and genes associated with Notch signaling. Here we use a medium-throughput recording strategy and unbiased analysis to show that significant individual to individual variation exists in wildtype larval zebrafish turning preference. We classify stable left, right, and unbiased turning types, with most individuals exhibiting a directional preference. We show unbiased behavior is not due to a loss of photo-responsiveness but reduced persistence in same-direction turning. Raising larvae at elevated temperature selectively reduces the leftward turning type and impacts rostral PT neurons, specifically. Exposure to conspecifics, variable salinity, environmental enrichment, and physical disturbance does not significantly impact inter-individual turning bias. Pharmacological manipulation of Notch signaling disrupts habenula development and turn bias individuality in a dose dependent manner, establishing a direct role of Notch signaling. Last, a mutant allele of a known Notch pathway affecter gene, gsx2, disrupts turn bias individuality, implicating that brain regions independent of the previously established habenula-rostral PT likely contribute to inter-individual variation. These results establish that larval zebrafish is a powerful vertebrate model for inter-individual variation with established neural targets showing sensitivity to specific environmental and gene signaling disruptions. Our results provide new insight into how variation is generated in the vertebrate nervous system.
Heparin-Binding Growth-Associated Molecule (Pleiotrophin) Affects Sensory Signaling and Selected Motor Functions in Mouse Model of Anatomically Incomplete Cervical Spinal Cord Injury
Authors: Kulesskaya Natalia , Molotkov Dmitry , Sliepen Sonny , Mugantseva Ekaterina , Garcia Horsman Arturo , Paveliev Mikhail , Rauvala Heikki
Published: December 2021

Heparin-binding growth-associated molecule (pleiotrophin) is a neurite outgrowth-promoting secretory protein that lines developing fiber tracts in juvenile CNS (central nervous system). Previously, we have shown that heparin-binding growth-associated molecule (HB-GAM) reverses the CSPG (chondroitin sulfate proteoglycan) inhibition on neurite outgrowth in the culture medium of primary CNS neurons and enhances axon growth through the injured spinal cord in mice demonstrated by two-photon imaging. In this study, we have started studies on the possible role of HB-GAM in enhancing functional recovery after incomplete spinal cord injury (SCI) using cervical lateral hemisection and hemicontusion mouse models. In vivo imaging of blood-oxygen-level-dependent (BOLD) signals associated with functional activity in the somatosensory cortex was used to assess the sensory functions during vibrotactile hind paw stimulation. The signal displays an exaggerated response in animals with lateral hemisection that recovers to the level seen in the sham-operated mice by injection of HB-GAM to the trauma site. The effect of HB-GAM treatment on sensory-motor functions was assessed by performance in demanding behavioral tests requiring integration of afferent and efferent signaling with central coordination. Administration of HB-GAM either by direct injection into the trauma site or by intrathecal injection improves the climbing abilities in animals with cervical hemisection and in addition enhances the grip strength in animals with lateral hemicontusion without affecting the spontaneous locomotor activity. Recovery of sensory signaling in the sensorimotor cortex by HB-GAM to the level of sham-operated mice may contribute to the improvement of skilled locomotion requiring integration of spatiotemporal signals in the somatosensory cortex.
Secondary Epileptogenesis: Common to See, but Possible to Treat?
Authors: Shen Yujia , Gong Yiwei , Ruan Yeping , Chen Zhong , Xu Cenglin
Published: December 2021

Secondary epileptogenesis is a common phenomenon in epilepsy, characterized by epileptiform discharges from the regions outside the primary focus. It is one of the major reasons for pharmacoresistance and surgical failure. Compared with primary epileptogenesis, the mechanism of secondary epileptogenesis is usually more complex and diverse. In this review, we aim to summarize the characteristics of secondary epileptogenesis from both clinical and laboratory studies in a historical view. Mechanisms of secondary epileptogenesis in molecular, cellular, and circuity levels are further presented. Potential treatments targeting the process are discussed as well. At last, we highlight the importance of circuitry studies, which would further illustrate precise treatments of secondary epileptogenesis in the future.
Gut Microbiome, Inflammation, and Cerebrovascular Function: Link Between Obesity and Cognition
Authors: Olsthoorn Lisette , Vreeken Debby , Kiliaan Amanda J.
Published: December 2021

Obesity affects 13% of the adult population worldwide and this number is only expected to increase. Obesity is known to have a negative impact on cardiovascular and metabolic health, but it also impacts brain structure and function; it is associated with both gray and white matter integrity loss, as well as decreased cognitive function, including the domains of executive function, memory, inhibition, and language. Especially midlife obesity is associated with both cognitive impairment and an increased risk of developing dementia at later age. However, underlying mechanisms are not yet fully revealed. Here, we review recent literature (published between 2010 and March 2021) and discuss the effects of obesity on brain structure and cognition, with a main focus on the contributions of the gut microbiome, white adipose tissue (WAT), inflammation, and cerebrovascular function. Obesity-associated changes in gut microbiota composition may cause increased gut permeability and inflammation, therewith affecting cognitive function. Moreover, excess of WAT in obesity produces pro-inflammatory adipokines, leading to a low grade systemic peripheral inflammation, which is associated with decreased cognition. The blood-brain barrier also shows increased permeability, allowing among others, peripheral pro-inflammatory markers to access the brain, leading to neuroinflammation, especially in the hypothalamus, hippocampus and amygdala. Altogether, the interaction between the gut microbiota, WAT inflammation, and cerebrovascular integrity plays a significant role in the link between obesity and cognition. Future research should focus more on the interplay between gut microbiota, WAT, inflammation and cerebrovascular function to obtain a better understanding about the complex link between obesity and cognitive function in order to develop preventatives and personalized treatments.
Effects of Lactobacillus plantarum FZU3013-Fermented Laminaria japonica on Lipid Metabolism and Gut Microbiota in Hyperlipidaemic Rats
Authors: Hu Jin-Peng , Zheng Ting-Ting , Zeng Bin-Fen , Wu Man-Ling , Shi Rui , Zhang Ye , Chen Li-Jiao , Cheng Wen-Jian , Liang Peng
Published: December 2021

In this study, we explored the effect of Lactobacillus plantarum FZU3013-fermented Laminaria japonica (LPLJ) supplementation to prevent hyperlipidaemia in rats fed with a high-fat diet (HFD). The results indicate that LPLJ supplementation improved serum and hepatic biochemical indicators (p < 0.05), elevated short-chain fatty acid levels, reduced HFD-induced accumulation of lipid droplets in the liver, modulated the relative abundance of some microbial phylotypes, and reduced hyperlipidaemia in HFD-fed rats by adjusting the aminoacyl-tRNA, phenylalanine, tyrosine, and tryptophan biosynthetic pathways, as well as the phenylalanine, D-glutamine and D-glutamate, and glutathione metabolic pathways. Additionally, hepatic mRNA levels of the genes involved in lipid metabolism and bile acid homeostasis were significantly reduced by LPLJ intervention (p < 0.05). These results suggest that LPLJ has a positive effect on modulating lipid metabolism and has the potential to be a functional food that can help prevent hyperlipidaemia.
Predictors of Polypharmacy Among Elderly Patients in China: The Role of Decision Involvement, Depression, and Taking Chinese Medicine Behavior
Authors: Chen Chaoyi , Feng Zhanchun , Fu Qian , Wang Jia , Zheng Zehao , Chen Hao , Feng Da
Published: December 2021

Introduction: The prevalence of polypharmacy is gradually increasing in geriatrics, which may contribute to adverse effects, such as potential drug–drug and drug–disease interactions. These side effects remain an important challenge in patient safety, which has a significant impact on mortality and incidence rate.

Aims: Therefore, this study aims to understand the epidemiology of polypharmacy and identify factors that have an impact on the management of potentially inappropriate prescribing.

Methods: This study is a cross-sectional study, analyzing the prescription data from 720 hospitalized patients aged 50+ with a random cluster sampling method. We used inverse probability treatment weighting (IPTW) method to group and match polypharmacy and non-polypharmacy patients, and logistic regression was conducted to explore the factors associated with polypharmacy.

Results: The prevalence of polypharmacy accounted for 50.14% among the old patients in this study. Female patients (67.34%) have more polypharmacy than male patients, and key predictors associated with polypharmacy in the logistic regression model included the following: domicile (AOR = 0.63, 95% CI 0.42–0.95), annual income (AOR = 0.38, 95% CI 0.20–0.70), the number of chronic diseases (AOR = 3.68, 95% CI 2.69–5.06), taking Chinese medicine (AOR = 1.70, 95% CI 1.22–2.36), decision involvement (AOR = 1.49 95% CI 1.10–2.03), and depression (AOR = 1.42, 95% CI 1.03–1.96).

Conclusion: Polypharmacy is common among the participants with chronic diseases in Hubei province, China. The study emphasizes that gerontology practitioners should be prudent in applying clinical guidelines to provide personalized, comprehensive assessment of decision making of prescriptions, especially in socioeconomically deprived areas.
Pharmacokinetic Evaluation of Eltrombopag in ITP Pediatric Patients
Authors: Dionisi Marco , Cairoli Sara , Simeoli Raffaele , De Gennaro Francesca , Paganelli Valeria , Carta Roberto , Rossi Francesca , Dionisi-Vici Carlo , Palumbo Giuseppe , Goffredo Bianca Maria
Published: December 2021

Background: Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, approved for refractory primary immune thrombocytopenia (ITP) in pediatric patients. In two pediatric RCTs, EPAG led to an improvement of platelet counts and a reduction in bleeding severity. However, a significant number of pediatric patients did not achieve the primary endpoints. We performed a pharmacokinetic evaluation of EPAG in pediatric patients with refractory ITP.

Methods: Outpatients aged from 1 to 17 y, affected by refractory ITP to first-line treatment, were enrolled for a pharmacokinetic assessment. The analysis of drug plasma concentration was performed by the LC-MS/MS platform. Non-compartmental and statistical subgroup analyses were carried out using the R package ncappc.

Results: Among 36 patients eligible for PK analysis, the median dose of EPAG given once daily was 50 mg. The EPAG peak occurs between 2 and 4 h with a population Cmax and AUC 0–24 geo-mean of 23, 38 μg/ml, and 275, 4 µg*h/mL, respectively. The pharmacokinetic profile of EPAG did not show a dose proportionality. Female patients showed a statistically significant increase of dose-normalized exposure parameters, increasing by 110 and 123% for Cmax and AUC 0–24, respectively, when compared to male patients. Patients aged 1–5 y showed values increased by more than 100% considering both exposure parameters, compared to older children. Furthermore, patients presenting complete response (83%), showed augmented EPAG exposure parameters compared to subjects with partial or no response.

Conclusion: These data highlight the need to further explore the variability of EPAG exposure and its pharmacokinetic/pharmacodynamic profile in pediatric patients also in a real-life setting.
Pre-Steady-State Kinetics of the SARS-CoV-2 Main Protease as a Powerful Tool for Antiviral Drug Discovery
Authors: Zakharova Maria Yu. , Kuznetsova Alexandra A. , Uvarova Victoria I. , Fomina Anastasiia D. , Kozlovskaya Liubov I. , Kaliberda Elena N. , Kurbatskaia Inna N. , Smirnov Ivan V. , Bulygin Anatoly A. , Knorre Vera D. , Fedorova Olga S. , Varnek Alexandre , Osolodkin Dmitry I. , Ishmukhametov Aydar A. , Egorov Alexey M. , Gabibov Alexander G. , Kuznetsov Nikita A.
Published: December 2021

The design of effective target-specific drugs for COVID-19 treatment has become an intriguing challenge for modern science. The SARS-CoV-2 main protease, Mpro, responsible for the processing of SARS-CoV-2 polyproteins and production of individual components of viral replication machinery, is an attractive candidate target for drug discovery. Specific Mpro inhibitors have turned out to be promising anticoronaviral agents. Thus, an effective platform for quantitative screening of Mpro-targeting molecules is urgently needed. Here, we propose a pre–steady-state kinetic analysis of the interaction of Mpro with inhibitors as a basis for such a platform. We examined the kinetic mechanism of peptide substrate binding and cleavage by wild-type Mpro and by its catalytically inactive mutant C145A. The enzyme induces conformational changes of the peptide during the reaction. The inhibition of Mpro by boceprevir, telaprevir, GC-376, PF-00835231, or thimerosal was investigated. Detailed pre–steady-state kinetics of the interaction of the wild-type enzyme with the most potent inhibitor, PF-00835231, revealed a two-step binding mechanism, followed by covalent complex formation. The C145A Mpro mutant interacts with PF-00835231 approximately 100-fold less effectively. Nevertheless, the binding constant of PF-00835231 toward C145A Mpro is still good enough to inhibit the enzyme. Therefore, our results suggest that even noncovalent inhibitor binding due to a fine conformational fit into the active site is sufficient for efficient inhibition. A structure-based virtual screening and a subsequent detailed assessment of inhibition efficacy allowed us to select two compounds as promising noncovalent inhibitor leads of SARS-CoV-2 Mpro.
A Novel Spider Toxin Inhibits Fast Inactivation of the Nav1.9 Channel by Binding to Domain III and Domain IV Voltage Sensors
Authors: Peng Shuijiao , Chen Minzhi , Xiao Zhen , Xiao Xin , Luo Sen , Liang Songping , Zhou Xi , Liu Zhonghua
Published: December 2021

Venomous animals have evolved to produce peptide toxins that modulate the activity of voltage-gated sodium (Nav) channels. These specific modulators are powerful probes for investigating the structural and functional features of Nav channels. Here, we report the isolation and characterization of δ-theraphotoxin-Gr4b (Gr4b), a novel peptide toxin from the venom of the spider Grammostola rosea. Gr4b contains 37-amino acid residues with six cysteines forming three disulfide bonds. Patch-clamp analysis confirmed that Gr4b markedly slows the fast inactivation of Nav1.9 and inhibits the currents of Nav1.4 and Nav1.7, but does not affect Nav1.8. It was also found that Gr4b significantly shifts the steady-state activation and inactivation curves of Nav1.9 to the depolarization direction and increases the window current, which is consistent with the change in the ramp current. Furthermore, analysis of Nav1.9/Nav1.8 chimeric channels revealed that Gr4b preferentially binds to the voltage-sensor of domain III (DIII VSD) and has additional interactions with the DIV VSD. The site-directed mutagenesis analysis indicated that N1139 and L1143 in DIII S3-S4 linker participate in toxin binding. In sum, this study reports a novel spider peptide toxin that may slow the fast inactivation of Nav1.9 by binding to the new neurotoxin receptor site-DIII VSD. Taken together, these findings provide insight into the functional role of the Nav channel DIII VSD in fast inactivation and activation.
Exosome-Mediated eCIRP Release From Macrophages to Induce Inflammation in Sepsis
Authors: Murao Atsushi , Tan Chuyi , Jha Alok , Wang Ping , Aziz Monowar
Published: December 2021

Extracellular cold-inducible RNA-binding protein (eCIRP) is an important damage-associated molecular pattern (DAMP). Despite our understanding of the potentially harmful effects of eCIRP in sepsis, how eCIRP is released from cells remains elusive. Exosomes are endosome-derived extracellular vesicles, which carry proteins, lipids, and nucleic acids to facilitate intercellular communication and several extracellular functions. We hypothesized that eCIRP is released via exosomes to induce inflammation in sepsis. Exosomes isolated from the supernatants of LPS-treated macrophage culture and serum of endotoxemia and polymicrobial sepsis mice showed high purity, as revealed by their unique median sizes ranging between 70 and 126 nm in diameter. eCIRP levels of the exosomes were significantly increased after LPS treatment in the supernatants of macrophage culture, mouse serum, and cecal ligation and puncture (CLP)-induced sepsis mouse serum. Protease protection assay demonstrated the majority of eCIRP was present on the surface of exosomes. Treatment of WT macrophages and mice with exosomes isolated from LPS-treated WT mice serum increased TNFα and IL-6 production. However, treatment with CIRP−/- mice serum exosomes significantly decreased these levels compared with WT exosome-treated conditions. CIRP−/- mice serum exosomes significantly decreased neutrophil migration in vitro compared with WT exosomes. Treatment of mice with serum exosomes isolated from CIRP−/- mice significantly reduced neutrophil infiltration into the peritoneal cavity. Our data suggest that eCIRP can be released via exosomes to induce cytokine production and neutrophil migration. Thus, exosomal eCIRP could be a potential target to inhibit inflammation.
Long Noncoding RNA and Circular RNA Expression Profiles of Monocyte-Derived Dendritic Cells in Autoimmune Hepatitis
Authors: Yang Fan , Fan Xiaoli , Liu Yifeng , Shen Yi , Zhao Shenglan , Zheng Yanyi , Men Ruoting , Xie Yan , Yang Li
Published: December 2021

Autoimmune hepatitis (AIH) is a chronic liver disease caused by disruption of liver immune homeostasis. The effect of dendritic cells (DCs) on the pathogenesis of AIH is not fully understood. Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play critical roles in the regulation of cell function. In this study, we analyzed the immunophenotypic characteristics of DCs in the peripheral blood. The percentage of mature DCs was higher in AIH patients than in healthy controls (HCs), and the proportion of mature DCs decreased after treatment. We isolated monocyte-derived DCs (moDCs) from the peripheral blood, obtained whole RNA-sequencing (RNA-seq) data for the moDCs from the two groups, and identified differentially expressed (DE) lncRNAs, circRNAs, miRNAs and mRNAs. In addition, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for the DE mRNAs and constructed competing endogenous RNA (ceRNA) networks. ENST00000543334, hsa_circ_0000279, and hsa_circ_0005076 were selected and validated by RT-qPCR. These results provide a possible molecular mechanism of DCs in the pathogenesis of AIH and identify some potential therapeutic targets.
Thirty Years in Silicon Photonics: A Personal View
Authors: Pavesi Lorenzo
Published: December 2021

Silicon Photonics, the technology where optical devices are fabricated by the mainstream microelectronic processing technology, was proposed almost 30 years ago. I joined this research field at its start. Initially, I concentrated on the main issue of the lack of a silicon laser. Room temperature visible emission from porous silicon first, and from silicon nanocrystals then, showed that optical gain is possible in low-dimensional silicon, but it is severely counterbalanced by nonlinear losses due to free carriers. Then, most of my research focus was on systems where photons show novel features such as Zener tunneling or Anderson localization. Here, the game was to engineer suitable dielectric environments (e.g., one-dimensional photonic crystals or waveguide-based microring resonators) to control photon propagation. Applications of low-dimensional silicon raised up in sensing (e.g., gas-sensing or bio-sensing) and photovoltaics. Interestingly, microring resonators emerged as the fundamental device for integrated photonic circuit since they allow studying the hermitian and non-hermitian physics of light propagation as well as demonstrating on-chip heavily integrated optical networks for reconfigurable switching applications or neural networks for optical signal processing. Finally, I witnessed the emergence of quantum photonic devices, where linear and nonlinear optical effects generate quantum states of light. Here, quantum random number generators or heralded single-photon sources are enabled by silicon photonics. All these developments are discussed in this review by following my own research path.
Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease
Authors: Houshyar Yashar , Massimino Luca , Lamparelli Luigi Antonio , Danese Silvio , Ungaro Federica
Published: December 2021

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.
Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases
Authors: Cai Zhensheng , Deng Xia , Jia Jue , Wang Dong , Yuan Guoyue
Published: December 2021

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.
Predictors of Psychological Distress and Coronavirus Fears in the First Recovery Phase of the Coronavirus Disease 2019 Pandemic in Germany
Authors: Biermann Miriam , Vonderlin Ruben , Mier Daniela , Witthöft Michael , Bailer Josef
Published: December 2021

Objectives: While previous research has mainly focused on the impact of the first acute phase of the COVID-19 pandemic on mental health, little empirical knowledge exists about depression, anxiety, and somatic symptom levels and possible predictors of symptom levels in the pandemic’s recovery phase. The present study aimed to analyze the mental burden of a convenience ample of the general German population during the first recovery phase of the pandemic and to identify significant predictors of symptom levels.

Methods: Standardized measures of anxiety (GAD-2), depression (PHQ-2), somatic symptoms (PHQ-15), and health anxiety, as well as measures of COVID-19 fears and possible vulnerability factors, were administered through a national, cross-sectional online survey (n = 2160, mean age 42.7 years, 75% female), asking participants for their current symptom levels and their symptom levels prior to the COVID-19 pandemic.

Results: Our findings show significantly elevated levels of depression, anxiety, somatic symptoms, and health anxiety in the recovery period compared to before the pandemic. The current prevalence rates based on self-reporting were 26.7% for depression, 24.5% for anxiety, and 29% for somatization. The strongest predictors of these symptom reports included domain-specific pre-existing symptom levels, neuroticism, biological COVID-19 risk factors, avoidance of illness information, and younger age. The most important predictors of COVID-19 fears were subjective COVID-19 risk perception, followed by pre-existing health anxiety, the number of biological COVID-19 risk factors, older age, neuroticism, avoidance of illness information and female gender.

Discussion: These findings indicate the need for specific psychological programs to help individuals with enhanced psychological and biological vulnerability to cope better with the mental distress experienced during all phases of the ongoing COVID-19 crisis.
Novel Evidence for the Increasing Prevalence of Unique Names in China: A Reply to Ogihara
Authors: Bao Han-Wu-Shuang , Cai Huajian , Jing Yiming , Wang Jianxiong
Published: December 2021

In this study, we aimed to address three comments proposed by Ogihara on a recent study where we found that unique names in China have become increasingly popular from 1950 to 2009. Using a large representative sample of Chinese names (N = 2.1 million), we replicated the increase in uniqueness of Chinese names from 1920 to 2005, especially since the 1970s, with multiple uniqueness indices based on name-character frequency and name-length deviation. Over the years, Chinese characters that are rare in daily life or naming practice were more often used in given names, and the length of given names became more deviant from typical practice (i.e., more one-character and three-character given names and higher standard deviation of name length). Taken together, these findings not only reconfirmed the increasing prevalence of unique names but also demonstrated the validity of various indices in assessing name uniqueness in China.
Creativity and Life Satisfaction in Spanish University Students. Effects of an Emotionally Positive and Creative Program
Authors: Caballero-García Presentación A. , Sánchez Ruiz Sara
Published: December 2021

There is an increasing demand by society that university students demonstrate competitive skills to enable them to achieve greater success when entering the workplace. Creativity and life satisfaction correlate positively with academic performance, productivity, and excellence in the working environment. The presence of creativity and emotional intelligence in the curriculum and teaching methods in Spanish universities, however, is surprisingly lacking. Studies that examine gender differences in these variables provide conflicting results. The purpose of our research is to analyse the changes produced in both creativity and life satisfaction in university students by a positive emotional and creative intervention and explore individual differences by gender. The methodology used was a quasi-experimental pre- test/post- test design with experimental/control groups. Three hundred university students (23% men and 77% women) from the Community of Madrid (Spain) completed three exercises that evaluated creativity and life satisfaction. The results show significantly higher results in creativity and life satisfaction in women, who continued to achieve high results after the intervention. Finally, we discuss the need for emotional and creative education in universities and focus on the employability and the guarantee of equal opportunities through the development of these competencies.
Early Adolescents’ Social Achievement Goals and Perceived Relational Support: Their Additive and Interactive Effects on Social Behavior
Authors: Shin Huiyoung
Published: December 2021

The current study examined the additive and interactive effects of early adolescents’ social achievement goals and perceived relational support from teachers and peers on their social behavior. Adolescents’ social achievement goals (i.e., social development, social demonstration-approach, and social demonstration-avoidance), perceived relational support from teachers and peers, and social behavior (i.e., overt and relational aggression, prosocial behavior, and anxious solitary behavior) were assessed in a sample of fifth and sixth graders (Mage= 12.5;N= 677) nested within 26 classrooms. Multilevel modeling results indicated that social goals and relational support from teachers and peers made additive contributions to adolescents’ social behavior. Results also indicated the evidence of interactive effects, such that relational support from teachers was negatively associated with overt and relational aggression primarily among adolescents who had high social demonstration-approach goals. Findings underscore the need to consider adolescents’ social goals in conjunction with their perceived relational support for educators and practitioners.
Do Children Need Adult Support During Sociodramatic Play to Develop Executive Functions? Experimental Evidence
Authors: Veresov Nikolai , Veraksa Aleksander , Gavrilova Margarita , Sukhikh Vera
Published: December 2021

The cultural-historical approach provides the deep theoretical grounds for the analysis of children’s play. Vygotsky suggested three critical features of play: switching to an imaginary situation, taking on a play role, and acting according to a set of rules defined by the role. Collaboration, finding ideas and materials for creating an imaginary situation, defining play roles, and planning the plot are complex tasks for children. However, the question is, do children need educator’s support during the play to develop their executive functions, and to what extent? This experimental study was aimed at answering this inquiry. The four modes of sociodramatic play were created which differed in the adult intervention, from non-involvement in the play to its entire organization. The play could be child-led (with adult help), adult-led, or free (without any adult intervention); and there was also a control group where the children heard the same stimulus stories as the other groups but then followed them up with a drawing activity instead of a play activity. The study revealed that, firstly, the ways of educator’s involvement in the play differed in their potential in respect to the development of executive functions, and, secondly, this influence was not equal for different components of executive functions. Free play in the experiment was not a beneficial condition for the development of any of the studied components of executive functions, compared to the conditions involving the participation of an adult in the play. Furthermore, the type of adult intervention stimulated the development of various executive functions. The entire organization of the play by the adult had a positive impact of their general development. In contrast, the adult’s assistance in the organization of the children’s play had a positive effect on the development of inhibitory control. The study results can be helpful when considering educational practices within a cultural-historical approach to engaging the potential of play in children’s learning and development around the world.
Genotoxicity of Marijuana in Mono-Users
Authors: Fabian-Morales Eunice , Fernández-Cáceres Carmen , Gudiño Adriana , Andonegui Elguera Marco A. , Torres-Arciga Karla , Escobar Arrazola Marco Armando , Tolentino García Laura , Alfaro Mora Yair E. , Oliva-Rico Diego A. , Cáceres Gutiérrez Rodrigo E. , Domínguez Ortíz Julieta , Castro Hernández Clementina , Herrera Montalvo Luis A. , Díaz-Negrete David Bruno , Reynoso-Noverón Nancy
Published: December 2021

Marijuana (Cannabissp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.
Studies on Children With Developmental Coordination Disorder in the Past 20 Years: A Bibliometric Analysis via CiteSpace
Authors: Wu Mei-Qin , Wu De-Qing , Hu Chun-Ping , Iao Lai-Sang
Published: December 2021

Children with developmental coordination disorder (DCD) have been commonly observed and drawn an increasing amount of attention over the past decades. The aim of the present study is to evaluate the origin, current hotspots, and research trends on children with DCD using a bibliometric tool. After searching with “children” and “developmental coordination disorder” as the “topic” and “title” words, respectively, 635 original articles with 12,559 references were obtained from the electronic databases, Web of Science Core Collection (WoSCC). CiteSpace V.5.7.R2 was used to perform the analysis. The number of publications in this field was increasing over the past two decades. John Cairney from the Department of Family Medicine, McMaster University, Canada, was found to be the most productive researcher. Meanwhile, McMaster University and Canada were the most productive research institution and country, respectively. Reference and journal co-citation analyses revealed the top landmark articles and clusters in this field. Clumsiness was the most strength burst keyword. Moreover, task, meta-analysis, difficulty, adult, and impact will be the active research hotspots in future. These findings provide the trends and frontiers in the field of children with DCD, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.
Measurement Properties of Canadian Agility and Movement Skill Assessment for Children Aged 9–12 Years Using Rasch Analysis
Authors: Chang Jindong , Yong Liming , Yan Hai , Wang Jibing , Song Naiqing
Published: December 2021

The Canadian Agility and Movement Skill Assessment (CAMSA) was recently widely used to assess fundamental motor skills in children. Although the CAMSA is reported to be reliable and valid, its measurement properties are not clear. This study aimed to examine the measurement properties of the CAMSA in a sample of Chinese children using Rasch analysis. The study sample was from 1,094 children aged 9–12 years in Zunyi City, Guizhou Province. Descriptive data were analyzed using SPSS 24.0 software, and the dichotomous data were analyzed by Winsteps version 4.5.4 and Facets 3.67.1 software performing Rasch analysis. The present study investigated CAMSA measurement characteristics by Rasch analysis, including the reliability of the rating instrument, unidimensionality, item-fit statistics, and differential item functioning (DIF). Inter-rater reliability and retest reliability showed that the CAMSA had a good internal consistency. Rasch analysis indicated that the CAMSA was unidimensional, locally independent, and had a good item-fit-statistic. Additionally, the CAMSA displayed a good fit for the item separation index (12.50 > 2.0), as well as for item reliability (0.99 > 0.90). However, the item difficulty of the CAMSA did not fit well with personal ability, and a significant DIF was found across genders. In the Chinese children sample test, the CAMSA demonstrated appropriate goodness-of-fit validity and rater reliability. Thus, future research will explore item difficulty and person ability fit, as well as DIF across genders.
The Environmental Factors Associated With Fatigue of Frontline Nurses in the Infection Disease Nursing Unit
Authors: Ma Ming , Adeney Michael , Long Hao , He Baojie
Published: December 2021

The workload in the Infection Disease Nursing Unit (IDNU) is increasing dramatically due to COVID-19, and leads to the prevalence of fatigue among the frontline nurses, threatening their health, and safety. The built environment and design could fundamentally affect the fatigue of nurses for a long-term perspective. This article aims to extract the environmental factors of IDNU and explore nurses' perceptions of these factors on the work-related fatigue. It would produce evidences for mitigating the fatigue by environmental interferons. A cross-sectional design was employed by combination of focus group interview and written survey. Environmental factors of IDNU were collected from healthcare design experts (n = 8). Nurses (n = 64) with frontline COVID-19 experiences in IDNU were recruited to assess these factors individually. Four environmental factors were identified as: Nursing Distance (ND), Spatial Crowdness (SC), Natural Ventilation, and Light (NVL), and Spatial Privacy (SP). Among them, ND was considered as the most influential factor on the physical fatigue, while SP was on the psychological fatigue. Generally, these environmental factors were found to be more influential on the physical fatigue than the psychological fatigue. Technical titles were found to be associated with the nurses' perceptions of fatigue by these environmental factors. Nurse assistant and practical nurse were more likely to suffer from the physical fatigue by these factors than senior nurse. The result indicated that environmental factors of IDNU were associated with the nurses' fatigue, particularly on the physical aspect. Environmental interventions of design could be adopted to alleviate the fatigue by these factors such as reducing the ND and improving the spatial privacy. The accurate interventional measures should be applied to fit nurses' conditions due to their technical titles. More attention should be given to the low-ranking nurses, who account for the majority and are much vulnerable to the physical fatigue by environmental factors.
Efficacy and Safety of Fusion Imaging in Radiofrequency Ablation of Hepatocellular Carcinoma Compared to Ultrasound: A Meta-Analysis
Authors: Jie Tao , Guoying Feng , Gang Tang , Zhengrong Shi , Maoping Li
Published: December 2021

Background: Radiofrequency ablation (RFA), generally performed under real-time guidance of ultrasound which is safe and effective, is a common minimally invasive therapy for treating hepatocellular carcinoma. Fusion imaging (FI) is a newly developed imaging method, which integrates CT/MRI accurate imaging and matches the characteristics of real-time ultrasound imaging, thereby providing a new approach to guide tumor ablation therapy. However, the efficacy and safety of FI as opposed to ultrasound in tumor ablation remains unclear.

Objective: The present study sought to evaluate the difference in the efficacy and safety between FI and ultrasound in radiofrequency surgery for the treatment of hepatocellular carcinoma through a metaanalysis.

Materials and Methods: Searching for studies comparing the efficacy and safety of FI and ultrasound in radiofrequency of hepatocellular carcinoma in PubMed, Embase, and Cochrane Library databases for articles published until April 2021. Random or fixed effect models were used for statistical analysis. Metaanalysis and sensitivity analysis were used on the included studies.

Results: A total of six studies met predefined inclusion criteria, and were finally included in the analysis. Sensitivity and subgroup analyses, based on predetermined patient characteristics, allowed minimization of bias. In the RFA of hepatocellular carcinoma, FI decreased 1-year overall survival (OS) when compared with ultrasound. But FI was not significantly different from ultrasound in terms of technical efficiency, 1-, 2-, and 3-year local tumor progression (LTP), complications, as well as 2-year OS. Subgroup analysis, based on tumor mean diameter, showed that FI reduced the rate of 1- and 2-year LTP in patients with tumors of mean diameter ≥15 mm when compared with ultrasound. Moreover, operative complications could be reduced in patients with tumor mean diameter <15 mm using FI, compared with ultrasound.

Conclusion: Overall, these results showed that FI may have some effects on improving efficacy and safety of thermal ablation in HCC patients, relative to ultrasound. However, it may be a more effective method for managing large lesions, as well as those that are difficult to ablate. Further large-scale and well-designed randomized controlled trials are needed to validate these findings.