bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol on the Metabolic Reprogramming in Liver: Implications for Advanced Atherosclerosis
Authors: Ma Ying , Li Dongliang , Liu Wenfeng , Liu Xiaoxiao , Xu Yingqi , Zhong Xinrui , Zhi Fengnan , Jia Xueling , Jiang Yanan , Fan Yuhua
Published: October 2021

Background/Aims: Atherosclerosis (AS) is one of the major leading causes of death globally, which is highly correlated with metabolic abnormalities. Resveratrol (REV) exerts beneficial effects on atherosclerosis. Our aim is to clarify the involvement of liver metabolic reprogramming and the atheroprotective effects of REV.

Methods: ApoE-deficient mice were administered with normal diet (N), high-fat diet (H), or HFD with REV (HR). Twenty-four weeks after treatment, Oil Red O staining was used to assess the severity of AS. Non-targeted metabolomics was employed to obtain metabolic signatures of the liver from different groups.

Results: High-fat diet–induced AS was alleviated by REV, with less lipid accumulation in the lesions. The metabolic profiles of liver tissues from N, H, and HR groups were analyzed. A total of 1,146 and 765 differentially expressed features were identified between N and H groups, and H and HR groups, respectively. KEGG enrichment analysis uncovered several metabolism-related pathways, which are potential pathogenesis mechanisms and therapeutic targets including “primary bile acid biosynthesis,” “phenylalanine metabolism,” and “glycerophospholipid metabolism.” We further conducted trend analysis using 555 metabolites with one-way ANOVA, where p < 0.05 and PLS-DA VIP >1. We found that REV could reverse the detrimental effect of high-fat diet–induced atherosclerosis. These metabolites were enriched in pathways including “biosynthesis of unsaturated fatty acids” and “intestinal immune network for IgA production.” The metabolites involved in these pathways could be the potential biomarkers for AS-related liver metabolic reprogramming and the mechanism of REV treatment.

Conclusions: REV exerted atheroprotective effects partially by modulating the liver metabolism.
Dynamic Changes of Serum Heart Type-Fatty Acid Binding Protein in Cancer Patients Treated With Immune Checkpoint Inhibitors
Authors: Yuan Ming , Zang Li , Xu Aiqing , Gong Mengqi , Liu Qing , Huo Bin , Wang Jinhuan , Fu Huaying , Tse Gary , Roever Leonardo , Li Guangping , Wang Haitao , Liu Tong
Published: October 2021

Objective: Immune checkpoint inhibitors (ICIs) are effective anti-cancer drugs that can improve survival in cancer patients, but their use may be associated with adverse cardiovascular side effects. Therefore, there is a clinical unmet need to identify non-invasive biomarker to detect subclinical cardiac toxicity after ICI treatment. The aim of this study is to examine the plasma levels of biomarkers in cancer survivors who were treated with ICIs.

Patients and Methods: In a cohort of 19 cancer patients, biomarkers were evaluated at baseline, 1 month, 3 and 6 months after ICI administration. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included cardiac troponin I (cTnI), high-sensitivity C-reactive protein (Hs-CRP), N-terminal pro–B-type natriuretic peptide (NT-pro BNP), CK (creatine kinase), CK-MB (creatine kinase-MB), Pentraxin-related protein 3 (PTX3), growth differentiation factor 15 (GDF-15), heart type-fatty acid binding protein (H-FABP) and galectin 3 (Gal-3).

Results: H-FABP, but not other biomarkers, were increased at 3 months, which persisted at 6 months (529.28 ± 312.83 vs. 752.33 ± 283.65 vs. 808.00 ± 289.69 pg/ml, p = 0.031 and p = 0.013). Left ventricular ejection fraction (63.00 ± 4.15% vs. 63.74 ± 4.07%, p > 0.05) was not significantly reduced at this time point.

Conclusions: H-FABP, but not other biomarkers, were increased in patients who were treated using ICIs. H-FABP might be a more sensitive biomarker to detect ICI-related subclinical myocardial damage than traditional cardiac biomarkers.
Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors
Authors: Strawn Jeffrey R. , Poweleit Ethan A. , Uppugunduri Chakradhara Rao S. , Ramsey Laura B.
Published: October 2021

Therapeutic drug monitoring (TDM) is uncommon in child and adolescent psychiatry, particularly for selective serotonin reuptake inhibitors (SSRIs)—the first-line pharmacologic treatments for depressive and anxiety disorders. However, TDM in children and adolescents offers the opportunity to leverage individual variability of antidepressant pharmacokinetics to shed light on non-response and partial response, understand drug-drug interactions, evaluate adherence, and characterize the impact of genetic and developmental variation in pharmacokinetic genes. This perspective aims to educate clinicians about TDM principles and examines evolving uses of TDM in SSRI-treated youths and their early applications in clinical practice, as well as barriers to TDM in pediatric patients. First, the impact of pharmacokinetic genes on SSRI pharmacokinetics in youths could be used to predict tolerability and response for some SSRIs (e.g., escitalopram). Second, plasma concentrations are significantly influenced by adherence, which may relate to decreased efficacy. Third, pharmacometric analyses reveal interactions with proton pump inhibitors, oral contraceptives, cannabinoids, and SSRIs in youths. Rapid developments in TDM and associated modeling have enhanced the understanding of variation in SSRI pharmacokinetics, although the treatment of anxiety and depressive disorders with SSRIs in youths often remains a trial-and-error process.
Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
Authors: Moriyama Hiroshi , Nomura Sadahiro , Imoto Hirochika , Inoue Takao , Fujiyama Yuichi , Haji Kohei , Maruta Yuichi , Ishihara Hideyuki , Suzuki Michiyasu
Published: October 2021

Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.
A Study on the Attention of Yoga and Its Development Based on Complex Network Theory
Authors: Li Pengchao , Miao Qinghong , Meng Yuchi , Ning Jie , Long Jing , Huang Junya
Published: October 2021

Taking Baidu search index as the data source, this research collects yoga-related data in various provinces in China, analyzes the public’s attention to yoga on the Internet from the perspective of the complex network theory, so as to dig out characteristics of those who are interested in yoga as well as the temporal and spatial change of yoga attention from 2011 to 2020. Then, by transforming the time series into a network through the VG model and HVG model, the paper analyzes the network characteristics and predicts the popularity of yoga. Furthermore, the publicity of yoga and the public’s attention to it are analyzed, considering the policy, national education level, the influence of TV, mobile phone and other communication equipment, so as to help the market to provide corresponding products and services in a targeted manner and to promote the healthy development of the yoga industry.
Fecal Bile Acids Profile of Crewmembers Consuming the Same Space Food in a Spacecraft Simulator
Authors: Dong Hai-Sheng , Shen Qi-Bing , Lan Hai-Yun , Zhao Wei , Cao Ping , Chen Pu
Published: October 2021

Introduction: Recently, bile acids (BAs) are increasingly being considered as unique metabolic integrators and not just for the cholesterol metabolism and absorption of dietary lipids. Human BAs profiles are evolved to be individual under different environmental, dietary, and inherited factors. Variation of BAs for crewmembers from freshly prepared kitchen diets to wholly prepackaged industrial foods in a ground-based spacecraft simulator has not been clearly interpreted.

Methods: Three crewmembers were confined in a docked spacecraft and supplied with 7 days periodic wholly prepackaged industrial foods for 50 days. Fecal samples were collected before entry in the spacecraft simulator and after evacuation. Determination of 16 kinds of BAs was carried out by high-performance liquid chromatography tandem mass spectrometry method.

Results: Bile acids metabolism is sensitive to diet and environment transition from freshly prepared kitchen diets in the canteen to wholly prepackaged industrial foods in a ground-based spacecraft simulator, which is also specific to individuals. A significant positive relationship with a coefficient of 0.85 was found for primary BAs as chenodeoxycholic acid (CDCA) and cholic acid (CA), and a significantly negative relationship with a coefficient of −0.69 for secondary BAs as lithocholic acid (LCA) and deoxycholic acid (DCA).

Discussion: The profile of BA metabolism of individuals who share the same food in the same environment appears to be unique, suggesting that the inherent ability of different individuals to adapt to diet and environment varies. Since the transition from the free diet in open space to whole prepackaged space food diet in a space station simulator causes the variations of BAs pool in an individual manner, assessment of BA metabolic profiles provides a new perspective for personalized diet design, astronaut selection and training, and space flight diet acclimatization.
The Abscopal Effects of Cranial Irradiation Induce Testicular Damage in Mice
Authors: Guo Ling , Qin Tong-Zhou , Liu Li-Yuan , Lai Pan-Pan , Xue Yi-Zhe , Jing Yun-Tao , Zhang Wei , Li Wei , Li Jing , Ding Gui-Rong
Published: September 2021

To investigate whether the abscopal effects of cranial irradiation (C-irradiation) cause testicular damage in mice, male C57BL/6 mice (9weeks of age) were randomly divided into a sham irradiation group, a shielded group and a C-irradiation group and administered sham/shielded irradiation or C-irradiation at a dose rate of 2.33Gy/min (5Gy/d for 4 d consecutively). All mice were sacrificed at 4weeks after C-irradiation. We calculated the testis index, observed testicular histology by haematoxylin-eosin (HE) staining and observed testicular ultrastructure by transmission electron microscopy. Western blotting was used to determine the protein levels of Bax, Bcl-2, Cleaved caspase 3, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in the testes of mice. Immunofluorescence staining was performed to detect the expression of Cleaved caspase 3 and 3β hydroxysteroid dehydrogenase (3βHSD), and a TUNEL assay was used to confirm the location of apoptotic cells. The levels of testosterone (T), GDNF and SCF were measured by ELISA. We also evaluated the sperm quality in the cauda epididymides by measuring the sperm count, abnormality, survival rate and apoptosis rate. The results showed that there was no significant difference in testicular histology, ultrastructure or sperm quality between the shielded group and sham group. Compared with the sham/shielded group, the C-irradiation group exhibited a lower testis index and severely damaged testicular histology and ultrastructure at 4weeks after C-irradiation. The levels of apoptosis in the testes increased markedly in the C-irradiation group, especially in spermatogonial stem cells. The levels of serum T and testicular 3βHSD did not obviously differ between the sham group and the C-irradiation group, but the levels of GDNF and SCF in the testes increased in the C-irradiation group, compared with the sham group. In addition, the sperm count and survival rate decreased in the C-irradiation group, while the abnormality and apoptosis rate increased. Under these experimental conditions, the abscopal effects of C-irradiation induced testicular damage with regard to both structure and function and ultimately decreased sperm quality in mice. These findings provide novel insights into prevention and treatment targets for male reproductive damage induced by C-irradiation.
A Damaged-Informed Lung Ventilator Model for Ventilator Waveforms
Authors: Agrawal Deepak K. , Smith Bradford J. , Sottile Peter D. , Albers David J.
Published: October 2021

Motivated by a desire to understand pulmonary physiology, scientists have developed physiological lung models of varying complexity. However, pathophysiology and interactions between human lungs and ventilators, e.g., ventilator-induced lung injury (VILI), present challenges for modeling efforts. This is because the real-world pressure and volume signals may be too complex for simple models to capture, and while complex models tend not to be estimable with clinical data, limiting clinical utility. To address this gap, in this manuscript we developed a new damaged-informed lung ventilator (DILV) model. This approach relies on mathematizing ventilator pressure and volume waveforms, including lung physiology, mechanical ventilation, and their interaction. The model begins with nominal waveforms and adds limited, clinically relevant, hypothesis-driven features to the waveform corresponding to pulmonary pathophysiology, patient-ventilator interaction, and ventilator settings. The DILV model parameters uniquely and reliably recapitulate these features while having enough flexibility to reproduce commonly observed variability in clinical (human) and laboratory (mouse) waveform data. We evaluate the proof-in-principle capabilities of our modeling approach by estimating 399 breaths collected for differently damaged lungs for tightly controlled measurements in mice and uncontrolled human intensive care unit data in the absence and presence of ventilator dyssynchrony. The cumulative value of mean squares error for the DILV model is, on average, ≈12 times less than the single compartment lung model for all the waveforms considered. Moreover, changes in the estimated parameters correctly correlate with known measures of lung physiology, including lung compliance as a baseline evaluation. Our long-term goal is to use the DILV model for clinical monitoring and research studies by providing high fidelity estimates of lung state and sources of VILI with an end goal of improving management of VILI and acute respiratory distress syndrome.
Lactate as an Astroglial Signal Augmenting Aerobic Glycolysis and Lipid Metabolism
Authors: Horvat Anemari , Zorec Robert , Vardjan Nina
Published: September 2021

Astrocytes, heterogeneous neuroglial cells, contribute to metabolic homeostasis in the brain by providing energy substrates to neurons. In contrast to predominantly oxidative neurons, astrocytes are considered primarily as glycolytic cells. They take up glucose from the circulation and in the process of aerobic glycolysis (despite the normal oxygen levels) produce L-lactate, which is then released into the extracellular space via lactate transporters and possibly channels. Astroglial L-lactate can enter neurons, where it is used as a metabolic substrate, or exit the brain via the circulation. Recently, L-lactate has also been considered to be a signaling molecule in the brain, but the mechanisms of L-lactate signaling and how it contributes to the brain function remain to be fully elucidated. Here, we provide an overview of L-lactate signaling mechanisms in the brain and present novel insights into the mechanisms of L-lactate signaling via G-protein coupled receptors (GPCRs) with the focus on astrocytes. We discuss how increased extracellular L-lactate upregulates cAMP production in astrocytes, most likely viaL-lactate-sensitive Gs-protein coupled GPCRs. This activates aerobic glycolysis, enhancing L-lactate production and accumulation of lipid droplets, suggesting that L-lactate augments its own production in astrocytes (i.e., metabolic excitability) to provide more L-lactate for neurons and that astrocytes in conditions of increased extracellular L-lactate switch to lipid metabolism.
Seasonality and Species Specificity of Submerged Macrophyte Biomass in Shallow Lakes Under the Influence of Climate Warming and Eutrophication
Authors: Wu Haoping , Hao Beibei , Jo Hyunbin , Cai Yanpeng
Published: October 2021

Climate warming and eutrophication caused by anthropogenic activities strongly affect aquatic ecosystems. Submerged macrophytes usually play a key role in shallow lakes and can maintain a stable clear state. It is extremely important to study the effects of climate warming and eutrophication on the growth of submerged macrophytes in shallow lakes. However, the responses of submerged macrophytes to climate warming and eutrophication are still controversial. Additionally, the understanding of the main pathways impacting submerged macrophytes remains to be clarified. In addition, the influence of seasonality on the growth responses of submerged macrophytes to climate warming and eutrophication requires further elucidation. In this study, we conducted a series of mesocosm experiments with four replicates across four seasons to study the effects of rising temperature and nutrient enrichment on the biomass of two submerged macrophytes, Potamogeton crispus and Elodea canadensis. Our results demonstrated the seasonality and species specificity of plant biomass under the influence of climate warming and eutrophication, as well as the main explanatory factors in each season. Consistent with the seasonal results, the overall results showed that E. canadensis biomass was directly increased by rising temperature rather than by nutrient enrichment. Conversely, the overall results showed that P. crispus biomass was indirectly reduced by phosphorus enrichment via the strengthening of competition among primary producers. Distinct physiological and morphological traits may induce species-specific responses of submerged macrophytes to climate warming and eutrophication, indicating that further research should take interspecies differences into account.
Water Sorption and Desorption of Isolated Cuticles From Three Woody Species With Focus on Ilex aquifolium
Authors: Vega Clara , Valbuena-Carabaña María , Gil Luis , Fernández Victoria
Published: October 2021

The cuticle is a lipid-rich layer that protects aerial plant organs against multiple stress factors such as dehydration. In this study, cuticle composition and structure in relation to water loss are examined in a broad ecophysiological context, taking into consideration leaf age and side from Ilex aquifolium (holly) in comparison with Eucalyptus globulus (eucalypt) and Prunus laurocerasus (cherry laurel). Enzymatically isolated cuticular membranes from holly leaves were studied under three treatment conditions: natural (no chemical treatment), after dewaxing, and after methanolysis, and the rate of water loss was assessed. Structural and chemical changes were evaluated using different microscopy techniques and by Fourier transform infrared (FTIR) spectroscopy. The potential mechanisms of solute absorption by holly leaves were additionally evaluated, also testing if its prickly leaf margin may facilitate uptake. The results indicate that the treatment conditions led to structural changes, and that chemical composition was hardly affected because of the occurrence of cutan. Structural changes led to more hydrophilic adaxial surfaces, which retained more water and were more efficient than natural cuticles, while changes were not significant for abaxial surfaces. Across natural cuticles, age was a significant factor for eucalypt but not for holly. Young eucalypt cuticles were the group that absorbed more water and had the lowest water loss rate. When comparing older leaf cuticles of the three species, cherry laurel was found to absorb more water, which was, however, lost more slowly, compared with the other species. Evidence was gained that holly leaves can absorb foliar-applied solutes (traced after calcium chloride application) through the adaxial and abaxial surfaces, the adaxial mid veins, and to a lower extent, the spines. In conclusion, for the species examined, the results show variations in leaf cuticle composition and structure in relation to leaf ontogeny, and water sorption and desorption capacity.
Global Investigation of TBL Gene Family in Rose (Rosa chinensis) Unveils RcTBL16 Is a Susceptibility Gene in Gray Mold Resistance
Authors: Tian Yu , Zhang Shiya , Liu Xintong , Zhang Zhao
Published: October 2021

The TRICHOME BIREFRINGENCE-LIKE (TBL) family is an important gene family engaged in the O-acetylation of cell wall polysaccharides. There have been a few reports showing that TBL participated in the resistance against phytopathogens in Arabidopsis and rice. However, no relevant studies in rose (Rosa sp.) have been published. In this study, a genome-wide analysis of the TBL gene family in rose was presented, including their phylogenetic relationships, gene structure, chromosomal positioning, and collinearity analysis. The phylogenetic analysis revealed a total of 50 RcTBL genes in the rose genome, and they are unevenly distributed across all seven chromosomes. The occurrence of gene duplication events suggests that both the whole genome duplication and partial duplication may play a role in gene duplication of RcTBLs. The analysis of Ka/Ks showed that the replicated RcTBL genes underwent mainly purifying selection with limited functional differentiation. Gene expression analysis indicated that 12 RcTBLs were down-regulated upon the infection of Botrytis cinerea, the causal agent of the gray mold disease of rose. These RcTBLs may be a sort of candidate genes for regulating the response of rose to B. cinerea. Through virus-induced gene silencing, RcTBL16 was shown to be associated with susceptibility to gray mold in rose. Through this study, meaningful information for further studies on the function of the TBL protein family in rose is provided.
Functional Analyses of Flavonol Synthase Genes From Camellia sinensis Reveal Their Roles in Anther Development
Authors: Shi Yufeng , Jiang Xiaolan , Chen Linbo , Li Wei-Wei , Lai Sanyan , Fu Zhouping , Liu Yajun , Qian Yumei , Gao Liping , Xia Tao
Published: October 2021

Flavonoids, including flavonol derivatives, are the main astringent compounds of tea and are beneficial to human health. Many researches have been conducted to comprehensively identify and characterize the phenolic compounds in the tea plant. However, the biological function of tea flavonoids is not yet understood, especially those accumulated in floral organs. In this study, the metabolic characteristics of phenolic compounds in different developmental stages of flower buds and various parts of the tea flower were investigated by using metabolomic and transcriptomic analyses. Targeted metabolomic analysis revealed varying accumulation patterns of different phenolic polyphenol compounds during flowering; moreover, the content of flavonol compounds gradually increased as the flowers opened. Petals and stamens were the main sites of flavone and flavonol accumulation. Compared with those of fertile flowers, the content of certain flavonols, such as kaempferol derivatives, in anthers of hybrid sterile flowers was significantly low. Transcriptomic analysis revealed different expression patterns of genes in the same gene family in tea flowers. The CsFLSb gene was significantly increased during flowering and was highly expressed in anthers. Compared with fertile flowers, CsFLSb was significantly downregulated in sterile flowers. Further functional verification of the three CsFLS genes indicated that CsFLSb caused an increase in flavonol content in transgenic tobacco flowers and that CsFLSa acted in leaves. Taken together, this study highlighted the metabolic properties of phenolic compounds in tea flowers and determined how the three CsFLS genes have different functions in the vegetative and reproductive organs of tea plants. Furthermore, CsFLSb could regulated flavonol biosynthesis in tea flowers, thus influencing fertility. This research is of great significance for balancing the reproductive growth and vegetative growth of tea plants.
The Problematic Concept of Native Speaker in Psycholinguistics: Replacing Vague and Harmful Terminology With Inclusive and Accurate Measures
Authors: Cheng Lauretta S. P. , Burgess Danielle , Vernooij Natasha , Solís-Barroso Cecilia , McDermott Ashley , Namboodiripad Savithry
Published: October 2021

Though the term NATIVE SPEAKER/SIGNER is frequently used in language research, it is inconsistently conceptualized. Factors, such as age, order, and context of acquisition, in addition to social/cultural identity, are often differentially conflated. While the ambiguity and harmful consequences of the term NATIVE SPEAKER have been problematized across disciplines, much of this literature attempts to repurpose the term in order to include and/or exclude certain populations. This paper problematizes NATIVE SPEAKER within psycholinguistics, arguing that the term is both unhelpful to rigorous theory construction and harmful to marginalized populations by reproducing normative assumptions about behavior, experience, and identity. We propose that language researchers avoid NATIVE SPEAKER altogether, and we suggest alternate ways of characterizing language experience/use. The vagueness of NATIVE SPEAKER can create problems in research design (e.g., through systematically excluding certain populations), recruitment (as participants’ definitions might diverge from researchers’), and analysis (by distilling continuous factors into under-specified binary categories). This can result in barriers to cross-study comparison, which is particularly concerning for theory construction and replicability. From a research ethics perspective, it matters how participants are characterized and included: Excluding participants based on binary/essentialist conceptualizations of nativeness upholds deficit perspectives toward multilingualism and non-hegemonic modes of language acquisition. Finally, by implicitly assuming the existence of a critical period, NATIVE SPEAKER brings with it theoretical baggage which not all researchers may want to carry. Given the issues above and how ‘nativeness’ is racialized (particularly in European and North American contexts), we ask that researchers consider carefully whether exclusion of marginalized/minoritized populations is necessary or justified—particularly when NATIVE SPEAKER is used only as a way to achieve linguistic homogeneity. Instead, we urge psycholinguists to explicitly state the specific axes traditionally implied by NATIVENESS that they wish to target. We outline several of these (e.g., order of acquisition, allegiance, and comfort with providing intuitions) and give examples of how to recruit and describe participants while eschewing NATIVE SPEAKER. Shifting away from harmful conventions, such as NATIVE SPEAKER, will not only improve research design and analysis, but also is one way we can co-create a more just and inclusive field.
Psychometric Properties of a German Online Version of the Gudjonsson Suggestibility Scale 1
Authors: Hein Fee-Elisabeth , Scheuble Vera , Beauducel André , Leue Anja
Published: October 2021

Suggestibility is a trait dimension that has been differentiated into Yield and Shift dimensions. Yield refers to the susceptibility to suggestive item content in a first question series (Yield 1) and a second question series following negative feedback (Yield 2). Shift describes the tendency to change answers over the two series of questions depending on social pressure. This study aimed at investigating the psychometric properties and the factor structure of a German online version of the Gudjonsson Suggestibility Scale 1 (GSS 1) and measurement invariance of suggestibility scores for gender and research institution. A total of N=560 (n=287 female; age: M=24.20, SD=4.60years) students participated in the study. We present Stanine norms for the application of the online GSS 1. Results supported the theoretical basis of the GSS by revealing the two expected suggestibility factors: Yield and Shift. As expected, a leading factor and a non-leading factor were identified for Yield 1 and Yield 2 and a single factor for Shift. We report psychometric properties (e.g., item difficulty, part-whole corrected item-total correlations, reliability coefficients). We compare the factorial structure of the German online GSS 1 with former versions of the GSS 1. Our data suggest widely measurement invariance for gender and research institution on Yield 1 and Yield 2.
Navigational Behavior of Humans and Deep Reinforcement Learning Agents
Authors: Rigoli Lillian M. , Patil Gaurav , Stening Hamish F. , Kallen Rachel W. , Richardson Michael J.
Published: October 2021

Rapid advances in the field of Deep Reinforcement Learning (DRL) over the past several years have led to artificial agents (AAs) capable of producing behavior that meets or exceeds human-level performance in a wide variety of tasks. However, research on DRL frequently lacks adequate discussion of the low-level dynamics of the behavior itself and instead focuses on meta-level or global-level performance metrics. In doing so, the current literature lacks perspective on the qualitative nature of AA behavior, leaving questions regarding the spatiotemporal patterning of their behavior largely unanswered. The current study explored the degree to which the navigation and route selection trajectories of DRL agents (i.e., AAs trained using DRL) through simple obstacle ridden virtual environments were equivalent (and/or different) from those produced by human agents. The second and related aim was to determine whether a task-dynamical model of human route navigation could not only be used to capture both human and DRL navigational behavior, but also to help identify whether any observed differences in the navigational trajectories of humans and DRL agents were a function of differences in the dynamical environmental couplings.
Construct Validation of Self-Determination Theory in Second Language Scale: The Bifactor Exploratory Structural Equation Modeling Approach
Authors: Alamer Abdullah
Published: September 2021

The present study aimed to assess the construct validity of the Self-Determination Theory in Second Language Scale (SDT-L2; Alamer, 2021). The study involved 266 undergraduate students learning English as a second language (L2) in Saudi Arabia. The factorial structure of the SDT-L2 was examined using the advanced bifactor-Exploratory Structural Equation Modeling (ESEM) method. The scale provided adequate composite reliability and the bifactor ESEM provided unique details about the multidimensionality of the scale which accounted for the specific constructs (i.e., intrinsic, identified, introjected, and external regulations) and the general constructs (i.e., autonomous motivation and controlled motivation), and allowed for assessment of convergent and discriminant validity. Predictive validity was established by showing that autonomous motivation significantly predicted L2 performance, while controlled motivation did not. Overall, the study demonstrated the usefulness of the bifactor ESEM for construct validation purposes and the results showed that SDT-L2 is a valid scale to assess students’ L2 motivation based on SDT perspective.
A Preliminary Exploration of Factors Affecting a University Entrepreneurship Ecosystem
Authors: Wang Xuyan , Sun Xiaoyang , Liu Shuhua , Mu Chen
Published: September 2021

This study examines the factors that affect the formation and operation of the university entrepreneurship ecosystem (UEE). Employing the case-study methodology, this research attempts to provide an evidence-based analysis of the existing theoretical framework of the UEE and verify the role of elements in it through empirical experience as described in semi-structured interviews with 33 respondents on and off an American university. Findings reveal that extracurricular activities, networks, entrepreneurial culture, and leadership have an important impact on the formation and operation of the UEE. Specifically, compared with formal courses, as important carriers, extracurricular activities have a more positive impact on the entrepreneurship of students. Different levels of networks can promote the circulation and exchange of resources. Culture is an important factor in forming and promoting individual entrepreneurial behavior and their agglomeration in the UEE. Clear vision and long-term commitments to entrepreneurship, namely leadership, play a leading role in the formation and development of a UEE.
Cross-Dialectal Novel Word Learning and Borrowing
Authors: Wu Junru , Zheng Wei , Han Mengru , Schiller Niels O.
Published: October 2021

The objective of this paper was to study the cognitive processes underlying cross-dialectal novel word borrowing and loanword establishment in a Standard-Chinese-to-Shanghainese (SC-SH) auditory lexical learning and borrowing experiment. To investigate these underlying cognitive processes, SC-SH bi-dialectals were compared with SC monolectals as well as bi-dialectals of SC and other Chinese dialects (OD) to investigate the influence of short-term and long-term linguistic experience. Both comprehension and production borrowings were tested. This study found that early and proficient bi-dialectism, even if it is not directly related to the recipient dialect of lexical borrowing, has a protective effect on the ability of cross-dialectal lexical borrowing in early adulthood. Bi-dialectals tend to add separate lexical representations for incidentally encountered dialectal variants, while monolectals tend to assimilate dialectal variants to standard forms. Bi-dialectals, but not monolectals, use etymologically related morphemes between the source and recipient dialects to create nonce-borrowing compounds. Dialectal variability facilitates lexical borrowingviaenriching instead of increasing the short-term lexical experience of learners. The long-term bi-dialectal experience of individuals, as well as their short-term exposure to each specific loanword, may collectively shape the route of lexical evolution of co-evolving linguistic varieties.
Feeling Anxious Amid the COVID-19 Pandemic: Factors Associated With Anxiety Symptoms Among Nurses in Hong Kong
Authors: Yeung Nelson Chun-yiu , Wong Eliza Lai-yi , Cheung Annie Wai-ling , Yeoh Eng-kiong , Wong Samuel Yeung-shan
Published: October 2021

Background: The coronavirus (COVID-19) pandemic has increased the burden for the medical systems around the world. In Hong Kong, the pandemic not only affects the local populations, but also the healthcare workers. Healthcare workers, especially nurses, involving in COVID-19 treatments are highly susceptible to adverse psychological outcomes (e.g., anxiety symptoms). Studies have shown that socio-demographic characteristics, COVID-19-specific worries, and work settings-related variables are associated with healthcare workers' well-being during the COVID-19 pandemic. However, relevant studies for nurses in Hong Kong are limited. This study examined the psychosocial correlates of anxiety symptoms among nurses in Hong Kong.

Methods: Nurses (N = 1,510) working in hospitals and community settings were recruited through nursing associations in Hong Kong between August 8, 2020 and September 22, 2020. They were invited to complete a cross-sectional survey measuring their anxiety symptoms, sociodemographic characteristics, COVID-19-specific worries, and satisfaction with work and workplace pandemic-control guidelines.

Results: 17.2% of nurses reported moderate to severe levels of anxiety symptoms. Results from hierarchical regressions found that higher COVID-19-specific worries (contracting COVID-19, family members contracting COVID-19 due to their nursing work, insufficient protective equipment at workplace) (βs ranged from 0.07 to 0.20, ps < 0.01), higher perceived stigma of being a healthcare worker (β = 0.18, p < 0.001), and lower work satisfaction (β = −0.21, p < 0.001) were associated with higher anxiety symptoms.

Conclusion: A moderate proportion of nurses in Hong Kong did report levels of anxiety symptoms amid the COVID-19 pandemic. Futures studies could focus on the contributing factors of anxiety symptoms to design for effective strategies to promote nurses' well-being during pandemic situations.
Label-Free Liquid Chromatography–Mass Spectrometry Proteomic Analysis of the Urinary Proteome for Measuring the Escitalopram Treatment Response From Major Depressive Disorder
Authors: Huan Yuhang , Wei Jing , Zhou Jingjing , Liu Min , Yang Jian , Gao Youhe
Published: September 2021

Major depressive disorder (MDD) is a common mental disorder that can cause substantial impairments in quality of life. Clinical treatment is usually built on a trial-and-error method, which lasts ~12 weeks to evaluate whether the treatment is efficient, thereby leading to some inefficient treatment measures. Therefore, we intended to identify early candidate urine biomarkers to predict efficient treatment response in MDD patients. In this study, urine samples were collected twice from 19 respondent and 10 non-respondent MDD patients receiving 0-, 2-, and 12-week treatments with escitalopram. Differential urinary proteins were subsequently analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Our two pilot tests suggested that the urine proteome reflects changes associated with major depressive disorder at the early stage of treatment measures. On week 2, 20 differential proteins were identified in the response group compared with week 0, with 14 of these proteins being associated with the mechanisms of MDD. In the non-response group, 60 differential proteins were identified at week 2, with 28 of these proteins being associated with the mechanisms of MDD. In addition, differential urinary proteins at week 2 between the response and non-response groups can be clearly distinguished by using orthogonal projection on latent structure-discriminant analysis (OPLS-DA). Our small pilot tests indicated that the urine proteome can reflect early effects of escitalopram therapy between the response and non-response groups since at week 2, which may provide potential early candidate urine biomarkers to predict efficient treatment measures in MDD patients.
Changes in Regional Homogeneity of Medication-Free Major Depressive Disorder Patients With Different Onset Ages
Authors: Zhang Zijian , Chen Yayun , Wei Wei , Yang Xiao , Meng Yajing , Yu Hua , Guo Wanjun , Wang Qiang , Deng Wei , Li Tao , Ma Xiaohong
Published: October 2021

Background: Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on onset ages. Our aim was to determine whether regional homogeneity (ReHo) changes in early-onset depression (EOD) and late-onset depression (LOD) are different, which could also delineate EOD and LOD.

Methods: Ninety-one MDD patients and 115 healthy controls (HCs) were recruited, and resting-state functional magnetic resonance imaging data were collected. The ReHo comparison was conducted using analysis of variance.

Results: Compared with HCs, MDD patients showed decreased ReHo in the left precentral gyrus and the left middle cingulum area, and increased ReHo in the left middle orbital frontal gyrus and superior temporal gyrus. Compared with LOD patients, young HC separately, EOD patients had significantly increased ReHo in the right inferior frontal triangular gyrus and the left postcentral gyrus. However, compared with young HC, EOD patients showed decreased ReHo in the right superior frontal gyrus/supplementary motor area and the right medial frontal gyrus. ReHo in the right inferior frontal triangular gyrus was negatively correlated with the severity of cognitive disturbance in LOD patients (r = −0.47, p = 0.002), but not in EOD patients (r = 0.21, p = 0.178).

Conclusion: MDD patients with different onset ages may have different pathophysiological mechanisms; the EOD patients had more abnormal ReHo than LOD patients in the prefrontal lobe, especially the right inferior frontal triangular gyrus.
Clinical Utility of Functional Near-Infrared Spectroscopy for Assessment and Prediction of Suicidality: A Systematic Review
Authors: Lee Y. Q. , Tay Gabrielle W. N. , Ho Cyrus S. H.
Published: October 2021

Introduction: Suicide is a pressing psychiatric concern worldwide with no established biomarker. While there is some evidence of the clinical utility of functional near-infrared spectroscopy (fNIRS) in assessing and predicting suicidality, no systematic review of such evidence has been conducted to date. Therefore, this review aimed to systematically review and gather evidence from existing studies that used fNIRS signals to assess suicidality and its associated changes in the brain, and those that examined how such signals correlated with suicide symptomatology.

Methods: PubMed, EMBASE, and Cochrane Library databases were used in a systematic literature search for English-language articles published between 2000 and December 19, 2020 that focused on the utility of fNIRS for (i) assessing suicidality and its associated changes in the brain, and (ii) correlating with suicide symptomatology. Studies were included if they utilised fNIRS to evaluate variations in fNIRS-measured cerebral hemodynamic responses in patients with different mental disorders (e.g., major depressive disorder, schizophrenia), as well as in healthy controls, of any age group. Quality of evidence was assessed using the Newcastle-Ottawa quality assessment scale.

Results: A total of 7 cross-sectional studies were included in this review, all of which had acceptable quality. Across all studies, fNIRS demonstrated reduced cerebral hemodynamic changes in suicidal individuals when compared to non-suicidal individuals. One study also demonstrated the potential of fNIRS signals in correlating with the severity of suicidality.

Conclusions: This review provides a comprehensive, updated review of evidence supporting the clinical utility of fNIRS in the assessment and prediction of suicidality. Further studies involving larger sample sizes, standardised methodology, and longitudinal follow-ups are needed.
Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments
Authors: Verdura Edgard , Pérez-Cano Laura , Sabido-Vera Rubén , Guney Emre , Hyvelin Jean-Marc , Durham Lynn , Gomez-Mancilla Baltazar
Published: September 2021

Fragile X syndrome (FXS) is the most frequent monogenic cause of autism or intellectual disability, and research on its pathogenetic mechanisms has provided important insights on this neurodevelopmental condition. Nevertheless, after 30 years of intense research, efforts to develop treatments have been mostly unsuccessful. The aim of this review is to compile evidence from existing research pointing to clinical, genetic, and therapeutic response heterogeneity in FXS and highlight the need of implementing precision medicine-based treatments. We comment on the high genetic and phenotypic heterogeneity present in FXS, as a contributing factor to the difficulties found during drug development. Given that several clinical trials have showed a non-negligeable fraction of positive responders to drugs targeting core FXS symptoms, we propose that success of clinical trials can be achieved by tackling the underlying heterogeneity in FXS by accurately stratifying patients into drug-responder subpopulations. These precision medicine-based approaches, which can be first applied to well-defined monogenic diseases such as FXS, can also serve to define drug responder profiles based on specific biomarkers or phenotypic features that can associate patients with different genetic backgrounds to a same candidate drug, thus repositioning a same drug for a larger number of patients with NDDs.
Directly and Indirectly Targeting the Glycine Modulatory Site to Modulate NMDA Receptor Function to Address Unmet Medical Needs of Patients With Schizophrenia
Authors: Pei Ju-Chun , Luo Da-Zhong , Gau Shiang-Shin , Chang Chia-Yuan , Lai Wen-Sung
Published: October 2021

Schizophrenia is a severe mental illness that affects ~1% of the world's population. It is clinically characterized by positive, negative, and cognitive symptoms. Currently available antipsychotic medications are relatively ineffective in improving negative and cognitive deficits, which are related to a patient's functional outcomes and quality of life. Negative symptoms and cognitive deficits are unmet by the antipsychotic medications developed to date. In recent decades, compelling animal and clinical studies have supported the NMDA receptor (NMDAR) hypofunction hypothesis of schizophrenia and have suggested some promising therapeutic agents. Notably, several NMDAR-enhancing agents, especially those that function through the glycine modulatory site (GMS) of NMDAR, cause significant reduction in psychotic and cognitive symptoms in patients with schizophrenia. Given that the NMDAR-mediated signaling pathway has been implicated in cognitive/social functions and that GMS is a potential therapeutic target for enhancing the activation of NMDARs, there is great interest in investigating the effects of direct and indirect GMS modulators and their therapeutic potential. In this review, we focus on describing preclinical and clinical studies of direct and indirect GMS modulators in the treatment of schizophrenia, including glycine, D-cycloserine, D-serine, glycine transporter 1 (GlyT1) inhibitors, and D-amino acid oxidase (DAO or DAAO) inhibitors. We highlight some of the most promising recently developed pharmacological compounds designed to either directly or indirectly target GMS and thus augment NMDAR function to treat the cognitive and negative symptoms of schizophrenia. Overall, the current findings suggest that indirectly targeting of GMS appears to be more beneficial and leads to less adverse effects than direct targeting of GMS to modulate NMDAR functions. Indirect GMS modulators, especially GlyT1 inhibitors and DAO inhibitors, open new avenues for the treatment of unmet medical needs for patients with schizophrenia.