bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible Changes in BDNF Expression in MK-801-Induced Hippocampal Astrocytes Through NMDAR/PI3K/ERK Signaling
Authors: Yu Wenjuan , Fang Hongwei , Zhang Lei , Hu Miaowen , He Sidi , Li Huafang , Zhu Hao
Published: May 2021

Dizocilpine (MK-801), a non-competitive N-methyl-D-aspartic acid receptor (NMDA-R) antagonist, can induce schizophrenia-like symptoms in healthy individuals, implicating NMDA-R hypofunction in disease pathogenesis. Brain-derived neurotrophic factor (BDNF) is also implicated in schizophrenia, and expression is regulated by NMDA-R activity, suggesting a functional link. We previously found that BDNF signaling was upregulated by MK-801 in cultured hippocampal astrocytes, but the underlying mechanism is not clear. To address this issue, the levels of BDNF expression and secretion were evaluated in hippocampal astrocytes incubated with MK-801 by ELISA and qPCR, with and without NMDA co-incubation or pretreatment of either the ERK1/2 inhibitor, PD98059 or the PI3K inhibitor, LY294002. The apoptosis, viability, and proliferation of the astrocytes were also examined. In the current study, we demonstrate that MK-801 treatment (20 μM for 5 days) enhances the proliferation of rat cultured hippocampal astrocytes. Expression of BDNF mRNA was enhanced after 24 h in MK-801, but returned to near baseline over the next 24 h in the continued presence of MK-801. However, two successive 24-h treatments enhanced BDNF expression. These application regimens had no effect on apoptosis or proliferation rate. Co-addition of NMDA significantly inhibited MK-801-induced upregulation of BDNF. Similarly, MK-801-induced BDNF upregulation was blocked by pretreatment with inhibitors of PI3K and ERK1/2, but not by inhibitors of p38 and JNK. These findings suggested that astrocytes may contribute to the acute neurological and behavioral response to MK-801 treatment via a transient increase in BDNF expression involving NMDA-R–PI3K–ERK signaling.
Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech
Authors: Abel Maria , Pfister Robert , Hussein Iman , Alsalloum Fahd , Onyinzo Christina , Kappl Simon , Zech Michael , Demmel Walter , Staudt Martin , Kudernatsch Manfred , Berweck Steffen
Published: May 2021

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce.

Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C>T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search.

Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably.

Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity.
The Expanding Horizon of Neural Stimulation for Hyperkinetic Movement Disorders
Authors: Latorre Anna , Rocchi Lorenzo , Sadnicka Anna
Published: May 2021

Novel methods of neural stimulation are transforming the management of hyperkinetic movement disorders. In this review the diversity of approach available is showcased. We first describe the most commonly used features that can be extracted from oscillatory activity of the central nervous system, and how these can be combined with an expanding range of non-invasive and invasive brain stimulation techniques. We then shift our focus to the periphery using tremor and Tourette's syndrome to illustrate the utility of peripheral biomarkers and interventions. Finally, we discuss current innovations which are changing the landscape of stimulation strategy by integrating technological advances and the use of machine learning to drive optimization.
Health-Risk Behaviors and Dietary Patterns Among Jordanian College Students: A Pilot Study
Authors: Alkhalidy Hana , Orabi Aliaa , Alzboun Tamara , Alnaser Khadeejah , Al-Shami Islam , Al-Bayyari Nahla
Published: May 2021

Background/Aims:Health promotion and the incorporation of health-protective behaviors in people's lifestyles have a great role in enhancing individuals' overall health and well-being. College students are at increased risk of developing unhealthy dietary and lifestyle behaviors. A cross-sectional pilot study was conducted to assess the health-risk behaviors among undergraduate college students at Jordan University of Science and Technology.

Methods:The final sample included 136 students, with a mean age of 21.1 ± 2.37 years, mostly females (69%). A self-reported questionnaire was used for data collection about dietary and lifestyle behaviors among college students. The questionnaire consisted of four parts: sociodemographic characteristics, body weight classifications, lifestyle behaviors, and dietary patterns and intake, and eating behaviors.

Results:Most of the students did not meet the daily recommendations for fruit (76%) and vegetable (82%) intake. Males were significantly consuming fast food more frequently (p= 0.019), and smoked cigarettes (p< 0.001) or hookah (p= 0.015) more frequently than did females. Further, the majority met the recommendations for physical activity (81%), but exceeded recommendations for sedentary behavior. Females were more likely to have normal weight or be underweight (OR = 4.865), to have a fear of weight gain (OR = 3.387), and to have the recommended sleeping hours (OR = 7.685) than were males.

Conclusion:The results indicate the health-risk behaviors and the gender-related differences among college students.
IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways
Authors: Nisar Muhammad Azhar , Zheng Qin , Saleem Muhammad Zubair , Ahmmed Bulbul , Ramzan Muhammad Noman , Ud Din Syed Riaz , Tahir Naeem , Liu Shuai , Yan Qiu
Published: May 2021

Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.
CRISPR/Cas9 uPAR Gene Knockout Results in Tumor Growth Inhibition, EGFR Downregulation and Induction of Stemness Markers in Melanoma and Colon Carcinoma Cell Lines
Authors: Biagioni Alessio , Chillà Anastasia , Del Rosso Mario , Fibbi Gabriella , Scavone Francesca , Andreucci Elena , Peppicelli Silvia , Bianchini Francesca , Calorini Lido , Li Santi Anna , Ragno Pia , Margheri Francesca , Laurenzana Anna
Published: May 2021

uPAR is a globular protein, tethered to the cell membrane by a GPI-anchor involved in several cancer-related properties and its overexpression commonly correlates with poor prognosis and metastasis. We investigated the consequences of uPAR irreversible loss in human melanoma and colon cancer cell lines, knocking out its expression by CRISPR/Cas9. We analyzed through flow cytometry, western blotting and qPCR, the modulation of the most known cancer stem cells-associated genes and the EGFR while we observed the proliferation rate exploiting 2D and 3D cellular models. We also generated uPAR “rescue” expression cell lines as well as we promoted the expression of only its 3’UTR to demonstrate the involvement of uPAR mRNA in tumor progression. Knocking out PLAUR, uPAR-encoding gene, we observed an inhibited growth ratio unexpectedly coupled with a significant percentage of cells acquiring a stem-like phenotype. In vivo experiments demonstrated that uPAR loss completely abrogates tumorigenesis despite the gained stem-like profile. Nonetheless, we proved that the reintroduction of the 3’UTR of PLAUR gene was sufficient to restore the wild-type status validating the hypothesis that such a region may act as a “molecular sponge”. In particular miR146a, by binding PLAUR 3’ UTR region might be responsible for uPAR-dependent inhibition of EGFR expression.
Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies
Authors: Abbas Hussein A. , Wierda William G.
Published: May 2021

Bruton tyrosine kinase (BTK) is a validated target for treatment of B-cell malignancies, and oral inhibitors of BTK have emerged as a standard of care for these diseases. Acalabrutinib is a second generation, highly selective, potent, covalent BTK inhibitor that exhibits minimal off-target activity in in vitro assays, providing the potential to improve tolerability over the first-in-class BTK inhibitor, ibrutinib. Acalabrutinib was approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) in the US in 2017 and 2019, respectively. Acalabrutinib is also undergoing trials for other B-cell malignancies, both as monotherapy and in combinations. In this review, we discuss results from clinical trials evaluating the efficacy and safety of acalabrutinib in patients with CLL, MCL, and Waldenstrom’s macroglobulinemia. Recent phase 3 data showed that acalabrutinib improved progression-free survival (PFS) compared with rituximab plus idelalisib or rituximab plus bendamustine in patients with relapsed/refractory CLL, and acalabrutinib with or without obinutuzumab improved PFS compared with chlorambucil plus obinutuzumab in patients with treatment-naïve CLL. Overall, acalabrutinib had a tolerable safety profile, with most adverse events being grade 1/2 severity (most commonly headache and diarrhea) and a low rate of discontinuation due to adverse events.
Evaluation of Cell Surface Vimentin Positive Circulating Tumor Cells as a Diagnostic Biomarker for Lung Cancer
Authors: Xie Xiaohong , Wang Liqiang , Wang Xinni , Fan Wan-Hung , Qin Yinyin , Lin Xinqing , Xie Zhanhong , Liu Ming , Ouyang Ming , Li Shiyue , Zhou Chengzhi
Published: May 2021

Background

Circulating tumor cells (CTCs) represent a collection of heterogeneous cells. Studies have shown epithelial CTCs and folate receptor (FR) positive CTCs could be used as diagnostic biomarkers for lung cancer (LC). This study aimed to determine whether cell surface vimentin (CSV) positive CTCs could be used as a biomarker for LC as well.

Methods

78 treatment-naïve non-small-cell lung cancer (NSCLC) patients, 21 patients with benign lung diseases (BLD) and 9 healthy donors (HD) were enrolled in this study. CTC detection was performed using CytoSorter® mesenchymal CTC kit (CSV). The correlation between CSV positive CTCs (CSV-CTCs) and LC patients’ clinicopathological characteristics would be evaluated, and diagnostic performances of CSV-CTCs and serum tumor markers for LC would be compared.

Results

CTC detection rates (average CTC count: range) in LC patients, patients with BLD and HD were 83.33% (2.47: 0-8), 47.62% (0.5: 0-3) and 0% (0: 0), respectively. CSV-CTCs could be used to differentiate LC patients from the patients with BLD and HD (P < 0.0001). CSV-CTCs were correlated with cancer stage, lymph node involvement and distant metastasis (P = 0.0062, 0.0014 and 0.0021, respectively). With a CTC cut-off value of 2, CSV-CTCs would have a sensitivity and specificity of 0.67 and 0.87, respectively, for diagnosing LC. CSV-CTC positive rates showed statistical differences among HD, BLD patients and LC patients at different cancer stages (P < 0.0001). Furthermore, CSV-CTC positive rates were positively correlated with tumor size, lymph node involvement and distant metastasis (P = 0.0163, 0.0196 and 0.03, respectively). CSV-CTCs had a better diagnostic performance than serum tumor makers, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125) and CA153.

Conclusion

When CTC cut-off is set to 2 CTCs per 7.5 mL of blood, CSV-CTCs can be considered as an acceptable biomarker for diagnosing LC with a sensitivity and specificity of 0.67 and 0.87, respectively.
Case Report: Spontaneous Intramural Hematoma of the Colon Secondary to Low Molecular Weight Heparin Therapy
Authors: Zhu Ye , Wang Chao , Xu Chao , Liu Jia
Published: May 2021

Background: Hematoma of the colon is a rare hemorrhagic complication that affects patients accepting low molecular weight heparin (LMWH) therapy. Only scarce cases of colon hematoma have been reported, usually in children or patients accepting warfarin therapy.

Case summary: A 76-year-old Chinese man was diagnosed with atrial fibrillation and heart failure, with cardiac function NYHA grade III on March 21, 2018. This patient was given LMWH for anticoagulation therapy and developed a colon hematoma on the third day of hospitalization. Abdominal computed tomography (CT) showed the thickening of areas of the colon up to 110 mm × 78 mm in thickness, which was a symptom of colon hematoma. The patient underwent conservative treatment successfully. On March 27, the patient’s abdominal pain was alleviated, and a CT scan showed that the intestinal hematoma was absorbed.

Conclusions: The most frequent minor bleeding events of LMWH anticoagulation are hemorrhage and subcutaneous hematoma. This case demonstrated that bowel hematoma despite its low incidence should be considered as an ADR of LMWH therapy, especially among patients who present with gastrointestinal symptoms.
Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats
Authors: Yao Xiang , Yang Wenping , Ren Zhendong , Zhang Haoran , Shi Dafa , Li Yanfei , Yu Ziyang , Guo Qiu , Yang Guangwei , Gu Yingjiang , Zhao Hairong , Ren Ke
Published: May 2021

Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro.

Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis.

Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p < 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p < 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p < 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1β in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p < 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p < 0.01).

Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α.
Informing Pharmacokinetic Models With Physiological Data: Oral Population Modeling of L-Serine in Humans
Authors: Bosley J. R. , Björnson Elias , Zhang Cheng , Turkez Hasan , Nielsen Jens , Uhlen Mathias , Borén Jan , Mardinoglu Adil
Published: May 2021

To determine how to set optimal oral L-serine (serine) dose levels for a clinical trial, existing literature was surveyed. Data sufficient to set the dose was inadequate, and so an (n = 10) phase I-A calibration trial was performed, administering serine with and without other oral agents. We analyzed the trial and the literature data using pharmacokinetic (PK) modeling and statistical analysis. The therapeutic goal is to modulate specific serine-related metabolic pathways in the liver using the lowest possible dose which gives the desired effect since the upper bound was expected to be limited by toxicity. A standard PK approach, in which a common model structure was selected using a fit to data, yielded a model with a single central compartment corresponding to plasma, clearance from that compartment, and an endogenous source of serine. To improve conditioning, a parametric structure was changed to estimate ratios (bioavailability over volume, for example). Model fit quality was improved and the uncertainty in estimated parameters was reduced. Because of the particular interest in the fate of serine, the model was used to estimate whether serine is consumed in the gut, absorbed by the liver, or entered the blood in either a free state, or in a protein- or tissue-bound state that is not measured by our assay. The PK model structure was set up to represent relevant physiology, and this quantitative systems biology approach allowed a broader set of physiological data to be used to narrow parameter and prediction confidence intervals, and to better understand the biological meaning of the data. The model results allowed us to determine the optimal human dose for future trials, including a trial design component including IV and tracer studies. A key contribution is that we were able to use human physiological data from the literature to inform the PK model and to set reasonable bounds on parameters, and to improve model conditioning. Leveraging literature data produced a more predictive, useful model.
Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway
Authors: Mou Shan-Qi , Zhou Zi-Ying , Feng Hong , Zhang Nan , Lin Zheng , Aiyasiding Xiahenazi , Li Wen-Jing , Ding Wen , Liao Hai-Han , Bian Zhou-Yan , Tang Qi-Zhu
Published: May 2021

Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.

Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.

Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.

Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.
Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation
Authors: Aihaiti Yirixiati , Song Cai Yong , Tuerhong Xiadiye , Ni Yang Yan , Ma Yao , Shi Zheng Hai , Xu Ke , Xu Peng
Published: May 2021

Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of RA fibroblast-like synoviocytes (RA-FLSs) is the critical factor in progression of RA. Naringin has been reported to exert anti-inflammatory and antioxidant effect in acute and chronic animal models of RA. However, the therapeutic effect and underlying mechanisms of naringin in human RA-FLS remain unclear. Based on network pharmacology, the corresponding targets of naringin were identified using SwissTargetPrediction database, STITCH database, and Comparative Toxicogenomics Database. Deferentially expressed genes (DEGs) in RA were obtained from the GEO database. The protein–protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to pathogenesis of RA were integrated manually. Further, in vitro studies were carried out based on network pharmacology. 99 target genes were intersected between targets of naringin and DEGs. The PPI network and topological analysis indicated that IL-6, MAPK8, MMP-9, TNF, and MAPK1 shared the highest centrality among all. GO analysis and KEGG analysis indicated that target genes were mostly enriched in (hsa05200) pathways in cancer, (hsa05161) hepatitis B, (hsa04380) osteoclast differentiation, (hsa04151) PI3K-Akt signaling pathway, and (hsa05142) Chagas disease (American trypanosomiasis). In vitro studies revealed that naringin exposure was found to promote apoptosis of RA-FLS, increased the activation of caspase-3, and increased the ratio of Bax/Bcl-2 in a dose-dependent manner. Furthermore, treatment of naringin attenuated the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in TNF-ɑ–induced RA-FLS. Moreover, treatment of naringin inhibited the phosphorylation of Akt and ERK in RA-FLS. Network pharmacology provides a predicative strategy to investigate the therapeutic effects and mechanisms of herbs and compounds. Naringin inhibits inflammation and MMPs production and promotes apoptosis in RA-FLS via PI3K/Akt and MAPK/ERK signaling pathways.
Metabolic Aspects of Adenosine Functions in the Brain
Authors: Garcia-Gil Mercedes , Camici Marcella , Allegrini Simone , Pesi Rossana , Tozzi Maria Grazia
Published: May 2021

Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.
Gompertz Law in Clean Foam Coalescence
Authors: Oh Gun , Gonçalves Marta , Weon Byung Mook
Published: May 2021

Clean foams tend to age with time through sequential coalescence events. This study evaluates aging dynamics in clean foams by measuring bubble populations from coalescence simulation experiments and adopting biological population dynamics analysis. The population dynamics of bubbles in clean foams during coalescence show that the mortality rates of individual bubbles change exponentially with time, regardless of initial simulation conditions, consistent with the Gompertz mortality law commonly observed in biological aging. This result would be beneficial in understanding the aging dynamics of clean foams.
Laser-Induced Breakdown Spectroscopy for the Discrimination of Explosives Based on the ReliefF Algorithm and Support Vector Machines
Authors: Zhao Yu , Wang Q. Q. , Cui Xutai , Teng Geer , Wei Kai , Liu Haida
Published: May 2021

Real-time explosive detectors must be developed to facilitate the rapid implementation of appropriate protective measures against terrorism. We report a simple yet efficient methodology to classify three explosives and three non-explosives by using laser-induced breakdown spectroscopy. However, the similarity existing among the spectral emissions collected from the explosives resulted in the difficulty of separating samples. We calculated the weights of lines by using the ReliefF algorithm and then selected six line regions that could be identified from the arrangement of weights to calculate the area of each line region. A multivariate statistical method involving support vector machines was followed for the construction of the classification model. Several models were constructed using full spectra, 13 lines, and 100 lines selected by the arrangement of weights and areas of the selected line regions. The highest correct classification rate of the model reached 100% by using the six line regions.
Development of a Novel Web Camera-Based Contact-Free Major Depressive Disorder Screening System Using Autonomic Nervous Responses Induced by a Mental Task and Its Clinical Application
Authors: Unursaikhan Batbayar , Tanaka Nobuaki , Sun Guanghao , Watanabe Sadao , Yoshii Masako , Funahashi Kazuki , Sekimoto Fumihiro , Hayashibara Fumiaki , Yoshizawa Yutaka , Choimaa Lodoiravsal , Matsui Takemi
Published: May 2021

Background

To increase the consultation rate of potential major depressive disorder (MDD) patients, we developed a contact-type fingertip photoplethysmography-based MDD screening system. With the outbreak of SARS-CoV-2, we developed an alternative to contact-type fingertip photoplethysmography: a novel web camera-based contact-free MDD screening system (WCF-MSS) for non-contact measurement of autonomic transient responses induced by a mental task.

Methods

The WCF-MSS measures time-series interbeat intervals (IBI) by monitoring color tone changes in the facial region of interest induced by arterial pulsation using a web camera (1920 × 1080 pixels, 30 frames/s). Artifacts caused by body movements and head shakes are reduced. The WCF-MSS evaluates autonomic nervous activation from time-series IBI by calculating LF (0.04–0.15 Hz) components of heart rate variability (HRV) corresponding to sympathetic and parasympathetic nervous activity and HF (0.15–0.4 Hz) components equivalent to parasympathetic activities. The clinical test procedure comprises a pre-rest period (Pre-R; 140 s), mental task period (MT; 100 s), and post-rest period (Post-R; 120 s). The WCF-MSS uses logistic regression analysis to discriminate MDD patients from healthy volunteers via an optimal combination of four explanatory variables determined by a minimum redundancy maximum relevance algorithm: HF during MT (HFMT), the percentage change of LF from pre-rest to MT (%ΔLF(Pre–R⇒MT)), the percentage change of HF from pre-rest to MT (%ΔHF(Pre–R⇒MT)), and the percentage change of HF from MT to post-rest (%ΔHF(MT⇒Post–R)). To clinically test the WCF-MSS, 26 MDD patients (16 males and 10 females, 20–58 years) were recruited from BESLI Clinic in Tokyo, and 27 healthy volunteers (15 males and 12 females, 18–60 years) were recruited from Tokyo Metropolitan University and RICOH Company, Ltd. Electrocardiography was used to calculate HRV variables as references.

Result

The WCF-MSS achieved 73% sensitivity and 85% specificity on 5-fold cross-validation. IBI correlated significantly with IBI from reference electrocardiography (r= 0.97,p< 0.0001). Logit scores and subjective self-rating depression scale scores correlated significantly (r= 0.43,p< 0.05).

Conclusion

The WCF-MSS seems a promising contact-free MDD screening apparatus. This method enables web camera built-in smartphones to be used as MDD screening systems.
The Pitfalls of in vivo Cardiac Physiology in Genetically Modified Mice – Lessons Learnt the Hard Way in the Creatine Kinase System
Authors: Lygate Craig A.
Published: May 2021

In order to fully understand gene function, at some point, it is necessary to study the effects in an intact organism. The creation of the first knockout mouse in the late 1980’s gave rise to a revolution in the field of integrative physiology that continues to this day. There are many complex choices when selecting a strategy for genetic modification, some of which will be touched on in this review, but the principal focus is to highlight the potential problems and pitfalls arising from the interpretation ofin vivocardiac phenotypes. As an exemplar, we will scrutinize the field of cardiac energetics and the attempts to understand the role of the creatine kinase (CK) energy buffering and transport system in the intact organism. This story highlights the confounding effects of genetic background, sex, and age, as well as the difficulties in interpreting knockout models in light of promiscuous proteins and metabolic redundancy. It will consider the dose-dependent effects and unintended consequences of transgene overexpression, and the need for experimental rigour in the context ofin vivophenotyping techniques. It is intended that this review will not only bring clarity to the field of cardiac energetics, but also aid the non-expert in evaluating and critically assessing data arising fromin vivogenetic modification.
Political Preferences, Knowledge, and Misinformation About COVID-19: The Case of Brazil
Authors: Gramacho Wladimir , Turgeon Mathieu , Kennedy John , Stabile Max , Mundim Pedro Santos
Published: May 2021

The COVID-19 pandemic has led to a vast research agenda focusing on how citizens acquire knowledge about the virus and the health expert guidelines to protect themselves and their close ones against it. While many countries and regions have been accounted for, there still remains a substantial gap with respect to public opinion about the virus in Latin America, most notably in Brazil, which currently has the second highest in number of fatalities in the world. In this article, we employ a national survey of Brazilians (n = 2,771) to measure and explain knowledge and misinformation about the coronavirus and its illness, COVID-19. Our focus concerns the role of political preferences in a context of high elite polarization with a sitting government that has systematically downplayed the risks associated with the coronavirus and its illness. Our findings are clear: political preferences play a substantial role in explaining differences in knowledge about the coronavirus and COVID-19, more than conventional determinants of learning like motivation, ability, and opportunities. Specifically, we find that supporters of President Jair Bolsonaro—an avid science and COVID-19 denier—know significantly less about the coronavirus and its illness and are more likely to believe in a conspiracy theory that claims that the coronavirus was purposefully created in a Chinese laboratory to promote China's economic power, when compared to Brazilians who are less supportive of him and his government. Our findings carry important implications for how Brazilians take informational cues from political elites in that—even in a major event like a global pandemic—supporters of the president are as likely as ever to “follow their leader” and deny expert-backed scientific evidence.
The Effect of Social Support on Athlete Burnout in Weightlifters: The Mediation Effect of Mental Toughness and Sports Motivation
Authors: Shang Yao , Yang Shi-Yong
Published: May 2021

Objectives: Athlete burnout is a crucial concern affecting the development and athletic performance of young weightlifters. To reduce or relieve the prevalence of athlete burnout, this study examined the relationship across social support, sports motivation, mental toughness, and athlete burnout in weightlifters.

Methods: A total of 315 weightlifters aged 17–28 years old (151 males, 164 females; Mage = 18.89 years, SD = 3.66) from Sichuan, Chongqing, and Shanxi in China participated in this survey. The Perceived Available Support in Sport Questionnaire (PASS-Q), Sports Motivation Questionnaire (SMQ), Sports Mental Toughness Questionnaire (SMTQ), and Athlete Burnout Questionnaire (ABQ) were used in this study. SPSS Statistics 19.0, AMOS 21.0, and PROCESS 3.0 macro were used to analyze the collected data.

Results: The results indicated that weightlifters’ social support could negatively significantly affect athlete burnout [beta = −0.398; 95% confidence interval (CI): −0.3699, −0.2184; P < 0.05) via mental toughness and sports motivation. The mediation analysis revealed that they had partial mediating effect, including three paths: First, social support had a direct effect on athlete burnout (beta = −0.150; 95% CI: −0.1824, −0.0397; P < 0.05); second, sport mental toughness had a mediating effect on athlete burnout (beta = −0.113; 95% CI: −0.1703, −0.0631; P < 0.05); and finally, sports motivation had a mediating effect on athlete burnout (beta = −0.124; 95% CI: −0.1751, −0.0793; P < 0.05).

Conclusion: The findings revealed that social support could inhibit or prevent athlete burnout via mental toughness and sports motivation; thus, to decrease or relieve the prevalence of burnout in weightlifters, it is an important solution to enhance their social support.
Something Old, Something New, Something Borrowed, Something Taboo: Interaction and Creativity in Humour
Authors: Maraev Vladislav , Breitholtz Ellen , Howes Christine , Larsson Staffan , Cooper Robin
Published: May 2021

In this paper we treat humorous situations as a series of events underpinned by topoi, principles of reasoning recognised within a socio-cultural community. We claim that humorous effect in jokes and other discourse is often created by the juxtaposition of topoi evoked. A prerequisite for this is that there is a shift where the interpreter of the discourse updates their information state with regard to a second topos being evoked. This view of humour is consistent with an incremental analysis of dialogue, and we therefore argue that interaction is central both for humour creation and interpretation. We point out some different ways in which topoi are juxtaposed in humorous dialogues as well as in jokes published in social media or in joke books, and take jokes from the coronavirus pandemic as an example because this makes lots of new topoi available and therefore offers the opportunity of creating novel jokes based on the juxtaposition of the new and existing topoi. We explore how the mechanisms of inference in dialogue can be applied to humour through the four elements from our title: old (existing), new (not previously existing), borrowed (associated with a different situation) and taboo (inappropriate in the context).
Self-Sacrifice Is Not the Only Way to Practice Filial Piety for Chinese Adolescents in Conflict With Their Parents
Authors: Wu Chih-Wen , Yeh Kuang-Hui
Published: May 2021

We applied the theoretical perspective of the dual filial piety model to consider the diversity of parent–child conflict resolution strategies in order to determine whether Chinese adolescents use strategies other than self-sacrifice to practice filial piety when in conflict with their parents. Study 1 utilized a cross-sectional design with 247 valid responses. The structural equation modeling analysis indicated that Taiwanese adolescents’ authoritarian filial piety (AFP) beliefs are positively related to use of a self-sacrifice strategy, and reciprocal filial piety (RFP) beliefs are positively related to use of compatibility and compromise strategies. Adolescents’ AFP and RFP beliefs are negatively related to use of utility and escape strategies. Study 2 applied a temporal separation procedure with a 1-year lag to remedy common method variance bias. Analysis of 1,063 valid responses replicated the findings of Study 1 and indicated that adolescents’ function-oriented appraisal of conflict can play a mediating role between RFP and the use of the compatibility and compromise strategies. These findings broaden the understanding of filial piety in modern Chinese societies and have implications for adolescents’ well-being and family life.
Down and High: Reflections Regarding Depression and Cannabis
Authors: Langlois Catherine , Potvin Stéphane , Khullar Atul , Tourjman Smadar Valérie
Published: May 2021

In light of the recent changes in the legal status of cannabis in Canada, the understanding of the potential impact of the use of cannabis by individuals suffering from depression is increasingly considered as being important. It is fundamental that we look into the existing literature to examine the influence of cannabis on psychiatric conditions, including mood disorders. In this article, we will explore the relationship that exists between depression and cannabis. We will examine the impact of cannabis on the onset and course of depression, and its treatment. We have undertaken a wide-ranging review of the literature in order to address these questions. The evidence from longitudinal studies suggest that there is a bidirectional relationship between cannabis use and depression, such that cannabis use increases the risk for depression and vice-versa. This risk is possibly higher in heavy users having initiated their consumption in early adolescence. Clinical evidence also suggests that cannabis use is associated with a worse prognosis in individuals with major depressive disorder. The link with suicide remains controversial. Moreover, there is insufficient data to determine the impact of cannabis use on cognition in individuals with major depression disorder. Preliminary evidence suggesting that the endogenous cannabinoid system is involved in the pathophysiology of depression. This will need to be confirmed in future positron emission tomography studies. Randomized controlled trials are needed to investigate the potential efficacy of motivational interviewing and/or cognitive behavioral therapy for the treatment of cannabis use disorder in individuals with major depressive major disorder. Finally, although there is preclinical evidence suggesting that cannabidiol has antidepressant properties, randomized controlled trials will need to properly investigate this possibility in humans.
Factors Associated With Workplace Bullying and the Mental Health of Construction Industry Apprentices: A Mixed Methods Study
Authors: Ross Victoria , Mathieu Sharna L. , Wardhani Rachmania , Gullestrup Jorgen , Kõlves Kairi
Published: May 2021

Young Australian males working in the construction industry are twice as likely to take their own lives than other young Australian males. This group is also at high risk for poor mental health and alcohol and other drug related harm. Previous research has indicated a bullying culture within this industry, directed particularly toward apprentices and those new to the industry. This Australian study applied an exploratory sequential mixed methods design to explore issues faced by apprentices, estimate the prevalence of bullying and explore the factors associated with bullying and the mental health of apprentices. The results revealed that a substantial proportion of construction industry apprentices experience workplace bullying, are exposed to suicidal behaviors, and personally experience suicidal ideation. Multivariate analyses showed that bullying in apprentices was significantly associated with greater psychological distress, as well as being a 3rd year apprentice or not currently in an active apprenticeship. Results also indicated that bullying may be associated with substance use, lower levels of well-being, working nights away from home, the plumbing trades, and working for larger organizations. The outcomes from this study have important implications for the construction industry and will be vital for informing policies and evidence-based interventions to address bullying and mental health in this sector.
Individual Insomnia Symptom and Increased Hazard Risk of Cardiocerebral Vascular Diseases: A Meta-Analysis
Authors: Hu Shiyu , Lan Tao , Wang Yang , Ren Lijie
Published: May 2021

Objective: Previous studies suggested that insomnia was associated with an increased risk of cardiocerebral vascular diseases (CVDs) but not clear in different insomnia symptoms. We performed a meta-analysis to investigate the association of individual insomnia symptoms and risk of CVDs.

Methods: In this meta-analysis, we systematically searched published articles by using electronic databases including PubMed, Cochrane Library, MedLine, and Google Scholar. Studies were enrolled if they indicated clear insomnia symptoms, prospective, and evaluated the association of insomnia symptoms and CVD outcome in adults free of CVDs at baseline.

Results: There were seven prospective cohort studies with sample sizes ranging from 2,960 to 487,200 included in this meta-analysis. Mean follow-up duration was 10.6 years. Insomnia symptoms of having difficulty initiating or maintaining sleep (DIS or DMS), non-restorative sleep (NRS), and early morning awakening (EMA) were analyzed in this study. All studies were compared under a random-effects model. NRS, DIS, and DMS were, respectively, related to 16% [hazard ratio (HR) 1.16, 95% CI 1.07–1.24], 22% (HR 1.22, 95% CI 1.06–1.40), and 14% (HR 1.14, 95% CI 1.02–1.27) higher risk of first-ever CVD incidence during the follow-up. Based on our analysis, EMA was not a risk factor of CVDs (HR 1.06, 95% CI 0.99–1.13).

Conclusion: This study suggested that symptoms of DIS, DIM, or NRS were associated with a higher risk of CVD incidence in insomnia patients free of CVDs at baseline. But this association was not significant in insomnia patients complaining about EMA.