bluuebunny/crossref_metadata_2025 huggingface dataset:
Voxel-Wise Feature Selection Method for CNN Binary Classification of Neuroimaging Data
Authors: Messina Domenico , Borrelli Pasquale , Russo Paolo , Salvatore Marco , Aiello Marco
Published: April 2021

Voxel-wise group analysis is presented as a novel feature selection (FS) technique for a deep learning (DL) approach to brain imaging data classification. The method, based on a voxel-wise two-sample t-test and denoted as t-masking, is integrated into the learning procedure as a data-driven FS strategy. t-Masking has been introduced in a convolutional neural network (CNN) for the test bench of binary classification of very-mild Alzheimer’s disease vs. normal control, using a structural magnetic resonance imaging dataset of 180 subjects. To better characterize the t-masking impact on CNN classification performance, six different experimental configurations were designed. Moreover, the performances of the presented FS method were compared to those of similar machine learning (ML) models that relied on different FS approaches. Overall, our results show an enhancement of about 6% in performance when t-masking was applied. Moreover, the reported performance enhancement was higher with respect to similar FS-based ML models. In addition, evaluation of the impact of t-masking on various selection rates has been provided, serving as a useful characterization for future insights. The proposed approach is also highly generalizable to other DL architectures, neuroimaging modalities, and brain pathologies.
Statistical Properties of Musical Creativity: Roles of Hierarchy and Uncertainty in Statistical Learning
Authors: Daikoku Tatsuya , Wiggins Geraint A. , Nagai Yukie
Published: April 2021

Creativity is part of human nature and is commonly understood as a phenomenon whereby something original and worthwhile is formed. Owing to this ability, humans can produce innovative information that often facilitates growth in our society. Creativity also contributes to esthetic and artistic productions, such as music and art. However, the mechanism by which creativity emerges in the brain remains debatable. Recently, a growing body of evidence has suggested that statistical learning contributes to creativity. Statistical learning is an innate and implicit function of the human brain and is considered essential for brain development. Through statistical learning, humans can produce and comprehend structured information, such as music. It is thought that creativity is linked to acquired knowledge, but so-called “eureka” moments often occur unexpectedly under subconscious conditions, without the intention to use the acquired knowledge. Given that a creative moment is intrinsically implicit, we postulate that some types of creativity can be linked to implicit statistical knowledge in the brain. This article reviews neural and computational studies on how creativity emerges within the framework of statistical learning in the brain (i.e., statistical creativity). Here, we propose a hierarchical model of statistical learning: statistically chunking into a unit (hereafter and shallow statistical learning) and combining several units (hereafter and deep statistical learning). We suggest that deep statistical learning contributes dominantly to statistical creativity in music. Furthermore, the temporal dynamics of perceptual uncertainty can be another potential causal factor in statistical creativity. Considering that statistical learning is fundamental to brain development, we also discuss how typical versus atypical brain development modulates hierarchical statistical learning and statistical creativity. We believe that this review will shed light on the key roles of statistical learning in musical creativity and facilitate further investigation of how creativity emerges in the brain.
DNA Hypermethylation Induced by L-Methionine Leads to Oligodendroglial and Myelin Deficits and Schizophrenia-Like Behaviors in Adolescent Mice
Authors: Chen Xianjun , Huang Nan-Xin , Cheng Yong-Jie , Cai Qi-Yan , Tian Yan-Ping , Chen Xing-Shu , Xiao Lan
Published: April 2021

Increasing evidence has demonstrated that in addition to dysfunction of neuronal circuitry, oligodendroglial dysfunction and/or disruption of white matter integrity are found in the brains of patients with schizophrenia. DNA methylation, a well-established risk factor for schizophrenia, has been demonstrated to cause neuronal dysfunction; however, whether dysregulation of DNA methylation contributes to oligodendroglial/myelin deficits in the pathogenesis of schizophrenia remains unclear. In the present study, by using L-methionine-treated mice, we confirmed that mice with DNA hypermethylation exhibited an anxious phenotype, impaired sociability, and sensorimotor gating deficits. Notably, DNA hypermethylation in oligodendroglial cells led to dysregulation of multiple oligodendroglia-specific transcription factors, which indicated disruption of the transcriptional architecture. Furthermore, DNA hypermethylation caused a reduction of oligodendroglial lineage cells and myelin integrity in the frontal white matter of mice. Taken together, these results indicate that DNA hypermethylation leads to oligodendroglial and/or myelin deficits, which may, at least in part, contribute to schizophrenia-like behaviors in mice. This study provides new insights into the possibility that precise modulation of DNA methylation status in oligodendroglia could be beneficial for the white matter pathology in schizophrenia.
Functional 3-Dimensional Retinal Organoids: Technological Progress and Existing Challenges
Authors: Fathi Meimanat , Ross Cody T. , Hosseinzadeh Zohreh
Published: April 2021

Stem cell scientists have developed methods for the self-formation of artificial organs, often referred to as organoids. Organoids can be used as model systems for research in multiple biological disciplines. Yoshiki Sasai’s innovation for deriving mammalian retinal tissue fromin vitrostem cells has had a large impact on the study of the biology of vision. New developments in retinal organoid technology provide avenues forin vitromodels of human retinal diseases, studies of pathological mechanisms, and development of therapies for retinal degeneration, including electronic retinal implants and gene therapy. Moreover, these innovations have played key roles in establishing models for large-scale drug screening, studying the stages of retinal development, and providing a human model for personalized therapeutic approaches, like cell transplants to replace degenerated retinal cells. Here, we first discuss the importance of human retinal organoids to the biomedical sciences. Then, we review various functional features of retinal organoids that have been developed. Finally, we highlight the current limitations of retinal organoid technologies.
Case Report: Detection of SARS-CoV-2 From Cerebrospinal Fluid in a 34-Month-Old Child With Encephalitis
Authors: Cheraghali Fatemeh , Tahamtan Alireza , Hosseini Seyed Ahmad , Gharib Mohammad Hadi , Moradi Abdolvahab , Razavi Nikoo Hadi , Tabarraei Alijan
Published: April 2021

Novel coronavirus (severe acute respiratory syndrome-coronavirus-2: SARS-CoV-2), which arose from Wuhan, China, has rapidly spread to other countries and developed into a pandemic. Although the respiratory manifestations of SARS-CoV-2 are well-documented, there is a considerable challenge regarding the direct and/or indirect infection in other organs. Several preliminary reports confirmed neurological manifestations in the SARS-CoV-2-infected patients. Here, we report the detection of SARS-CoV-2 from the nasopharyngeal swab and cerebrospinal fluid (CSF) in a 34-month-old child with encephalitis. This finding expands the spectrum of the neurological manifestations associated with SARS-CoV-2 infection.
Infrared Thermal Imaging for Evaluation of Clubfoot After the Ponseti Casting Method—An Exploratory Study
Authors: Ganesan Balasankar , Yip Joanne , Luximon Ameersing , Gibbons Paul J. , Chivers Alison , Balasankar Suchita Kothe , Tong Raymond Kai-Yu , Chai Rifai , Al-Jumaily Adel
Published: April 2021

Background:Conservative treatment, Ponseti method, has been considered as a standard method to correct the clubfoot deformity among Orthopedic society. Although the result of conservative methods have been reported with higher success rates than surgical methods, many more problems have been reported due to improper casting, casting pressure or bracing discomfort. Nowadays, infrared thermography (IRT) is widely used as a diagnostic tool to assess musculoskeletal disorders or injuries by detecting temperature abnormalities. Similarly, the foot skin temperature evaluation can be added along with the current subjective evaluation to predict if there is any casting pressure, excessive manipulation, or overcorrections of the foot, and other bracing pressure-related complications.

Purpose:The main purpose of this study was to explore the foot skin temperature changes before and after using of manipulation and weekly castings.

Methods:This is an explorative study design. Infrared Thermography (IRT), E33 FLIR thermal imaging camera model, was used to collect the thermal images of the clubfoot before and after casting intervention. A total of 120 thermal images (Medial region of the foot–24, Lateral side of the foot–24, Dorsal side of the foot−24, Plantar side of the foot−24, and Heel area of the foot–24) were collected from the selected regions of the clubfoot.

Results:The results of univariate statistical analysis showed that significant temperature changes in some regions of the foot after casting, especially, at the 2nd (M = 32.05°C, SD = 0.77,p= 0.05), 3rd (M = 31.61, SD = 1.11; 95% CI: 31.27–31.96;p= 0.00), and 6th week of evaluation on the lateral side of the foot (M = 31.15°C, SD = 1.59; 95% CI: 30.75–31.54,p= 0.000). There was no significant temperature changes throughout the weekly casting in the medial side of the foot. In the heel side of the foot, significant temperature changes were noticed after the third and fourth weeks of casting.

Conclusion:This study found that a decreased foot skin temperature on the dorsal and lateral side of the foot at the 6th week of thermography evaluation. The finding of this study suggest that the infrared thermography (IRT) might be useful as an adjunct assessment tool to evaluate the thermophysiological changes, which can be used to predict the complications caused by improper casting, over manipulative or stretching and casting-pressure related complications.
Size of Patent Ductus Arteriosus and Echocardiographic Markers of Shunt Volume in Preterm Infants Based on Postnatal Age
Authors: Choi Eui Kyung , Park Kyu Hee , Choi Byung Min
Published: April 2021

Objective: This study was conducted in order to compare the strength of correlation between echocardiographic markers of shunt volume and patent ductus arteriosus (PDA) diameter based on postnatal age.

Methods: This retrospective study focused on preterm infants (aged <32 weeks of gestation) admitted to the Neonatal Intensive Care Unit of Korea University Ansan Hospital, between April 2014 and December 2017, who studied serial targeted neonatal echocardiography (TNE) for PDA during hospitalization. The association between echocardiographic characteristics and duct size was divided into the following days: within 3 days (very early, VE), 4–7 days after birth (early, E), and after 8 days of birth (late, L).

Results: We found 113 assessments conducted on 57 infants in the VE period, 92 assessments on 40 infants in the E period, and 342 assessments on 37 infants in the L period. Median gestational age and birth weight were 28+2 weeks of gestation and 1,115 g, respectively. In the univariate regression analysis, we found a statistically significant correlation between PDA diameter and all TNE markers in the E and L days, but not in the VE period. Only ductal velocity [coefficient of determination (R2) = 0.224], antegrade left pulmonary artery diastolic flow velocity (R2 = 0.165), left ventricular output (LVO)/superior vena cava (SVC) flow ratio (R2 = 0.048), and E/A wave ratio (R2 = 0.092) showed weak correlations with PDA diameter in the VE period. The slopes of the regressions showed significant changes based on postnatal age in the maximum ductal velocity, left atrium/aorta ratio, LVO/SVC flow ratio, and LVO.

Conclusions: It is difficult to predict the echocardiographic markers of shunt volume based on the PDA diameter in preterm infants younger than 4 days. A better understanding of the changes in the hemodynamic consequences of PDA based on postnatal age is needed when considering treatment.
Children's Daily Routine Response to COVID-19 Emergency Measures in Serbia
Authors: Vuković Jovan , Matić Radenko M. , Milovanović Ivana M. , Maksimović Nebojša , Krivokapić Dragan , Pišot Saša
Published: April 2021

Objective: The emergence of coronavirus in Serbia as well as in other European countries led to the declaration of a state of emergency, which, among other measures, included a switch to online education, the lockdown of public life and organized sports, and a curfew from 5 pm to 5 am. This study aimed to investigate the extent to which these measures affected children's daily routines. More specifically, it aimed to determine how children maintained their learning, physical activity, and screen time routines from the period before the state of emergency was declared.

Methods: Response to an online parent-reported questionnaire was conducted (N = 450). The factorial validity of the scales was prepared using confirmatory factor analysis, with acceptable fit indices. Based on that, the authors tested the interrelations between dimensions using structural equation modeling in SPSS, AMOS 24.0.

Results: The study results indicate a positive relationship between school achievement and study time (β = 0.25). They also indicate that children who were physically active before the pandemic continued their activities during the emergency state (β = 0.53). Physical activity impact during the COVID-19 emergency measures reduces children's behavior changes (β = 0.55). Finally, they highlight that children who spent more time with multimedia content had greater changes in anxiety, sensitivity, nervousness, and worry due to COVID-19 emergency measures (β = −0.38).

Conclusions: Healthy lifestyle habits formed in childhood are suggested to be responsible for the greater “resistance to change” shown by the children from this study.
A Combination of Atorvastatin and Aspirin Enhances the Pro-Regenerative Interactions of Marrow Stromal Cells and Stroke-Derived Monocytes In Vitro
Authors: Satani Nikunj , Zhang Xu , Giridhar Kaavya , Wewior Natalia , Cai Chunyan , Aronowski Jaroslaw , Savitz Sean I.
Published: April 2021

Background and Purpose: Marrow stromal cells (MSCs) are being tested in clinical trials for stroke patients. MSCs appear to promote recovery through secretomes that promote modulation of immune cells, including myeloid phagocytes. Many stroke patients have comorbidities such as metabolic syndrome, hypertension, hypercholesterolemia, and diabetes for which they are prescribed medications that might affect the function of MSCs and monocytes (Mo) when they are administered in stroke patients. We studied the effects of the two most commonly prescribed stroke medications, statin and statin plus aspirin, on the secretomes of MSCs and their modulation of Mo derived from stroke patients.

Methods: Human MSCs, Mo and their co-cultures were exposed to atorvastatin or atorvastatin plus aspirin followed by secretome analysis at 24 h. Monocytes were isolated from healthy controls as well as stroke patients with NIHSS ranging from 11 to 20. Secretome composition was measured using multiplex immunoassay. We used MTT assay to measure proliferation of monocytes. The mixed model was used to analyze experimental data. p-values less than 0.05 were considered significant.

Results: Atorvastatin and aspirin combination increased the release of IL-1RA from stroke Mo. In MSCs, atorvastatin and aspirin combination reduced the release of pro-inflammatory cytokines such as IL-6, IL-8, MCP-1 and IFN-γ. Atorvastatin alone reduced the release of IL-6, IL-8 and MCP-1 from co-cultures of stroke monocytes and MSCs. Combination of atorvastatin and aspirin had additive effect on reducing the secretion of IL-6 from co-cultures of stroke Mo and MSCs.

Conclusion: Atorvastatin, alone and in combination with aspirin can promote anti-inflammatory effect by modulating the secretome profile of Mo and MSCs. Our results suggest that stroke trials involving the use of intravenous MSCs should consider the effect of aspirin and atorvastatin, both of which are administered to the majority of hospitalized ischemic stroke patients.
Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling
Authors: Paraiso Ines L. , Tran Thai Q. , Magana Armando Alcazar , Kundu Payel , Choi Jaewoo , Maier Claudia S. , Bobe Gerd , Raber Jacob , Kioussi Chrissa , Stevens Jan F.
Published: April 2021

The farnesoid X receptor (FXR) plays a critical role in the regulation of lipid and bile acid (BA) homeostasis. Hepatic FXR loss results in lipid and BA accumulation, and progression from hepatic steatosis to nonalcoholic steatohepatitis (NASH). This study aimed to evaluate the effects of xanthohumol (XN), a hop-derived compound mitigating metabolic syndrome, on liver damage induced by diet and FXR deficiency in mice. Wild-type (WT) and liver-specific FXR-null mice (FXRLiver−/−) were fed a high-fat diet (HFD) containing XN or the vehicle formation followed by histological characterization, lipid, BA and gene profiling. HFD supplemented with XN resulted in amelioration of hepatic steatosis and decreased BA concentrations in FXRLiver−/− mice, the effect being stronger in male mice. XN induced the constitutive androstane receptor (CAR), pregnane X receptor (PXR) and glucocorticoid receptor (GR) gene expression in the liver of FXRLiver−/− mice. These findings suggest that activation of BA detoxification pathways represents the predominant mechanism for controlling hydrophobic BA concentrations in FXRLiver−/− mice. Collectively, these data indicated sex-dependent relationship between FXR, lipids and BAs, and suggest that XN ameliorates HFD-induced liver dysfunction via FXR-dependent and independent signaling.
Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice
Authors: Xu Lieqiang , Lin Guoshu , Yu Qiuxia , Li Qiaoping , Mai Liting , Cheng Juanjuan , Xie Jianhui , Liu Yuhong , Su Ziren , Li Yucui
Published: April 2021

Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved in vivo efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. In vitro, DHB exhibited significant XOD inhibitory activity (IC50 value, 34.37 μM). The in vivo results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney.
Emerging Cell-Based Therapies in Chronic Lung Diseases: What About Asthma?
Authors: Cereta Andressa Daronco , Oliveira Vinícius Rosa , Costa Ivan Peres , Afonso João Pedro Ribeiro , Fonseca Adriano Luís , de Souza Alan Robson Trigueiro , Silva Guilherme Augusto Moreira , Mello Diego A. C. P. G. , Oliveira Luis Vicente Franco de , da Palma Renata Kelly
Published: April 2021

Asthma is a widespread disease characterized by chronic airway inflammation. It causes substantial disability, impaired quality of life, and avoidable deaths around the world. The main treatment for asthmatic patients is the administration of corticosteroids, which improves the quality of life; however, prolonged use of corticosteroids interferes with extracellular matrix elements. Therefore, cell-based therapies are emerging as a novel therapeutic contribution to tissue regeneration for lung diseases. This study aimed to summarize the advancements in cell therapy involving mesenchymal stromal cells, extracellular vesicles, and immune cells such as T-cells in asthma. Our findings provide evidence that the use of mesenchymal stem cells, their derivatives, and immune cells such as T-cells are an initial milestone to understand how emergent cell-based therapies are effective to face the challenges in the development, progression, and management of asthma, thus improving the quality of life.
CYP2D6 Genetic Variation and Its Implication for Vivax Malaria Treatment in Madagascar
Authors: Mehlotra Rajeev K. , Gaedigk Andrea , Howes Rosalind E. , Rakotomanga Tovonahary A. , Ratsimbasoa Arsene C. , Zimmerman Peter A.
Published: April 2021

Plasmodium vivax is one of the five human malaria parasite species, which has a wide geographical distribution and can cause severe disease and fatal outcomes. It has the ability to relapse from dormant liver stages (hypnozoites), weeks to months after clearance of the acute blood-stage infection. An 8-aminoquinoline drug primaquine (PQ) can clear the hypnozoites, and thus can be used as an anti-relapse therapeutic agent. Recently, a number of studies have found that its efficacy is compromised by polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene; decreased or absence of CYP2D6 activity contributes to PQ therapeutic failure. The present study sought to characterize CYP2D6 genetic variation in Madagascar, where populations originated from admixture between Asian and African populations, vivax malaria is endemic, and PQ can be deployed soon to achieve national malaria elimination. In a total of 211 samples collected from two health districts, CYP2D6 decreased function alleles CYP2D6*10, *17, *29, *36+*10, and *41 were observed at frequencies of 3.55–17.06%. In addition, nonfunctional alleles were observed, the most common of which were CYP2D6*4 (2.13%), *5 (1.66%), and the *4x2 gene duplication (1.42%). Given these frequencies, 34.6% of the individuals were predicted to be intermediate metabolizers (IM) with an enzyme activity score (AS) ≤ 1.0; both the IM phenotype and AS ≤ 1.0 have been found to be associated with PQ therapeutic failure. Furthermore, the allele and genotype frequency distributions add to the archaeological and genomic evidence of Malagasy populations constituting a unique, Asian-African admixed origin. The results from this exploratory study provide fresh insights about genomic characteristics that could affect the metabolism of PQ into its active state, and may enable optimization of PQ treatment across human genetic diversity, which is critical for achieving P. vivax elimination.
The Role of Renin-Angiotensin-Aldosterone System in the Heart and Lung: Focus on COVID-19
Authors: Mascolo Annamaria , Scavone Cristina , Rafaniello Concetta , De Angelis Antonella , Urbanek Konrad , di Mauro Gabriella , Cappetta Donato , Berrino Liberato , Rossi Francesco , Capuano Annalisa
Published: April 2021

The renin-angiotensin-aldosterone system (RAAS) firstly considered as a cardiovascular circulating hormonal system, it is now accepted as a local tissue system that works synergistically or independently with the circulating one. Evidence states that tissue RAAS locally generates mediators with regulatory homeostatic functions, thus contributing, at some extent, to organ dysfunction or disease. Specifically, RAAS can be divided into the traditional RAAS pathway (or classic RAAS) mediated by angiotensin II (AII), and the non-classic RAAS pathway mediated by angiotensin 1–7. Both pathways operate in the heart and lung. In the heart, the classic RAAS plays a role in both hemodynamics and tissue remodeling associated with cardiomyocyte and endothelial dysfunction, leading to progressive functional impairment. Moreover, the local classic RAAS may predispose the onset of atrial fibrillation through different biological mechanisms involving inflammation, accumulation of epicardial adipose tissue, and electrical cardiac remodeling. In the lung, the classic RAAS regulates cell proliferation, immune-inflammatory response, hypoxia, and angiogenesis, contributing to lung injury and different pulmonary diseases (including COVID-19). Instead, the local non-classic RAAS counteracts the classic RAAS effects exerting a protective action on both heart and lung. Moreover, the non-classic RAAS, through the angiotensin-converting enzyme 2 (ACE2), mediates the entry of the etiological agent of COVID-19 (SARS-CoV-2) into cells. This may cause a reduction in ACE2 and an imbalance between angiotensins in favor of AII that may be responsible for the lung and heart damage. Drugs blocking the classic RAAS (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) are well known to exert a cardiovascular benefit. They are recently under evaluation for COVID-19 for their ability to block AII-induced lung injury altogether with drugs stimulating the non-classic RAAS. Herein, we discuss the available evidence on the role of RAAS in the heart and lung, summarizing all clinical data related to the use of drugs acting either by blocking the classic RAAS or stimulating the non-classic RAAS.
MAZ51 Blocks the Tumor Growth of Prostate Cancer by Inhibiting Vascular Endothelial Growth Factor Receptor 3
Authors: Yamamura Aya , Nayeem Md Junayed , Muramatsu Hiroyuki , Nakamura Kogenta , Sato Motohiko
Published: April 2021

Vascular endothelial growth factor (VEGF) signaling plays a critical role in the carcinogenesis and tumor development of several cancer types. However, its pathological significance in prostate cancer, one of the most frequent and lethal malignancies in men, remains unclear. In the present study, we focused on a pathological role of the VEGF receptors (VEGFRs), and examined their expression and effects of MAZ51 (an inhibitor of the tyrosine kinase of VEGFR-3) on cell proliferation, migration, and tumor growth in human prostate cancer cells. The expression level of VEGFR-3 was higher in androgen-independent and highly metastatic prostate cancer PC-3 cells than in other prostate PrEC, LNCaP, and DU145 cells. In PC-3 cells, VEGFR-3 and Akt were phosphorylated following a stimulation with 50 ng/ml VEGF-C, and these phosphorylations were blocked by 3 μM MAZ51. Interestingly, PC-3 cells themselves secreted VEGF-C, which was markedly larger amount compared with PrEC, LNCaP, and DU145 cells. MAZ51 reduced the expression of VEGFR-3 but not VEGFR-1 and VEGFR-2. The proliferation of PC-3 cells was inhibited by MAZ51 (IC50 = 2.7 μM) and VEGFR-3 siRNA, and partly decreased by 100 nM GSK690693 (an Akt inhibitor) and 300 nM VEGFR2 Kinase Inhibitor I. MAZ51 and VEGFR-3 siRNA also attenuated the VEGF-C-induced migration of PC-3 cells. Moreover, MAZ51 blocked the tumor growth of PC-3 cells in a xenograft mouse model. These results suggest that VEGFR-3 signaling contributes to the cell proliferation, migration, and tumor growth of androgen-independent/highly metastatic prostate cancer. Therefore, the inhibition of VEGFR-3 has potential as a novel therapeutic target for the treatment for prostate cancer.
Supplemental Learning in Respiratory Physiology for Healthcare Professionals Towards Successful Treatment of COVID-19
Authors: Wallace Helen , Angus Robert
Published: April 2021

The immunological and pathophysiological response to COVID-19 can cause severe respiratory impairment affecting gas exchange and lung mechanics. Such was the scale of the respiratory support needed during the first wave of the pandemic, that recruitment of non-respiratory clinical staff was essential to help deal with the growing number of cases. It quickly became apparent that it was vital to rapidly equip these healthcare professionals with appropriate physiological knowledge and practical skills if therapies were to be applied effectively. Furthermore, the unravelling of unusual clinical features of COVID-19, further highlighted a need for knowledge of long-established principles of respiratory physiology. An online digital educational resource, or “respiratory learning tool kit” was developed with interactive material including visualisations, animations, and pathophysiological examples to facilitate understanding. The learning outcomes were centred on physiological principles, essential for understanding the pathophysiology relating to COVID-19, and management and treatment. Topics included principles of gas exchange, gas transport, homeostasis and central control of respiration. These basic physiological principles were linked to pathophysiology and clinical skills around oxygen administration and non-invasive supports such as Continuous Positive Airway Pressure (CPAP). From the degree of engagement and evaluation comments, it was clear that the resource successfully achieved its aim—to increase physiological knowledge and its practical understanding, enabling healthcare professionals to practice with confidence in such an uncertain environment.
Comparison and Functional Analysis of Chemosensory Protein Genes From Eucryptorrhynchus scrobiculatus Motschulsky and Eucryptorrhynchus brandti Harold
Authors: Wang Qian , Wen Xiaojian , Lu Yi , Wen Junbao
Published: April 2021

The tree-of-heaven root weevil (Eucryptorrhynchus scrobiculatus) and the tree-of-heaven trunk weevil (Eucryptorrhynchus brandti) are closely related species that monophagously feed on the same host plant, the Ailanthus altissima (Mill) Swingle, at different locations. However, the mechanisms of how they select different parts of the host tree are unclear. As chemosensory systems play important roles in host location and oviposition, we screened candidate chemosensory protein genes from the transcriptomes of the two weevils at different developmental stages. In this study, we identified 12 candidate chemosensory proteins (CSPs) of E. scrobiculatus and E. brandti, three EscrCSPs, and one EbraCSPs, respectively, were newly identified. The qRT-PCR results showed that EscrCSP7/8a/9 and EbraCSP7/8/9 were significantly expressed in adult antennae, while EscrCSP8a and EbraCSP8 shared low sequence identity, suggesting that they may respond to different odorant molecule binding. Additionally, EbraCSP6 and EscrCSP6 were mainly expressed in antennae and proboscises and likely participate in the process of chemoreception. The binding simulation of nine volatile compounds of the host plant to EscrCSP8a and EbraCSP8 indicated that (1R)-(+)-alpha-pinene, (–)-beta-caryophyllene, and beta-elemen have higher binding affinities with EscrCSP8a and lower affinities with EbraCSP8. In addition, there were seven, two, and one EbraCSPs mainly expressed in pupae, larvae, and eggs, respectively, indicating possible developmental-related roles in E. brandti. We screened out several olfactory-related possible CSP genes in E. brandti and E. scrobiculatus and simulated the binding model of CSPs with different compounds, providing a basis for explaining the niche differentiation of the two weevils.
Ion Transporters and Osmoregulation in the Kidney of Teleost Fishes as a Function of Salinity
Authors: Takvam Marius , Wood Chris M. , Kryvi Harald , Nilsen Tom O.
Published: April 2021

Euryhaline teleosts exhibit major changes in renal function as they move between freshwater (FW) and seawater (SW) environments, thus tolerating large fluctuations in salinity. In FW, the kidney excretes large volumes of water through high glomerular filtration rates (GFR) and low tubular reabsorption rates, while actively reabsorbing most ions at high rates. The excreted product has a high urine flow rate (UFR) with a dilute composition. In SW, GFR is greatly reduced, and the tubules reabsorb as much water as possible, while actively secreting divalent ions. The excreted product has a low UFR, and is almost isosmotic to the blood plasma, with Mg2+, SO42–, and Cl–as the major ionic components. Early studies at the organismal level have described these basic patterns, while in the last two decades, studies of regulation at the cell and molecular level have been implemented, though only in a few euryhaline groups (salmonids, eels, tilapias, and fugus). There have been few studies combining the two approaches. The aim of the review is to integrate known aspects of renal physiology (reabsorption and secretion) with more recent advances in molecular water and solute physiology (gene and protein function of transporters). The renal transporters addressed include the subunits of the Na+, K+- ATPase (NKA) enzyme, monovalent ion transporters for Na+, Cl–, and K+(NKCC1, NKCC2, CLC-K, NCC, ROMK2), water transport pathways [aquaporins (AQP), claudins (CLDN)], and divalent ion transporters for SO42–, Mg2+, and Ca2+(SLC26A6, SLC26A1, SLC13A1, SLC41A1, CNNM2, CNNM3, NCX1, NCX2, PMCA). For each transport category, we address the current understanding at the molecular level, try to synthesize it with classical knowledge of overall renal function, and highlight knowledge gaps. Future research on the kidney of euryhaline fishes should focus on integrating changes in kidney reabsorption and secretion of ions with changes in transporter function at the cellular and molecular level (gene and protein verification) in different regions of the nephrons. An increased focus on the kidney individually and its functional integration with the other osmoregulatory organs (gills, skin and intestine) in maintaining overall homeostasis will have applied relevance for aquaculture.
Relationships Between Annual and Perennial Seagrass (Ruppia sinensis) Populations and Their Sediment Geochemical Characteristics in the Yellow River Delta
Authors: Gu Ruiting , Song Xiaoyue , Zhou Yi , Xu Shaochun , Xu Shuai , Yue Shidong , Zhang Yu , Zhang Xiaomei
Published: April 2021

Annual and perennial populations commonly occur for the same submerged aquatic angiosperm species, yet relationships between population types and sediment characteristics are poorly understood. In the current study two Ruppia sinensis habitats with annual and perennial populations were surveyed in the Yellow River Delta (YRD). Biomass and seasonal seed bank size were used to evaluate population status and potential recruitment capacity. Sediment geochemical parameters including moisture, sulfide, Chl a, carbohydrate, OM, TOC, TN, and TP were measured to compare sediment nutrient composition and variability. The results revealed a higher biomass and larger seed bank in the annual R. sinensis population compared with the perennial population. The P levels in sediments between the two R. sinensis populations were similar; while the N level in the sediment of the annual population was significantly higher than the perennial population, which might support the recruitment of vegetative shoots when a large amount of seeds germinated during wet periods. The annual population exhibited greater resilience after habitat desiccation, with the population recovering rapidly once water appeared. The results of this study add to the knowledge of R. sinensis populations and their sediment geochemical characteristics, and can be used as a reference for Ruppia population conservation and management.
Evidence of Recombination Suppression Blocks on the Y Chromosome of Date Palm (Phoenix dactylifera)
Authors: Torres Maria F. , Mohamoud Yasmin A. , Younuskunju Shameem , Suhre Karsten , Malek Joel A.
Published: April 2021

The genus Phoenix includes the fruit producing date palm tree among 14 species that are all dioecious. Females produce the fruit that are high in sugar content and used in multiple countries ranging from North Africa to South Asia, especially from the Phoenix dactylifera, Phoenix sylvestris, and Phoenix canariensis species. While females produce the fruit, understanding of the genetic basis of sex control only began recently. Through genus-wide sequencing of males and females we recently identified three genes that are conserved in all males and absent in all females of the genus and confirmed an XY sex chromosome system. While our previous study focused on conservation of male-specific sequences at the genus-level, it would be of interest to better understand the spread of male-specific sequences away from the core conserved male genes on the Y chromosome during speciation. To this end, we enumerated male-specific 16 bp sequences using three male/female pairs from the western subpopulation of date palm and documented the density of these sequences in contigs of a phased date palm genome assembly. Here we show that male specific sequences in the date palm Y chromosome have likely spread in defined events that appear as blocks of varying density with significant changes in density between them. Collinearity of genes in these blocks with oil palm shows high synteny with chromosome 10 between megabase 15 and 23 and reveals that large sections of the date palm Y chromosome have maintained the ancestral structure even as recombination has stopped between X and Y.
Community Violence Exposure and Externalizing Problem Behavior Among Chinese High School Students: The Moderating Role of Parental Knowledge
Authors: Zhang Yibo , Chen Yuanyuan , Zhang Wei
Published: April 2021

Adolescents' community violence exposure (CVE) has been demonstrated with a range of behavioral and psychological problems, but the processes that explain these correlations are not clear. In our 2017 study, the mediating role of deviant peer affiliation in the relationship between CVE and externalizing problem behaviors has been confirmed. However, the moderating effect of parental factors is still unclear. Therefore, a new group (high school group) was adopted in this study to further explore the moderating effect of parental knowledge based on also confirming the mediating effect of deviant peer affiliation. Stratified-cluster sampling was used to recruit 1,797 volunteers who completed questionnaires on CVE, deviant peer affiliation, parental knowledge, and externalizing problem behaviors. The results of the structural equation modeling were: on the basis of our previous research, we further analyzed the mediating role of deviant peer affiliation, and the mediated association was moderated by parental knowledge. Especially when the school climate is added as a covariate, the moderating effect of parental knowledge has changed, that is, the positive association between CVE and externalizing problem behaviors was much stronger for adolescents who reported lower levels of parental knowledge than for those who reported higher levels of parental knowledge. The results support the assumptions of social learning theory and have implications for interventions of community violence.
Effects of Information Overload, Communication Overload, and Inequality on Digital Distrust: A Cyber-Violence Behavior Mechanism
Authors: Fan Mingyue , Huang Yuchen , Qalati Sikandar Ali , Shah Syed Mir Muhammad , Ostic Dragana , Pu Zhengjia
Published: April 2021

In recent years, there has been an escalation in cases of cyber violence, which has had a chilling effect on users' behavior toward social media sites. This article explores the causes behind cyber violence and provides empirical data for developing means for effective prevention. Using elements of the stimulus–organism–response theory, we constructed a model of cyber-violence behavior. A closed-ended questionnaire was administered to collect data through an online survey, which results in 531 valid responses. A proposed model was tested using partial least squares structural equation modeling using SmartPLS 3.0, v (3.2.8). Research findings show that information inequality is a strong external stimulus with a significant positive impact on digital distrust and negative emotion. However, the effects of information overload on digital distrust and the adverse effects of communication overload on negative emotions should not be ignored. Both digital distrust and negative emotions have significant positive impacts on cyber violence and cumulatively represent 11.5% changes in cyber violence. Furthermore, information overload, communication overload, information inequality, and digital distrust show a 27.1% change in negative emotions. This study also presents evidence for competitive mediation of digital distrust by information overload, information inequality, and cyber violence. The results of this study have implications for individual practitioners and scholars, for organizations, and at the governmental level regarding cyber-violence behavior. To test our hypotheses, we have constructed an empirical, multidimensional model, including the role of specific mediators in creating relationships.
Associations of Partnership Quality and Father-to-Child Attachment During the Peripartum Period. A Prospective-Longitudinal Study in Expectant Fathers
Authors: Knappe Susanne , Petzoldt Johanna , Garthus-Niegel Susan , Wittich Julia , Puls Hans-Christian , Huttarsch Isabell , Martini Julia
Published: April 2021

Background: During the transition to parenthood, a complex network of relationships unfolds between father, mother and the child. Expectant parents begin bonding with their unborn child, with this antenatal process supposedly being predictive for later postnatal attachment and child mental health. At the same time, couples may experience a change in partnership quality. While the majority of previous studies focused on associations between psychopathology, partnership quality and attachment from the perspective of mothers, the changes in partnership quality and attachment from the perspective of fathers has gained far less attention.

Methods: Data were derived from the Maternal Anxiety and it's Relation to Infants' Development (MARI) study. N = 109 expectant fathers were recruited during mid-pregnancy (22 to 26 week of gestation). Lifetime anxiety and depressive disorders (DSM-IV) were assessed with a standardized diagnostic interview (CIDI). Paternal partnership characteristics and father-to-child attachments were assessed using standardized questionnaires at the second trimester, 10 days after delivery and 4 months after delivery in N = 76 fathers. Analyses were based on bivariate, robust and multivariate regression analyses.

Results: Fathers did not report an overall decrease in partnership quality during the peripartum period. However, fathers with comorbid anxiety and depressive disorders reported lower partnership satisfaction at postpartum, as compared to unaffected fathers. Fathers with pure depressive disorders reported lower intensity of antenatal attachment. Paternal antenatal partnership quality was positively associated with antenatal father-to-child attachment. Furthermore, antenatal father-to-child attachment, as well as ante- and postnatal partnership quality in fathers, were positively related to postnatal father-to-child attachment.

Conclusions: Antenatal father-to-child-attachment and paternal partnership quality appear to be promising targets for the prevention of postnatal attachment problems in fathers. The associations between partnership quality and attachment to the child further support an interpersonal approach in perinatal research, treatment and intervention, and may also feed into awareness programs that encourage expectant fathers to actively engage in relationships as early as during pregnancy—both with the mother and the unborn child.
Relational Spirituality and Transgenerational Obligations: The Role of Family in Lay Explanatory Models of Post-traumatic Stress Disorder in Male Cameroonian Asylum Seekers and Undocumented Migrants in Europe
Authors: Grupp Freyja , Skandrani Sara , Moro Marie Rose , Mewes Ricarda
Published: April 2021

Context: Diasporic Cameroonians are increasingly leading a transnational life in which family members are sustained through networks of relations and obligations. However, before arriving in Europe, the vast majority of African migrants who take the Mediterranean route are exposed to trauma and hardship. Moreover, the joint occurrence of forced displacement, trauma, and extended separation from families has a significant impact on mental health.

Objectives: This study explores the role of culture-specific conceptualizations of family structures and transnationalism in explanatory models of post-traumatic stress disorder (PTSD) among male Cameroonian asylum-seekers and undocumented migrants in Europe.

Methods: An in-depth study of two samples of Cameroonian migrants with a precarious residency status in Europe was conducted. Focus group discussions and interviews were carried out with asylum seekers in Germany (n = 8) and undocumented migrants and failed asylum seekers in France (n = 9). The verbatim transcripts of these interviews served as the data for interpretative phenomenological analyses.

Results, Analysis, and Discussion: Family was conceptualized in religious and spiritual terms, and relational spirituality appeared to be a crucial element of family cohesion. Explanatory models of PTSD were mainly based on an intersection of family and spirituality. The disrespect of transgenerational, traditional, and spiritual obligations toward parents and ancestral spirits represented a crucial causal attribution for post-traumatic symptoms.

Conclusions: Conceptualizations of post-traumatic stress were based on a collective family and spiritual level instead of an individualized illness-centered perception. The Western psychological and psychiatric perspective on post-traumatic stress might conflict with traditional, religious, and spiritual practices in the context of family conceptualizations of Cameroonian forced migrants with a precarious residency status.