bluuebunny/crossref_metadata_2025 huggingface dataset:
Dental Care for a Child with Congenital Hydrocephalus: A Case Report with 12-Month Follow-Up
Authors: Alsayed Tolibah Yasser , Kouchaji Chaza , Lazkani Thuraya , Abbara Mohammad Tamer , Jbara Saffana , Baghdadi Ziad D.
Published: January 2021

Hydrocephalus affects the central nervous system as a result of progressive ventricular dilatation from the accumulation of cerebrospinal fluid in the brain’s lateral ventricles. This paper reports on the oral characteristics of a child with congenital hydrocephalus, discusses her complex dental care needs, and presents dental management of this case. Despite the complex and challenging dental needs, this child received dental treatment in a chairside approach without general anesthesia. A thorough knowledge of the patient’s medical condition, together with expert clinical skills, was indispensable for managing the child and improving the quality and length of her life.
Efficacy of an Intervention to Reduce Stigma Beliefs and Attitudes among Primary Care and Mental Health Professionals: Two Cluster Randomised-Controlled Trials
Authors: Eiroa-Orosa Francisco José , Lomascolo María , Tosas-Fernández Anaïs
Published: January 2021

Although it may seem paradoxical, primary care and mental health professionals develop prejudices and discriminatory attitudes towards people with mental health problems in a very similar way to the rest of the population. The main objective of this project was to design, implement and evaluate two awareness-raising interventions respectively tailored to reduce stigmatising beliefs and attitudes towards persons with a mental health diagnosis among primary care (PC) and mental health (MH) professionals. These interventions were developed by Obertament, the Catalan alliance against stigma and discrimination in mental health. Activists from this organisation with lived experience of mental health diagnosis carried out awareness-raising interventions in PC and MH health centres. The Targeted, Local, Credible, Continuous Contact (TLC3) methodology was adapted to the Catalan healthcare context. The efficacy of these interventions was evaluated using two prospective double-blind cluster-randomised-controlled trials. Stigmatizing beliefs and behaviours were measured with the Opening Minds Stigma Scale for Health Care Providers in PC centres and with the Beliefs and Attitudes towards Mental Health Service users’ rights in MH centres. Reductions in both PC and MH professionals’ stigmatising beliefs and attitudes were found in the 1-month follow-up, although a ‘rebound effect’ at the 3-month follow up was detected. This emphasizes the importance of the continuity of the presence of anti-stigma activities and messages. Attrition rates were high, which can hamper the reliability of the results. Further follow-up studies should enquiry effects of long-term interventions aimed at reducing stigmatising beliefs and attitudes among primary care and mental health professionals using assessment systems that include the measurement of knowledge acquired and actual behavioural change.
Social Functioning as a Mediator between Developmental Language Disorder (DLD) and Emotional Problems in Adolescents
Authors: Forrest Claire L. , Gibson Jenny L. , St Clair Michelle C.
Published: January 2021

Adolescents with Developmental Language Disorder (DLD) are at risk for increased feelings of anxiety and depression compared to their typically developing (TD) peers. However, the underlying pathways involved in this relationship are unclear. In this initial study of the ‘social mediation hypothesis’, we examine social functioning as a mediator of emotional problems in a cross-sectional sample of adolescents with DLD and age- and sex-matched controls. Preliminary data from twenty-six participants with DLD and 27 participants with typical language development (TLD, 11–17 years) were compared on self- and parent-reported measures of social functioning and emotional outcomes. There was little evidence of group differences in self-reported social functioning and emotional outcomes, but parent-report of SDQ Peer Problems and Emotional Problems in the DLD group was significantly higher than in the TLD group. Parent-reported peer problems mediated parent-reported emotional problems, accounting for 69% of the relationship between DLD status and emotional problems. Parents of adolescents with DLD, but not adolescents themselves, report significantly higher peer and emotional problems compared to TLD peers. The hypotheses generated from these novel data suggest further investigation into adolescents’ perceptions of socioemotional difficulties and friendships should be examined.
The Heterogeneous Effects of Participation in Shadow Education on Mental Health of High School Students in Taiwan
Authors: Chen I-Chien , Kuan Ping-Yin
Published: January 2021

The effect of shadow education or private supplementary education (PSE) on school achievement has been prolifically studied, but its impact on well-being remains understudied. This study examines the heterogeneous effect of PSE participation on school achievement and depression symptoms among high schoolers in Taiwan. The study uses panel data of the Taiwan Upper Secondary Database (TUSD) in the 2014 and 2015 academic years. We join the inverse-probability-of-treatment weighting (IPTW) approach and the seemingly unrelated regression (SUR) model to estimate the effects of PSE participation patterns on two correlated outcomes, comprehensive assessment of high school entrance examination and self-reported depression symptoms in the 11th grade. The latent class analysis identifies five PSE participation patterns: always-taker, early-adopter, dropout, late-adopter, and explorer, to predict the effect of PSE on the scores of entrance examination and later depression symptoms in high school (n = 7708, mean age = 15.33). The findings suggest that PSE participation in junior high is positively associated with academic achievement. However, PSE participation also increases depression symptoms, particularly in the case of always-takers. In other words, while always-takers increase their school achievement in transition into high school, their risks of suffering from depression are also higher than their peers.
A Radiographic and Clinical Comparison of Immediate vs. Early Loading (4 Weeks) of Implants with a New Thermo-Chemically Treated Surface: A Randomized Clinical Trial
Authors: Albertini Matteo , Herrero-Climent Federico , Díaz-Castro Carmen María , Nart Jose , Fernández-Palacín Ana , Ríos-Santos José Vicente , Herrero-Climent Mariano
Published: January 2021

Background: Implant dentistry has evolved over time, resulting in better treatment outcomes for both patients and clinicians. The aim of this trial was to test whether the immediate loading of implants with a platform-switching design influences the marginal bone level, compared to four-week loading, after one year of follow-up. Moreover, a comparison of clinical data regarding implant survival, implant stability, and patient-reported outcome measures (PROMs) was conducted. Methods: Klockner® VEGA® implants with a ContacTi® surface were placed in partially edentulous patients in the posterior areas. Group A received an immediately loaded prosthesis (one week) and Group B received an early-loaded prosthesis (four weeks). All abutments were placed at the time of surgery. Radiographic and clinical data were recorded. Results: Twenty-one patients were treated (35 implants). No implants were lost during the study. The final marginal bone level did not show differences between groups. The bone loss at 12 months at the implant level was 0.00 mm for both groups (median). The final implant quotient stability (ISQ) values did not differ between groups (median 73 and 70.25), nor did the other clinical parameters or PROMs. Conclusions: The results suggest that neither of the loading protocols with the implants used influenced the marginal bone level—not the osseointegration rate, clinical conditions, or PROMs.
The Development Strategy of Home-Based Exercise in China Based on the SWOT-AHP Model
Authors: Li Hanming , Chen Xingquan , Fang Yiwei
Published: January 2021

In view of the increasing importance of sports to people and the impact of COVID-19 on people’s lives, home-based exercise has become a popular choice for people to keep fit due to its unique advantages and its popularity is expected to keep growing in the future. Therefore, it is necessary to determine the development direction of home-based exercise and put in the corresponding efforts. However, there is currently a lack of research on all aspects of home-based exercise. The purpose of this research was to investigate the effective sustainable development strategy of home-based exercise in China through a SWOT (Strengths, Weaknesses, Opportunities and Threats) and AHP (Analytic Hierarchy Process) hybrid model. Thirteen factors corresponding to the SWOT analysis were identified through a literature review and expert opinions. The results show that in China the advantages and potential outweigh the weaknesses and threats of home-based exercise. Home-based exercise should grasp the external development opportunities and choose the SO development strategic type that combines internal strengths and external opportunities. As the core for the development of home-based exercise, this strategy should be given priority. To sum up, home-based exercise is believed to have a bright future.
Journalistic Fact-Checking of Information in Pandemic: Stakeholders, Hoaxes, and Strategies to Fight Disinformation during the COVID-19 Crisis in Spain
Authors: López-García Xosé , Costa-Sánchez Carmen , Vizoso Ángel
Published: January 2021

The public health crisis created by COVID-19 represents a challenge for journalists and the media. Specialised information in healthcare and science has turned into a need to deal with the current situation as well as the demand for information by society. In this context of increased uncertainty, the circulation of fake news on social networks and messaging applications has proliferated, producing what has been known as ‘infodemic’. This paper is focused on the fact-checking of journalistic content using a combined methodology: content analysis of information denied by the main Spanish fact-checking platforms (Maldita and Newtral) and an in-depth questionnaire to these stakeholders. The results confirm the quantitative and qualitative evolution of disinformation. Quantitatively, more fact-checking is performed during the state of alarm. Qualitatively, hoaxes increase in complexity as the pandemic evolves, in such a way that disinformation engineering takes place, and it is expected to continue until the development of a vaccine.
Residential Radon in Manizales, Colombia: Results of a Pilot Study
Authors: Giraldo-Osorio Alexandra , Ruano-Ravina Alberto , Pérez-Ríos Mónica , Varela-Lema Leonor , Barros-Dios Juan Miguel , Arias-Ortiz Nelson Enrique
Published: January 2021

Radon is a colorless, odorless, and tasteless noble gas, causally related with the onset of lung cancer. We aimed to describe the distribution of radon exposure in the municipality of Manizales, Colombia, in order to estimate the population’s exposure and establish the percentage of dwellings that surpass reference levels. A cross-sectional study representing all geographical areas was carried out by measuring indoor radon concentrations. Participants answered a short questionnaire. Alpha-track type radon detectors were installed in all residences for six months. The detectors were subsequently processed at the Galician Radon Laboratory, an accredited laboratory at the University of Santiago de Compostela. A total of 202 homes were measured. Seventy-seven percent of the sampled houses were three stories high, their median age was 30 years, and half were inhabited by three people or fewer. For most dwellings, the building materials of walls and flooring were brick and covered cement, respectively. Results showed a geometric mean of radon concentration of 8.5 Bq/m3 and a maximum value of 50 Bq/m3. No statistically significant differences were found either between the geometric mean of the dwelling’s site, the height at which detectors were placed inside the home, or the wall and flooring materials, or between mean 222Rn concentrations in rural and urban areas. No dwelling surpassed the 222Rn reference level established by the WHO. This study shows that residential radon levels in Manizales, Colombia, seem to be low, though a more in-depth approach should be carried out. Despite these results, it is essential to create a national radon program and establish a radon concentration reference level for Colombia in line with international recommendations.
Adsorption and Conformation Behavior of Lysozyme on a Gold Surface Determined by QCM-D, MP-SPR, and FTIR
Authors: Komorek Paulina , Martin Elisha , Jachimska Barbara
Published: January 2021

The physicochemical properties of protein layers at the solid–liquid interface are essential in many biological processes. This study aimed to link the structural analysis of adsorbed lysozyme at the water/gold surface at pH 7.5 in a wide range of concentrations. Particular attention was paid to the protein’s structural stability and the hydration of the protein layers formed at the interface. Complementary methods such as multi-parameter surface plasmon resonance (MP-SPR), quartz crystal microbalance with energy dissipation (QCM-D), and infrared spectroscopy (FTIR) were used for this purpose. The MP-SPR and QCM-D studies showed that, during the formation of a monolayer on the gold surface, the molecules’ orientation changes from side-on to end-on. In addition, bilayer formation is observed when adsorbing in the high-volume concentration range >500 ppm. The degree of hydration of the monolayer and bilayer varies depending on the degree of surface coverage. The hydration of the system decreases with filling the layer in both the monolayer and the bilayer. Hydration for the monolayer varies in the range of 50–70%, because the bilayer is much higher than 80%. The degree of hydration of the adsorption layer has a crucial influence on the protein layers’ viscoelastic properties. In general, an increase in the filling of a layer is characterized by a rise in its rigidity. The use of infrared spectroscopy allowed us to determine the changes taking place in the secondary structure of lysozyme due to its interaction with the gold surface. Upon adsorption, the content of II-structures corresponding to β-turn and random lysozyme structures increases, with a simultaneous decrease in the content of the β-sheet. The increase in the range of β-turn in the structure determines the lysozyme structure’s stability and prevents its aggregation.
A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer’s and Parkinson’s Disease
Authors: Lee Jun , Kim Hong , Kim Jong , Yook Tae , Kim Kyeong , Lee Joo , Yang Gabsik
Published: January 2021

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aβ and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1β, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.
Relevance of Notch Signaling for Bone Metabolism and Regeneration
Authors: Ballhause Tobias M. , Jiang Shan , Baranowsky Anke , Brandt Sabine , Mertens Peter R. , Frosch Karl-Heinz , Yorgan Timur , Keller Johannes
Published: January 2021

Notch1-4 receptors and their signaling pathways are expressed in almost all organ systems and play a pivotal role in cell fate decision by coordinating cell proliferation, differentiation and apoptosis. Differential expression and activation of Notch signaling pathways has been observed in a variety of organs and tissues under physiological and pathological conditions. Bone tissue represents a dynamic system, which is constantly remodeled throughout life. In bone, Notch receptors have been shown to control remodeling and regeneration. Numerous functions have been assigned to Notch receptors and ligands, including osteoblast differentiation and matrix mineralization, osteoclast recruitment and cell fusion and osteoblast/osteoclast progenitor cell proliferation. The expression and function of Notch1-4 in the skeleton are distinct and closely depend on the temporal expression at different differentiation stages. This review addresses the current knowledge on Notch signaling in adult bone with emphasis on metabolism, bone regeneration and degenerative skeletal disorders, as well as congenital disorders associated with mutant Notch genes. Moreover, the crosstalk between Notch signaling and other important pathways involved in bone turnover, including Wnt/β-catenin, BMP and RANKL/OPG, are outlined.
The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo
Authors: Cheng Kai-Chun , Hsu Yun-Tzu , Liu Wangta , Huang Huey-Lan , Chen Liang-Yu , He Chen-Xi , Sheu Shwu-Jiuan , Chen Kuo-Jen , Lee Po-Yen , Lin Yi-Hsiung , Chiu Chien-Chih
Published: January 2021

Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24–48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light’s effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.
The Influence of the Extremely Low Frequency Electromagnetic Field on Clear Cell Renal Carcinoma
Authors: Cios Aleksandra , Ciepielak Martyna , Stankiewicz Wanda , Szymański Łukasz
Published: January 2021

The development of new technologies and industry is conducive to the increase in the number and variety of electromagnetic field (EMF) sources in our environment. The main sources of EMF are high-voltage lines, household appliances, audio/video devices, mobile phones, radio stations, and radar devices. In the growing use of electronic devices, scientists are increasingly interested in the effects of EMF on human health. Even though many studies on the effects of EMF have already been carried out, none of them has shown a significant effect on mammals, including humans. Moreover, it is not entirely clear how EMF influences cell behavior. The International Agency for Research on Cancer on 31 May 2011, classified PEM as a possible carcinogenic factor. This study aimed to investigate the effect of the electromagnetic field on morphological and functional changes in clear cell renal carcinoma. The research was carried out on in vitro cultures of four cell lines: HEK293, 786-O 769-P, and Caki1. The results of the research showed that the EMF of low frequency had a slight effect on the viability of cells. EMF, which induced cell arrest in the G1 phase, increased the number of early apoptotic cells and decreased the number of viable cells in the 786-O line. EMF did not affect the proliferation and viability of HEK293 cells. Extreme low-frequency EMF (ELF-EMF) also showed an inhibitory effect on the migration and metastatic properties of clear cell kidney cancer cells. Moreover, shortly after the end of ELF-EMF exposure, significant increases in ROS levels were observed in all tested cell lines. As part of the work, it was shown that low-frequency EMF shows an inhibitory effect on the proliferation of primary cancer cells, diminishing their migratory, invasive, and metastatic abilities. It also increases the apoptosis of cancer cells and the amount of reactive oxygen species. Based on the results of our research, we want to point up that the effect of ELF-EMF depends on a specific metabolic state or at a specific stage in the cell cycle of the cells under study.
Lithography Processable Ta2O5 Barrier-Layered Chitosan Electric Double Layer Synaptic Transistors
Authors: Kim Sung-Hun , Cho Won-Ju
Published: January 2021

We proposed a synaptic transistor gated using a Ta2O5 barrier-layered organic chitosan electric double layer (EDL) applicable to a micro-neural architecture system. In most of the previous studies, a single layer of chitosan electrolyte was unable to perform lithography processes due to poor mechanical/chemical resistance. To overcome this limitation, we laminated a high-k Ta2O5 thin film on chitosan electrolyte to ensure high mechanical/chemical stability to perform a lithographic process for micropattern formation. Artificial synaptic behaviors were realized by protonic mobile ion polarization in chitosan electrolytes. In addition, neuroplasticity modulation in the amorphous In–Ga–Zn-oxide (a-IGZO) channel was implemented by presynaptic stimulation. We also demonstrated synaptic weight changes through proton polarization, excitatory postsynaptic current modulations, and paired-pulse facilitation. According to the presynaptic stimulations, the magnitude of mobile proton polarization and the amount of weight change were quantified. Subsequently, the stable conductance modulation through repetitive potential and depression pulse was confirmed. Finally, we consider that proposed synaptic transistor is suitable for advanced micro-neural architecture because it overcomes the instability caused when using a single organic chitosan layer.
Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus
Authors: Amend Anaïs , Wickli Natalie , Schäfer Anna-Lena , Sprenger Dalina T. L. , Manz Rudolf A. , Voll Reinhard E. , Chevalier Nina
Published: January 2021

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.
Structural Features and Phylogenetic Implications of Four New Mitogenomes of Caliscelidae (Hemiptera: Fulgoromorpha)
Authors: Gong Nian , Yang Lin , Chen Xiang-Sheng
Published: January 2021

To explore the differences in mitogenome variation and phylogenetics among lineages of the Hemiptera superfamily Fulgoroidea, we sequenced four new mitogenomes of Caliscelidae: two species of the genus Bambusicaliscelis (Caliscelinae: Caliscelini), namely Bambusicaliscelis flavus and B. fanjingensis, and two species of the genus Youtuus (Ommatidiotinae: Augilini), namely Youtuus strigatus and Y. erythrus. The four mitogenomes were 15,922–16,640 bp (base pair) in length, with 37 mitochondrial genes and an AT-rich region. Gene content and arrangement were similar to those of most other sequenced hexapod mitogenomes. All protein-coding genes (PCGs) started with a canonical ATN or GTG and ended with TAA or an incomplete stop codon single T. Except for two transfer RNAs (tRNAs; trnS1 and trnV) lacking a dihydrouridine arm in the four species and trnC lacking a dihydrouridine stem in the Youtuus species, the remaining tRNAs could fold into canonical cloverleaf secondary structures. Phylogenetic analyses based on sequence data of 13 PCGs in the 28 Fulgoroidea species and two outgroups revealed that Delphacidae was monophyletic with strong support. Our data suggest that Fulgoridae is more ancient than Achilidae. Furthermore, Flatidae, Issidae, and Ricaniidae always cluster to form a sister group to Caliscelidae.
Effects of Subchronic Administrations of Vortioxetine, Lurasidone, and Escitalopram on Thalamocortical Glutamatergic Transmission Associated with Serotonin 5-HT7 Receptor
Authors: Okada Motohiro , Matsumoto Ryusuke , Yamamoto Yoshimasa , Fukuyama Kouji
Published: January 2021

The functional suppression of serotonin (5-HT) type 7 receptor (5-HT7R) is forming a basis for scientific discussion in psychopharmacology due to its rapid-acting antidepressant-like action. A novel mood-stabilizing atypical antipsychotic agent, lurasidone, exhibits a unique receptor-binding profile, including a high affinity for 5-HT7R antagonism. A member of a novel class of antidepressants, vortioxetine, which is a serotonin partial agonist reuptake inhibitor (SPARI), also exhibits a higher affinity for serotonin transporter, serotonin receptors type 1A (5-HT1AR) and type 3 (5-HT3R), and 5-HT7R. However, the effects of chronic administration of lurasidone, vortioxetine, and the selective serotonin reuptake inhibitor (SSRI), escitalopram, on 5-HT7R function remained to be clarified. Thus, to explore the mechanisms underlying the clinical effects of vortioxetine, escitalopram, and lurasidone, the present study determined the effects of these agents on thalamocortical glutamatergic transmission, which contributes to emotional/mood perception, using multiprobe microdialysis and 5-HT7R expression using capillary immunoblotting. Acute local administration of a 5-HT7R agonist and antagonist into the mediodorsal thalamic nucleus (MDTN) enhanced and reduced thalamocortical glutamatergic transmission, induced by N-methyl-D-aspartate (NMDA)/glutamate receptor inhibition in the reticular thalamic nucleus (RTN). Acute local administration of a relevant therapeutic concentration of vortioxetine and lurasidone into the MDTN suppressed the thalamocortical glutamatergic transmission via 5-HT7R inhibition, whereas that of escitalopram activated 5-HT7R. Subchronic administration of effective doses of vortioxetine and lurasidone (for 7 days) reduced the thalamocortical glutamatergic transmission, but escitalopram did not affect it, whereas subchronic administration of these three agents attenuated the stimulatory effects of the 5-HT7R agonist on thalamocortical glutamatergic transmission. Subchronic administration of effective doses of vortioxetine, lurasidone, and escitalopram downregulated the 5-HT7R expression of the plasma membrane in the MDTN; the 5-HT7R downregulation induced by vortioxetine and lurasidone was observed at 3 days, but that induced by escitalopram required a longer duration of 7 days. These results indicate that chronic administration of vortioxetine, escitalopram, and lurasidone generate downregulation of 5-HT7R in the thalamus; however, the direct inhibition of 5-HT7R associated with vortioxetine and lurasidone generates more rapid downregulation than the indirect elevation of the extracellular serotonin level via serotonin transporter inhibition by escitalopram.
Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells
Authors: Takahashi Yuwa , Watanabe Norihisa , Kamio Noriaki , Yokoe Sho , Suzuki Ryuta , Sato Shuichi , Iinuma Toshimitsu , Imai Kenichi
Published: January 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.
The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers
Authors: Hases Linnea , Ibrahim Ahmed , Chen Xinsong , Liu Yanghong , Hartman Johan , Williams Cecilia
Published: January 2021

Colorectal cancer (CRC) is the third leading cause of cancer deaths. Advances within bioinformatics, such as machine learning, can improve biomarker discovery and ultimately improve CRC survival rates. There are clear sex differences in CRC characteristics, but the impact of sex has not been considered with regards to CRC biomarkers. Our aim here was to investigate sex differences in the transcriptome of a normal colon and CRC, and between paired normal and tumor tissue. Next, we attempted to identify CRC diagnostic and prognostic biomarkers and investigate if they are sex-specific. We collected paired normal and tumor tissue, performed RNA-seq, and applied feature selection in combination with machine learning to identify the top CRC diagnostic biomarkers. We used The Cancer Genome Atlas (TCGA) data to identify sex-specific CRC diagnostic biomarkers and performed an overall survival analysis to identify sex-specific prognostic biomarkers. We found transcriptomic sex differences in both the normal colon tissue and in CRC. Forty-four of the top-ranked biomarkers were sex-specific and 20 biomarkers showed a sex-specific prognostic value. Our data show the importance of sex in the discovery of CRC biomarkers. We propose 20 sex-specific CRC prognostic biomarkers, including ESM1, GUCA2A, and VWA2 for males and CLDN1 and FUT1 for females.
The Stemness-High Human Colorectal Cancer Cells Promote Angiogenesis by Producing Higher Amounts of Angiogenic Cytokines via Activation of the Egfr/Akt/Nf-κB Pathway
Authors: Chung Shin-Yi , Chao Ta-Chung , Su Yeu
Published: January 2021

Purpose: Cancer stem cells (CSCs) are responsible for cancer metastasis by stimulating tumor angiogenesis via various mechanisms. To elucidate the potential of the stemness-high human colorectal cancer (CRC) cells (i.e., CRCSCs) in activating angiogenesis, effects of the GATA6-overexpressing HCT-116 and HT-29 human CRC clones established previously by us in promoting the angiogenesis of human umbilical vein endothelial cells (HUVECs) were examined. Methods: Angiogenesis-promoting effects (i.e., migration, invasion, DNA synthesis, and tube formation) in HUVECs of the conditioned media (CM) from various human CRC clones were analyzed. MMP activities were assessed using a zymography assay. Western blotting and selective inhibitors were used to dissect the signaling pathway involved. IHC was used to examine the vascular density in tumor xenografts. Results: We found that the conditioned media (CM) collected from the GATA6-overexpressing clones enhanced angiogenesis of HUVECs more effectively which might be attributed partly to a higher MMP-9 production by HUVECs. Subsequently, elevated levels of IL-8 and VEGF-A were detected in the CM whose tube formation-enhancing activities were abolished by the co-treatment with either a VEGFR2 inhibitor or an IL-8 neutralizing antibody. Interestingly, increased production of these cytokines in the GATA6-overexpressing clones was due to an EGFR/AKT-mediated activation of NF-κB. Furthermore, not only were the levels of CD31 and endomucin but also the blood vessel density was much higher in the xenograft tumors grown from these clones. Conclusion: Our findings demonstrate that human CRCSCs promote a stronger angiogenesis by producing higher amounts of angiogenic factors through activation of the EGFR/AKT/NF-κB pathway.
Manipulation of Focal Adhesion Signaling by Pathogenic Microbes
Authors: Murphy Korinn N. , Brinkworth Amanda J.
Published: January 2021

Focal adhesions (FAs) serve as dynamic signaling hubs within the cell. They connect intracellular actin to the extracellular matrix (ECM) and respond to environmental cues. In doing so, these structures facilitate important processes such as cell–ECM adhesion and migration. Pathogenic microbes often modify the host cell actin cytoskeleton in their pursuit of an ideal replicative niche or during invasion to facilitate uptake. As actin-interfacing structures, FA dynamics are also intimately tied to actin cytoskeletal organization. Indeed, exploitation of FAs is another avenue by which pathogenic microbes ensure their uptake, survival and dissemination. This is often achieved through the secretion of effector proteins which target specific protein components within the FA. Molecular mimicry of the leucine–aspartic acid (LD) motif or vinculin-binding domains (VBDs) commonly found within FA proteins is a common microbial strategy. Other effectors may induce post-translational modifications to FA proteins through the regulation of phosphorylation sites or proteolytic cleavage. In this review, we present an overview of the regulatory mechanisms governing host cell FAs, and provide examples of how pathogenic microbes have evolved to co-opt them to their own advantage. Recent technological advances pose exciting opportunities for delving deeper into the mechanistic details by which pathogenic microbes modify FAs.
Cellular and Molecular Players in the Interplay between Adipose Tissue and Breast Cancer
Authors: Reggiani Francesca , Falvo Paolo , Bertolini Francesco
Published: January 2021

The incidence and severity of obesity are rising in most of the world. In addition to metabolic disorders, obesity is associated with an increase in the incidence and severity of a variety of types of cancer, including breast cancer (BC). The bidirectional interaction between BC and adipose cells has been deeply investigated, although the molecular and cellular players involved in these mechanisms are far from being fully elucidated. Here, we review the current knowledge on these interactions and describe how preclinical research might be used to clarify the effects of obesity over BC progression and morbidity, with particular attention paid to promising therapeutic interventions.
Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS
Authors: Kim Da Hye , Kim Jeong-Hwan , Hwangbo Hyun , Kim So Young , Ji Seon Yeong , Kim Min Yeong , Cha Hee-Jae , Park Cheol , Hong Su Hyun , Kim Gi-Young , Park Seh-Kwang , Jeong Ji-Won , Kim Mi-Young , Choi Yung Hyun , Lee Hyesook
Published: January 2021

Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.
Monokaryotic Pleurotus sapidus Strains with Intraspecific Variability of an Alkene Cleaving DyP-Type Peroxidase Activity as a Result of Gene Mutation and Differential Gene Expression
Authors: Krahe Nina-Katharina , Berger Ralf G. , Witt Martin , Zorn Holger , Omarini Alejandra B. , Ersoy Franziska
Published: January 2021

The basidiomycete Pleurotus sapidus produced a dye-decolorizing peroxidase (PsaPOX) with alkene cleavage activity, implying potential as a biocatalyst for the fragrance and flavor industry. To increase the activity, a daughter-generation of 101 basidiospore-derived monokaryons (MK) was used. After a pre-selection according to the growth rate, the activity analysis revealed a stable intraspecific variability of the strains regarding peroxidase and alkene cleavage activity of PsaPOX. Ten monokaryons reached activities up to 2.6-fold higher than the dikaryon, with MK16 showing the highest activity. Analysis of the PsaPOX gene identified three different enzyme variants. These were co-responsible for the observed differences in activities between strains as verified by heterologous expression in Komagataella phaffii. The mutation S371H in enzyme variant PsaPOX_high caused an activity increase alongside a higher protein stability, while the eleven mutations in variant PsaPOX_low resulted in an activity decrease, which was partially based on a shift of the pH optimum from 3.5 to 3.0. Transcriptional analysis revealed the increased expression of PsaPOX in MK16 as reason for the higher PsaPOX activity in comparison to other strains producing the same PsaPOX variant. Thus, different expression profiles, as well as enzyme variants, were identified as crucial factors for the intraspecific variability of the PsaPOX activity in the monokaryons.
Prediction of Protein–Protein Binding Interactions in Dimeric Coiled Coils by Information Contained in Folding Energy Landscapes
Authors: Georgoulia Panagiota S. , Bjelic Sinisa
Published: January 2021

Coiled coils represent the simplest form of a complex formed between two interacting protein partners. Their extensive study has led to the development of various methods aimed towards the investigation and design of complex forming interactions. Despite the progress that has been made to predict the binding affinities for protein complexes, and specifically those tailored towards coiled coils, many challenges still remain. In this work, we explore whether the information contained in dimeric coiled coil folding energy landscapes can be used to predict binding interactions. Using the published SYNZIP dataset, we start from the amino acid sequence, to simultaneously fold and dock approximately 1000 coiled coil dimers. Assessment of the folding energy landscapes showed that a model based on the calculated number of clusters for the lowest energy structures displayed a signal that correlates with the experimentally determined protein interactions. Although the revealed correlation is weak, we show that such correlation exists; however, more work remains to establish whether further improvements can be made to the presented model.
A Novel Multiprotein Bridging Factor 1-Like Protein Induces Cyst Wall Protein Gene Expression and Cyst Differentiation in Giardia lamblia
Authors: Huang Shao-Wei , Lin Zi-Qi , Tung Szu-Yu , Su Li-Hsin , Ho Chun-Che , Lee Gilbert Aaron , Sun Chin-Hung
Published: January 2021

The capacity to synthesize a protective cyst wall is critical for infectivity of Giardia lamblia. It is of interest to know the mechanism of coordinated synthesis of three cyst wall proteins (CWPs) during encystation, a differentiation process. Multiprotein bridging factor 1 (MBF1) gene family is a group of transcription coactivators that bridge various transcription factors. They are involved in cell growth and differentiation in yeast and animals, or in stress response in fungi and plants. We asked whether Giardia has MBF1-like genes and whether their products influence gene expression. BLAST searches of the Giardia genome database identified one gene encoding a putative MBF1 protein with a helix-turn-helix domain. We found that it can specifically bind to the AT-rich initiator promoters of the encystation-induced cwp1-3 and myb2 genes. MBF1 localized to cell nuclei and cytoplasm with higher expression during encystation. In addition, overexpression of MBF1 induced cwp1-3 and myb2 gene expression and cyst generation. Mutation of the helixes in the helix-turn-helix domain reduced cwp1-3 and myb2 gene expression and cyst generation. Chromatin immunoprecipitation assays confirmed the binding of MBF1 to the promoters with its binding sites in vivo. We also found that MBF1 can interact with E2F1, Pax2, WRKY, and Myb2 transcription factors that coordinately up-regulate the cwp genes during encystation. Using a CRISPR/Cas9 system for targeted disruption of mbf1 gene, we found a downregulation of cwp1-3 and myb2 genes and decrease of cyst generation. Our results suggest that MBF1 is functionally conserved and positively regulates Giardia cyst differentiation.
Plantar Mechanical Stimulation Maintains Slow Myosin Expression in Disused Rat Soleus Muscle via NO-Dependent Signaling
Authors: Sharlo Kristina A. , Paramonova Inna I. , Lvova Irina D. , Mochalova Ekaterina P. , Kalashnikov Vitaliy E. , Vilchinskaya Natalia A. , Tyganov Sergey A. , Konstantinova Tatyana S. , Shevchenko Tatiana F. , Kalamkarov Grigoriy R. , Shenkman Boris S.
Published: January 2021

It was observed that gravitational unloading during space missions and simulated microgravity in ground-based studies leads to both transformation of slow-twitch muscle fibers into fast-twitch fibers and to the elimination of support afferentation, leading to the “switching-off” of postural muscle motor units electrical activity. In recent years, plantar mechanical stimulation (PMS) has been found to maintain the neuromuscular activity of the hindlimb muscles. Nitric oxide (NO) was shown to be one of the mediators of muscle fiber activity, which can also promote slow-type myosin expression. We hypothesized that applying PMS during rat hindlimb unloading would lead to NO production upregulation and prevention of the unloading-induced slow-to-fast fiber-type shift in rat soleus muscles. To test this hypothesis, Wistar rats were hindlimb suspended and subjected to daily PMS, and one group of PMS-subjected animals was also treated with nitric oxide synthase inhibitor (L-NAME). We discovered that PMS led to sustained NO level in soleus muscles of the suspended animals, and NOS inhibitor administration blocked this effect, as well as the positive effects of PMS on myosin I and IIa mRNA transcription and slow-to-fast fiber-type ratio during rat hindlimb unloading. The results of the study indicate that NOS activity is necessary for the PMS-mediated prevention of slow-to-fast fiber-type shift and myosin I and IIa mRNA transcription decreases during rat hindlimb unloading.
Social Media Adoption by Health Professionals: A TAM-Based Study
Authors: Khan Md Irfanuzzaman , Saleh M Abu , Quazi Ali
Published: January 2021

This research identifies the underlying drivers impacting on healthcare professionals’ social media usage behaviours using the technology acceptance model (TAM) as the theoretical lens. A self-administered survey questionnaire was developed and administered to 219 healthcare professionals. Data are analysed applying the structural equation modelling (SEM) technique. The SEM model demonstrated an acceptable model fit (χ2 = 534.241; df, 239, χ2/df = 2.235, RMSEA = 0.06, IFI = 0.92, TLI = 0.93, and CFI = 0.92) and indicates content quality, perceived risk, perceived credibility, peer influence, confirmation of expectations, supporting conditions, and perceived cost significantly influence the notion of perceived social media usefulness. Furthermore, perceived social media usefulness positively affects social media usage behaviour of healthcare professionals. This research generates important insights into what drives the adoption of social media by healthcare professionals. These insights could help develop social media guidelines and strategies to improve the state of professional interactions between health professionals and their clients.