bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Parental Behavior towards Children’s Use of Media and Screen-Devices: The Development and Psychometrical Properties of a Media Parenting Scale for Parents of School-Aged Children
Authors: Lukavská Kateřina , Vacek Jaroslav , Hrabec Ondřej , Božík Michal , Slussareff Michaela , Píšová Martina , Kocourek David , Svobodová Lucie , Gabrhelík Roman
Published: August 2021

Children’s excessive screen use is associated with health risks such as obesity, sleep problems, attention problems, and others. The effect of parental regulative efforts focused on screen/media use (media parenting) is currently unclear and difficult to examine given the heterogeneity of measuring tools used for its assessment. We aimed to develop an inventory that would enable reliable and valid measurement of media parenting practices (especially active and restrictive mediation) in parents of primary school children. The inventory builds on existing tools, it is comprehensive, yet easy to use in research setting. The original MEPA-36 (36 items) and revised MEPA-20 (20 items) inventories were examined using data from 341 Czech and Slovak parents of children aged between 6 and 10 years. Psychometrical properties were estimated using confirmatory factor and reliability analyses. Model fit was better for MEPA-20 and similar to other currently available tools. Both active and restrictive mediation subscales demonstrated high internal consistency. The internal consistency of newly constructed risky mediation subscales (risky active, risky restrictive, and over-protective mediation) was low. MEPA-20, especially active and restrictive mediation subscales, can be recommended for research on media parenting in context of screen/media use of school-aged children.
Effect of Maternal Factors on Problematic Smartphone Use among Elementary School Children
Authors: Lee Eun Jee , Kim Hee Sun
Published: August 2021

Mothers play a key role in ensuring their children’s healthy life. This study aimed to identify the maternal factors affecting problematic smartphone use in children. We adopted a cross-sectional descriptive design using structured questionnaires. Participants were fourth to sixth grade elementary school students in Korea (n = 184). The following maternal factors were evaluated: maternal mediation, children’s perception of mothers’ smartphone use, mother–child communication, and parenting style. Data regarding maternal factors’ effect on problematic smartphone use were analyzed by computing descriptive statistics and logistic regression analysis using SPSS Win 27.0. The results show that the maternal factors that influenced problematic smartphone use in children were maternal control over smartphone usage (odds ratio (OR) = 5.10, 95% confidence interval (CI): 1.33–19.60), smartphone usage time for social network service (OR = 1.52, 95% CI: 1.10–2.01), and problematic mother–child communication (OR = 1.07, 95% CI: 1.00–1.14). Therefore, to promote appropriate smartphone use among school children, it is necessary to develop an intervention comprising maternal supervision of their children’s smartphones, guidance provision for social network service usage, and strategies for the reinforcement of positive mother–child communication.
Psychometric Properties and Cultural Adaptation of the Polish Version of the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ)
Authors: Czapla Michał , Juárez-Vela Raúl , Rozensztrauch Anna , Karniej Piotr , Uchmanowicz Izabella , Santolalla-Arnedo Iván , Baska Alicja
Published: August 2021

Background: Chronic non-communicable diseases (NCDs), sometimes referred to as lifestyle diseases, are the most common cause of death and disability worldwide. Thus, healthcare professionals should be equipped with tools, knowledge, skills, and competencies in the newly distinguished field of lifestyle medicine. The purpose of this study was to test the psychometric properties of the Polish version of the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ). The Polish version of the HLPCQ would further provide Polish healthcare professionals with a useful and convenient tool for routine lifestyle assessment while giving HLPCQ novel use and potential for further research. Methods: Before testing its psychometric properties, the HLPCQ was translated and adapted from the original Greek version into Polish. Subsequently, we tested the instrument’s psychometric properties on a sample of 2433 participants. In addition, we tested the factorial validity of the HLPCQ using confirmatory and exploratory factor analysis. Results: There were more female than male participants (91.78%). Most of them were middle-aged (30.40 ± 7.71), single (39.62%), and living with family (70.65%). In terms of residence, 1122 (46.12%) participants lived in cities with a population of over 500,000. In terms of reliability, the internal consistency of the Polish version and its domains is excellent. Cronbach’s alpha for each of the domains of the scale ranged between 0.6 and 0.9. Conclusions: The Polish version of the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ) has good characteristics of factorial validity and can be used in clinical practice and research.
#AllforJan: How Twitter Users in Europe Reacted to the Murder of Ján Kuciak—Revealing Spatiotemporal Patterns through Sentiment Analysis and Topic Modeling
Authors: Kovács Tamás , Kovács-Győri Anna , Resch Bernd
Published: August 2021

Social media platforms such as Twitter are considered a new mediator of collective action, in which various forms of civil movements unite around public posts, often using a common hashtag, thereby strengthening the movements. After 26 February 2018, the #AllforJan hashtag spread across the web when Ján Kuciak, a young journalist investigating corruption in Slovakia, and his fiancée were killed. The murder caused moral shock and mass protests in Slovakia and in several other European countries, as well. This paper investigates how this murder, and its follow-up events, were discussed on Twitter, in Europe, from 26 February to 15 March 2018. Our investigations, including spatiotemporal and sentiment analyses, combined with topic modeling, were conducted to comprehensively understand the trends and identify potential underlying factors in the escalation of the events. After a thorough data pre-processing including the extraction of spatial information from the users’ profile and the translation of non-English tweets, we clustered European countries based on the temporal patterns of tweeting activity in the analysis period and investigated how the sentiments of the tweets and the discussed topics varied over time in these clusters. Using this approach, we found that tweeting activity resonates not only with specific follow-up events, such as the funeral or the resignation of the Prime Minister, but in some cases, also with the political narrative of a given country affecting the course of discussions. Therefore, we argue that Twitter data serves as a unique and useful source of information for the analysis of such civil movements, as the analysis can reveal important patterns in terms of spatiotemporal and sentimental aspects, which may also help to understand protest escalation over space and time.
Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation
Authors: Di Micco Simone , Musella Simona , Sala Marina , Scala Maria C. , Andrei Graciela , Snoeck Robert , Bifulco Giuseppe , Campiglia Pietro , Fasano Alessio
Published: August 2021

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the pathogen responsible for the outbreak of a severe, rapidly developing pneumonia (Coronavirus disease 2019, COVID-19). The virus enzyme, called 3CLpro or main protease (Mpro), is essential for viral replication, making it a most promising target for antiviral drug development. Recently, we adopted the drug repurposing as appropriate strategy to give fast response to global COVID-19 epidemic, by demonstrating that the zonulin octapeptide inhibitor AT1001 (Larazotide acetate) binds Mpro catalytic domain. Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials.
The Emerging Role of Stress Granules in Hepatocellular Carcinoma
Authors: Dolicka Dobrochna , Foti Michelangelo , Sobolewski Cyril
Published: August 2021

Stress granules (SGs) are small membrane-free cytosolic liquid-phase ordered entities in which mRNAs are protected and translationally silenced during cellular adaptation to harmful conditions (e.g., hypoxia, oxidative stress). This function is achieved by structural and functional SG components such as scaffold proteins and RNA-binding proteins controlling the fate of mRNAs. Increasing evidence indicates that the capacity of cells to assemble/disassemble functional SGs may significantly impact the onset and the development of metabolic and inflammatory diseases, as well as cancers. In the liver, the abnormal expression of SG components and formation of SG occur with chronic liver diseases, hepatocellular carcinoma (HCC), and selective hepatic resistance to anti-cancer drugs. Although, the role of SG in these diseases is still debated, the modulation of SG assembly/disassembly or targeting the expression/activity of specific SG components may represent appealing strategies to treat hepatic disorders and potentially cancer. In this review, we discuss our current knowledge about pathophysiological functions of SGs in HCC as well as available molecular tools and drugs capable of modulating SG formation and functions for therapeutic purposes.
MiR1885 Regulates Disease Tolerance Genes in Brassica rapa during Early Infection with Plasmodiophora brassicae
Authors: Paul Parameswari , Chhapekar Sushil Satish , Rameneni Jana Jeevan , Oh Sang Heon , Dhandapani Vignesh , Subburaj Saminathan , Shin Sang-Yoon , Ramchiary Nirala , Shin Chanseok , Choi Su Ryun , Lim Yong Pyo
Published: August 2021

Clubroot caused by Plasmodiophora brassicae is a severe disease of cruciferous crops that decreases crop quality and productivity. Several clubroot resistance-related quantitative trait loci and candidate genes have been identified. However, the underlying regulatory mechanism, the interrelationships among genes, and how genes are regulated remain unexplored. MicroRNAs (miRNAs) are attracting attention as regulators of gene expression, including during biotic stress responses. The main objective of this study was to understand how miRNAs regulate clubroot resistance-related genes in P. brassicae-infected Brassica rapa. Two Brassica miRNAs, Bra-miR1885a and Bra-miR1885b, were revealed to target TIR-NBS genes. In non-infected plants, both miRNAs were expressed at low levels to maintain the balance between plant development and basal immunity. However, their expression levels increased in P. brassicae-infected plants. Both miRNAs down-regulated the expression of the TIR-NBS genes Bra019412 and Bra019410, which are located at a clubroot resistance-related quantitative trait locus. The Bra-miR1885-mediated down-regulation of both genes was detected for up to 15 days post-inoculation in the clubroot-resistant line CR Shinki and in the clubroot-susceptible line 94SK. A qRT-PCR analysis revealed Bra019412 expression was negatively regulated by miR1885. Both Bra019412 and Bra019410 were more highly expressed in CR Shinki than in 94SK; the same expression pattern was detected in multiple clubroot-resistant and clubroot-susceptible inbred lines. A 5′ rapid amplification of cDNA ends analysis confirmed the cleavage of Bra019412 by Bra-miR1885b. Thus, miR1885s potentially regulate TIR-NBS gene expression during P. brassicae infections of B. rapa.
The Antihypertensive Drug Telmisartan Protects Oligodendrocytes from Cholesterol Accumulation and Promotes Differentiation by a PPAR-γ-Mediated Mechanism
Authors: Bernardo Antonietta , Malara Mariagiovanna , Bertuccini Lucia , De Nuccio Chiara , Visentin Sergio , Minghetti Luisa
Published: August 2021

Our previous studies have demonstrated that specific peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists play a fundamental role in oligodendrocyte progenitor (OP) differentiation, protecting them against oxidative and inflammatory damage. The antihypertensive drug Telmisartan (TLM) was shown to act as a PPAR-γ modulator. This study investigates the TLM effect on OP differentiation and validates its capability to restore damage in a pharmacological model of Niemann-Pick type C (NPC) disease through a PPAR-γ-mediated mechanism. For the first time in purified OPs, we demonstrate that TLM-induced PPAR-γ activation downregulates the type 1 angiotensin II receptor (AT1), the level of which naturally decreases during differentiation. Like other PPAR-γ agonists, we show that TLM promotes peroxisomal proliferation and promotes OP differentiation. Furthermore, TLM can offset the OP maturation arrest induced by a lysosomal cholesterol transport inhibitor (U18666A), which reproduces an NPC1-like phenotype. In the NPC1 model, TLM also reduces cholesterol accumulation within peroxisomal and lysosomal compartments and the contacts between lysosomes and peroxisomes, revealing that TLM can regulate intracellular cholesterol transport, crucial for myelin formation. Altogether, these data indicate a new potential use of TLM in hypomyelination pathologies such as NPC1, underlining the possible repositioning of the drug already used in other pathologies.
Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis
Authors: MacDonald Iona J. , Tsai Hsiao-Chi , Chang An-Chen , Huang Chien-Chung , Yang Shun-Fa , Tang Chih-Hsin
Published: August 2021

Osteoblasts and osteoclasts are major cellular components in the bone microenvironment and they play a key role in the bone turnover cycle. Many risk factors interfere with this cycle and contribute to bone-wasting diseases that progressively destroy bone and markedly reduce quality of life. Melatonin (N-acetyl-5-methoxy-tryptamine) has demonstrated intriguing therapeutic potential in the bone microenvironment, with reported effects that include the regulation of bone metabolism, acceleration of osteoblastogenesis, inhibition of osteoclastogenesis and the induction of apoptosis in mature osteoclasts, as well as the suppression of osteolytic bone metastasis. This review aims to shed light on molecular and clinical evidence that points to possibilities of melatonin for the treatment of both osteoporosis and osteolytic bone metastasis. It appears that the therapeutic qualities of melatonin supplementation may enable existing antiresorptive osteoporotic drugs to treat osteolytic metastasis.
Porous Biphasic Calcium Phosphate Granules from Oyster Shell Promote the Differentiation of Induced Pluripotent Stem Cells
Authors: Ho Wen-Fu , Lee Mei-Hwa , Thomas James L. , Li Jin-An , Wu Shih-Ching , Hsu Hsueh-Chuan , Lin Hung-Yin
Published: August 2021

Oyster shells are rich in calcium, and thus, the potential use of waste shells is in the production of calcium phosphate (CaP) minerals for osteopathic biomedical applications, such as scaffolds for bone regeneration. Implanted scaffolds should stimulate the differentiation of induced pluripotent stem cells (iPSCs) into osteoblasts. In this study, oyster shells were used to produce nano-grade hydroxyapatite (HA) powder by the liquid-phase precipitation. Then, biphasic CaP (BCP) bioceramics with two different phase ratios were obtained by the foaming of HA nanopowders and sintering by two different two-stage heat treatment processes. The different sintering conditions yielded differences in structure and morphology of the BCPs, as determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) surface area analysis. We then set out to determine which of these materials were most biocompatible, by co-culturing with iPSCs and examining the gene expression in molecular pathways involved in self-renewal and differentiation of iPSCs. We found that sintering for a shorter time at higher temperatures gave higher expression levels of markers for proliferation and (early) differentiation of the osteoblast. The differences in biocompatibility may be related to a more hierarchical pore structure (micropores within macropores) obtained with briefer, high-temperature sintering.
Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis
Authors: Ferrari Davide , Casciano Fabio , Secchiero Paola , Reali Eva
Published: August 2021

Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments.
Battling Chemoresistance in Cancer: Root Causes and Strategies to Uproot Them
Authors: Ramos Alisha , Sadeghi Samira , Tabatabaeian Hossein
Published: August 2021

With nearly 10 million deaths, cancer is the leading cause of mortality worldwide. Along with major key parameters that control cancer treatment management, such as diagnosis, resistance to the classical and new chemotherapeutic reagents continues to be a significant problem. Intrinsic or acquired chemoresistance leads to cancer recurrence in many cases that eventually causes failure in the successful treatment and death of cancer patients. Various determinants, including tumor heterogeneity and tumor microenvironment, could cause chemoresistance through a diverse range of mechanisms. In this review, we summarize the key determinants and the underlying mechanisms by which chemoresistance appears. We then describe which strategies have been implemented and studied to combat such a lethal phenomenon in the management of cancer treatment, with emphasis on the need to improve the early diagnosis of cancer complemented by combination therapy.
Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study
Authors: Formichi Caterina , Fignani Daniela , Nigi Laura , Grieco Giuseppina Emanuela , Brusco Noemi , Licata Giada , Sabato Claudia , Ferretti Elisabetta , Sebastiani Guido , Dotta Francesco
Published: August 2021

Type 2 diabetes (T2D) represents one of the major health issues of this century. Despite the availability of an increasing number of anti-hyperglycemic drugs, a significant proportion of patients are inadequately controlled, thus highlighting the need for novel biomarkers to guide treatment selection. MicroRNAs (miRNAs) are small non-coding RNAs, proposed as useful diagnostic/prognostic markers. The aim of our study was to identify a miRNA signature occurring in responders to glucagon-like peptide 1 receptor agonists (GLP1-RA) therapy. We investigated the expression profile of eight T2D-associated circulating miRNAs in 26 prospectively evaluated diabetic patients in whom GLP1-RA was added to metformin. As expected, GLP1-RA treatment induced significant reductions of HbA1c and body weight, both after 6 and 12 months of therapy. Of note, baseline expression levels of the selected miRNAs revealed two distinct patient clusters: “high expressing” and “low expressing”. Interestingly, a significantly higher percentage of patients in the high expression group reached the glycemic target after 12 months of treatment. Our findings suggest that the evaluation of miRNA expression could be used to predict the likelihood of an early treatment response to GLP1-RA and to select patients in whom to start such treatment, paving the way to a personalized medicine approach.
Trans-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta (Aβ42) and Protect from Aβ42 Induced Oxidative Damage in Yeast Models of Alzheimer’s Disease
Authors: Dhakal Sudip , Ramsland Paul A. , Adhikari Benu , Macreadie Ian
Published: August 2021

Finding an effective therapeutic to prevent or cure AD has been difficult due to the complexity of the brain and limited experimental models. This study utilized unmodified and genetically modified Saccharomyces cerevisiae as model organisms to find potential natural bioactive compounds capable of reducing intracellular amyloid beta 42 (Aβ42) and associated oxidative damage. Eleven natural bioactive compounds including mangiferin, quercetin, rutin, resveratrol, epigallocatechin gallate (EGCG), urolithin A, oleuropein, rosmarinic acid, salvianolic acid B, baicalein and trans-chalcone were screened for their ability to reduce intracellular green fluorescent protein tagged Aβ42 (GFP-Aβ42) levels. The two most effective compounds from the screens were combined in varying concentrations of each to study the combined capacity to reduce GFP-Aβ42. The most effective combinations were examined for their effect on growth rate, turnover of native Aβ42 and reactive oxygen species (ROS). The bioactive compounds except mangiferin and urolithin A significantly reduced intracellular GFP-Aβ42 levels. Baicalein and trans-chalcone were the most effective compounds among those that were screened. The combination of baicalein and trans-chalcone synergistically reduced GFP-Aβ42 levels. A combination of 15 μM trans-chalcone and 8 μM baicalein was found to be the most synergistic combination. The combination of the two compounds significantly reduced ROS and Aβ42 levels in yeast cells expressing native Aβ42 without affecting growth of the cells. These findings suggest that the combination of baicalein and trans-chalcone could be a promising multifactorial therapeutic strategy to cure or prevent AD. However, further studies are recommended to look for similar cytoprotective activity in humans and to find an optimal dosage.
Plasma Rich in Growth Factors in the Treatment of Endodontic Periapical Lesions in Adult Patients: Case Reports
Authors: Machut Katarzyna , Zoltowska Agata , Pawlowska Elzbieta , Derwich Marcin
Published: August 2021

Platelet-rich fibrin (PRF) is an autologous blood concentrate obtained without anticoagulants by centrifugation of patients’ peripheral venous blood. PRF is considered to enhance the formation of new bone. The aim of this manuscript was to present two case reports of permanent teeth with closed apexes with periapical lesions, treated endodontically with the use of PRF. The root canals were mechanically cleaned and shaped with NiTi files and irrigated with 5.25% sodium hypochlorite (NaOCl), 40% citric acid (CA), and triple distillated water. Before the canal systems were obturated, A-PRF was used as a scaffold and was placed below the cementodentinal junction with hand pluggers. Cone beam computerized tomography (CBCT) was used to assess the resolutions of periapical radiolucencies. After 6 months, the measurements of both periapical lesions were significantly reduced. Although the performed root canal treatments (RCTs) can definitely be recognized as successful, it must be emphasized that mechanical shaping and cleaning of the root canals with special disinfecting solutions significantly affect the clinical efficacy of RCT. It seems impossible to state that PRF played a leading role in the healing process of the presented periapical lesions. Further studies must be performed to assess whether RCT of mature teeth with an additional PRF application is superior to RCT performed alone.
Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?
Authors: Segner Helmut , Bailey Christyn , Tafalla Carolina , Bo Jun
Published: August 2021

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.
Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer’s Disease
Authors: Aaseth Jan , Skalny Anatoly V. , Roos Per M. , Alexander Jan , Aschner Michael , Tinkov Alexey A.
Published: August 2021

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer’s disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.
Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
Authors: Sere Péter , Zsigri Nikolett , Raffai Timea , Furdan Szabina , Győri Fanni , Crunelli Vincenzo , Lőrincz Magor L.
Published: August 2021

(1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5–4 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple neuronal circuits have been involved in their modulation and associated comorbidities including the serotonergic system. Neuronal activity in one of the major synaptic input structures to the brainstem dorsal raphé nucleus (DRN), the lateral hypothalamus (LH), has not been characterized. (2) Methods: We used viral tract tracing and optogenetics combined with in vitro and in vivo electrophysiology to assess the involvement of the LH in absence epilepsy in a genetic rodent model. (3) Results: We found that a substantial fraction of LH neurons project to the DRN of which a minority is GABAergic. The LH to DRN projection can lead to monosynaptic iGluR mediated excitation in DRN 5-HT neurons. Neuronal activity in the LH is coupled to SWDs. (4) Conclusions: Our results indicate that a brain area involved in the regulation of autonomic functions and heavily innervating the RN is involved in ASs. The decreased activity of LH neurons during SWDs could lead to both a decreased excitation and disinhibition in the DRN. These results support a long-range subcortical regulation of serotonergic neuromodulation during ASs and further our understanding of the state-dependence of these seizures and some of their associated comorbidities.
IGF-1 and IGFBP-3 in Inflammatory Cachexia
Authors: Martín Ana Isabel , Priego Teresa , Moreno-Ruperez Álvaro , González-Hedström Daniel , Granado Miriam , López-Calderón Asunción
Published: August 2021

Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic–growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic–GH–IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.
Piezoelectric Microvibration Mitigates Estrogen Loss-Induced Osteoporosis and Promotes Piezo1, MicroRNA-29a, and Wnt3a Signaling in Osteoblasts
Authors: Wu Re-Wen , Lian Wei-Shiung , Chen Yu-Shan , Ko Jih-Yang , Wang Shao-Yu , Jahr Holger , Wang Feng-Sheng
Published: August 2021

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.
Topic Modeling for Analyzing Topic Manipulation Skills
Authors: Hwang Seok-Ju , Lee Yoon-Kyoung , Kim Jong-Dae , Park Chan-Young , Kim Yu-Seop
Published: August 2021

There are many ways to communicate with people, the most representative of which is a conversation. A smooth conversation should not only be written in a grammatically appropriate manner, but also deal with the subject of conversation; this is known as language ability. In the past, this ability has been evaluated by language analysis/therapy experts. However, this process is time-consuming and costly. In this study, the researchers developed a Hallym Systematic Analyzer of Korean language to automate the conversation analysis process traditionally conducted by language analysis/treatment experts. However, current morpheme analyzers or parsing analyzers can only evaluate certain elements of a conversation. Therefore, in this paper, we added the ability to analyze the topic manipulation skills (the number of topics and the rate of topic maintenance) using the existing Hallym Systematic Analyzer of Korean language. The purpose of this study was to utilize the topic modeling technique to automatically evaluate topic manipulation skills. By quantitatively evaluating the topic management capabilities that were previously evaluated in a conventional manner, it was possible to automatically analyze language ability in a wider range of aspects. The experimental results show that the automatic analysis methodology presented in this study achieved a very high level of correlation with language analysis/therapy professionals.
Three Complete Mitochondrial Genomes of Orestes guangxiensis, Peruphasma schultei, and Phryganistria guangxiensis (Insecta: Phasmatodea) and Their Phylogeny
Authors: Xu Ke-Ke , Chen Qing-Ping , Ayivi Sam Pedro Galilee , Guan Jia-Yin , Storey Kenneth B. , Yu Dan-Na , Zhang Jia-Yong
Published: August 2021

Insects of the order Phasmatodea are mainly distributed in the tropics and subtropics and are best known for their remarkable camouflage as plants. In this study, we sequenced three complete mitochondrial genomes from three different families: Orestes guangxiensis, Peruphasma schultei, and Phryganistria guangxiensis. The lengths of the three mitochondrial genomes were 15,896 bp, 16,869 bp, and 17,005 bp, respectively, and the gene composition and structure of the three stick insects were identical to those of the most recent common ancestor of insects. The phylogenetic relationships among stick insects have been chaotic for a long time. In order to discuss the intra- and inter-ordinal relationship of Phasmatodea, we used the 13 protein-coding genes (PCGs) of 85 species for maximum likelihood (ML) and Bayesian inference (BI) analyses. Results showed that the internal topological structure of Phasmatodea had a few differences in both ML and BI trees and long-branch attraction (LBA) appeared between Embioptera and Zoraptera, which led to a non-monophyletic Phasmatodea. Consequently, after removal of the Embioptera and Zoraptera species, we re-performed ML and BI analyses with the remaining 81 species, which showed identical topology except for the position of Tectarchus ovobessus (Phasmatodea). We recovered the monophyly of Phasmatodea and the sister-group relationship between Phasmatodea and Mantophasmatodea. Our analyses also recovered the monophyly of Heteropterygidae and the paraphyly of Diapheromeridae, Phasmatidae, Lonchodidae, Lonchodinae, and Clitumninae. In this study, Peruphasma schultei (Pseudophasmatidae), Phraortes sp. YW-2014 (Lonchodidae), and species of Diapheromeridae clustered into the clade of Phasmatidae. Within Heteropterygidae, O. guangxiensis was the sister clade to O. mouhotii belonging to Dataminae, and the relationship of (Heteropteryginae + (Dataminae + Obriminae)) was recovered.
Association between Early Absolute Neutrophil Count and Level of D-Dimer among Patients with COVID-19 Infection in Central Taiwan
Authors: Chao Wen-Cheng , Wu Chieh-Liang , Huang Jin-An , Chai Jyh-Wen , Teng Chieh-Lin , Lee Wen-Lieng , Fu Yun-Ching , Chen Shih-Ann
Published: August 2021

Thromboembolism is a critical event in patients with coronavirus disease (COVID)-19 infection and highly associated with neutrophil extracellular traps. D-dimer has been found to be an essential thromboembolism-associated biomarker; however, the association between absolute neutrophil count (ANC) and level of D-dimer in patients with COVID-19 infection remains unclear. In this study, we enrolled consecutive patients with COVID-19 admitted to Taichung Veterans General Hospital (TCVGH), a referral center in central Taiwan with 20 airborne infection isolation rooms. Spearman correlation was used to determine the association between ANC and level of D-dimer in distinct time periods. A total of 28 consecutive patients with COVID-19 infection were enrolled, and 32.1% (9/28) of them required mechanical ventilation. Patients requiring mechanical ventilation had a higher ANC (8225 vs. 3427/µL, p < 0.01) and levels of D-dimer (6.0 vs. 0.6 mg/L, p < 0.01) compared with those without mechanical ventilation. Notably, we identified five patients with image-proven thromboembolic events during the hospital course, with the number of patients with pulmonary embolism, venous thrombosis and acute ischemic stroke were 2, 1, and 2, respectively. We found that ANC within 4 days correlated with the level of D-dimer to a moderate level (r = 0.71, p < 0.05), and the association between ANC and D-dimer no longer exist after day 5. In conclusion, we found highly prevalent thromboembolic events among patients with severe COVID-19 infection in central Taiwan and identified the association between early ANC and D-dimer. More studies are warranted to elucidate the underlying mechanism.
FMR1 and AKT/mTOR Signaling in Human Granulosa Cells: Functional Interaction and Impact on Ovarian Response
Authors: Rehnitz Julia , Capp Edison , Messmer Birgitta , Nguyen Xuan Phuoc , Germeyer Ariane , Freis Alexander , Dietrich Jens Erik , Hinderhofer Karin , Strowitzki Thomas , Vogt Peter H.
Published: August 2021

We aimed to determine whether a functional link with impact on female ovarian reserve exists between FMR1 expression and expression ratios of AKT/mTOR signaling genes in human granulosa cells in vivo, as suggested from prior in vitro data. Three hundred and nine women, who were classified as normal (NOR; n = 225) and poor (POR; n = 84) responders based on their ovarian reserve, were recruited during stimulation for assisted reproductive techniques. Expressions of FMR1 and of key genes of the AKT/mTOR and AKT/FOXO1/3 signaling pathways were comparatively analyzed in their granulosa cells. FMR1 expression in granulosa cells of NOR and POR correlated significantly with AKT1, TSC2, mTOR, and S6K expression. No correlation was found between FMR1 and FOXO1 in all, and FOXO3 expression in POR, patients. AKT1 expression was significantly higher and FOXO1 expression lower in POR samples, whereas AKT1 expression was lower and FOXO1 expression was higher in NOR samples. In human native granulosa cells, FMR1 expression significantly correlated with the expression of key genes of the AKT/mTOR signaling pathway, but not with the FOXO1/3 signaling pathway. Our data point to a functional link between FMR1 expression and expression of the AKT/mTOR signaling pathway genes controlling human follicular maturation.
Effect of Preterm Birth on Cardiac and Cardiomyocyte Growth and the Consequences of Antenatal and Postnatal Glucocorticoid Treatment
Authors: Vrselja Amanda , Pillow J. Jane , Black M. Jane
Published: August 2021

Preterm birth coincides with a key developmental window of cardiac growth and maturation, and thus has the potential to influence long-term cardiac function. Individuals born preterm have structural cardiac remodelling and altered cardiac growth and function by early adulthood. The evidence linking preterm birth and cardiovascular disease in later life is mounting. Advances in the perinatal care of preterm infants, such as glucocorticoid therapy, have improved survival rates, but at what cost? This review highlights the short-term and long-term impact of preterm birth on the structure and function of the heart and focuses on the impact of antenatal and postnatal glucocorticoid treatment on the immature preterm heart.
Canonical TGFβ Signaling and Its Contribution to Endometrial Cancer Development and Progression—Underestimated Target of Anticancer Strategies
Authors: Zakrzewski Piotr K.
Published: August 2021

Endometrial cancer is one of the leading gynecological cancers diagnosed among women in their menopausal and postmenopausal age. Despite the progress in molecular biology and medicine, no efficient and powerful diagnostic and prognostic marker is dedicated to endometrial carcinogenesis. The canonical TGFβ pathway is a pleiotropic signaling cascade orchestrating a variety of cellular and molecular processes, whose alterations are responsible for carcinogenesis that originates from different tissue types. This review covers the current knowledge concerning the canonical TGFβ pathway (Smad-dependent) induced by prototypical TGFβ isoforms and the involvement of pathway alterations in the development and progression of endometrial neoplastic lesions. Since Smad-dependent signalization governs opposed cellular processes, such as growth arrest, apoptosis, tumor cells growth and differentiation, as well as angiogenesis and metastasis, TGFβ cascade may act both as a tumor suppressor or tumor promoter. However, the final effect of TGFβ signaling on endometrial cancer cells depends on the cancer disease stage. The multifunctional role of the TGFβ pathway indicates the possible utilization of alterations in the TGFβ cascade as a potential target of novel anticancer strategies.
Combined Neutrophil-to-Lymphocyte and Platelet-Volume-to-Platelet Ratio (NLR and PVPR Score) Represents a Novel Prognostic Factor in Advanced Gastric Cancer Patients
Authors: Konopka Kamil , Micek Agnieszka , Ochenduszko Sebastian , Streb Joanna , Potocki Paweł , Kwinta Łukasz , Wysocki Piotr J.
Published: August 2021

Background: Chemotherapy is a cornerstone of treatment in advanced gastric cancer (GC) with a proven impact on overall survival, however, reliable predictive markers are missing. The role of various inflammatory markers has been tested in gastric cancer patients, but there is still no general consensus on their true clinical applicability. High neutrophil-to-lymphocyte (NLR) and low (medium)-platelets-volume-to-platelet ratio (PVPR) are known markers of unspecific immune system activation, correlating significantly with outcomes in advanced GC patients. Methods: Metastatic GC patients (N:155) treated with chemotherapy +/− trastuzumab were enrolled in this retrospective study. Pre-treatment NLR and PVPR, as well as other inflammatory markers were measured in peripheral blood. Univariate Cox regression was conducted to find markers with a significant impact on overall survival (OS) and progression-free survival (PFS). Spearman correlation and Cohen’s kappa was used to analyze multicollinearity. Multiple multivariable Cox regression models were built to study the combined impact of NLR and PVPR, as well as other known prognostic factors on OS. Results: Elevated NLR was significantly associated with increased risk of death (HR = 1.95; 95% CI: 1.17–3.24), and lower PVPR was significantly associated with improved outcomes (HR = 0.53; 95% CI: 0.32–0.90). A novel inflammatory marker, based on a combination of NLR and PVPR, allows for the classification of GC patients into three prognostic groups, characterized by median OS of 8.4 months (95% CI 5.8–11.1), 10.5 months (95% CI 8.8–12.1), and 15.9 months (95% CI 13.5–18.3). Conclusion: The NLR and PVPR score (elevated NLR and decreased PVPR) is a marker of detrimental outcome of advanced GC patients treated with chemotherapy.
The Use of Point-of-Care Ultrasound (POCUS) in the Diagnosis of Deep Vein Thrombosis
Authors: Varrias Dimitrios , Palaiodimos Leonidas , Balasubramanian Prasanth , Barrera Christian , Nauka Peter , Arfaras-Melainis Angelos , Zamora Christian , Zavras Phaedon , Napolitano Marzio , Gulani Perminder , Ntaios George , Faillace Robert , Galen Benjamin
Published: August 2021

Acute lower extremity proximal deep venous thrombosis (DVT) requires accurate diagnosis and treatment in order to prevent embolization and other complications. Point-of-care ultrasound (POCUS), a clinician performed, and clinician interpreted bedside ultrasound examination has been increasingly used for DVT evaluation mainly in the urgent and critical care setting, but also in the ambulatory clinics and the medical wards. Studies have demonstrated that POCUS has excellent diagnostic accuracy for acute proximal DVT when performed by well-trained users. However, there is significant heterogeneity among studies on the necessary extent of training and universally acceptable standardized education protocols are needed. In this review, we summarize the evidence that supports the use of POCUS to diagnose acute proximal DVT and focus on methodology and current technology, sensitivity and specificity, pre-test probability and the role of D-dimer, time and resources, education, limitations, and future directions.
Catalase Predicts In-Hospital Mortality after Out-of-Hospital Cardiac Arrest
Authors: Früh Anton , Bileck Andrea , Muqaku Besnik , Wurm Raphael , Neuditschko Benjamin , Arfsten Henrike , Galli Lukas , Kriechbaumer Lukas , Hubner Pia , Goliasch Georg , Heinz Gottfried , Holzer Michael , Sterz Fritz , Adlbrecht Christopher , Gerner Christopher , Distelmaier Klaus
Published: August 2021

The generation of harmful reactive oxygen species (ROS), including hydrogen peroxide, in out-of-hospital cardiac arrest (OHCA) survivors causes systemic ischemia/reperfusion injury that may lead to multiple organ dysfunction and mortality. We hypothesized that the antioxidant enzyme catalase may attenuate these pathophysiological processes after cardiac arrest. Therefore, we aimed to analyze the predictive value of catalase levels for mortality in OHCA survivors. In a prospective, single-center study, catalase levels were determined in OHCA survivors 48 h after the return of spontaneous circulation. Thirty-day mortality was defined as the study end point. A total of 96 OHCA survivors were enrolled, of whom 26% (n = 25) died within the first 30 days after OHCA. The median plasma intensity levels (log2) of catalase were 8.25 (IQR 7.64–8.81). Plasma levels of catalase were found to be associated with mortality, with an adjusted HR of 2.13 (95% CI 1.07–4.23, p = 0.032). A Kaplan–Meier analysis showed a significant increase in 30-day mortality in patients with high catalase plasma levels compared to patients with low catalase levels (p = 0.012). High plasma levels of catalase are a strong and independent predictor for 30-day mortality in OHCA survivors. This indicates that ROS-dependent tissue damage is playing a crucial role in fatal outcomes of post-cardiac syndrome patients.