bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Oral Health Behaviors, Health Belief Model, and Absolute Risk Aversion on the Willingness of Japanese University Students to Undergo Regular Dental Check-Ups: A Cross-Sectional Study
Authors: Sumita Ichiro , Toyama Naoki , Ekuni Daisuke , Maruyama Takayuki , Yokoi Aya , Fukuhara Daiki , Uchida-Fukuhara Yoko , Nakahara Momoko , Morita Manabu
Published: October 2022

Oral health behaviors, risk aversion, and the health belief model are associated with health behaviors. However, there have been few studies that investigated the association between these factors and the willingness to undergo regular dental check-ups. The purpose of this cross-sectional study was to investigate the associations between the willingness of Japanese university students to undergo regular dental check-ups and oral health behaviors, the health belief model, and absolute risk aversion. An analysis was conducted with the cooperation of questionnaire respondents (n = 748) who underwent dental check-ups at Okayama University. The students answered questionnaires on oral health behaviors, the health belief model, absolute risk aversion, and willingness to undergo regular dental check-ups. The logistic regression analysis showed significant positive associations (p < 0.05) between oral health behaviors (use of the inter-dental brush and the dental floss) and the health belief model with the willingness to undergo regular dental check-ups. However, there was no significant association with absolute risk aversion (p > 0.05). These results suggest that willingness to undergo regular dental check-ups was associated with oral health behaviors and the health belief model, but not with absolute risk aversion.
Musculoskeletal Pain in Undergraduate Students Is Significantly Associated with Psychological Distress and Poor Sleep Quality
Authors: Alsaadi Saad M.
Published: October 2022

Musculoskeletal pain (MSKP), psychological distress, and poor sleep quality are common among undergraduate university students. Yet, few studies have assessed the association between MSKP and psychological distress and poor sleep quality. This cross-sectional study was conducted to determine this association among undergraduate students at a major public university in Saudi Arabia. MSKP was assessed using the Nordic Musculoskeletal Questionnaire, psychological distress using the Depression, Anxiety and Stress (DASS-21) questionnaire, and sleep quality using the Pittsburgh Sleep Quality Index. A total of 339 undergraduate students from various specialties provided complete responses and were included. The most common site of MSKP in the past 12 months and the past 7 days were neck pain (54.6% and 41.9%, respectively) and low back pain (49.4% and 48.2%, respectively). There was no difference in the prevalence of MSKP across colleges. The reported MSKP in the past 12 months and 7 days were significantly associated with the students’ level of anxiety and stress as well as sleep quality (p < 0.05 for all), while depression was only significantly associated with MSKP in the past 7 days.
The New and Key Roles for Psychological Contract Status and Engagement in Predicting Various Performance Behaviors of Nurses
Authors: Rodwell John , Gulyas Andre , Johnson Dianne
Published: October 2022

The study examines the impact of the psychological contract (PC), including the often-studied PC breach in addition to the novel approach of PC status, as predictors of performance among nurses, mediated by engagement, job satisfaction, and psychological distress. A sample of 177 nurses and midwives from a medium to a large hospital in Australia completed a self-report questionnaire. Structural equation modelling was used to determine associations between the predictors (i.e., negative affectivity (NA), PC breach, PC status)), mediating variables (i.e., engagement, job satisfaction, and psychological distress), and three types of performance behaviors: organizational citizenship behavior for the individual, for the organization (OCBI, OCBO) and in-role behavior (IRB) simultaneously. Specifically, psychological contract status positively predicted engagement, whereas breach negatively predicted engagement and positively predicted job satisfaction. NA positively predicted distress, and distress negatively predicted OCBO and IRB. Lastly, engagement positively predicted job satisfaction, OCBI, OCBO, and IRB. The findings indicate that psychological contract status may predict engagement (and in turn, performance) over and above psychological contract breach, and thus this novel construct should be examined further. The importance of engagement for predicting the performance behaviors and mental health of nurses may also offer new insights.
Young People Awareness of Sexually Transmitted Diseases and Contraception: A Portuguese Population-Based Cross-Sectional Study
Authors: Silva Carlos Franclim , Silva Inês , Rodrigues Alexandra , Sá Luísa , Beirão Daniel , Rocha Paula , Santos Paulo
Published: October 2022

Adolescents and young adults are an important target concerning reducing health-risk behavior adoption, including sexual health. Studying their knowledge concerning sexuality and their main counsellors, can be an important step in targeting an updated health promotion approach. This study characterized adolescents and young adults’ knowledge and attitudes about sexually transmitted diseases (STDs), and contraception, prospecting for their main trusted counseling sources. We conducted a cross-sectional, population-based, self-report survey of 746 individuals aged between 14 and 24 years from Paredes, Portugal. The questionnaire included many dimensions, as demographic characteristics, youth behavior, currently sexually active status, main counselors concerning health topics, awareness, and knowledge about STDs and contraception. Mean age of the participants was 18.3 years, 50.5% of them had started their sexual activity. Males present themselves as more sexually active, starting earlier, and have more sexual partners than females. Participants reported an adequate knowledge perception about STDs and contraception methods, however we found different patterns on specific STDs and contraceptive methods, according to gender, age, and sexually active status. Our results help design specific interventions to reach youth, community, and healthcare providers, pointing out the value of bringing people to the center of health policies.
Interaction between the Participation in and the Impact on Mental Health Service Users and Their Relatives of a Multicomponent Empowerment-Based Psychosocial Intervention
Authors: Eiroa-Orosa Francisco José , San Pío Maria Jesús , Marcet Gemma , Sibuet Isabela , Rojo Emilio
Published: October 2022

Relatives play an important role in the recovery journey of mental health service users. Interventions directed either at service users or their relatives may influence the other person as well. The project ‘Activa’t per la salut mental’ (Get active for mental health) consisted of a series of four interventions addressed at people diagnosed with mental disorders and their relatives to help them in their recovery process, increasing their agency and quality of life. The main objective of the present study is to evaluate the interaction of the participation of service users on their relatives’ outcomes and vice versa. The impact of the project was evaluated within a randomised controlled trial. The treatment group had access to all the circuit interventions, while the control group received treatment as usual and could only access one of the interventions. All participants were evaluated at baseline, six months, and twelve months after the end of the first intervention. Service users were evaluated with the Stages of Recovery Instrument, and relatives with the Family Burden Interview Schedule II and the Duke-UNC-11 questionnaires. The interaction of participation and impact between service users and their relatives was analysed by means of correlational analyses within the intervention group (n = 111, service users mean age = 40.6, 40% women; relatives mean age = 56.7, 72% women). Service users’ baseline characteristics (being in a relationship, educational level, employment, and younger age) influenced in the level of participation of relatives and vice versa (lower educational level). The results also indicated correlations between participation and outcomes at various points as well as the evolution of service users’ recovery and the care burden of relatives. Service users’ participation levels interacted with the decrease of relatives’ frequency of burden and the first steps of their own recovery journey (moratorium, awareness, and preparation) while relative’s participation just interacted with the evolution of two stages of service users’ recovery levels (preparation and growth). These results can be extremely helpful in fostering interactive benefits in future projects addressing the wellbeing of mental health service users and their relatives. Future studies could use specific designs to explore the directionality of the causality of these effects.
Adulthood Employment Trajectories and Later Life Mental Health before and after the Onset of the COVID-19 Pandemic
Authors: Cabib Ignacio , Budnevich-Portales Carlos , Azar Ariel
Published: October 2022

Background: This life course study has two aims. First, to explore how diverse employment trajectories across adulthood are related to older people’s mental health in Chile, a country with no research in this field, and second, to analyze these associations before and after the onset of the COVID-19 pandemic. Methods: We use data from the nationally-representative and longitudinal ‘Chilean Social Protection Survey’ sequence analysis to reconstruct employment trajectory types, and bivariate and multivariate analyses to measure their association with depressive symptoms. Results: Our findings indicate that formal labor force patterns in adulthood show the lowest burden of depressive symptomology before and after the onset of the overwhelming COVID-19 pandemic when controlling for traditional risk factors. Conclusion: We emphasize that policymakers in both the labor market and public health domains must consider the relationship between informal employment pathways in adulthood and poorer mental health in old age. Public policies should improve the conditions and quality of jobs during adulthood and promote more formalization in the labor market to address the high uncertainty involving low social protection, which is strongly associated with severe mental health problems in later life.
Optimizing Agricultural Input and Production for Different Types of at-Risk Peasant Households: An Empirical Study of Typical Counties in the Yimeng Mountain Area of Northern China
Authors: Yu Yuanhe , Wang Liang , Lin Jinkuo , Li Zijun
Published: October 2022

Using typical counties in the Yimeng Mountain area of northern China as an example, this paper analyzed the household and agricultural input characteristics of different types of peasant households using survey data from 262 farm households. The target minimization of the total absolute deviations (MOTAD) model was applied to determine the optimal combinations in the allocation of agricultural input factors and production for different types of at-risk peasant households to obtain the ideal agricultural income. The relevant results are twofold. (1) The agricultural input behaviors of different types of peasant households vary significantly. The highest levels of agricultural land, labor, and yield-increasing and labor-saving inputs included I part-time peasant households (I PTPH), followed by full-time peasant households (FTPH), while the input levels of II part-time peasant households (II PTPH) and non-agricultural peasant households (NAPH) with higher levels of non-agricultural employment gradually decreased. In general, an increase in peasant households’ part-time employment revealed an inverted U-shaped trend in the agricultural input level, with a trajectory of I PTPH > FTPH > II PTPH > NAPH. (2) The current agricultural inputs and production combinations of different types of peasant households have room for improvement. It is necessary to adjust agricultural inputs and optimize production combinations to obtain target incomes. Overall, all types of peasant households must streamline labor inputs and increase capital inputs, except for I PTPH, for which capital inputs should be reduced. Following optimization, economic crops gradually replace grain crops, and the optimal agricultural incomes of peasant households will be improved. The study results provide practical policy insights for reducing agricultural production risks and improving agricultural production incomes.
Google Earth Engine as Multi-Sensor Open-Source Tool for Monitoring Stream Flow in the Transboundary River Basin: Doosti River Dam
Authors: Pakdel-Khasmakhi Hadis , Vazifedoust Majid , Paudyal Dev Raj , Chadalavada Sreeni , Alam Md Jahangir
Published: October 2022

Understanding the effects of global change and human activities on water supplies depends greatly on surface water dynamics. A comprehensive examination of the hydroclimatic variations at the transboundary level is essential for the development of any adaptation or mitigation plans to deal with the negative effects of climate change. This research paper examines the hydroclimatic factors that contribute to the desiccation of the Doosti Dam’s basin in the transboundary area using multisensor satellite data from the Google Earth Engine (GEE) platform. The Mann–Kendall and Sens slope estimator test was applied to the satellite datasets to analyse the spatial and temporal variation of the hydroclimate variables and their trend over the transboundary area for 18 years from 2004 to 2021 (as the dam began operating in 2005). Statistical analysis results showed decreasing trends in temperature and an increase in rainfall with respect to station-observed available data. Evapotranspiration and irrigated area development followed the increasing pattern and a slight decrease in snow cover. The results confirmed a large expansion of the irrigated area, especially during the winter growing season. The increase in irrigated cultivated areas during both winter and summer seasons is possibly the main reason for the diversion of water to meet the irrigation requirements of the developed agriculture areas. The approach followed in this study could be applied to any location around the globe to evaluate the hydrological conditions and spatiotemporal changes in response to climate change, trend analysis and human activities.
Docetaxel Resistance in Castration-Resistant Prostate Cancer: Transcriptomic Determinants and the Effect of Inhibiting Wnt/β-Catenin Signaling by XAV939
Authors: Pudova Elena , Kobelyatskaya Anastasiya , Katunina Irina , Snezhkina Anastasiya , Nyushko Kirill , Fedorova Maria , Pavlov Vladislav , Bulavkina Elizaveta , Dalina Alexandra , Tkachev Sergey , Alekseev Boris , Krasnov George , Volodin Vsevolod , Kudryavtseva Anna
Published: October 2022

Castration-resistant prostate cancer (CRPC) is a common form of prostate cancer in which docetaxel-based chemotherapy is used as the first line. The present study is devoted to the analysis of transcriptome profiles of tumor cells in the development of resistance to docetaxel as well as to the assessment of the combined effect with the XAV939 tankyrase inhibitor on maintaining the sensitivity of tumor cells to chemotherapy. RNA-Seq was performed for experimental PC3 cell lines as well as for plasma exosome samples from patients with CRPC. We have identified key biological processes and identified a signature based on the expression of 17 mRNA isoforms associated with the development of docetaxel resistance in PC3 cells. Transcripts were found in exosome samples, the increased expression of which was associated with the onset of progression of CRPC during therapy. The suppression of pathways associated with the participation of cellular microtubules has also been shown when cells are treated with docetaxel in the presence of XAV939. These results highlight the importance of further research into XAV939 as a therapeutic agent in the treatment of CRPC; moreover, we have proposed a number of mRNA isoforms with high predictive potential, which can be considered as promising markers of response to docetaxel.
SARS-CoV-2 RNA Testing Using Different Assays—Impact on Testing Strategies in a Clinical Setting
Authors: Eibinger Gerald M. , Kessler Harald H. , Stelzl Evelyn , Vander Klaus , Weber-Lassacher Anita , Renner Wilfried , Herrmann Markus
Published: October 2022

In order to assess SARS-CoV-2 real time quantitative polymerase chain reaction (RT-qPCR) results in a real-life setting, three independent laboratories in Graz (Austria) set up a continuous cross comparison schedule. The following test systems were used: The QIAGEN NeuMoDx SARS-CoV-2 Assay, the Allplex™ 2019-nCoV Assay (Seegene) on a MicroLab Nimbus (Hamilton) platform combined with RealStar SARS-CoV-2 RT-PCR Assay (Altona Diagnostics GmbH), and the cobas SARS-CoV-2 test on a fully automated cobas 6800 system (Roche). A total of 200 samples were analysed, 184 (92%) were found to be concordant with all testing platforms, 14 (7%) discordant. Two (1%) samples tested invalid on a single platform and were excluded from further analysis. Discordant results were distributed randomly across the assays. The Ct values from all assays correlated closely with each other. All discordant samples showed Ct values ≥ 26. SARS-CoV-2 RT-qPCR assays may show considerable variability, especially in samples with low viral RNA concentrations. Decision makers should thus balance the advantages and disadvantages of RT-qPCR for mass screening and adopt suitable strategies that ensure a rational management of positive samples with high Ct values.
The PINK1 p.Asn521Thr Variant Is Associated with Earlier Disease Onset in GRN/C9orf72 Frontotemporal Lobar Degeneration
Authors: Rossi Giacomina , Salvi Erika , Benussi Luisa , Mehmeti Elkadia , Geviti Andrea , Bellini Sonia , Longobardi Antonio , Facconi Alessandro , Carrara Matteo , Bonvicini Cristian , Nicsanu Roland , Saraceno Claudia , Ricci Martina , Giaccone Giorgio , Binetti Giuliano , Ghidoni Roberta
Published: October 2022

Genetic frontotemporal lobar degeneration (FTLD) is characterized by heterogeneous phenotypic expression, with a disease onset highly variable even in patients carrying the same mutation. Herein we investigated if variants in lysosomal genes modulate the age of onset both in FTLD due to GRN null mutations and C9orf72 expansion. In a total of 127 subjects (n = 74 GRN mutations and n = 53 C9orf72 expansion carriers), we performed targeted sequencing of the top 98 genes belonging to the lysosomal pathway, selected based on their high expression in multiple brain regions. We described an earlier disease onset in GRN/C9orf72 pedigrees in subjects carrying the p.Asn521Thr variant (rs1043424) in PTEN-induced kinase 1 (PINK1), a gene that is already known to be involved in neurodegenerative diseases. We found that: (i) the PINK1 rs1043424 C allele is significantly associated with the age of onset; (ii) every risk C allele increases hazard by 2.11%; (iii) the estimated median age of onset in homozygous risk allele carriers is 10–12 years earlier than heterozygous/wild type homozygous subjects. A replication study in GRN/C9orf72 negative FTLD patients confirmed that the rs1043424 C allele was associated with earlier disease onset (−5.5 years in CC versus A carriers). Understanding the potential mechanisms behind the observed modulating effect of the PINK1 gene in FTLD might prove critical for identifying biomarkers and/or designing drugs to modify the age of onset, especially in GRN/C9orf72-driven disease.
Could Targeted Pharmacotherapies Exert a “Disease Modification Effect” in Patients with Chronic Plaque Psoriasis?
Authors: Bellinato Francesco , Chiricozzi Andrea , Piaserico Stefano , Targher Giovanni , Gisondi Paolo
Published: October 2022

Chronic plaque psoriasis is an immune-mediated skin disease with a chronic relapsing course, affecting up to ~2–3% of the general adult population worldwide. The interleukin (IL)-23/Th17 axis plays a key role in the pathogenesis of this skin disease and may represent a critical target for new targeted pharmacotherapies. Cutaneous lesions tend to recur in the same body areas, likely because of the reactivation of tissue-resident memory T cells. The spillover of different pro-inflammatory cytokines into systemic circulation can promote the onset of different comorbidities, including psoriatic arthritis. New targeted pharmacotherapies may lead to almost complete skin clearance and significant improvements in the patient’s quality of life. Accumulating evidence supports the notion that early intervention with targeted pharmacotherapies could beneficially affect the clinical course of psoriatic disease at three different levels: (1) influencing the immune cells infiltrating the skin and gene expression, (2) the prevention of psoriasis-related comorbidities, especially psoriatic arthritis, and (3) the improvement of the patient’s quality of life and reduction of cumulative life course impairment. The main aim of this narrative review is to summarize the effects that new targeted pharmacotherapies for psoriasis may have on the immune scar, both at the molecular and cellular level, on psoriatic arthritis and on the patient’s quality of life.
New Insights into Psoriasis
Authors: Nedoszytko Boguslaw , Owczarczyk-Saczonek Agnieszka , Krasowska Dorota , Szczerkowska-Dobosz Aneta
Published: October 2022

Psoriasis is a chronic inflammatory skin disease with many comorbidities resulting from not only local but also systemic inflammation [...]
Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)
Authors: Ferrera René , Védère Marie , Lo-Grasso Megane , Augeul Lionel , Chouabe Christophe , Bidaux Gabriel , Baetz Delphine
Published: October 2022

Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts.
An Inflamed and Infected Reconstructed Human Epidermis to Study Atopic Dermatitis and Skin Care Ingredients
Authors: Cadau Sébastien , Gault Manon , Berthelemy Nicolas , Hsu Chiung-Yueh , Danoux Louis , Pelletier Nicolas , Goudounèche Dominique , Pons Carole , Leprince Corinne , André-Frei Valérie , Simon Michel , Pain Sabine
Published: October 2022

Atopic dermatitis (AD), the most common inflammatory skin disorder, is a multifactorial disease characterized by a genetic predisposition, epidermal barrier disruption, a strong T helper (Th) type 2 immune reaction to environmental antigens and an altered cutaneous microbiome. Microbial dysbiosis characterized by the prevalence of Staphylococcus aureus (S. aureus) has been shown to exacerbate AD. In recent years, in vitro models of AD have been developed, but none of them reproduce all of the pathophysiological features. To better mimic AD, we developed reconstructed human epidermis (RHE) exposed to a Th2 pro-inflammatory cytokine cocktail and S. aureus. This model well reproduced some of the vicious loops involved in AD, with alterations at the physical, microbial and immune levels. Our results strongly suggest that S. aureus acquired a higher virulence potential when the epidermis was challenged with inflammatory cytokines, thus later contributing to the chronic inflammatory status. Furthermore, a topical application of a Castanea sativa extract was shown to prevent the apparition of the AD-like phenotype. It increased filaggrin, claudin-1 and loricrin expressions and controlled S. aureus by impairing its biofilm formation, enzymatic activities and inflammatory potential.
Self-Amplifying RNA Approach for Protein Replacement Therapy
Authors: Papukashvili Dimitri , Rcheulishvili Nino , Liu Cong , Ji Yang , He Yunjiao , Wang Peng George
Published: October 2022

Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.
Exploring the Multi-Faceted Role of Sirtuins in Glioblastoma Pathogenesis and Targeting Options
Authors: Kunadis Elena , Piperi Christina
Published: October 2022

Recent advances in glioblastoma (GB) research have shed light on the molecular characteristics, the defected intracellular signaling pathways, and the genetic and epigenetic alterations involved in their pathogenesis. Despite constant efforts, GB remains an aggressive malignant tumor with limited therapeutic approaches, poor prognosis, and a low survival rate. Emerging evidence points towards the crucial impact of epigenetic post-translational modifications in cancer development with emphasis on the regulatory role of histone deacetylation in several key cellular processes, including metabolic pathways, regulation of stress response, senescence, proliferation, DNA repair, and apoptosis. The silent information regulator proteins (Sirtuins) are deacetylases of histone and non-histone proteins that have been recently implicated in the initiation as well as in the progression of GB. Herein, we provide a critical overview of the emerging functional role and mechanism of action of the seven Sirtuins (SIRT1-7) in GB and discuss their potential targeting options in clinical practice.
BaZFP1, a C2H2 Subfamily Gene in Desiccation-Tolerant Moss Bryum argenteum, Positively Regulates Growth and Development in Arabidopsis and Mosses
Authors: Zhou Ping , Liu Xiujin , Li Xiaoshuang , Zhang Daoyuan
Published: October 2022

C2H2 zinc finger protein (C2H2-ZFP) plays an important role in regulating plant growth, development, and response to abiotic stress. To date, there have been no analyses of the C2H2-ZFP family in desiccation-tolerant moss. In this study, we identified 57 BaZFP transcripts across the Bryum argenteum (B. argenteum) transcriptome. The BaZFP proteins were phylogenetically divided into four groups (I–IV). Additionally, we studied the BaZFP1 gene, which is a nuclear C2H2-ZFP and acts as a positive regulator of growth and development in both moss and Arabidopsis thaliana. The complete coding sequence of the BaZFP1 gene was isolated from B. argenteum cDNA, which showed a high expression level in a dehydration–rehydration treatment process. The overexpression of the BaZFP1 gene in the Physcomitrium patens and B. argenteum promoted differentiation and growth of gametophytes. Heterologous expression in Arabidopsis regulated the whole growth and development cycle. In addition, we quantitatively analyzed the genes related to growth and development in transgenic moss and Arabidopsis, including HLS1, HY5, ANT, LFY, FT, EIN3, MUS, APB4, SEC6, and STM1, and found that their expression levels changed significantly. This study may pave the way for substantial insights into the role of C2H2-ZFPs in plants as well as suggest appropriate candidate genes for crop breeding.
A Timeframe for SARS-CoV-2 Genomes: A Proof of Concept for Postmortem Interval Estimations
Authors: Pardo-Seco Jacobo , Bello Xabier , Gómez-Carballa Alberto , Martinón-Torres Federico , Muñoz-Barús José Ignacio , Salas Antonio
Published: October 2022

Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an unknown SARS-CoV-2 genome in a population (hereafter, estimated time of a queried genome [QG]; tE-QG) can be easily predicted using a phylogenetic model based on a robust reference genome database of the virus, and information on their sampling dates. We evaluate several phylogeny-based approaches, including modeling evolutionary (substitution) rates of the SARS-CoV-2 genome (~10−3 substitutions/nucleotide/year) and the mutational (substitutions) differences separating the QGs from the reference genomes (RGs) in the database. Owing to the mutational characteristics of the virus, the present Viral Molecular Clock Dating (VMCD) method covers timeframes going backwards from about a month in the past. The method has very low errors associated to the tE-QG estimates and narrow intervals of tE-QG, both ranging from a few days to a few weeks regardless of the mathematical model used. The SARS-CoV-2 model represents a proof of concept that can be extrapolated to any other microorganism, provided that a robust genome sequence database is available. Besides obvious applications in epidemiology and microbiology investigations, there are several contexts in forensic casework where estimating tE-QG could be useful, including estimation of the postmortem intervals (PMI) and the dating of samples stored in hospital settings.
A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy
Authors: Orlando Valeria , Di Tommaso Silvia , Alesi Viola , Loddo Sara , Genovese Silvia , Catino Giorgia , Martucci Licia , Roberti Maria Cristina , Trivisano Marina , Dentici Maria Lisa , Specchio Nicola , Dallapiccola Bruno , Ferretti Alessandro , Novelli Antonio
Published: October 2022

Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genome mapping (OGM) and genome sequencing, is crucial for disclosing and characterizing cryptic chromosomal rearrangements at high resolutions. We report on a patient with a complex developmental and epileptic encephalopathy in which karyotype analysis showed a de novo balanced translocation involving the long arms of chromosomes 2 and 18. Microarray analysis detected a 194 Kb microdeletion at 2q24.3 involving the SCN2A gene, which was considered the likely translocation breakpoint on chromosome 2. However, OGM redefined the translocation breakpoints by disclosing a paracentric inversion at 2q24.3 disrupting SCN1A. This combined genomic high-resolution approach allowed a fine characterization of the CGR, which involves two different chromosomes with four breakpoints. The patient’s phenotype resulted from the concomitant loss of function of SCN1A and SCN2A.
Insulin-like Peptide Receptor (ILPR) in the Cuttlefish Sepiella japonica: Characterization, Expression, and Regulation of Reproduction
Authors: Lü Zhenming , Liu Yantao , Yan Jun , Zhang Yao , Gong Li , Liu Bingjian , Liu Jing , Xu Zhijin , Liu Liqin
Published: October 2022

Insulin-like peptide receptor (ILPR) can effectively regulate ovarian development in invertebrates, but its effect in cuttlefish has not been reported. We isolated and characterized a ILPR gene from Sepiella japonica, referred to as SjILPR. This gene displayed significant homologies to Octopus bimaculoides ILPR, and contained all typical features of insulin receptors and tyrosine kinase domain structure. SjILPR is expressed in all detected tissues, with the highest expression in the ovary. During ovarian development stages, its expression levels in the ovary, pancreas, and liver were correlated to the female reproductive cycle. After the silencing of SjILPR in vivo, comparative transcriptome analysis identified 4314 differentially expressed genes (DEGs) in the injected group, including 2586 down-regulated genes and 1728 up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that 832 DEGs were assigned to 222 pathways, many pathways of which were related to gonadal development. Four down-regulated genes relevant to ovarian development (Vitellogenin 1, Vitellogenin 2, Cathepsin L1-like, and Follistatin) were selected to confirm the accuracy of RNA-seq data by qRT-PCR. These results showed that SjILPR might regulate ovarian development to control reproduction by affecting the expression of the relevant genes in female S. japonica.
The Ring World: Eversion of Small Double-Stranded Polynucleotide Circlets at the Origin of DNA Double Helix, RNA Polymerization, Triplet Code, Twenty Amino Acids, and Strand Asymmetry
Authors: Norris Victor , Demongeot Jacques
Published: October 2022

It is not entirely clear why, at some stage in its evolution, terrestrial life adopted double-stranded DNA as the hereditary material. To explain this, we propose that small, double-stranded, polynucleotide circlets have special catalytic properties. We then use this proposal as the basis for a ‘view from here’ that we term the Circlet hypothesis as part of a broader Ring World. To maximize the potential explanatory value of this hypothesis, we speculate boldly about the origins of several of the fundamental characteristics and briefly describe the main methods or treatments applied. The principal prediction of the paper is that the highly constrained, conformational changes will occur preferentially in dsDNA, dsRNA and hybrid RNA-DNA circlets that are below a critical size (e.g., 306 bp) and that these will favor the polymerization of precursors into RNA and DNA. We conclude that the Circlet hypothesis and the Ring World therefore have the attraction of offering the same solution to the fundamental problems probably confronting both the earliest cells and the most recent ones.
Absence of CCR2 Promotes Proliferation of Alveolar Macrophages That Control Lung Inflammation in Acute Respiratory Distress Syndrome in Mice
Authors: Oliveira Vivian Louise Soares de , Pollenus Emilie , Berghmans Nele , Queiroz-Junior Celso Martins , Blanter Marfa , Mattos Matheus Silvério , Teixeira Mauro Martins , Proost Paul , Van den Steen Philippe E. , Amaral Flávio Almeida , Struyf Sofie
Published: October 2022

Acute respiratory distress syndrome (ARDS) consists of uncontrolled inflammation that causes hypoxemia and reduced lung compliance. Since it is a complex process, not all details have been elucidated yet. In a well-controlled experimental murine model of lipopolysaccharide (LPS)-induced ARDS, the activity and viability of macrophages and neutrophils dictate the beginning and end phases of lung inflammation. C-C chemokine receptor type 2 (CCR2) is a critical chemokine receptor that mediates monocyte/macrophage activation and recruitment to the tissues. Here, we used CCR2-deficient mice to explore mechanisms that control lung inflammation in LPS-induced ARDS. CCR2−/− mice presented higher total numbers of pulmonary leukocytes at the peak of inflammation as compared to CCR2+/+ mice, mainly by enhanced influx of neutrophils, whereas we observed two to six-fold lower monocyte or interstitial macrophage numbers in the CCR2−/−. Nevertheless, the time needed to control the inflammation was comparable between CCR2+/+ and CCR2−/−. Interestingly, CCR2−/− mice presented higher numbers and increased proliferative rates of alveolar macrophages from day 3, with a more pronounced M2 profile, associated with transforming growth factor (TGF)-β and C-C chemokine ligand (CCL)22 production, decreased inducible nitric oxide synthase (Nos2), interleukin (IL)-1β and IL-12b mRNA expression and increased mannose receptor type 1 (Mrc1) mRNA and CD206 protein expression. Depletion of alveolar macrophages significantly delayed recovery from the inflammatory insult. Thus, our work shows that the lower number of infiltrating monocytes in CCR2−/− is partially compensated by increased proliferation of resident alveolar macrophages during the inflammation control of experimental ARDS.
Read Count Patterns and Detection of Cancerous Copy Number Alterations in Plasma Cell-Free DNA Whole Exome Sequencing Data for Advanced Non-Small Cell Lung Cancer
Authors: Jang Ho , Choi Chang-Min , Lee Seung-Hyeun , Lee Sungyong , Jeong Mi-Kyung
Published: October 2022

Plasma cell-free DNA (cfDNA) sequencing data have been widely studied for early diagnosis and treatment response or recurrence monitoring of cancers because of the non-invasive benefits. In cancer studies, whole exome sequencing (WES) is mostly used for discovering single nucleotide variants (SNVs), but it also has the potential to detect copy number alterations (CNAs) that are mostly discovered by whole genome sequencing or microarray. In clinical settings where the quantity of the acquired blood from the patients is limited and where various sequencing experiments are not possible, providing various types of mutation information such as CNAs and SNVs using only WES will be helpful in the treatment decision. Here, we questioned whether the plasma cfDNA WES data for patients with advanced non-small cell lung cancer (NSCLC) could be exploited for CNA detection. When the read count (RC) signals of the WES data were investigated, a similar fluctuation pattern was observed among the signals of different samples, and it can be a major challenge hindering CNA detection. When these RC patterns among cfDNA were suppressed by the method we proposed, the cancerous CNAs were more distinguishable in some samples with higher cfDNA quantity. Although the potential to detect CNAs using the plasma cfDNA WES data for NSCLC patients was studied here, further studies with other cancer types, with more samples, and with more sophisticated techniques for bias correction are required to confirm our observation. In conclusion, the detection performance for cancerous CNAs can be improved by controlling RC bias, but it depends on the quantity of cfDNA in plasma.
Review: Influence of 25(OH)D Blood Concentration and Supplementation during Pregnancy on Preeclampsia Development and Neonatal Outcomes
Authors: Karpova Nataliia , Dmitrenko Olga , Arshinova Ekaterina , Nurbekov Malik
Published: October 2022

Briefly, 25-hydroxyvitamin D (25(OH)D) plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother–placenta–fetus system. The low quantity of 25(OH)D during pregnancy can lead to an elevated risk for preeclampsia occurrence. Despite the numerous studies on the association of 25(OH)D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review, we summarize and analyze study data on the effects of 25(OH)D deficiency and supplementation on pregnancy, labor, and fetal and neonatal outcomes.
APOE Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism
Authors: Civeira-Marín María , Cenarro Ana , Marco-Benedí Victoria , Bea Ana M. , Mateo-Gallego Rocío , Moreno-Franco Belén , Ordovás José M. , Laclaustra Martín , Civeira Fernando , Lamiquiz-Moneo Itziar
Published: October 2022

The association between APOE genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and APOE genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS. APOE genotyping was carried out by the Sanger method in both cohorts. APOE4 carriers had significantly lower levels of CRP than APOE3 carriers. Furthermore, APOE4 carriers had cholesterol-enriched LDL particles compared to APOE2 carriers. APOE4 carriers also had higher concentrations of small, medium, and large LDL particles. CRP levels were not associated with lipoprotein particle number, size, or composition. GlycA levels were not associated with APOE genotypes. However, GlycA levels were significantly associated with the size and the amount of cholesterol contained in HDL, VLDL, and LDL particles. APOE genotype influences CRP concentration regardless of lipid profile. APOE2 carriers showed the highest CRP levels, followed by APOE3 and APOE4. A more atherogenic lipid profile, but not inflammatory markers could partly explain the higher CVD risk observed in APOE4 carriers.
Novel Hydroxypyridine Compound Protects Brain Cells against Ischemic Damage In Vitro and In Vivo
Authors: Blinova Ekaterina , Turovsky Egor , Eliseikina Elena , Igrunkova Alexandra , Semeleva Elena , Golodnev Grigorii , Termulaeva Rita , Vasilkina Olga , Skachilova Sofia , Mazov Yan , Zhandarov Kirill , Simakina Ekaterina , Belanov Konstantin , Zalogin Saveliy , Blinov Dmitrii
Published: October 2022

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells. Ca2+ dynamics was studied using fluorescent bioimaging and a Fura-2 probe, cell viability was assessed using cytochemical staining with propidium iodide, and gene expression was assessed by a real-time polymerase chain reaction. The compound anti-ischemic efficacy in vivo was evaluated on a model of irreversible middle cerebral artery (MCA) occlusion in Sprague-Dawley male rats. Brain morphological changes and antioxidant capacity were assessed one week after the pathology onset. The severity of neurological disorder was evaluated dynamically. 3-EA suppressed cortical cell death in a dose-dependent manner under the excitotoxic effect of glutamate and ischemia/reoxygenation. Pre-incubation of cerebral cortex cells with 10–100 µM 3-EA led to significant stagnation in Ca2+ concentration in a cytosol ([Ca2+]i) of neurons and astrocytes suffering GluTox and OGD. Decreasing intracellular Ca2+ and establishing a lower [Ca2+]i baseline inhibited necrotic cell death in an acute experiment. The mechanism of 3-EA cytoprotective action involved changes in the baseline and ischemia/reoxygenation-induced expression of genes encoding anti-apoptotic proteins and proteins of the oxidative status; this led to inhibition of the late irreversible stages of apoptosis. Incubation of brain cortex cells with 3-EA induced an overexpression of the anti-apoptotic genes BCL-2, STAT3, and SOCS3, whereas the expression of genes regulating necrosis and inflammation (TRAIL, MLKL, Cas-1, Cas-3, IL-1β and TNFa) were suppressed. 3-EA 18.0 mg/kg intravenous daily administration for 7 days following MCA occlusion preserved rats’ cortex neuron population, decreased the severity of neurological deficit, and spared antioxidant capacity of damaged tissues. 3-EA demonstrated proven short-term anti-ischemic activity in vivo and in vitro, which can be associated with antioxidant activity and the ability to target necrotic and apoptotic death. The compound may be considered a potential neuroprotective molecule for further pre-clinical investigation.
The Impact of Intermittent Hypoxia on Metabolism and Cognition
Authors: Shobatake Ryogo , Ota Hiroyo , Takahashi Nobuyuki , Ueno Satoshi , Sugie Kazuma , Takasawa Shin
Published: October 2022

Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that result in oxidative stress and systemic inflammation. Since SAS is epidemiologically strongly correlated with type 2 diabetes/insulin resistance, obesity, hypertension, and dyslipidemia included in metabolic syndrome, the effects of IH on gene expression in the corresponding cells of each organ have been studied intensively to clarify the molecular mechanism of the association between SAS and metabolic syndrome. Dementia has recently been recognized as a serious health problem due to its increasing incidence, and a large body of evidence has shown its strong correlation with SAS and metabolic disorders. In this narrative review, we first outline the effects of IH on the expression of genes related to metabolism in neuronal cells, pancreatic β cells, hepatocytes, adipocytes, myocytes, and renal cells (mainly based on the results of our experiments). Next, we discuss the literature regarding the mechanisms by which metabolic disorders and IH develop dementia to understand how IH directly and indirectly leads to the development of dementia.