bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Distancing Associations with COVID-19 Infection and Mortality Are Modified by Crowding and Socioeconomic Status
Authors: VoPham Trang , Weaver Matthew D. , Adamkiewicz Gary , Hart Jaime E.
Published: April 2021

The SARS-CoV-2 virus is a public health emergency. Social distancing is a key approach to slowing disease transmission. However, more evidence is needed on its efficacy, and little is known on the types of areas where it is more or less effective. We obtained county-level data on COVID-19 incidence and mortality during the first wave, smartphone-based average social distancing (0–5, where higher numbers indicate more social distancing), and census data on demographics and socioeconomic status. Using generalized linear mixed models with a Poisson distribution, we modeled associations between social distancing and COVID-19 incidence and mortality, and multiplicative interaction terms to assess effect modification. In multivariable models, each unit increase in social distancing was associated with a 26% decrease (p < 0.0001) in COVID-19 incidence and a 31% decrease (p < 0.0001) in COVID-19 mortality. Percent crowding, minority population, and median household income were all statistically significant effect modifiers. County-level increases in social distancing led to reductions in COVID-19 incidence and mortality but were most effective in counties with lower percentages of black residents, higher median household incomes, and with lower levels of household crowding.
Increased Compulsivity in Adulthood after Early Adolescence Immune Activation: Preclinical Evidence
Authors: Mora Santiago , Martín-González Elena , Prados-Pardo Ángeles , Flores Pilar , Moreno Margarita
Published: April 2021

Immune activation during early developmental stages has been proposed as a contributing factor in the pathogenesis of neuropsychiatric conditions such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism in both human and animal studies. However, its relationship with the vulnerability to inhibitory control deficit, which is a shared feature among those conditions, remains unclear. The present work studied whether postnatal immune activation during early adolescence, combined with exposure to early-life adverse events, could lead to adult vulnerability to impulsive and/or compulsive behaviors. Male Wistar rats were exposed to lipopolysaccharide (LPS) in early adolescence at postnatal day 26 (PND26). During peripuberal period, half of the animals were exposed to a mild stress protocol. In adulthood, behavioral assessment was performed with the aid of the sustained attentional 5-choice serial reaction time (5-CSRT) task, schedule-induced polydipsia (SIP), and open-field locomotor activity and novelty reactivity. Rats exposed to LPS showed more compulsive responses than their control counterparts on 5-CSRT task, although no differences were observed in SIP or locomotor responses. Our study contributes to the knowledge of the relationship between immune activation and inhibitory control deficit. Future studies should aim to disentangle how, and to what extent, immune activation impacts behavior, and to understand the role of early life mild stress.
Insights about Screen-Use Conflict from Discussions between Mothers and Pre-Adolescents: A Thematic Analysis
Authors: Francis Kathleen , Scholten Hanneke , Granic Isabela , Lougheed Jessica , Hollenstein Tom
Published: April 2021

Digital screens have become an integral part of everyday life. In the wake of the digital swell, pre-adolescents and their parents are learning to navigate seemingly new terrain regarding digital media use. The present study aimed to investigate parent and pre-adolescent perceptions of screen use and the source of conflict surrounding digital media. We employed a qualitative thematic analysis of 200 parent and pre-adolescent dyads discussing screen use. Our analysis showed five overarching themes for screen use perceptions and conflict: screen time, effects of screen use, balance, rules, and reasons for screen use. In contrast to previous studies that mainly focused on parental perceptions, we were also able to shed light on pre-adolescent perceptions of screen use and the difference in opinions with their parents. Furthermore, we found that patterns of the source of screen use conflict were oftentimes rooted in the age-old developmental tug of war between autonomy-seeking pre-adolescents and authority-seeking parents. Though navigating autonomy-granting and seeking behavior is familiar to developmental scientists, negotiating these challenges in a new digital world is unfamiliar. Autonomy support, open dialogue, and playful interaction between parents and children are needed to understand and resolve conflict of digital media use in family contexts.
Risk of Pneumonia in Pediatric Patients Following Minor Chest Trauma: A Population-Based Retrospective Cohort Study
Authors: Chou Ying-Hsiang , Tai Li-Hsiu , Chan Chi-Ho , Liu Haw-Yu , Yeh Han-Wei , Wang Yu-Hsun , Lin Chiao-Wen , Yang Shun-Fa , Chen Ying-Cheng , Yeh Chao-Bin
Published: April 2021

This study investigated the association between minor chest trauma and the risk of pneumonia among pediatric patients in a Taiwanese health care setting. For this retrospective population-based cohort study, the Longitudinal Health Insurance Database was used to analyze the data of patients with a minor chest injury between 2010 and 2012. Data were analyzed through a multivariate analysis with a multiple Cox regression model. Patients were divided into a chest trauma group (n = 6592) and a non-chest trauma group (n = 882,623). An increased risk of pneumonia was observed in the chest trauma group (hazard ratio = 1.23; 95% confidence interval = 1.02–1.49) compared to the non-chest trauma group. In conclusion, this population-based cohort study demonstrated that pediatric patients with minor chest trauma are at an increased risk of pneumonia. The short-term adverse effects of pneumonia could be severe when a patient suffers from mild chest trauma.
Physical Activity Regulates TNFα and IL-6 Expression to Counteract Inflammation in Cystic Fibrosis Patients
Authors: Nigro Ersilia , Polito Rita , Elce Ausilia , Signoriello Giuseppe , Iacotucci Paola , Carnovale Vincenzo , Gelzo Monica , Zarrilli Federica , Castaldo Giuseppe , Daniele Aurora
Published: April 2021

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA.
Application of a Fuzzy Logic Based Methodology to Validate the Hydrochemical Characterization and Determining Seasonal Influence of a Watershed Affected by Acid Mine Drainage
Authors: Davila Jose M. , Sarmiento Aguasanta M. , Aroba Javier , Fortes Juan C. , Grande Jose A. , Santisteban Maria , Cordoba Francisco , Leiva Mercedes , Luís Ana T.
Published: April 2021

The Odiel River Basin, located in the Iberian Pyrite Belt (IPB), is heavily affected by acid mine drainage (AMD), which occurs when pyritic minerals from sulfide mining areas are exposed to atmospheric, hydrological or biological weathering. This paper presents a hydrochemical characterization of parameters in the Odiel River Basin by means of Fuzzy Logic and data mining methodologies to determine the seasonal influence of AMD in polluted waters that have not been used before for a basin in this environmental area. This technique was proven to be effective, providing results that could not be achieved by using classic statistics, because it allows us to characterize the different parameters separately and also their relationships in waters affected by AMD in a qualitative manner based on the antecedents and according to the conditions (rules) imposed by the consequents (in this case, the Fe(II) and accumulated rainfall over 30 days). Thus, it was possible to confirm that hydrochemistry is greatly affected by seasonal changes, with a higher pH in the wet season (up to 8.59) compared to 2.12, the minimum pH value reached in the dry season. Accordingly, higher concentrations of most of the metals were observed in the dry season (e.g., up to 4000 mg/L of Fe (II)), with the exception of the values found after the first rains that occur in the early fall. With the use of the Fuzzy Logic technique, it was observed that, during the wet season, lixiviates with a higher Fe content have higher metal concentrations, and in the dry season, the behavior is the opposite.
High-Frequency Audiometry for Early Detection of Hearing Loss: A Narrative Review
Authors: Škerková Michaela , Kovalová Martina , Mrázková Eva
Published: April 2021

The WHO considers hearing loss to be a major global problem. A literature search was conducted to see whether high-frequency audiometry (HFA) could be used for the early detection of hearing loss. A further aim was to see whether any differences exist in the hearing threshold using conventional audiometry (CA) and HFA in workers of different age groups exposed to workplace noise. Our search of electronic databases yielded a total of 5938 scientific papers. The inclusion criteria were the keywords “high frequency” and “audiometry” appearing anywhere in the article and the participation of unexposed people or a group exposed to workplace noise. Fifteen studies met these conditions; the sample size varied (51–645 people), and the age range of the people studied was 5–90 years. Commercial high-frequency audiometers and high-frequency headphones were used. In populations unexposed to workplace noise, significantly higher thresholds of 14–16 kHz were found. In populations with exposure to workplace noise, significantly higher statistical thresholds were found for the exposed group (EG) compared with the control group (CG) at frequencies of 9–18 kHz, especially at 16 kHz. The studies also showed higher hearing thresholds of 10–16 kHz in respondents aged under 31 years following the use of personal listening devices (PLDs) for longer than 5 years. The effect of noise-induced hearing loss (NIHL) first became apparent for HFA rather than CA. However, normative data have not yet been collected. Therefore, it is necessary to establish a uniform evaluation protocol accounting for age, sex, comorbidities and exposures, as well as for younger respondents using PLDs.
Spatial Patterns in Hospital-Acquired Infections in Portugal (2014–2017)
Authors: Teixeira Hugo , Freitas Alberto , Sarmento António , Nossa Paulo , Gonçalves Hernâni , Pina Maria de Fátima
Published: April 2021

Background: Hospital-Acquired Infections (HAIs) represent the most frequent adverse event associated with healthcare delivery and result in prolonged hospital stays and deaths worldwide. Aim: To analyze the spatial patterns of HAI incidence from 2014 to 2017 in Portugal. Methods: Data from the Portuguese Discharge Hospital Register were used. We selected episodes of patients with no infection on admission and with any of the following HAI diagnoses: catheter-related bloodstream infections, intestinal infections by Clostridium difficile, nosocomial pneumonia, surgical site infections, and urinary tract infections. We calculated age-standardized hospitalization rates (ASHR) by place of patient residence. We used empirical Bayes estimators to smooth the ASHR. The Moran Index and Local Index of Spatial Autocorrelation (LISA) were calculated to identify spatial clusters. Results: A total of 318,218 HAIs were registered, with men accounting for 49.8% cases. The median length of stay (LOS) was 9.0 days, and 15.7% of patients died during the hospitalization. The peak of HAIs (n = 81,690) occurred in 2015, representing 9.4% of the total hospital admissions. Substantial spatial inequalities were observed, with the center region presenting three times the ASHR of the north. A slight decrease in ASHR was observed after 2015. Pneumonia was the most frequent HAI in all age groups. Conclusion: The incidence of HAI is not randomly distributed in the space; clusters of high risk in the central region were seen over the entire study period. These findings may be useful to support healthcare policymakers and to promote a revision of infection control policies, providing insights for improved implementation.
The Association between Post-Migration Nutrition and Lifestyle Transition and the Risk of Developing Chronic Diseases among Sub-Saharan African Migrants: A Mixed Method Systematic Review Protocol
Authors: Akombi-Inyang Blessing , Huda Md. Nazmul , Schutte Aletta E. , Macniven Rona , Lin Sophia , Rawstorne Patrick , Xu Xiaoyue , Renzaho Andre
Published: April 2021

Sub-Saharan African (SSA) migrants face nutrition and lifestyle changes upon arrival in a host country. The shift in diet and lifestyle reflects post-migration acculturation and could predispose migrants to nutrition- and lifestyle- related chronic diseases. A mixed-methods systematic review of published studies and the grey literature on post-migration nutrition and lifestyle transition among SSA migrants will be undertaken. Studies published in English and conducted from 2000 to 2020 using quantitative and/or qualitative methods will be included. Ten bibliographic databases will be searched: Scopus, Ovid MEDLINE, EMBASE, Global Health, CINAHL, PubMed, ProQuest, PsycINFO, Informit and Web of Science. Data extraction will be informed by the Cochrane PROGRESS-Plus framework and the Joanna Briggs Institute manual. The quality of the included studies will be appraised for risk of bias using validated tools. An integrated approach to quantitative and qualitative data synthesis through data transformation will be undertaken, and a narrative synthesis of the findings will be provided. This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines and provides insight into the scope and parameters of the systematic review to be conducted. The aim of the review is to evaluate the association between post-migration nutrition and lifestyle transition and the risk of developing chronic diseases among SSA migrants in Australia. This review will provide insight into possible areas for interventions to improve the health of migrants. Systematic Review Registration: The protocol was registered with the PROSPERO international prospective register of systematic reviews CRD42020206560.
Supporting Positive Parenting and Promoting Healthy Living through Family Cooking Classes
Authors: Tørslev Mette Kirstine , Bjarup Thøgersen Dicte , Høstgaard Bonde Ane , Bloch Paul , Varming Annemarie
Published: April 2021

Background: The family is an important setting in the promotion of child health. The parent–child relationship affects the social and health development of children, and children’s healthy behaviors are associated with positive parenting strategies. The parent–child relationship is bi-directional and the connection between parenting and child health is complex. However, few parenting interventions work with parents and children together, and more knowledge is needed on how to develop and implement interventions promoting healthy parent–child relationships. Focusing on a family cooking class program, this study addresses how community initiatives engaging parents and children together can contribute to integrating parenting support with local health promotion. Methods: Participant-driven photo-elicited interviews (nine families), focus group evaluations (nine parents/14 children) and observations during cooking classes (10 classes) were applied to analyze the tools and mechanisms that can support positive parenting. Results: The study found that visual, practical and sensory learning techniques, applied in a context-sensitive learning environment that ensured guidance, safety and a friendly social atmosphere, contributed to positive parent–child interaction and bonding. Conclusion: The cooking program facilitated parenting practices that support child involvement and autonomy. Thus, the program constituted an effective intervention to strengthen parent–child relationships and positive parenting.
Efficiency of Human Resources in Public Hospitals: An Example from the Czech Republic
Authors: Vrabková Iveta , Vaňková Ivana
Published: April 2021

Healthcare is a highly sophisticated segment of the public sector, which requires not only highly professional and competent staff, but also a properly set ratio of healthcare professionals. In the Czech Republic, the state, as the main guarantor of health care, applied strong control through price and volume control. The aim of the paper is to define the differences in the technical efficiency of public hospitals, with regard to the size of hospitals and partial types of human resources. An input-oriented Data Envelopment Analysis model (DEA model) was chosen for modeling the technical efficiency of 47 public hospitals. The personnel performance concept of the evaluation of technical efficiency was further implemented in eight specific models, from the perspective of individual input variables relative to output variables and according to different assumptions regarding the character of economies of scale. The results of technical efficiency were analyzed using correlation, regression analysis, and the Bootstrap method. The least efficient hospitals in terms of hospital size are large hospitals, and the most balanced results have been achieved by medium-sized hospitals. The average efficiency rate in models that include all selected input and output variables is highest in medium-sized hospitals, with a value of 0.866 for CRS and an efficiency rate of 0.926 for VRS. The rationalization of human resources should be implemented in order not to reduce the quality of care provided.
Understanding the Differential Impact of Vegetation Measures on Modeling the Association between Vegetation and Psychotic and Non-Psychotic Disorders in Toronto, Canada
Authors: Abdullah Abu Yousuf Md , Law Jane , Butt Zahid A. , Perlman Christopher M.
Published: April 2021

Considerable debate exists on whether exposure to vegetation cover is associated with better mental health outcomes. Past studies could not accurately capture people’s exposure to surrounding vegetation and heavily relied on non-spatial models, where the spatial autocorrelation and latent covariates could not be adjusted. Therefore, a suite of five different vegetation measures was used to separately analyze the association between vegetation cover and the number of psychotic and non-psychotic disorder cases in the neighborhoods of Toronto, Canada. Three satellite-based and two area-based vegetation measures were used to analyze these associations using Poisson lognormal models under a Bayesian framework. Healthy vegetation cover was found to be negatively associated with both psychotic and non-psychotic disorders. Results suggest that the satellite-based indices, which can measure both the density and health of vegetation cover and are also adjusted for urban and environmental perturbations, could be better alternatives to simple ratio- and area-based measures for understanding the effect of vegetation on mental health. A strong dominance of spatially structured latent covariates was found in the models, highlighting the importance of adopting a spatial approach. This study can provide critical guidelines for selecting appropriate vegetation measures and developing spatial models for future population-based epidemiological research.
The Whitening Effect and Histological Safety of Nonthermal Atmospheric Plasma Inducing Tooth Bleaching
Authors: Nam Seoul-Hee , Choi Byul Bo Ra , Kim Gyoo-Cheon
Published: April 2021

Various light sources have been applied to enhance the bleaching effect. This study was to identify the histological evaluation in oral soft tissues, as well as tooth color change after tooth bleaching by nonthermal atmospheric pressure plasma (NAPP). Nine New Zealand adult female rabbits were randomly divided into three groups (n = 3): group 1 received no treatment; group 2 was treated with NAPP and 15% carbamide peroxide (CP), which contains 5.4% H2O2, and group 3 was treated with 15% CP without NAPP. Color change (ΔE) was measured using the Shade Eye NCC colorimeter. Animals were euthanized one day later to analyze the histological responses occurring in oral soft tissues, including pulp, gingiva, tongue, buccal mucosa, and hard and soft palates. Changes in all samples were analyzed by hematoxylin and eosin staining and Masson’s trichrome. Teeth treated with plasma showed higher ΔE than that obtained with bleaching agents alone. Overall, the histological characteristics observed no appreciable changes. The combinational treatment of plasma had not indicated inflammatory responses as well as thermal damages. NAPP did not cause histological damage in oral soft tissues during tooth bleaching. We suggest that NAPP could be a novel alternative energy source to conventional light sources for tooth bleaching.
The Role of Leptin in Fetal Growth during Pre-Eclampsia
Authors: de Knegt Victoria E. , Hedley Paula L. , Kanters Jørgen K. , Thagaard Ida N. , Krebs Lone , Christiansen Michael , Lausten-Thomsen Ulrik
Published: April 2021

Leptin is secreted by the placenta and has a multi-facetted role in the regulation of functions related to pregnancy. Metabolic disorders and insufficient homeostatic compensatory mechanisms involving leptin during pregnancy play a decisive role in the development of pre-eclampsia (PE) and give rise to compromised intrauterine growth conditions and aberrant birth weight of offspring. This review was compiled to elucidate the metabolic background of PE and its relationship with adverse intrauterine growth conditions through the examination of leptin as well as to describe possible mechanisms linking leptin to fetal growth restriction. This review illustrates that leptin in PE is dysregulated in maternal, fetal, and placental compartments. There is no single set of unifying mechanisms within the spectrum of PE, and regulatory mechanisms involving leptin are specific to each situation. We conclude that dysregulated leptin is involved in fetal growth at many levels through complex interactions with parallel pregnancy systems and probably throughout the entirety of pregnancy.
Hydroxyurea and Caffeine Impact pRb-like Protein-Dependent Chromatin Architecture Profiles in Interphase Cells of Vicia faba
Authors: Musiałek Marcelina W. , Deckert Joanna , Rybaczek Dorota
Published: April 2021

The survival of cells depends on their ability to replicate correctly genetic material. Cells exposed to replication stress can experience a number of problems that may lead to deregulated proliferation, the development of cancer, and/or programmed cell death. In this article, we have induced prolonged replication arrest via hydroxyurea (HU) treatment and also premature chromosome condensation (PCC) by co-treatment with HU and caffeine (CF) in the root meristem cells of Vicia faba. We have analyzed the changes in the activities of retinoblastoma-like protein (RbS807/811ph). Results obtained from the immunocytochemical detection of RbS807/811ph allowed us to distinguish five unique activity profiles of pRb. We have also performed detailed 3D modeling using Blender 2.9.1., based on the original data and some final conclusions. 3D models helped us to visualize better the events occurring within the nuclei and acted as a high-resolution aid for presenting the results. We have found that, despite the decrease in pRb activity, its activity profiles were mostly intact and clearly recognizable, with some local alterations that may correspond to the increased demand in transcriptional activity. Our findings suggest that Vicia faba’s ability to withstand harsh environments may come from its well-developed and highly effective response to replication stress.
Application of Nitrate, Ammonium, or Urea Changes the Concentrations of Ureides, Urea, Amino Acids and Other Metabolites in Xylem Sap and in the Organs of Soybean Plants (Glycine max (L.) Merr.)
Authors: Ono Yuki , Fukasawa Masashige , Sueyoshi Kuni , Ohtake Norikuni , Sato Takashi , Tanabata Sayuri , Toyota Ryo , Higuchi Kyoko , Saito Akihiro , Ohyama Takuji
Published: April 2021

Soybean (Glycine max (L.) Merr.) plants form root nodules and fix atmospheric dinitrogen, while also utilizing the combined nitrogen absorbed from roots. In this study, nodulated soybean plants were supplied with 5 mM N nitrate, ammonium, or urea for 3 days, and the changes in metabolite concentrations in the xylem sap and each organ were analyzed. The ureide concentration in the xylem sap was the highest in the control plants that were supplied with an N-free nutrient solution, but nitrate and asparagine were the principal compounds in the xylem sap with nitrate treatment. The metabolite concentrations in both the xylem sap and each organ were similar between the ammonium and urea treatments. Considerable amounts of urea were present in the xylem sap and all the organs among all the treatments. Positive correlations were observed between the ureides and urea concentrations in the xylem sap as well as in the roots and leaves, although no correlations were observed between the urea and arginine concentrations, suggesting that urea may have originated from ureide degradation in soybean plants, possibly in the roots. This is the first finding of the possibility of ureide degradation to urea in the underground organs of soybean plants.
NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia
Authors: Barresi Vincenza , Di Bella Virginia , Andriano Nellina , Privitera Anna Provvidenza , Bonaccorso Paola , La Rosa Manuela , Iachelli Valeria , Spampinato Giorgia , Pulvirenti Giulio , Scuderi Chiara , Condorelli Daniele F. , Lo Nigro Luca
Published: April 2021

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.
Selenium Nanocomposites in Natural Matrices as Potato Recovery Agent
Authors: Perfileva Alla I. , Nozhkina Olga A. , Ganenko Tatjana V. , Graskova Irina A. , Sukhov Boris G. , Artem’ev Alexander V. , Trofimov Boris A. , Krutovsky Konstantin V.
Published: April 2021

The paper presents a study of the effect of chemically synthesized selenium nanocomposites (Se NCs) in natural polymer matrices arabinogalactan (AG) and starch (ST) on the viability of the potato ring rot pathogen Clavibacter sepedonicus (Cms), potato plants in vitro, and the soil bacterium Rhodococcus erythropolis. It was found that the studied Se NCs have an antibacterial effect against the phytopathogenic Cms, reducing its growth rate and ability to form biofilms. It was revealed that Se NC based on AG (Se/AG NC) stimulated the growth and development of potato plants in vitro as well as their root formation. At the same time, Se did not accumulate in potato tissues after the treatment of plants with Se NCs. The safety of the Se NCs was also confirmed by the absence of a negative effect on the growth and biofilm formation of the soil bacterium R. erythropolis. The obtained results indicate that Se NCs are promising environmentally safe agents for the protection and recovery of cultivated plants from phytopathogenic bacteria.
Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ
Authors: Just-Borràs Laia , Cilleros-Mañé Víctor , Hurtado Erica , Biondi Olivier , Charbonnier Frédéric , Tomàs Marta , Garcia Neus , Tomàs Josep , Lanuza Maria A.
Published: April 2021

Physical exercise improves motor control and related cognitive abilities and reinforces neuroprotective mechanisms in the nervous system. As peripheral nerves interact with skeletal muscles at the neuromuscular junction, modifications of this bidirectional communication by physical activity are positive to preserve this synapse as it increases quantal content and resistance to fatigue, acetylcholine receptors expansion, and myocytes’ fast-to-slow functional transition. Here, we provide the intermediate step between physical activity and functional and morphological changes by analyzing the molecular adaptations in the skeletal muscle of the full BDNF/TrkB downstream signaling pathway, directly involved in acetylcholine release and synapse maintenance. After 45 days of training at different intensities, the BDNF/TrkB molecular phenotype of trained muscles from male B6SJLF1/J mice undergo a fast-to-slow transition without affecting motor neuron size. We provide further knowledge to understand how exercise induces muscle molecular adaptations towards a slower phenotype, resistant to prolonged trains of stimulation or activity that can be useful as therapeutic tools.
Serum APOA4 Pharmacodynamically Represents Administered Recombinant Human Hepatocyte Growth Factor (E3112)
Authors: Motoi Sotaro , Uesugi Mai , Obara Takashi , Moriya Katsuhiro , Arita Yoshihisa , Ogasawara Hideaki , Soejima Motohiro , Imai Toshio , Kawano Tetsu
Published: April 2021

Background: Hepatocyte growth factor (HGF) is an endogenously induced bioactive molecule that has strong anti-apoptotic and tissue repair activities. In this research, we identified APOA4 as a novel pharmacodynamic (PD) marker of the recombinant human HGF (rh-HGF), E3112. Methods: rh-HGF was administered to mice, and their livers were investigated for the PD marker. Candidates were identified from soluble proteins and validated by using human hepatocytes in vitro and an animal disease model in vivo, in which its c-Met dependency was also ensured. Results: Among the genes induced or highly enhanced after rh-HGF exposure in vivo, a soluble apolipoprotein, Apoa4, was found to be induced by rh-HGF in the murine liver. By using primary cultured human hepatocytes, the significant induction of human APOA4 was observed at the mRNA and protein levels, and it was inhibited in the presence of a c-Met inhibitor. Although mice constitutively expressed Apoa4 mRNA in the small intestine and the liver, the liver was the primary organ affected by administered rh-HGF to strongly induce APOA4 in a dose- and c-Met-dependent manner. Serum APOA4 levels were increased after rh-HGF administration, not only in normal mice but also in anti-Fas-induced murine acute liver failure (ALF), which confirmed the pharmacodynamic nature of APOA4. Conclusions: APOA4 was identified as a soluble PD marker of rh-HGF with c-Met dependency. It should be worthwhile to clinically validate its utility through clinical trials with healthy subjects and ALF patients.
Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles
Authors: Lee Yu-Jin , Park Song-Hee , Park Hye-Ree , Lee Young , Kang Hoon , Kim Jung-Eun
Published: April 2021

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/β-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression—including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1β, and IL-15—and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/β-catenin signaling pathway, such as in the Wnt families, β-catenin, phosphorylated GSK-3β and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/β-catenin and JAK/STAT pathways in hORSCs.
The Effect of Space Travel on Bone Metabolism: Considerations on Today’s Major Challenges and Advances in Pharmacology
Authors: Genah Shirley , Monici Monica , Morbidelli Lucia
Published: April 2021

Microgravity-induced bone loss is currently a significant and unresolved health risk for space travelers, as it raises the likelihood for irreversible changes that weaken skeletal integrity and the incremental onset of fracture injuries and renal stone formation. Another issue related to bone tissue homeostasis in microgravity is its capacity to regenerate following fractures due to weakening of the tissue and accidental events during the accomplishment of particularly dangerous tasks. Today, several pharmacological and non-pharmacological countermeasures to this problem have been proposed, including physical exercise, diet supplements and administration of antiresorptive or anabolic drugs. However, each class of pharmacological agents presents several limitations as their prolonged and repeated employment is not exempt from the onset of serious side effects, which limit their use within a well-defined range of time. In this review, we will focus on the various countermeasures currently in place or proposed to address bone loss in conditions of microgravity, analyzing in detail the advantages and disadvantages of each option from a pharmacological point of view. Finally, we take stock of the situation in the currently available literature concerning bone loss and fracture healing processes. We try to understand which are the critical points and challenges that need to be addressed to reach innovative and targeted therapies to be used both in space missions and on Earth.
Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?
Authors: Voss Martin , Kotrba Johanna , Gaffal Evelyn , Katsoulis-Dimitriou Konstantinos , Dudeck Anne
Published: April 2021

Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.
Molecular Mechanisms of Neural Circuit Development and Regeneration
Authors: Moons Lieve , De Groef Lies
Published: April 2021

The human brain contains 86 billion neurons [...]
iPSCs: A Preclinical Drug Research Tool for Neurological Disorders
Authors: Bonaventura Gabriele , Iemmolo Rosario , Attaguile Giuseppe Antonino , La Cognata Valentina , Pistone Brigida Sabrina , Raudino Giuseppe , D’Agata Velia , Cantarella Giuseppina , Barcellona Maria Luisa , Cavallaro Sebastiano
Published: April 2021

The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).
S-Nitrosylation in Tumor Microenvironment
Authors: Sharma Vandana , Fernando Veani , Letson Joshua , Walia Yashna , Zheng Xunzhen , Fackelman Daniel , Furuta Saori
Published: April 2021

S-nitrosylation is a selective and reversible post-translational modification of protein thiols by nitric oxide (NO), which is a bioactive signaling molecule, to exert a variety of effects. These effects include the modulation of protein conformation, activity, stability, and protein-protein interactions. S-nitrosylation plays a central role in propagating NO signals within a cell, tissue, and tissue microenvironment, as the nitrosyl moiety can rapidly be transferred from one protein to another upon contact. This modification has also been reported to confer either tumor-suppressing or tumor-promoting effects and is portrayed as a process involved in every stage of cancer progression. In particular, S-nitrosylation has recently been found as an essential regulator of the tumor microenvironment (TME), the environment around a tumor governing the disease pathogenesis. This review aims to outline the effects of S-nitrosylation on different resident cells in the TME and the diverse outcomes in a context-dependent manner. Furthermore, we will discuss the therapeutic potentials of modulating S-nitrosylation levels in tumors.
Double and Triple Differential Cross Sections for Single Ionization of Benzene by Electron Impact
Authors: Lozano Ana I. , Costa Filipe , Ren Xueguang , Dorn Alexander , Álvarez Lidia , Blanco Francisco , Limão-Vieira Paulo , García Gustavo
Published: April 2021

Experimental results for the electron impact ionization of benzene, providing double (DDCS) and triple differential cross sections (TDCS) at the incident energy of 90 eV, measured with a multi-particle momentum spectrometer, are reported in this paper. The most intense ionization channel is assigned to the parent ion (C6H6+) formation. The DDCS values are presented for three different transferred energies, namely 30, 40 and 50 eV. The present TDCS are given for two fixed values of the ejected electron energy (E2), at 5 and 10 eV, and an electron scattering angle (θ1) of 10°. Different features related to the molecular orbitals of benzene from where the electron is extracted are observed. In addition, a semi-empirical formula to be used as the inelastic angular distribution function in electron transport simulations has been derived from the present DDCS result and compared with other expressions available in the literature.
Role of ABCA7 in Human Health and in Alzheimer’s Disease
Authors: Dib Shiraz , Pahnke Jens , Gosselet Fabien
Published: April 2021

Several studies, including genome wide association studies (GWAS), have strongly suggested a central role for the ATP-binding cassette transporter subfamily A member 7 (ABCA7) in Alzheimer’s disease (AD). This ABC transporter is now considered as an important genetic determinant for late onset Alzheimer disease (LOAD) by regulating several molecular processes such as cholesterol metabolism and amyloid processing and clearance. In this review we shed light on these new functions and their cross-talk, explaining its implication in brain functioning, and therefore in AD onset and development.
pCTX-M3—Structure, Function, and Evolution of a Multi-Resistance Conjugative Plasmid of a Broad Recipient Range
Authors: Kern-Zdanowicz Izabela
Published: April 2021

pCTX-M3 is the archetypic member of the IncM incompatibility group of conjugative plasmids (recently referred to as IncM2). It is responsible for the worldwide dissemination of numerous antibiotic resistance genes, including those coding for extended-spectrum β-lactamases and conferring resistance to aminoglycosides. The IncM plasmids acquired during evolution diverse mobile genetic elements found in one or two multiple resistance regions, MRR(s), grouping antibiotic resistance genes as well as mobile genetic elements or their remnants. The IncM plasmids can be found in bacteria inhabiting various environments. The information on the structure and biology of pCTX-M3 is integrated in this review. It focuses on the functional modules of pCTX-M3 responsible for its replication, stable maintenance, and conjugative transfer, indicating that the host range of the pCTX-M3 replicon is limited to representatives of the family Enterobacteriaceae (Enterobacterales ord. nov.), while the range of recipients of its conjugation system is wide, comprising Alpha-, Beta-, and Gammaproteobacteria, and also Firmicutes.
A Crucial Role of Mitochondrial Dynamics in Dehydration Resistance in Saccharomyces cerevisiae
Authors: Chen Chang-Lin , Chen Ying-Chieh , Huang Wei-Ling , Lin Steven , Daugelavičius Rimantas , Rapoport Alexander , Chang Chuang-Rung
Published: April 2021

Mitochondria are dynamic organelles as they continuously undergo fission and fusion. These dynamic processes conduct not only mitochondrial network morphology but also activity regulation and quality control. Saccharomyces cerevisiae has a remarkable capacity to resist stress from dehydration/rehydration. Although mitochondria are noted for their role in desiccation tolerance, the mechanisms underlying these processes remains obscure. Here, we report that yeast cells that went through stationary growth phase have a better survival rate after dehydration/rehydration. Dynamic defective yeast cells with reduced mitochondrial genome cannot maintain the mitochondrial activity and survival rate of wild type cells. Our results demonstrate that yeast cells balance mitochondrial fusion and fission according to growth conditions, and the ability to adjust dynamic behavior aids the dehydration resistance by preserving mitochondria.
Modulation of Diverse Procoagulant Venom Activities by Combinations of Platinoid Compounds
Authors: Nielsen Vance G.
Published: April 2021

Procoagulant snake venoms have been inhibited by the ruthenium containing compounds CORM-2 and RuCl3 separately, presumably by interacting with critical histidine or other sulfur-containing amino acids on key venom enzymes. However, combinations of these and other platinoid containing compounds could potentially increase, decrease or not affect the procoagulant enzyme function of venom. Thus, the purpose of this investigation was to determine if formulations of platinoid compounds could inhibit venom procoagulant activity and if the formulated compounds interacted to enhance inhibition. Using a human plasma coagulation kinetic model to assess venom activity, six diverse venoms were exposed to various combinations and concentrations of CORM-2, CORM-3, RuCl3 and carboplatin (a platinum containing compound), with changes in venom activity determined with thrombelastography. The combinations of CORM-2 or CORM-3 with RuCl3 were found to enhance inhibition significantly, but not in all venoms nor to the same extent. In sharp contrast, carboplatin-antagonized CORM-2 mediated the inhibition of venom activity. These preliminary results support the concept that platinoid compounds may inhibit venom enzymatic activity at the same or different molecular sites and may antagonize inhibition at the same or different sites. Further investigation is warranted to determine if platinoid formulations may serve as potential antivenoms.