bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender
Authors: Boscutti Andrea , Pigoni Alessandro , Delvecchio Giuseppe , Lazzaretti Matteo , Mandolini Gian Mario , Girardi Paolo , Ferro Adele , Sala Michela , Abbiati Vera , Cappucciati Marco , Bellani Marcella , Perlini Cinzia , Rossetti Maria Gloria , Balestrieri Matteo , Damante Giuseppe , Bonivento Carolina , Rossi Roberta , Finos Livio , Serretti Alessandro , Brambilla Paolo ,   the GECOBIP Group
Published: March 2022

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.
Genotype-Dependent Antioxidative Response of Four Sweet Pepper Cultivars to Water Deficiency as Affected by Drought-Tolerant Bacillus safensis SS-2.7 and Bacillus thuringiensis SS-29.2 Strains
Authors: Lozo Jelena , Danojević Dario , Jovanović Živko , Nenadović Željka , Fira Djordje , Stanković Slaviša , Radović Svetlana
Published: March 2022

We examined the effect of drought-tolerant Bacillus safensis SS-2.7 and B. thuringiensis SS-29.2 strains on the response of four (133, 274, California Wonder—CalW, and Matica) sweet pepper genotypes to water deficiency conditions. Pepper seeds were sown in pots with (treated) and without (control) bacterial strain inoculation. After four weeks of growth under controlled conditions and regular watering, drought was imposed by completely withholding watering for seven days. Under conditions of normal watering, genotype 274 showed better seedling establishment than genotype 133 and CalW, while the slowest was genotype Matica. Antioxidant enzyme activity under drought conditions was genotype and bacterial treatment-dependent. The best response to bacterial treatment in order to cope with severe drought was found in the CalW genotype, while in genotype 133, we determined even faster plant decay during water deficiency in treated seeds. Inoculated seeds of the Matica genotype did not show different antioxidant enzyme activity under normal and drought conditions. According to the obtained results, we concluded that under drought conditions, the most susceptible was genotype 274, moderate susceptibility was detected in genotype 133, and CalW and Matica were the most tolerant genotypes. Our study demonstrates (1) that drought-tolerant Bacillus strains showed a plant growth-promoting effect on some selected pepper genotypes; (2) that there were genotype-dependent antioxidant enzyme activities under drought conditions in response to treatment with a particular bacterial strain; and (3) that we could expect a genotype-dependent response during biostimulant application, especially under stress conditions.
Impact of Pesticides on Human Health in the Last Six Years in Brazil
Authors: Lopes-Ferreira Monica , Maleski Adolfo Luis Almeida , Balan-Lima Leticia , Bernardo Jefferson Thiago Gonçalves , Hipolito Lucas Marques , Seni-Silva Ana Carolina , Batista-Filho Joao , Falcao Maria Alice Pimentel , Lima Carla
Published: March 2022

Every year, Brazil intensifies its activity in agriculture and, as a result, it has become one of the biggest consumers of pesticides in the world. The high rate of these substances raises environmental and human health concerns. Therefore, we collected papers from PubMed, Scopus, Scielo, and Web of Science databases, from 2015 to 2021. After a blind selection using the software Rayyan QCRI by two authors, 51 studies were included. Researchers from the South and the Southeast Brazilian regions contributed to most publications, from areas that concentrate agricultural commodity complexes. Among the pesticides described in the studies, insecticides, herbicides, and fungicides were the most frequent. The articles reported multiple toxic effects, particularly in rural workers. The results obtained can be used to direct policies to reduce the use of pesticides, and to protect the health of the population.
COVID-19 Vaccine Hesitancy: The Role of Information Sources and Beliefs in Dutch Adults
Authors: de Vries Hein , Verputten Wouter , Preissner Christian , Kok Gerjo
Published: March 2022

COVID-19 vaccine hesitancy may be regarded as a new pandemic hindering the elimination of or coping with COVID-19. This study assessed reasons for COVID-19 vaccine hesitancy using the I-Change Model (ICM) by considering the role of informational and psychosocial factors. A cross-sectional online survey using a convenience sample was conducted among Dutch adults (n = 240). The questionnaire assessed information factors, predisposing factors, awareness factors, motivational factors, preparatory actions, and vaccination intention. Vaccine hesitant participants (n = 58, 24%) had lower levels of education, more often paid work, and tended to have a religion other than Catholicism. They used written media less often and tended to visit websites of public health organizations less often, but used messaging services like WhatsApp more frequently. All participants had neutral intentions towards checking information credibility. Vaccine hesitant respondents had less knowledge about vaccination, lower perceived severity of getting sick and dying of COVID-19, and reported fewer exposures to cues about the advantages of COVID-19 vaccination. They were less convinced of the emotional and rational advantages of COVID-19 vaccination and expressed more negative feelings about it. They also reported more negative social norms concerning COVID-19 vaccination, and lower self-efficacy to get vaccinated and to cope with potential side-effects. The regression model explained 58% of the variance in vaccination intention. The results suggest that strategies are needed to: 1. Reduce fake news and stimulate information checking to foster well-informed decision-making; 2. Target both rational and emotional consequences of COVID-19, in addition to strategies for optimizing levels of knowledge. Campaigns should acknowledge the perceptions of the emotional disadvantages and increase perceptions of emotional advantages of COVID-19 vaccinations, such as reducing feelings of regret, and increasing feelings of freedom and reassurance.
Analysis of Stigma in Relation to Behaviour and Attitudes towards Mental Health as Influenced by Social Desirability in Nursing Students
Authors: Giralt Palou Rosa , Prat Vigué Gemma , Romeu-Labayen Maria , Tort-Nasarre Glòria
Published: March 2022

The training undergraduate nursing students receive, both in terms of theoretical input and clinical practice, may help to instil a less stigmatising perception of mental health. To analyse the perceived evolution of attitudes and expected behaviours, a longitudinal repeated measures study was conducted in a population of student nurses during their undergraduate mental health education. The Mental Illness: Clinicians’ Attitudes Scale, a Scale for measuring attitudes to the mentally ill among future Health workers, and the Reported and Intended Behaviour Scale were completed. A mixed linear model was used to assess the effect of each factor in the questionnaires before and after the various stages of the students’ training in mental health. The overall effect of each factor was assessed by testing the interaction between factor and group, both with and without adjustment with the Social Desirability Scale. The results showed that the clinical practice stage, due to the proximity to care for people with mental health problems, improves attitudes and behaviours towards mental health in students who have not had mental health problems, and also in younger students. In conclusion, integrated, holistic training during the period of clinical practice was associated with positive changes in the attitudes and intended behaviour.
Association between Happiness and Economic Status among Older Adults in Two Myanmar Regions
Authors: Sasaki Yuri , Shobugawa Yugo , Nozaki Ikuma , Takagi Daisuke , Nagamine Yuiko , Funato Masafumi , Chihara Yuki , Shirakura Yuki , Lwin Kay Thi , Zin Poe Ei , Bo Thae Zarchi , Sone Tomofumi , Win Hla Hla
Published: March 2022

Few studies have examined whether objective or subjective economic status (ES) has a greater association with the happiness of older adults, despite concerns regarding the growing economic cost of morbidity and their functional dependence in developing countries with aging populations. Thus, this study examined whether objective/subjective ES was associated with happiness in older adults in two Myanmar regions. A multistage random sampling procedure and face-to-face interviews were conducted in the urban and rural areas of Myanmar. The happiness of 1200 participants aged >60 years was evaluated using a single happiness score ranging from 0 (very unhappy) to 10 (very happy). The wealth index, used as an objective ES, was calculated from 17 household asset items, such as radio, washing machines, and television. Subjective ES was assessed by asking “Which of the following best describes your current financial situation in light of general economic conditions?” Responses ranged from “very difficult” to “very comfortable”. Both low objective and subjective ES were negatively associated with happiness, after adjusting for confounding variables and stratification by region (urban and rural areas). Although objective and subjective ES had similar associations with happiness in urban areas, subjective ES had a stronger association in rural areas.
Evolutionary Overview of Land Consolidation Based on Bibliometric Analysis in Web of Science from 2000 to 2020
Authors: Xu Xin , Chen Qianru , Zhu Zhenhong
Published: March 2022

Land consolidation is widely used as a powerful tool for land use management in many countries. In order to objectively reveal the current research status in the field of land consolidation, this paper uses the Bibliometrix and Biblioshiny software packages, and VOSviewer to analyze the literature in the field of land consolidation in the last 20 years of the Web of Science Core Collection Database. The results show that: (1) In the past two decades, the annual publication of papers on land consolidation rose. It can be divided into three stages: 2000–2007 for the embryonic period, 2008–2012 for the long-term, and 2013–2020 for the high-yield period. (2) Land consolidation studies covered 68 countries or regions. The top three countries were China, Poland, and the United States. China and the United States played an important role in international cooperation in the field of land consolidation, and Turkey mainly conducted independent research in the field of land consolidation. (3) Land consolidation, reclamation, China, remote sensing, and land fragmentation were the high-frequency keywords in the field of land consolidation in recent years. (4) The research focusing on the field of land consolidation involved its development course, its impact on ecosystem services, and the evaluation of its benefits. (5) The theme of land consolidation studies was shunted and evolved over time, and nine evolution paths could be summarized in the studies of cultivated land fragmentation, development course of land consolidation, and impacts of land consolidation on soil. Finally, this paper predicted the future research directions of land consolidation: exploring new methods for evaluating the benefits of land consolidation, the scale effects of the impact of land consolidation on ecosystem services, research on the mechanism and comprehensive effects of land consolidation on soil, research on land consolidation and rural revitalization, and land consolidation theory research.
Cigar Warning Noticing and Demographic and Usage Correlates: Analysis from the United States Population Assessment of Tobacco and Health Study, Wave 5
Authors: Gratale Stefanie K. , Teotia Arjun , Chen-Sankey Julia , Ganz Ollie , Delnevo Cristine D. , Strasser Andrew A. , Wackowski Olivia A.
Published: March 2022

Although cigars pose health risks similar to cigarettes, their packaging/marketing is not subject to commensurate regulation in the US. In a 2000 agreement with the Federal Trade Commission, seven major manufacturers agreed to use some form of cigar warning. In 2016, the Food and Drug Administration passed a rule requiring larger standardized warnings, but the requirement was successfully challenged in court. Here, we examined U.S. population-level trends in noticing existing cigarillo, traditional and filtered cigar warnings. We analyzed Wave 5 Population Assessment of Tobacco and Health adult data to assess prevalence of past-30 day warning noticing and associations with socio-demographic and tobacco use variables. Noticing was higher among current users of cigarillos (27%), filtered (34%) and traditional cigars (21%), than non-users (8% for each product, p < 0.0001), and among every-day vs. some-day users, established vs. experimental users, and past-30 day users vs. those without past-30 day use. Results varied by product, but generally indicated lower noticing among non-Hispanic Whites and dual cigarette users, but higher noticing among those purchasing cigars by the box/pack (vs. not purchasing for themselves). Low overall noticing but higher prevalence among frequent users underscores a need for a stronger, uniform cigar warning label policy in the US.
Effects of Impulsivity on Competitive Anxiety in Female Athletes: The Mediating Role of Mindfulness Trait
Authors: Terres-Barcala Lara , Albaladejo-Blázquez Natalia , Aparicio-Ugarriza Raquel , Ruiz-Robledillo Nicolás , Zaragoza-Martí Ana , Ferrer-Cascales Rosario
Published: March 2022

It has been demonstrated that athletes in competitive sports suffer from high levels of competitive anxiety, especially in the case of females. In this sense, it is necessary to identify possible risk and protective factors of those athletes in this collective who suffer from this type of anxiety. However, few studies analyze the relationship between Physical Activity (PA) and anxiety, identifying the possible mediation effect of trait variables such as impulsivity and mindfulness in female athletes. Hence, the aims of this study were: to determine differences between PA levels with anxiety, mindfulness, and impulsiveness; to identify the predictive value of sociodemographic factors and physical activity, impulsivity, and mindfulness on anxiety factors; and to analyze the possible mediating effects of mindfulness on the relationship between impulsivity and anxiety. A total of 242 female athletes underwent an assessment of physical activity, anxiety, mindfulness traits, and impulsivity using validated questionnaires. Data were analyzed according to (1) individual or collective sport, and (2) PA levels according to energy expended (METs min/day). Participants were grouped by light, moderate, and vigorous PA levels. There were 30.5% elite athletes and 73.2% collective sports athletes. Mean age was 22.1 years and mean light, moderate, and vigorous PA were 86.1 ± 136.2, 114.4 ± 159.8, and 370.1 ± 336.3 METs min/day, respectively. Those athletes performing vigorous PA exhibited lower levels of impulsiveness and higher mindfulness traits. As expected, the mindfulness trait was a mediating factor in the relationship between impulsiveness and each factor of competitive anxiety (cognitive, somatic, and self-efficacy). Female athletes could suffer competitive anxiety, especially those who present higher levels of impulsivity. However, higher levels of mindfulness traits seem to be a protective factor in the effects of impulsivity on anxiety in this population and have demonstrated to be significant mediators in this association. Further studies are needed with other female athletes to replicate these results and to determine the specific protective mechanisms of mindfulness traits in preventing competitive anxiety.
Wolfram Syndrome 1: From Genetics to Therapy
Authors: Rigoli Luciana , Caruso Valerio , Salzano Giuseppina , Lombardo Fortunato
Published: March 2022

Wolfram syndrome 1 (WS1) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. It is characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and sensorineural hearing loss (D) (DIDMOAD). The clinical picture may be complicated by other symptoms, such as urinary tract, endocrinological, psychiatric, and neurological abnormalities. WS1 is caused by mutations in the WFS1 gene located on chromosome 4p16 that encodes a transmembrane protein named wolframin. Many studies have shown that wolframin regulates some mechanisms of ER calcium homeostasis and therefore plays a role in cellular apoptosis. More than 200 mutations are responsible for WS1. However, abnormal phenotypes of WS with or without DM, inherited in an autosomal dominant mode and associated with one or more WFS1 mutations, have been found. Furthermore, recessive Wolfram-like disease without DM has been described. The prognosis of WS1 is poor, and the death occurs prematurely. Although there are no therapies that can slow or stop WS1, a careful clinical monitoring can help patients during the rapid progression of the disease, thus improving their quality of life. In this review, we describe natural history and etiology of WS1 and suggest criteria for a most pertinent approach to the diagnosis and clinical follow up. We also describe the hallmarks of new therapies for WS1.
Impacts of Supply Chain Competition on Firms’ Carbon Emission Reduction and Social Welfare under Cap-and-Trade Regulation
Authors: Xue Kelei , Sun Guohua
Published: March 2022

In the carbon neutrality era, firms are facing increasingly intense environmental pressure and market competition. This paper considers two competitive supply chains with consumers’ low-carbon preference under the cap-and-trade regulation, each of which consists of one manufacturer and one retailer. Considering competition or integration in vertical and horizontal directions, four different supply chain structures are modeled. By applying a game-theoretical approach, the equilibrium pricing, carbon emission reduction (CER) level, profit, and social welfare are obtained. Through comparison and analysis, the economic and environmental impacts of supply chain competition are explored. The results show that (1) the carbon quota acts as a kind of financial subsidy and brings direct economic profit to the supply chain, which cannot be used to incentivize the firm to invest in CER technology; (2) the HCVI strategy can bring the highest CER level, the most market demand, and social welfare among the four strategies; (3) for the enterprise and the government, it is recommended to take measures and enact policies to strengthen the vertical integration and horizontal competition between supply chains. Our study can guide firms on how to cope with increasingly fierce industry competition and environmental pressure by adjusting their operational decisions and supply chain structure.
Study on the Spatial and Temporal Distribution Characteristics and Influencing Factors of Particulate Matter Pollution in Coal Production Cities in China
Authors: Wang Ju , Li Tongnan , Li Zhuoqiong , Fang Chunsheng
Published: March 2022

In recent years, with the continuous advancement of China’s urbanization process, regional atmospheric environmental problems have become increasingly prominent. We selected 12 cities as study areas to explore the spatial and temporal distribution characteristics of atmospheric particulate matter in the region, and analyzed the impact of socioeconomic and natural factors on local particulate matter levels. In terms of time variation, the particulate matter in the study area showed an annual change trend of first rising and then falling, a monthly change trend of “U” shape, and an hourly change trend of double-peak and double-valley distribution. Spatially, the concentration of particulate matter in the central and southern cities of the study area is higher, while the pollution in the western region is lighter. In terms of social economy, PM2.5 showed an “inverted U-shaped” quadratic polynomial relationship with Second Industry and Population Density, while it showed a U-shaped relationship with Generating Capacity and Coal Output. The results of correlation analysis showed that PM2.5 and PM10 were significantly positively correlated with NO2, SO2, CO and air pressure, and significantly negatively correlated with O3 and air temperature. Wind speed was significantly negatively correlated with PM2.5, and significantly positively correlated with PM10. In terms of pollution transmission, the southwest area of Taiyuan City is a high potential pollution source area of fine particles, and the long-distance transport of PM2.5 in Xinjiang from the northwest also has a certain contribution to the pollution of fine particles. This study is helpful for us to understand the characteristics and influencing factors of particulate matter pollution in coal production cities.
Mixed Effect of Alcohol, Smoking, and Smokeless Tobacco Use on Hypertension among Adult Population in India: A Nationally Representative Cross-Sectional Study
Authors: Singh Prashant Kumar , Dubey Ritam , Singh Lucky , Singh Nishikant , Kumar Chandan , Kashyap Shekhar , Subramanian Sankaran Venkata , Singh Shalini
Published: March 2022

Sporadic evidence is available on the association of consuming multiple substances with the risk of hypertension among adults in India where there is a substantial rise in cases. This study assesses the mutually exclusive and mixed consumption patterns of alcohol, tobacco smoking and smokeless tobacco use and their association with hypertension among the adult population in India. Nationally representative samples of men and women drawn from the National Family and Health Survey (2015–2016) were analyzed. A clinical blood pressure measurement above 140 mmHg (systolic blood pressure) and 90 mmHg (diastolic blood pressure) was considered in the study as hypertension. Association between mutually exclusive categories of alcohol, tobacco smoking and smokeless tobacco and hypertension were examined using multivariate binary logistic regression models. Daily consumption of alcohol among male smokeless tobacco users had the highest likelihood to be hypertensive (OR: 2.32, 95% CI: 1.99–2.71) compared to the no-substance-users. Women who smoked, and those who used any smokeless tobacco with a daily intake of alcohol had 71% (OR: 1.71, 95% CI: 1.14–2.56) and 51% (OR: 1.51, 95% CI: 1.25–1.82) higher probability of being hypertensive compared to the no-substance-users, respectively. In order to curb the burden of hypertension among the population, there is a need for an integrated and more focused intervention addressing the consumption behavior of alcohol and tobacco.
Estimating Macroinvertebrate Biomass for Stream Ecosystem Assessments
Authors: Cummins Kenneth W. , Wilzbach Margaret , Kolouch Brigitte , Merritt Richard
Published: March 2022

We propose a field procedure for estimating the dry biomass of stream macroinvertebrates. Estimates are calculated using the mean values of the a and b regression coefficients from unpublished data and an extensive review of the relevant literature. The regression equation employed for calculating dry biomass is one that has been extensively used: Y = aXb, where Y = mg dry mass of an individual macroinvertebrate; X = mm total body length of an individual macroinvertebrate; a = intercept coefficient of the Y on X regression; and b = slope coefficient Y on X. The procedure was developed for use in the field, but dry mass estimates can also be made on preserved specimens. The case is made for presenting stream macroinvertebrate dry biomass data categorized by functional feeding groups (FFGs) and their component higher level taxa. The tables summarize the FFGs and their food resources, mean regression coefficients, dry biomass estimates for FFG-taxa by size and a comparison of their numerical-to-gravimetric surrogate FFG ratios to predict the stream environmental condition. A sizing template for rapidly sorting macroinvertebrates in the field is described. Thresholds for surrogate FFG ratios that directly predict measured stream ecosystem conditions are described.
Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis
Authors: Shindo Satoru , Savitri Irma Josefina , Ishii Takenobu , Ikeda Atsushi , Pierrelus Roodelyne , Heidari Alireza , Okubo Keisuke , Nakamura Shin , Kandalam Umadevi , Rawas-Qalaji Mohamad , Leon Elizabeth , Pastore Maria Rita , Hardigan Patrick , Kawai Toshihisa
Published: March 2022

Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.
The Study of Protein–Cyclitol Interactions
Authors: Dyrda-Terniuk Tetiana , Sugajski Mateusz , Pryshchepa Oleksandra , Śliwiak Joanna , Buszewska-Forajta Magdalena , Pomastowski Paweł , Buszewski Bogusław
Published: March 2022

Investigation of interactions between the target protein molecule and ligand allows for an understanding of the nature of the molecular recognition, functions, and biological activity of protein–ligand complexation. In the present work, non-specific interactions between a model protein (Bovine Serum Albumin) and four cyclitols were investigated. D-sorbitol and adonitol represent the group of linear-structure cyclitols, while shikimic acid and D-(–)-quinic acid have cyclic-structure molecules. Various analytical methods, including chromatographic analysis (HPLC-MS/MS), electrophoretic analysis (SDS-PAGE), spectroscopic analysis (spectrofluorimetry, Fourier transform infrared spectroscopy, and Raman spectroscopy), and isothermal titration calorimetry (ITC), were applied for the description of protein–cyclitol interactions. Additionally, computational calculations were performed to predict the possible binding places. Kinetic studies allowed us to clarify interaction mechanisms that may take place during BSA and cyclitol interaction. The results allow us, among other things, to evaluate the impact of the cyclitol’s structure on the character of its interactions with the protein.
Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model
Authors: Graça Ana L. , Domingues Rui M. A. , Calejo Isabel , Gómez-Florit Manuel , Gomes Manuela E.
Published: March 2022

Tendon injuries represent over 30–50% of musculoskeletal disorders worldwide, yet the available therapies do not provide complete tendon repair/regeneration and full functionality restoring. Extracellular vesicles (EVs), membrane-enclosed nanoparticles, have emerged as the next breakthrough in tissue engineering and regenerative medicine to promote endogenous tissue regeneration. Here, we developed a 3D human in vitro model mimicking the signature of pathological tendon and used it to evaluate the influence that different platelet-derived EVs might have in tendon tissue repair mechanisms. For this, different EV populations isolated from platelets, small EVs (sEVs) and medium EVs (mEVs), were added to the culture media of human tendon-derived cells (hTDCs) cultured on isotropic nanofibrous scaffolds. The platelet-derived EVs increased the expression of tenogenic markers, promoted a healthy extracellular matrix (ECM) remodeling, and the synthesis of anti-inflammatory mediators. These findings suggest that platelet EVs provided relevant biochemical cues that potentiated a recovery of hTDCs phenotype from a diseased to a healthy state. Thus, this study opens new perspectives for the translation of platelet-derived EVs as therapeutics.
A Comparative Transcriptome and Metabolome Combined Analysis Reveals the Key Genes and Their Regulatory Model Responsible for Glucoraphasatin Accumulation in Radish Fleshy Taproots
Authors: Li Xiaoman , Wang Peng , Wang Jinglei , Wang Haiping , Liu Tongjin , Zhang Xiaohui , Song Jiangping , Yang Wenlong , Wu Chunhui , Yang Haohui , Liu Liwang , Li Xixiang
Published: March 2022

Radish (Raphanus sativus L.) is rich in specific glucosinolates (GSLs), which benefit human health and special flavor formation. Although the basic GSLs metabolic pathway in Brassicaceae plants is clear, the regulating mechanism for specific glucosinolates content in radish fleshy taproots is not well understood. In this study, we discovered that there was a significant difference in the GSLs profiles and the content of various GSLs components. Glucoraphasatin (GRH) is the most predominant GSL in radish taproots of different genotypes as assessed by HPLC analysis. Further, we compared the taproot transcriptomes of three radish genotypes with high and low GSLs content by employing RNA-seq. Totally, we identified forty-one differentially expressed genes related to GSLs metabolism. Among them, thirteen genes (RsBCAT4, RsIPMDH1, RsMAM1a, RsMAM1b, RsCYP79F1, RsGSTF9, RsGGP1, RsSUR1, RsUGT74C1, RsST5b, RsAPK1, RsGSL-OH, and RsMYB28) were significantly higher co-expressed in the high content genotypes than in low content genotype. Notably, correlation analysis indicated that the expression level of RsMYB28, as an R2R3 transcription factor directly regulating aliphatic glucosinolate biosynthesis, was positively correlated with the GRH content. Co-expression network showed that RsMYB28 probably positively regulated the expression of the above genes, particularly RsSUR1, and consequently the synthesis of GRH. Moreover, the molecular mechanism of the accumulation of this 4-carbon (4C) GSL in radish taproots was explored. This study provides new perspectives on the GSLs accumulation mechanism and genetic improvements in radish taproots.
Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review
Authors: Caserta Donatella , De Marco Maria Paola , Besharat Aris Raad , Costanzi Flavia
Published: March 2022

It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors and the endometrial cancer has been poorly developed. A systematic review was performed using PubMed®/MEDLINE. A total of 25 in vivo and in vitro works were selected. Numerous endocrine disruptors were analyzed. The most relevant results showed how Bisphenol A (BPA) interacts with the carcinogenesis process on several levels. It has been demonstrated how BPA can interact with hormonal receptors and with different transcription proliferative and antiproliferative factors. Furthermore, the effect of Polycyclic aromatic hydrocarbons on Aryl hydrocarbon receptors was investigated, and the role of flame retardants in promoting proliferation and metastasis was confirmed. The results obtained demonstrate how the mechanisms of action of endocrine disruptors are manifold in the pathophysiology of endometrial cancer, acting on different levels of the cancerogenesis process.
Nanoplastics and Arsenic Co-Exposures Exacerbate Oncogenic Biomarkers under an In Vitro Long-Term Exposure Scenario
Authors: Barguilla Irene , Domenech Josefa , Rubio Laura , Marcos Ricard , Hernández Alba
Published: March 2022

The increasing accumulation of plastic waste and the widespread presence of its derivatives, micro- and nanoplastics (MNPLs), call for an urgent evaluation of their potential health risks. In the environment, MNPLs coexist with other known hazardous contaminants and, thus, an interesting question arises as to whether MNPLs can act as carriers of such pollutants, modulating their uptake and their harmful effects. In this context, we have examined the interaction and joint effects of two relevant water contaminants: arsenic and polystyrene nanoplastics (PSNPLs), the latter being a model of nanoplastics. Since both agents are persistent pollutants, their potential effects have been evaluated under a chronic exposure scenario and measuring different effect biomarkers involved in the cell transformation process. Mouse embryonic fibroblasts deficient for oxidative DNA damage repair mechanisms, and showing a cell transformation status, were used as a sensitive cell model. Such cells were exposed to PSNPLs, arsenic, and a combination PSNPLs/arsenic for 12 weeks. Interestingly, a physical interaction between both pollutants was demonstrated by using TEM/EDX methodologies. Results also indicate that the continuous co-exposure enhances the DNA damage and the aggressive features of the initially transformed phenotype. Remarkably, co-exposed cells present a higher proportion of spindle-like cells within the population, an increased capacity to grow independently of anchorage, as well as enhanced migrating and invading potential when compared to cells exposed to arsenic or PSNPLs alone. This study highlights the need for further studies exploring the long-term effects of contaminants of emerging concern, such as MNPLs, and the importance of considering the behavior of mixtures as part of the hazard and human risk assessment approaches.
Synthetic Circular miR-21 Sponge as Tool for Lung Cancer Treatment
Authors: Rama Ana R. , Quiñonero Francisco , Mesas Cristina , Melguizo Consolación , Prados Jose
Published: March 2022

Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we chose miR-21, which is upregulated and implicated in lung cancer. We constructed a miR-21 sponge and inserted it into a vector that facilitates circular RNA production (Circ-21) to study its effect on growth, colony formation, and migration in lung cancer cell lines and multicellular tumor spheroids (MTS). Circ-21 induced a significant and time-dependent decrease in the growth of A549 and LL2 cells, but not in L132 cells. Furthermore, A549 and LL2 cells transfected with Circ-21 showed a lower number of colonies and migration than L132. Similar findings were seen in A549 and LL2 Circ-21 MTS, which showed a significant decrease in volume growth, but not in L132 Circ-21 MTS. Based on this, the miR-21 circular sponge may suppress the processes of tumorigenesis and progression. Therefore, our system based on circular sponges seems to be effective, as a tool for the capture of other miRNAs.
Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research
Authors: Gunasekara Sachithra , Tamil Selvan Miruthula , Miller Craig A. , Rudd Jennifer M.
Published: March 2022

The ongoing COVID-19 pandemic continues to affect the lives, wellbeing, and stability of communities worldwide. The race to save human lives is critical, and the development of useful translational animal models to elucidate disease pathogenesis and prevention, and to test therapeutic interventions, is essential to this response. However, significant limitations exist with the currently employed animal models that slow our ability to respond to the pandemic. Non-human primates serve as an excellent animal model for SARS-CoV-2 disease and interventions, but the availability of these animals is scarce, and few facilities are able to house and utilize this model. Adapted murine models are accessible and improving but lack natural hACE-2 receptors and are only moderate representatives of human COVID-19 disease, transmission, and immune responses. On the other hand, there are several animal species that are both naturally and experimentally infected, such as domestic cats, hamsters, ferrets, and mink. Several of these have proven animal-to-animal transmission and evidence of significant clinical and histopathologic disease that mimics acute COVID-19 in humans. Mobilizing these nontraditional animal models could have a crucial role in SARS-CoV-2 research efficiency and impact. This review focuses on what is known about these nontraditional animal models, including their immune responses to SARS-CoV-2 infection, evidence of clinical and histopathologic disease, transmission potential, and the practicality of each model in a research setting. Comparative insight into these animal models for COVID-19 can strengthen the efforts to mitigate this pandemic.
Homeostasis of Mitochondrial Ca2+ Stores Is Critical for Signal Amplification in Drosophila melanogaster Olfactory Sensory Neurons
Authors: Wiesel Eric , Kaltofen Sabine , Hansson Bill S. , Wicher Dieter
Published: March 2022

Insects detect volatile chemosignals with olfactory sensory neurons (OSNs) that express olfactory receptors. Among them, the most sensitive receptors are the odorant receptors (ORs), which form cation channels passing Ca2+. OSNs expressing different groups of ORs show varying optimal odor concentration ranges according to environmental needs. Certain types of OSNs, usually attuned to high odor concentrations, allow for the detection of even low signals through the process of sensitization. By increasing the sensitivity of OSNs upon repetitive subthreshold odor stimulation, Drosophila melanogaster can detect even faint and turbulent odor traces during flight. While the influx of extracellular Ca2+ has been previously shown to be a cue for sensitization, our study investigates the importance of intracellular Ca2+ management. Using an open antenna preparation that allows observation and pharmacological manipulation of OSNs, we performed Ca2+ imaging to determine the role of Ca2+ storage in mitochondria. By disturbing the mitochondrial resting potential and induction of the mitochondrial permeability transition pore (mPTP), we show that effective storage of Ca2+ in the mitochondria is vital for sensitization to occur, and release of Ca2+ from the mitochondria to the cytoplasm promptly abolishes sensitization. Our study shows the importance of cellular Ca2+ management for sensitization in an effort to better understand the underlying mechanics of OSN modulation.
Should Advanced Friedreich’s Ataxia Be a Contraindication for Heart Transplantation? A Case Report of a Successful Procedure in a 58-Year-Old Patient
Authors: Valero María Jesús , Muñoz-Blanco Jose L. , Sanchez Alejandro Garrido , Cuerpo Gregorio , Castrodeza Javier , Navas Paula , Sousa Iago , Villa Adolfo , Fernández-Avilés Francisco , Martínez-Sellés Manuel
Published: March 2022

The information on heart transplantation (HT) in patients with Friedreich’s Ataxia (FA) is scarce, and the few published case reports are limited to young patients with mild neurological manifestations. We present the case of a 58-year-old patient with advanced FA (Scale for the Assessment and Rating of Ataxia [SARA] score 30/40), wheelchair-bound for the last 16 years and had urinary incontinence, dysarthria, and neurosensorial deafness. The patient was admitted for a refractory arrhythmic storm and had previous hypertrophic cardiomyopathy that evolved to dilated cardiomyopathy with severely reduced left ventricular ejection fraction and recurrent ventricular arrhythmias. A multidisciplinary team discussed the HT option. The patient was aware of the risks and benefits and considered worthy of the intervention, so he was listed for HT. After a successful surgical intervention, the patient had a long postoperative stay in ICU. He required a high dose of vasopressors, underwent hemofiltration for one month, suffered critical illness myopathy, had several respiratory infections and delayed tracheal extubation. Two and a half months after HT and almost five months at the hospital, the patient was successfully discharged. FA patients with severe heart conditions should be carefully evaluated by a multidisciplinary team to decide the candidacy for HT.
Complications and Mortality after Surgeries in Patients with Prior Stroke Who Received General and Neuraxial Anesthesia: A Propensity-Score Matched Study
Authors: Kao Yi-Ting , Chang Chuen-Chau , Yeh Chun-Chieh , Hu Chaur-Jong , Cherng Yih-Giun , Chen Ta-Liang , Liao Chien-Chang
Published: March 2022

Patients who previously suffered a stroke have increased risks of mortality and complications after surgeries, but the optimal anesthesia method is not fully understood. We aimed to compare the outcomes after surgeries for stroke patients who received general anesthesia (GA) and neuraxial anesthesia (NA). Using health insurance research data, we identified 36,149 stroke patients who underwent surgeries from 1 January 2008 to 31 December 2013. For balancing baseline covariates, the propensity-score-matching procedure was used to select adequate surgical patients who received GA and NA at a case–control ratio of 1:1. Multiple logistic regressions were applied to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative mortality and complications between surgical patients with prior stroke who received GA and NA. Among the 4903 matched pairs with prior stroke, patients with GA had higher risks of pneumonia (OR 2.00, 95% CI 1.62–2.46), pulmonary embolism (OR 3.30, 95% CI 1.07–10.2), acute renal failure (OR 3.51, 95% CI 1.13–2.10), intensive care unit stay (OR 3.74, 95% CI 3.17–4.41), and in-hospital mortality (OR 2.02, 95% CI 1.16–3.51) than those who received NA. Postoperative adverse events were associated with GA in patients aged more than 60 years and those who received digestive surgery (OR 3.11, 95% CI 2.08–4.66). We found that stroke patients undergoing GA had increased postoperative complications and mortality after surgery compared with those who received NA. However, these findings need more validation and evaluation by clinical trials.
A Bayesian Network Meta-Analysis of First-Line Treatments for Non-Small Cell Lung Cancer with High Programmed Death Ligand-1 Expression
Authors: Kim Jung Han , Jeong Soo Young , Lee Jae-Jun , Park Sung Taek , Kim Hyeong Su
Published: March 2022

We performed a Bayesian network meta-analysis (NMA) to suggest frontline treatments for advanced non-small cell lung cancer (NSCLC) showing high programmed death ligand-1 (PD-L1) expression. A total of 5237 patients from 22 studies were included. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference in survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771–1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for advanced NSCLC with high PD-L1 expression. However, considering that there was no significant difference in survival outcomes among treatment regimens incorporating immunotherapy and that ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression.
The Edible Gray Oyster Fungi Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm a Potent Waste Consumer, a Biofriendly Species with Antioxidant Activity Depending on the Growth Substrate
Authors: Mihai Raluca A. , Melo Heras Erly J. , Florescu Larisa I. , Catana Rodica D.
Published: March 2022

Nowadays, climate change is not the only threat facing our planet. There are also other types of pollution such as waste that poisons soils and water and kills plants, harming humans and animals. Sustainability represents a key issue for the actual Global Citizen. For this reason, our article is dedicated to offering biofriendly solutions to decrease wastes, give them a positive meaning, such as a substrate for an edible oyster fungus with nutritive and biological properties usefully for humans. Three types of wastes such as coconut coir, pine sawdust, and paper waste—representative symbols of pollution in Ecuador—have been tested as suitable growing substrate for the edible fungi Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm by analyzing parameters such as Biological Efficiency, Mushroom Yield, and Productive Rate. The influence of these “waste” substrates on the nutritive (protein content), biological characteristic (antioxidant activity), and the content of human-health-sustaining compounds (phenols, flavonoids) were also evaluated using the Kjeldahal, DPPH, ABTS, FRAP, and Folin–Ciocalteu methods. The results indicate that all the waste products represent desirable substrates for growing the edible fungi, with more focus on coconut coir waste (one of the principal pollution problems in Ecuador), but that also achieved the increase in the fungi’s desirable characteristics. Coconut coir waste could be an environmentally friendly solution that also offers for humans additional nutritive and healthy benefits.