bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a New Combination of Natural Extracts on Glaucoma-Related Retinal Degeneration
Authors: Molinari Claudio , Ruga Sara , Farghali Mahitab , Galla Rebecca , Fernandez-Godino Rosario , Clemente Nausicaa , Uberti Francesca
Published: August 2021

Background: Glaucoma is currently the leading cause of irreversible blindness; it is a neuropathy characterized by structural alterations of the optic nerve, leading to visual impairments. The aim of this work is to develop a new oral formulation able to counteract the early changes connected to glaucomatous degeneration. The composition is based on gastrodin and vitamin D3 combined with vitamin C, blackcurrant, and lycopene. Methods: Cells and tissues of the retina were used to study biological mechanisms involved in glaucoma, to slow down the progression of the disease. Experiments mimicking the conditions of glaucoma were carried out to examine the etiology of retinal degeneration. Results: Our results show a significant ability to restore glaucoma-induced damage, by counteracting ROS production and promoting cell survival by inhibiting apoptosis. These effects were confirmed by the intracellular mechanism that was activated following administration of the compound, either before or after the glaucoma induction. In particular, the main results were obtained as a preventive action of glaucoma, showing a beneficial action on all selected markers, both on cells and on eyecup preparations. It is therefore possible to hypothesize both the preventive and therapeutic use of this formulation, in the presence of risk factors, and due to its ability to inhibit the apoptotic cycle and to stimulate cell survival mechanisms, respectively. Conclusion: This formulation has exhibited an active role in the prevention or restoration of glaucoma damage for the first time.
Red Beetroot’s NMR-Based Metabolomics: Phytochemical Profile Related to Development Time and Production Year
Authors: Giampaoli Ottavia , Sciubba Fabio , Conta Giorgia , Capuani Giorgio , Tomassini Alberta , Giorgi Giorgio , Brasili Elisa , Aureli Walter , Miccheli Alfredo
Published: August 2021

Red beetroot (RB) is a well-known health-promoting food consumed worldwide. RB is commonly used in food processing and manufacturing thanks to the high content of components that can also be employed as natural coloring agents. These bioactive molecules vary their concentration depending on beetroot seasonality, harvest time and climate conditions. The first objective of this study was to evaluate the variation of the RB phytochemical profile related to the root development during three different harvest times, using an 1H-NMR-based metabolomic approach. Changes of carbohydrates and secondary metabolite concentrations were observed from July to September. Secondly, we compared the metabolic profiles of the final processed beet juices in three different production years to observe the effect of climate conditions on the RB’s final product metabotype. A PCA analysis performed on juice extracts showed that production years 2016 and 2017 were characterized by a high content of choline and betaine, while 2018 by a high content of amino acids and dopamine and a low content of inorganic nitrates. This study suggests that the harvest time and roots growth conditions could be used to modulate the RB phytochemical profile, according to the final requirements of use, food or coloring agent source.
Effects of Pre-Treatment Using Plasma on the Antibacterial Activity of Mushroom Surfaces
Authors: Mitra Sarmistha , Veerana Mayura , Choi Eun-Ha , Park Gyungsoon
Published: August 2021

Although non-thermal atmospheric pressure plasma is an efficient tool for preventing post-harvest microbial contamination, many studies have focused on the post-treatment of infected or contaminated foods. In this study, we examined the antimicrobial quality of mushrooms pre-treated with a non-thermal atmospheric pressure plasma jet (NTAPPJ) or plasma-treated water (PTW). The CFU (Colony Forming Unit) number of Escherichia coli inoculated on surfaces of mushrooms pre-treated with NTAPPJ or PTW was significantly reduced (about 60–75% for NTAPPJ and about 35–85% for PTW), and the reduction rate was proportional to the treatment time. Bacterial attachment and viability of the attached bacteria were decreased on NTAPPJ-treated mushroom surfaces. This may be caused by the increased hydrophilicity and oxidizing capacity observed on NTAPPJ-treated mushroom surfaces. In PTW-treated mushrooms, bacterial attachment was not significantly changed, but death and lipid peroxidation of the attached bacteria were significantly increased. Analysis of mushroom quality showed that loss of water content was greater in mushrooms treated with NTAPPJ compared to that in those with no treatment (control) and PTW treatment during storage. Our results suggest that pre-treatment with NTAPPJ or PTW can improve the antibacterial quality of mushroom surfaces by decreasing bacterial attachment (for NTAPPJ) and increasing bacterial lipid peroxidation (for both NTAPPJ and PTW).
Development of a Duck Genomic Reference Material by Digital PCR Platforms for the Detection of Meat Adulteration
Authors: Chen Xiaoyun , Ji Yi , Li Kai , Wang Xiaofu , Peng Cheng , Xu Xiaoli , Pei Xinwu , Xu Junfeng , Li Liang
Published: August 2021

Low-cost meat, such as duck, is frequently used to adulterate more expensive foods like lamb or beef in many countries. However, the lack of DNA-based reference materials has limited the quality control and detection of adulterants. Here, we report the development and validation of duck genomic DNA certified reference materials (CRMs) through the detection of the duck interleukin 2 (IL2) gene by digital PCR (dPCR) for the identification of duck meat in food products. The certified value of IL2 in CRMs was 5.78 ± 0.51 × 103 copies/μL with extended uncertainty (coverage factor k = 2) based on IL2 quantification by eight independent collaborating laboratories. Quantification of the mitochondrial gene cytb revealed a concentration of 2.0 × 106 copies/μL, as an information value. The CRMs were also used to determine the limit of detection (LOD) for six commercial testing kits, which confirmed that these kits meet or exceed their claimed sensitivity and are reliable for duck detection.
Study of the Evolution of Pigments from Freshly Pressed to ‘On-the-Shelf’ Extra-Virgin Olive Oils by Means of Near-UV Visible Spectroscopy
Authors: Borello Eleonora , Roncucci Daniele , Domenici Valentina
Published: August 2021

Spectroscopic non-destructive methods have high potentialities as fast, cheap and easy-to-be-used approaches to address olive oil quality and authenticity. Based on previous research where near-UV Visible spectroscopy was used to investigate extra-virgin olive oils (EVOOs) and their main pigments’ content (i.e., β-carotene, lutein, pheophytin a and pheophytin b), we have implemented the spectral deconvolution method in order to follow the EVOO’s life, from ‘freshly pressed’ to ‘on-the-shelf’ EVOO samples at different storage time. In the first part of the manuscript, the new implemented deconvolution spectroscopic method aimed to quantify two additional pigments, namely chlorophyll a and chlorophyll b, is described and tested on ‘ad hoc’ samples with known concentrations of chlorophylls. The effect of light exposure and acidification was investigated to test the reliability and robustness of the spectral deconvolution. In the second part of the work, this approach was used to study the kinetic of pigments’ degradation in several monocultivar fresh EVOO samples under optimal storage’s conditions. The results here reported show that this spectroscopic deconvolution approach is a good method to study fresh EVOOs too; moreover, the proposed method revealed to be sensitive to detect eventual stresses of olive oil samples stored in not-good conditions.
Development of Antioxidant and Stable Conjugated Linoleic Acid Pickering Emulsion with Protein Nanofibers by Microwave-Assisted Self-Assembly
Authors: Jiao Qiyang , Liu Ziyuan , Li Baoyun , Tian Bo , Zhang Ning , Liu Chunhong , Feng Zhibiao , Jiang Bin
Published: August 2021

Whey protein isolate nanofibrils (WPNFs) can be used as a novel stabilizer in the Pickering emulsion system to improve the water solubility, stability and bioavailability of lipophilic bioactive ingredients. In this study, conjugated linoleic acid (CLA) and WPNFs were used to prepare a stable Pickering emulsion. We used a transmission electron microscope, low-temperature scanning electron micrographs and other methods to evaluate the micromorphology, surface hydrophobicity and structural units of the obtained WPNFs. Compared with whey protein isolate/CLA Pickering emulsion, the WPNFs/CLA Pickering emulsion has greater ability to remove 2,2-Diphenyl-1-picrylhydrazyl and 2,2′-amino-di(2-ethyl-benzothiazoline sulphonic acid-6) ammonium salt free radicals. Furthermore, the WPNFs/CLA Pickering emulsion has a more stable effect in terms of droplet size and zeta potential over a wider range of ionic strength and temperature conditions. These findings indicate that Pickering emulsion stabilized by WPNFs is more suitable as a carrier of CLA, as it increases the solubility of CLA and has better active applications in biology and food.
LC-ESI/LTQOrbitrap/MS Metabolomic Analysis of Fennel Waste (Foeniculum vulgare Mill.) as a Byproduct Rich in Bioactive Compounds
Authors: Crescenzi Maria Assunta , D'Urso Gilda , Piacente Sonia , Montoro Paola
Published: August 2021

Food industries produce a high amount of waste every year. These wastes represent a source of bioactive compounds to be used to produce cosmetic and nutraceutical products. In this study, the possibility to retrain food waste as a potential source of bioactive metabolites is evaluated. In particular, metabolite profiles of different parts (bulb, leaves, stems and little stems) of fennel waste were investigated by liquid chromatography coupled with mass spectrometry (LC-ESI/LTQ Orbitrap MS). To discriminate the different plant parts, a Multivariate Data Analysis approach was developed. Metabolomic analysis allowed the identification of different metabolites mainly belonging to hydroxycinnamic acid derivatives, flavonoid glycosides, flavonoid aglycons, phenolic acids, iridoid derivatives and lignans. The identification of compounds was based on retention times, accurate mass measurements, MS/MS data, exploration on specific metabolites database and comparison with data reported in the literature for F. vulgare. Moreover, the presence of different oxylipins was relieved; these metabolites for the first time were identified in fennel. Most of the metabolites identified in F. vulgare possess anti-inflammatory, antioxidant and/or immunomodulatory properties. Considering that polyphenols are described to possess antioxidant activity, spectrophotometric tests were performed to evaluate the antioxidant activity of each part of the fennel.
Particularities of Forest Dynamics Using Higuchi Dimension. Parâng Mountains as a Case Study
Authors: Simion Adrian Gabriel , Andronache Ion , Ahammer Helmut , Marin Marian , Loghin Vlad , Nedelcu Iulia Daniela , Popa Cristian Mihnea , Peptenatu Daniel , Jelinek Herbert Franz
Published: August 2021

The legal or illegal losses and the natural disturbance regime of forest areas in Romania generate major imbalances in territorial systems. The main purpose of the current research was to examine the dynamics of the complexity of forests under the influence of forest loss but also to compare the applicability of Higuchi dimension. In this study, two fractal algorithms, Higuchi 1D (H1D) and Higuchi 2D (H2D), were used to determine qualitative and quantitative aspects based on images obtained from a Geographic Information System (GIS) database. The H1D analysis showed that the impact of forest loss has led to increased fragmentation of the forests, generating a continuous increase in the complexity of forest areas. The H2D analysis identified the complexity of forest morphology by the relationship between each pixel and the neighboring pixels from analyzed images, which allowed us to highlight the local characteristics of the forest loss. The H1D and H2D methods showed that they have the speed and simplicity required for forest loss analysis. Using this methodology complementary to GIS analyses, a relevant status of how forest loss occurred and their impact on tree-cover dynamics was obtained.
Alumina-Doped Silica Aerogels for High-Temperature Thermal Insulation
Authors: Wu Yu , Wang Xiaodong , Liu Lin , Zhang Ze , Shen Jun
Published: August 2021

In this study, we used two methods to prepare alumina-doped silica aerogels with the aim of increasing the thermal stability of silica aerogels. The first method was physical doping of α-Al2O3 nano powders, and the second method was to create a chemical compound via the co-precursor of TEOS and AlCl3·6H2O in different proportions. The shrinkage, chemical composition, and specific surface area (SSA) of samples after heating at different temperatures were analyzed. Our results show that the silicon hydroxyl groups of samples derived from AlCl3·6H2O gradually decreased and nearly disappeared after heating at 800 °C, which indicates the complete dehydration of the silicon hydroxyl. Thus, the samples exhibited a large linear shrinkage and decreased SSA after high-temperature heat treatment. By contrast, samples doped with α-Al2O3 powders retained abundant silicon hydroxyl groups, and the 6.1 wt.% α-Al2O3-doped sample exhibited the lowest linear shrinkage of 11% and the highest SSA of 1056 m2/g after heat treatment at 800 °C. The alumina-doped silica aerogels prepared using a simple and low-price synthesized method pave the way for the low-cost and large-scale production of high-temperature thermal insulation.
A Novel Epigenetic Regulator ZRF1: Insight into Its Functions in Plants
Authors: Feng Jing , Gao Yahui , Wang Kun , Jiang Mingguo
Published: August 2021

Recently, Zuotin-related factor 1 (ZRF1), an epigenetic regulator, was found to be involved in transcriptional regulation. In animals and humans, ZRF1 specifically binds to monoubiquitinated histone H2A through a ubiquitin-binding domain and derepresses Polycomb target genes at the beginning of cellular differentiation. In addition, ZRF1 can work as a tumor suppressor. According to bioinformatics analysis, ZRF1 homologs are widely found in plants. However, the current studies on ZRF1 in higher plants are limited and few in-depth studies of its functions have been reported. In this review, we aim to summarize the key role of AtZRF1a/b in Arabidopsis thaliana growth and development, as well as the research progress in this field in recent years.
Patterns of Cone-Beam Computed Tomography (CBCT) Utilization by Various Dental Specialties: A 4-Year Retrospective Analysis from a Dental and Maxillofacial Specialty Center
Authors: Friedlander-Barenboim Silvina , Hamed Wafi , Zini Avraham , Yarom Noam , Abramovitz Itzhak , Chweidan Harry , Finkelstein Tamar , Almoznino Galit
Published: August 2021

The study aimed to analyze the uses of cone-beam computed tomography (CBCT) in the diagnosis and treatment in various dental specialties. This 4-year cross-sectional study analyzed the records of 1409 individuals who underwent a CBCT at the Oral and Maxillofacial Center at Sheba Medical Center, Israel. The average age of the patients was 27.9 ± 11.5 (range: 9–86 years). Patients were referred for CBCT by the following departments: Oral and Maxillofacial Surgery (1063; 75.5%), Endodontics (182; 12.9%), Periodontology (122; 8.6%) and Orthodontics (42; 3.0%). Most CBCT radiographs evaluated the maxilla (774; 55.0%), followed by the mandible (481; 34.1%) and both (154; 10.9%). The target anatomical structures included: bone (694; 49.3%), teeth (307; 21.7%), and both jaws (408; 29.0%). The main indications for CBCT use were: assessment of anatomical structures and implant sites (787; 55.9%), determine root canals morphology (182; 12.9%), visualization of impacted teeth, tooth alignment, and localization (177; 12.6%), suspected cysts or tumors (148; 10.5%), evaluation of Temporomandibular joint disorders (106; 7.5%) and other reasons (9; 0.6%). In 279 (19.8%) of cases, the diagnosis changed following CBCT, mainly in Orthodontics tooth analysis (28 (66.7%); p < 0.001). Practitioners and health authorities should be aware of this baseline information regarding CBCT use in the diagnosis and assessment of various oral and maxillofacial pathologies, anomalies and tooth position relative to anatomic structures. Continuing research and publications of CBCT utilization and guidelines are recommended.
Effects of Exercise Programs on Anxiety in Individuals with Disabilities: A Systematic Review with a Meta-Analysis
Authors: Jacinto Miguel , Frontini Roberta , Matos Rui , Antunes Raul
Published: August 2021

Anxiety symptoms are increasingly prevalent in individuals and may affect their quality of life. Physical exercise (PE) has been shown to be an effective method for reducing anxiety symptoms in the general population. The present study aimed to identify if PE programs can be a good method to reduce anxiety symptoms in individuals with disabilities, through the methodology of a systematic review with a meta-analysis. The PubMed, Web of Science, Scopus, and SPORTDiscus databases were used, considering the period from 2001 to 2021. The descriptors used were: “cerebral palsy”, “motor disability”, “physical disability”, “vision impairment”, “visual impairment”, “vision disability”, “intellectual disability”, “mental retardation”, “intellectual disabilities”, “hearing impairment”, “hearing disability”, “multiple disabilities”, “physical activity”, “exercise”, “sport”, “training”, and “anxiety”, with the Boolean operator “AND” or “OR”. The systematic review with a meta-analysis was carried out in the period between May and June 2021. The Z values (Z-values) obtained to test the null hypothesis, according to which the difference between means is zero, demonstrated a Z = 2.957, and a corresponding p-value of 0.003. Thus, we can reject the null hypothesis, and affirm that PE promotes positive effects and can be a good method or methodology for the reduction of anxiety symptoms of individuals with disabilities.
Morphological Characterization of Tetraploids of Limonium sinuatum (L.) Mill. Produced by Oryzalin Treatment of Seeds
Authors: Mori Shiro , Yahata Masaki , Kuwahara Ayano , Shirono Yurina , Ueno Yasufumi , Hatanaka Misaki , Honda Yoshimi , Sugiyama Keita , Murata Naho , Okamoto Yoshihiro , Wagatsuma Takahiro
Published: August 2021

Limonium sinuatum (L.) Mill. (2n = 2x = 16) is a popular ornamental plant with dimorphism of pollen grains (type A and type B) and stigmas (papilla and cob-like). We applied polyploidy breeding to this species in order to introduce desirable traits. Tetraploid and mixoploid L. sinuatum plants were successfully obtained with oryzalin treatment of L. sinuatum ‘Early Blue’ seeds. All three tetraploids had increased leaf width, stomatal size, flower length, and pollen width compared to those of the diploid, and tetraploids had four germinal pores of pollen grains, whereas the diploid had three. All tetraploids had type A pollen grains and cob-like stigmas. Furthermore, the growth of cultivated tetraploid plants was slow, with later bolting and flowering times. Mixoploids Mixo-1 and Mixo-3 were estimated to be polyploidy periclinal chimeric plants consisting of a tetraploid L1 layer and diploid L2 layer, and Mixo-2 was estimated to be a polyploidy periclinal chimeric plant consisting of the diploid L1 layer and tetraploid L2 layer. Mixo-4 had tetraploid L1 and L2 layers. Mixoploids, except Mixo-4, had type A pollen grains and cob-like stigmas, whereas Mixo-4 had type B pollen grains and papilla stigmas. These polyploids will be useful as polyploidy breeding materials.
Does COVID-19 Promote Self-Service Usage among Modern Shoppers? An Exploration of Pandemic-Driven Behavioural Changes in Self-Collection Users
Authors: Wang Xueqin , Wong Yiik Diew , Yuen Kum Fai
Published: August 2021

Due to health concerns related to COVID-19, shoppers have learned to minimise social contact by adopting various contactless self-service technologies to fulfil their consumption needs. This study explores shoppers’ behavioural changes in relation to self-service, using the special research context of e-commerce self-collection services. By synthesising insights from the health psychology literature, this study proposes an affective-cognitive-social perspective to explain the pandemic-driven behavioural changes of self-collection users. The survey instrument is used for online data collection (n = 500), and a combined (descriptive and quantitative) method is adopted for data analysis. Our results suggest that, although with a relatively weak predictive power, the affective and cognitive appraisals of health risks lead to the reinforced usage of self-collection service. This also applies to the factors of action/coping planning and subjective norm. This study theoretically contributes to the self-service literature and creates managerial implications for retailers and logistics operators.
Factors Affecting Rapid Cognitive Decline in Patients with Alzheimer’s Disease: A Longitudinal Follow-Up Study
Authors: Pan Chih-Chuan , Chu Che-Sheng , Chen Chien-Liang , Chuang Yao-Chung , Chen Nai-Ching
Published: August 2021

We investigated the preventive and risk factors of rapid cognitive decline in patients with Alzheimer’s disease (AD). Using the Chang Gung Research Database (CGRD), we enrolled patients with AD aged over 65 years between 1 January 2001 and 30 May 2019, and followed up for at least two years. Rapid cognitive decline was defined by a Mini-Mental State Examination (MMSE) score decline of ≥4 in 2 years. A longer prescription of acetylcholinesterase inhibitors (AChEIs) was defined as 22 months based on the median treatment duration of the cohorts. The Cox proportional hazards regression model adjusted for age, sex, medication, and physical comorbidities was used to examine the candidate risk and protective factors. We analyzed data from 3846 patients with AD (1503 men, 2343 women) with a mean age and percentage of females of 77.8 ± 6.2 years and 60.9%, respectively. The mean duration of patients with AD receiving AChEIs was 658.7 ± 21.9 days. In general, 310 patients with AD showed a rapid cognitive decline, accounting for 8.1%. Treatment of a consecutive AChEI prescription for >22 months in patients with AD was a protective factor against rapid cognitive decline (adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.33–0.52, p < 0.001). Patients with AD aged >85 years (aHR = 0.53, 95% CI = 0.36–0.79, p < 0.01) and aged 75–85 years (aHR = 0.73, 95% CI = 0.57–0.93, p < 0.05) had a significantly lower risk of rapid cognitive decline than those aged 65–75 years. Additionally, patients with mild and moderate AD (clinical dementia rating (CDR = 1, aHR = 1.61, 95% CI = 1.26–2.07, p < 0.001; CDR = 2, aHR = 2.64, 95% CI = 1.90–3.65, p < 0.001) were more likely to have rapid cognitive decline than those with early AD (CDR = 0.5). Sex, medication with different types of AChEIs, and physical comorbidities were not associated with rapid cognitive decline. These findings indicate that it is important to maintain longer consecutive AChEI prescriptions in patients with AD to prevent cognitive decline.
Diverging from News Media: An Exploratory Study on the Changing Dynamics between Media and Public Attention on Cancer in China from 2011–2020
Authors: Huang Yangkun , Xu Xiaoping , Su Sini
Published: August 2021

Over the past decade, China has witnessed fast-paced technological advancements in the media industry, as well as major shifts in the health agenda portrayed in the media. Therefore, a key starting point when discussing health communication lies in whether media attention and public attention towards health issues are structurally aligned, and to what extent the news media guides public attention. Based on data mined from 73,060 sets of the Baidu Search Index and Media Index on 20 terms covering different types of cancer from 2011 to 2020, the Granger test demonstrates that, in the last decade, public attention and media attention towards cancer in China has gone through two distinct phases. During the first phase, 2011–2015, Chinese news media still held the key in transferring the salience of issues on most cancer types to the public. In the second phase, from 2016–2020, public attention towards cancer has gradually diverged from media coverage, mirroring the imbalance and mismatch between the demand of active public and the supply of cancer information from news media. This study provides an overview of the dynamic transition on cancer issues in China over a ten-year span, along with descriptive results on public and media attention towards specific cancer types.
“Hang in There!”: Mental Health in a Sample of the Italian Civil Protection Volunteers during the COVID-19 Health Emergency
Authors: Roncone Rita , Giusti Laura , Mammarella Silvia , Salza Anna , Bianchini Valeria , Lombardi Annalina , Prosperococco Massimo , Ursini Elio , Scaletta Valentina , Casacchia Massimo
Published: August 2021

Few studies have been conducted on civil volunteers and their emotional conditions concerning the current COVID-19 pandemic. The present study aimed to evaluate the impact of the COVID-19 emergency on the mental health (general well-being, depression level, and post-traumatic distress), coping strategies, and training needs in an Italian sample of 331 Civil Protection volunteers of the L’Aquila province, during the first nationwide “lockdown” (8 March–3 June 2020). The rate of respondents to the online survey was limited (11.5%), presumably because displaying distress would be considered a sign of “weakness”, making volunteers unable to do their jobs. More than 90% of the volunteers showed good mental health conditions and a wide utilization of positive coping strategies, with the less experienced displaying better emotional conditions compared to colleagues with 10 or more years of experience. The type of emergency, the relatively few cases of contagion and mortality in the territory compared to the rest of Italy, and the sense of helping the community, together with the awareness of their group identity, could have contributed to the reported well-being. These results may help to identify the needs of volunteers related to this new “urban” emergency to improve both their technical and emotional skills.
Toxicological Comparison of Mancozeb and Zoxamide Fungicides at Environmentally Relevant Concentrations by an In Vitro Approach
Authors: Lori Gabriele , Tassinari Roberta , Narciso Laura , Udroiu Ion , Sgura Antonella , Maranghi Francesca , Tait Sabrina
Published: August 2021

Mancozeb (MZ) and zoxamide (ZOX) are fungicides commonly used in pest control programs to protect vineyards. Their toxic and genotoxic potential were investigated in vitro on HepG2 and A549 cell lines at environmentally relevant concentrations. Cytotoxicity, apoptosis, necrosis and intracellular reactive oxygen species (ROS), comet assay and a micronucleus test with CREST immunofluorescence were used. The expression of a panel of genes involved in apoptosis/necrosis (BAX/BCL2), oxidative stress (NRF2), drug metabolism (CYP1A1) and DNA repair (ERCC1/OGG1) was evaluated by real-time PCR. Both fungicides were cytotoxic at the highest tested concentrations (295.7 and 463.4 µM, respectively); MZ induced necrosis, ZOX did not increase apoptosis but modulated BAX and BCL2 expression, suggesting a different mechanism. Both compounds did not increase ROS, but the induction of CYP1A1 and NRF2 expression supported a pro-oxidant mechanism. The comet assay evidenced MZ genotoxicity, whereas no DNA damage due to ZOX treatment was observed. Positive micronuclei were increased in both cell lines treated with MZ and ZOX, supporting their aneugenic potential. ERCC1 and OGG1 were differently modulated, indicating the efficient activation of the nucleotide excision repair system by both fungicides and the inhibition of the base excision repair system by MZ. Overall, MZ confirmed its toxicity and new ZOX-relevant effects were highlighted.
Neighborhood Exposures and Blood Pressure Outcomes: A Cross-Sectional Environmental Study among 19–53 Years-Old Parsis in Mumbai
Authors: Sehgal Hitakshi , Toscano William A.
Published: August 2021

The correlation between high blood pressure (BP) and urban neighborhood-level environmental determinants is understudied in low-income and middle-income countries (LMICs). We hypothesized that neighborhoods constitute exposures that affect resident-behaviors, metabolism and increased susceptibility to high BP. We studied urban clusters of Mumbai-Parsis (Zoroastrians), a founder population group, to minimize genetic variation and maximize exposure assessment. Participants from four neighborhoods were 19–53 years old and comprised 756 females and 774 males. We recorded healthy BPs (≤120/80 mmHg) in 59%, pre-hypertensive (≥121–139/81–89 mmHg) in 21% and high BP (≥140/90 mmHg) in 21% of the participants. A family history of hypertension had no correlation with high BP. We used the Neighborhood Accessibility Framework to compile a questionnaire in order to collect data on participants’ perception of space, third places, streetscape and experience, land use, connectivity, surveillance, pedestrian safety and public transport. Our results suggested that participants in neighborhoods with poorer BP outcomes reported lower accessibility scores for space, streetscape and experience, third places and connectivity. Our study evaluates how neighborhood-level determinants affect BP outcomes in order to contribute to the body of knowledge on primary preventive measures for high BP in urban LMIC populations. We concluded that neighborhood exposures affect resident-behaviors, which cause metabolic changes and increase susceptibility to high BP.
Use of Geographic Information Systems to Explore Associations between Neighborhood Attributes and Mental Health Outcomes in Adults: A Systematic Review
Authors: Park Young-Shin , McMorris Barbara J. , Pruinelli Lisiane , Song Ying , Kaas Merrie J. , Wyman Jean F.
Published: August 2021

Background: Neighborhood attributes are increasingly recognized as factors shaping mental health in adults. Geographic information systems (GIS) offer an innovative approach for quantifying neighborhood attributes and studying their influence on mental health outcomes. Our aim was to describe GIS applications used in neighborhood-related mental health research and how neighborhood attributes are related to depressive symptoms or psychological distress in community-residing adults. Methods: We conducted a systematic review of studies published in English that included GIS techniques and a validated questionnaire of depressive symptoms or psychological distress. Medline, PsycInfo, Embase, Scopus, CINAHL, GEOBASE, and Compedex were searched to June 2020. Study quality was assessed by a modification of the Joanna Briggs Institute’s Checklist for Analytical Cross-sectional Studies. Results: Thirty-two studies met the inclusion criteria. Studies varied in definitions of neighborhood and GIS-derived measurements of neighborhood attributes. Neighborhood attributes were significantly associated with mental health outcomes, although findings were not consistent. Moderating factors (e.g., gender, living conditions) significantly influenced depressive symptoms or psychological distress. Conclusion: Neighborhood attributes are important factors influencing mental health in adults. Consensus may be needed on how to standardize the neighborhood unit or GIS-derived measures of neighborhoods in order to explain depression or psychological distress in diverse adult populations.
A Realist Evaluation of Team Interventions in Acute Hospital Contexts—Use of Two Case Studies to Test Initial Programme Theories
Authors: Cunningham Una , De Brún Aoife , Willgerodt Mayumi , Abu-Rish Blakeney Erin , McAuliffe Eilish
Published: August 2021

Background: Designing and implementing team interventions to improve quality and safety of care in acute hospital contexts is challenging. There is little emphasis in the literature on how contextual conditions impact interventions or how specific active ingredients of interventions impact on team members’ reasoning and enact change. This realist evaluation helps to deepen the understanding of the enablers and barriers for effective team interventions in these contexts. Methods: Five previously developed initial programme theories were tested using case studies from two diverse hospital contexts. Data were collected from theory driven interviews (n = 19) in an Irish context and from previously conducted evaluative interviews (n = 16) in a US context. Data were explored to unpack the underlying social and psychological drivers that drove both intended and unintended outcomes. Patterns of regularity were identified and synthesised to develop middle-range theories (MRTs). Results: Eleven MRTs demonstrate how and why intervention resources introduced in specific contextual conditions enact reasoning mechanisms and generate intended and unintended outcomes for patients, team members, the team and organisational leaders. The triggered mechanisms relate to shared mental models; openness, inclusivity and connectedness; leadership and engagement; social identity and intrinsic motivational factors. Conclusions: The findings provide valuable information for architects and facilitators of team interventions in acute hospital contexts, as well as help identify avenues for future research. Dataset: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to their sensitive nature and potential identification of participants.
The Mediated Role of Credibility on Information Sources and Patient Awareness toward Patient Rights
Authors: Roth-Cohen Osnat , Levy Shalom , Zigdon Avi
Published: August 2021

Although patient rights are an important issue, this remains an understudied research area. Patients are unaware of their rights, lacking control of health care treatments they might deserve. This can contribute to sustaining inequality as well as failure in achieving welfare policy goals. Drawing on channel complementarity theory, the current study explored patients’ awareness toward their rights, and the credibility of information sources related to patient rights. In a web-based survey, 994 Israeli participants, suffering from chronic illness and using health services, were recruited. To examine the study’s theoretical framework and relationships among the constructs and test the hypotheses, a path analysis was conducted using Structural Equation Modeling. The research model depicts direct and indirect relationships between constructs, and the relevant coefficients. The results show a direct and positive interaction between information credibility and patient rights awareness (β = 0.10, p = 0.019). Information credibility partially mediates the relationship between public service information sources and patient rights awareness (bootstrap with 95% CI: 0.01–0.07; p = 0.015). The mass media information sources construct is directly and positively related to information credibility (β = 0.36, p = 0.000). Age was found as a moderator, indicating that information credibility is a factor only at lower ages. Therefore, patient rights should be systematically and reliably accessible in order to raise the awareness and trust of chronic patients regarding information about patient rights. Using planned health communication campaigns mainly via public service sources that are perceived as trustworthy can help contribute to approach patients more effectively and provide them with accessible and detailed information about their rights.
Spatial Distribution Assessment of Terrorist Attack Types Based on I-MLKNN Model
Authors: Zhao Ruifang , Xie Xiaolan , Zhang Xun , Jin Min , Hao Mengmeng
Published: August 2021

Terrorist attacks are harmful to lives and property and seriously affect the stability of the international community and economic development. Exploring the regularity of terrorist attacks and building a model for assessing the risk of terrorist attacks (a kind of public safety risk, and it means the possibility of a terrorist attack) are of great significance to the security and stability of the international community and to global anti-terrorism. We propose a fusion of Inverse Distance Weighting (IDW) and a Multi-label k-Nearest Neighbor (I-MLKNN)-based assessment model for terrorist attacks, which is in a grid-scale and considers 17 factors of socio-economic and natural environments, and applied the I-MLKNN assessment model to assess the risk of terrorist attacks in Southeast Asia. The results show the I-MLKNN multi-label classification algorithm is proven to be an ideal tool for the assessment of the spatial distribution of terrorist attacks, and it can assess the risk of different types of terrorist attacks, thus revealing the law of distribution of different types of terrorist attacks. The terrorist attack risk assessment results indicate that Armed Attacks, Bombing/Explosions and Facility/Infrastructure Attacks in Southeast Asia are high-risk terrorist attack events, and the southernmost part of Thailand and the Philippines are high-risk terrorist attack areas for terrorism. We do not only provide a reference for incorporating spatial features in multi-label classification algorithms, but also provide a theoretical basis for decision-makers involved in terrorist attacks, which is meaningful to the implementation of the international counter-terrorism strategy.
Human Milk Metabolic Hormones: Analytical Methods and Current Understanding
Authors: Suwaydi Majed A. , Gridneva Zoya , Perrella Sharon L. , Wlodek Mary E. , Lai Ching Tat , Geddes Donna T.
Published: August 2021

Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. However, HM hormone studies are sparse and heterogeneous in regard to the study design, sample collection, preparation and analysis methods. This review discussed the limitations of HM hormone analysis highlighting the gaps in pre-analytical and analytical stages. The methods used to quantify HM metabolic hormones (leptin, adiponectin, ghrelin, insulin, obestatin, resistin and apelin) can be classified as immunoassay, immunosensor and chromatography. Immunoassay methods (ELISA and RIA) have been predominantly used in the measurement of these HM hormones. The relative validity parameters of HM hormones analysis are often overlooked in publications, despite the complexity and differences of HM matrix when compared to that of plasma and urine. Therefore, appropriate reports of validation parameters of methodology and instrumentation are crucial for accurate measurements and therefore better understanding of the HM metabolic hormones and their influences on infant outcomes.
Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression
Authors: Hirano Shin-ichi , Yamamoto Haru , Ichikawa Yusuke , Sato Bunpei , Takefuji Yoshiyasu , Satoh Fumitake
Published: August 2021

While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.
Regulation of Proteolytic Activity to Improve the Recovery of Macrobrachium rosenbergii Nodavirus Capsid Protein
Authors: Selvaraj Bethilda Anne , Mariatulqabtiah Abdul Razak , Ho Kok Lian , Ng Chyan Leong , Yong Chean Yeah , Tan Wen Siang
Published: August 2021

The causative agent of white tail disease (WTD) in the giant freshwater prawn is Macrobrachium rosenbergii nodavirus (MrNV). The recombinant capsid protein (CP) of MrNV was previously expressed in Escherichia coli, and it self-assembled into icosahedral virus-like particles (VLPs) with a diameter of approximately 30 nm. Extensive studies on the MrNV CP VLPs have attracted widespread attention in their potential applications as biological nano-containers for targeted drug delivery and antigen display scaffolds for vaccine developments. Despite their advantageous features, the recombinant MrNV CP VLPs produced in E. coli are seriously affected by protease degradations, which significantly affect the yield and stability of the VLPs. Therefore, the aim of this study is to enhance the stability of MrNV CP by modulating the protease degradation activity. Edman degradation amino acid sequencing revealed that the proteolytic cleavage occurred at arginine 26 of the MrNV CP. The potential proteases responsible for the degradation were predicted in silico using the Peptidecutter, Expasy. To circumvent proteolysis, specific protease inhibitors (PMSF, AEBSF and E-64) were tested to reduce the degradation rates. Modulation of proteolytic activity demonstrated that a cysteine protease was responsible for the MrNV CP degradation. The addition of E-64, a cysteine protease inhibitor, remarkably improved the yield of MrNV CP by 2.3-fold compared to the control. This innovative approach generates an economical method to improve the scalability of MrNV CP VLPs using individual protease inhibitors, enabling the protein to retain their structural integrity and stability for prominent downstream applications including drug delivery and vaccine development.
Conditional Deletion of AP-2β in the Periocular Mesenchyme of Mice Alters Corneal Epithelial Cell Fate and Stratification
Authors: Walker Haydn , Taiyab Aftab , Deschamps Paula , Williams Trevor , West-Mays Judith A.
Published: August 2021

The cornea is an anterior eye structure specialized for vision. The corneal endothelium and stroma are derived from the periocular mesenchyme (POM), which originates from neural crest cells (NCCs), while the stratified corneal epithelium develops from the surface ectoderm. Activating protein-2β (AP-2β) is highly expressed in the POM and important for anterior segment development. Using a mouse model in which AP-2β is conditionally deleted in the NCCs (AP-2β NCC KO), we investigated resulting corneal epithelial abnormalities. Through PAS and IHC staining, we observed structural and phenotypic changes to the epithelium associated with AP-2β deletion. In addition to failure of the mutant epithelium to stratify, we also observed that Keratin-12, a marker of the differentiated epithelium, was absent, and Keratin-15, a limbal and conjunctival marker, was expanded across the central epithelium. Transcription factors PAX6 and P63 were not observed to be differentially expressed between WT and mutant. However, growth factor BMP4 was suppressed in the mutant epithelium. Given the non-NCC origin of the epithelium, we hypothesize that the abnormalities in the AP-2β NCC KO mouse result from changes to regulatory signaling from the POM-derived stroma. Our findings suggest that stromal pathways such as Wnt/β-Catenin signaling may regulate BMP4 expression, which influences cell fate and stratification.
Lectin-Mediated Bacterial Modulation by the Intestinal Nematode Ascaris suum
Authors: Midha Ankur , Goyette-Desjardins Guillaume , Goerdeler Felix , Moscovitz Oren , Seeberger Peter H. , Tedin Karsten , Bertzbach Luca D. , Lepenies Bernd , Hartmann Susanne
Published: August 2021

Ascariasis is a global health problem for humans and animals. Adult Ascaris nematodes are long-lived in the host intestine where they interact with host cells as well as members of the microbiota resulting in chronic infections. Nematode interactions with host cells and the microbial environment are prominently mediated by parasite-secreted proteins and peptides possessing immunomodulatory and antimicrobial activities. Previously, we discovered the C-type lectin protein AsCTL-42 in the secreted products of adult Ascaris worms. Here we tested recombinant AsCTL-42 for its ability to interact with bacterial and host cells. We found that AsCTL-42 lacks bactericidal activity but neutralized bacterial cells without killing them. Treatment of bacterial cells with AsCTL-42 reduced invasion of intestinal epithelial cells by Salmonella. Furthermore, AsCTL-42 interacted with host myeloid C-type lectin receptors. Thus, AsCTL-42 is a parasite protein involved in the triad relationship between Ascaris, host cells, and the microbiota.
Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells
Authors: Lin Martin Hsiu-Chu , Lai Ping-Shan , Chang Li-Ching , Huang Wei-Chao , Lee Ming-Hsueh , Chen Kuo-Tai , Chung Chiu-Yen , Yang Jen-Tsung
Published: August 2021

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured −34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.