bluuebunny/crossref_metadata_2025 huggingface dataset:
Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival
Authors: Dulskas Audrius , Patasius Ausvydas , Linkeviciute-Ulinskiene Donata , Zabuliene Lina , Smailyte Giedre
Published: August 2020

Background: We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer. Methods: Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment: sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018). Results: Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea. Analysis by cumulative dose of metformin showed significantly lower mortality risk in the highest cumulative dose category (HR 0.76, 95% CI 0.58–0.99). Conclusions: Our study showed that metformin might have a survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment.
Daily Exposure to Air Pollution Particulate Matter Is Associated with Atrial Fibrillation in High-Risk Patients
Authors: Gallo Elisa , Folino Franco , Buja Gianfranco , Zanotto Gabriele , Bottigliengo Daniele , Comoretto Rosanna , Marras Elena , Allocca Giuseppe , Vaccari Diego , Gasparini Gianni , Bertaglia Emanuele , Zoppo Franco , Calzolari Vittorio , Nangah Suh Rene , Ignatiuk Barbara , Lanera Corrado , Benassi Alessandro , Gregori Dario , Iliceto Sabino
Published: August 2020

Several epidemiological studies found an association between acute exposure to fine particulate matter of less than 2.5 μm and 10 μm in aerodynamic diameter (PM2.5 and PM10) and cardiovascular diseases, ventricular fibrillation incidence and mortality. The effects of pollution on atrial fibrillation (AF) beyond the first several hours of exposure remain controversial. A total of 145 patients with implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy defibrillators (ICD-CRT), or pacemakers were enrolled in this multicentric prospective study. Daily levels of PM2.5 and PM10 were collected from monitoring stations within 20 km of the patient’s residence. A Firth Logistic Regression model was used to evaluate the association between AF and daily exposure to PM2.5 and PM10. Exposure levels to PM2.5 and PM10 were moderate, being above the World Health Organization (WHO) PM2.5 and PM10 thresholds of 25 μg/m3 and 50 μg/m3, respectively, on 26% and 18% of the follow-up days. An association was found between daily levels of PM2.5 and PM10 and AF (95% confidence intervals (CIs) of 1.34–2.40 and 1.44–4.28, respectively) for an increase of 50 µg/m3 above the WHO threshold. Daily exposure to moderate PM2.5 and PM10 levels is associated with AF in patients who are not prone to AF.
The Financial Burden Associated with Medical Costs among Childhood Cancer Patients and Their Families Related to Their Socioeconomic Status: The Perspective of National Health Insurance Service
Authors: Chae Wonjeong , Kim Juyeong , Park Sohee , Park Eun-Cheol , Jang Sung-In
Published: August 2020

The number of cancer survivors is increasing as a consequence of improved therapeutic options. Many families are suffering from the resultant financial burden. Our study aims to determine the total medical cost for 5 years after the initial diagnosis of childhood cancers. A customized dataset from the Korean National Health Insurance Claims Database was requested for this study. A total of 7317 patients were selected to determine the total medical cost. The costs are presented as the 2% trimmed mean value to exclude extreme costs. The medical costs were further classified according to cancer type, treatment phase, and socioeconomic status. Multiple linear regression analyses were performed. The average total medical cost per patient is 36.8 million Korean Wons or 32,157 United States Dollars. Analysis of socioeconomic status revealed that the higher income group demonstrated higher medical expenditure when compared to other groups. Analysis of the treatment phase showed that costs associated with the early phase of treatment are the highest, especially in the first 3 months after initial diagnosis. To alleviate the financial burden and reduce the socioeconomic disparities associated with medical care and costs, a better understanding of the current experience of patients and their families is required.
In Their Own Words: A Qualitative Investigation of the Factors Influencing Maternal Postpartum Functioning in the United States
Authors: Albanese Ariana M. , Geller Pamela A. , Steinkamp Jackson M. , Barkin Jennifer L.
Published: August 2020

During the first twelve months postpartum, infants require intensive care and mothers are susceptible to physical and mental health concerns as they undergo a period of tremendous psychological and physiological adjustment. The mother’s level of postpartum functioning not only impacts her experience as a mother but also the infant and family unit. However, efforts to bolster functioning are lacking, and previous literature has identified a gap between what experts recommend and what mothers desire during the postpartum period. To address this, we conducted structured interviews with a diverse sample of 30 postpartum mothers to identify factors that mothers report are most influential to their postpartum functioning. In total, we identified 23 clinically actionable factors, all of which are backed by existing literature. In addition to an in-depth presentation of the qualitative findings, we also present a heat map to visualize the relevance of these factors to each of seven established domains of maternal functioning. Lastly, based on our findings, we offer a taxonomy of interventional strategies that could bolster maternal functioning during this critical period.
Nomophobia: Is the Fear of Being without a Smartphone Associated with Problematic Use?
Authors: Kaviani Fareed , Robards Brady , Young Kristie L. , Koppel Sjaan
Published: August 2020

Mobile phones are changing behaviour, relationships, communication and the dynamics of physical environments. As such, reliance on the device for everyday activities has increased. Consequently, “nomophobia”, defined as the fear of being without one’s mobile phone, has emerged as a new phobia. The current study aimed to determine if nomophobia can increase the likelihood of problematic dependent, prohibited and dangerous mobile phone use. The sample comprised 2838 participants (males n = 1337 females n = 1501) recruited from various online platforms. The instrument used to measure nomophobia was the Nomophobia Questionnaire (NMP-Q), while problematic mobile phone use was measured using the Problematic Mobile Phone Use Questionnaire (PMPUQ-R). The findings revealed a strong positive correlation between nomophobia and all three problematic use factors. In addition to nomophobia, regression models revealed younger age and more time spent on a mobile phone per day significantly increased problematic dependency, prohibited use and dangerous use. Males were more likely to engage in prohibited and dangerous use, while no significant gender differences were found in dependent use. These findings support the need for further research into the relationship between nomophobia and specific aspects of problematic mobile phone use, such as using a mobile phone while driving.
Exploring Perceptions of Internet-Delivered Cognitive Behaviour Therapy among Public Safety Personnel: Informing Dissemination Efforts
Authors: McCall Hugh C. , Sison Angelo P. , Burnett Jody L. , Beahm Janine D. , Hadjistavropoulos Heather D.
Published: August 2020

Background Public safety personnel (PSP) experience high rates of mental health disorders but have limited access to treatment. To improve treatment access, there is a growing interest in offering internet-delivered cognitive behaviour therapy (ICBT) to PSP. As attitudes towards ICBT can both impact and inform ICBT implementation efforts, this study examines perceptions of ICBT among PSP who viewed a poster (a commonly used method of advertising ICBT) or a poster supplemented with a story of a PSP who benefitted from ICBT. Methods Participants (N = 132) from various PSP sectors were randomly assigned to view a poster or a poster and a story. Participants then completed an online survey assessing their perceptions of ICBT using both qualitative and quantitative questions. We used a mixed-methods approach to analyze the data. Results No differences in perceptions of ICBT were identified between the conditions. Ratings of credibility, treatment expectancy, anticipated treatment adherence, and acceptability suggested that PSP had positive perceptions of ICBT. Most participants (93%) reported that they would access ICBT if they needed help with mental health concerns. Participants ranked therapist-guided ICBT as their second most preferred treatment, with psychologists ranked first. Female participants found ICBT more credible than male participants. More experienced PSP reported lower acceptability and anticipated adherence to ICBT. Conclusions The findings suggest that many PSP are likely to be receptive to ICBT even when a simple poster is used as a method of informing PSP of this treatment option. Further attention to improving the perceptions of ICBT among certain groups may be warranted.
Evaluation of Physical Activity and Lifestyle Interventions Focused on School Children with Obesity Using Accelerometry: A Systematic Review and Meta-Analysis
Authors: Jurado-Castro Jose Manuel , Gil-Campos Mercedes , Gonzalez-Gonzalez Hugo , Llorente-Cantarero Francisco Jesus
Published: August 2020

Despite the existence of global recommendations for physical activity and lifestyle to avoid childhood obesity, there are no specific recommendations for school-age children. The aim of this meta-analysis was to measure the effects of current interventions with a physical activity component on body mass index (BMI) Z-score and on the moderate and vigorous physical activity (MVPA) time, measured by accelerometry, and focused on children with obesity. Randomized controlled trial studies (RCTs) based on physical activity interventions focused on children with obesity (6 to 12 years old) from January 1991 to August 2018 were included. The post-intervention mean and standard deviation of the BMI Z-score and MVPA engaged time were extracted to calculate the results using random effects models. Of a total of 229 studies considered potentially eligible, only 10 RCTs met the inclusion criteria. There were improvements in the BMI Z-score for physical activity intervention groups, compared with non-intervention children in addition to a significant increase in time engaged in MVPA. In conclusion, interventions with a physical activity component in school-children with obesity seem to be effective at reducing BMI and producing an increase in time spent engaged in physical activity. Therefore, interventions based on physical activity should be considered one of the main strategies in treating childhood obesity.
Factors Related to Oral Healthcare Service Utilization among Korean Adults Aged 25–79 Years
Authors: Kim Han-Na , Han Sang-Jun , Jun Eun-Joo , Kim Jin-Bom
Published: August 2020

The factors related to oral healthcare service utilization (OHSU) among Korean adults aged 25–79 years were assessed using the Andersen model with the sixth Korean National Health and Nutrition Examination Survey data. The study included 12,937 participants aged 25–79 years who answered questions on the predisposing, enabling, and need factors related to OHSU at dental clinics within the past 1 year. Age, sex, and education level were selected as predisposing factors; household income, residence region, and national and private health insurance status as enabling factors; and self-perceived oral health, dental pain, chewing status, and discomfort while speaking as need factors. These factors were assessed using multivariable complex logistic regression models. OHSU at dental clinics within the past 1 year was lower among less-educated participants, those with low, middle–low, and middle–high household income levels, rural participants, those benefiting from the Medicaid system, and non-insured participants. OHSU was higher among older participants, those who rated their self-perceived oral health status as bad, those with experience of dental pain, and those who experienced discomfort while chewing and speaking. The need factors were the most influential. Thus, interventions to reduce inequalities in OHSU are required to promote oral health for all.
Impact of Parents’ Knowledge about the Development of Self-Esteem in Adolescents and Their Parenting Practice on the Self-Esteem and Suicidal Behavior of Urban High School Students in Nepal
Authors: Banstola Ratna Shila , Ogino Tetsuya , Inoue Sachiko
Published: August 2020

Background: Suicide is the third leading cause of death in adolescents worldwide, self-esteem is a strong protective factor, and parents may be able to provide interventions. This cross-sectional study aimed to determine how parents can help enhance their adolescent’s self-esteem and prevent suicidal behavior among adolescents in Nepal. Methods: Self-administered questionnaires were distributed to adolescents aged 13–19 years and their parents at eight high schools in three provinces in Nepal (n = 575 pairs). The data were analyzed using descriptive and inferential statistics (bivariate and multivariate regression analyses). Results: The mean self-esteem score of adolescents according to the Rosenberg Self-Esteem Scale was 16.59, and the prevalence of suicidal behavior was 11.3%. Parent’s knowledge about the development of self-esteem in adolescents was significantly positively related to parenting practice (communication, support, positive reinforcement, etc.) (B = 1.0, 95% confidence interval, CI 0.89–1.11) and authoritative parenting style (B = 0.2, 95% CI 0.15–0.25). Parental authoritativeness was positively associated with the self-esteem of their adolescents (B = 0.1, 95% CI 0.01–0.18), while adolescents with authoritarian parents were prone to suicidal risk behavior (adjusted odds ratio, AOR = 1.1, 95% CI 1.0–1.19). Conclusion: Counseling to parents based on our findings would be helpful to enhance the self-esteem and prevent suicidal risk behavior in their adolescent children.
CA9 Silencing Promotes Mitochondrial Biogenesis, Increases Putrescine Toxicity and Decreases Cell Motility to Suppress ccRCC Progression
Authors: Xu Jiatong , Zhu Songbiao , Xu Lina , Liu Xiaohui , Ding Wenxi , Wang Qingtao , Chen Yuling , Deng Haiteng
Published: August 2020

Carbonic anhydrase IX (CA9), a pH-regulating transmembrane protein, is highly expressed in solid tumors, and particularly in clear cell renal cell carcinoma (ccRCC). The catalytic mechanisms of CA9 are well defined, but its roles in mediating cell migration/invasion and survival in ccRCC remain to be determined. Here, we confirmed that the mRNA expression of CA9 in ccRCC was significantly higher than that in para-carcinoma tissues from analysis of the datasets in The Cancer Genome Atlas. CA9 knockdown upregulated oxidative phosphorylation-associated proteins and increased mitochondrial biogenesis, resulting in the reversal of the Warburg phenotype and the inhibition of cell growth. Our study revealed that CA9 knockdown upregulated mitochondrial arginase 2 (ARG2), leading to the accumulation of putrescine, which suppressed ccRCC proliferation. Surfaceomics analysis revealed that CA9 knockdown downregulated proteins associated with extracellular matrix (ECM)—receptor interaction and cell adhesion, resulting in decreased cell migration. CA9 silencing also downregulated amino acid transporters, leading to reduced cellular amino acids. Collectively, our data show that CA9 knockdown suppresses proliferation via metabolic reprogramming and reduced cell migration, reaffirming that CA9 is a potential therapeutic target for ccRCC treatment.
The Identification of Metabolites and Effects of Albendazole in Alfalfa (Medicago sativa)
Authors: Raisová Stuchlíková Lucie , Navrátilová Martina , Langhansová Lenka , Moťková Kateřina , Podlipná Radka , Szotáková Barbora , Skálová Lenka
Published: August 2020

Albendazole (ABZ), a widely used anthelmintic drug, enters the environment mainly via livestock excrements. To evaluate the environmental impact of ABZ, the knowledge of its uptake, effects and metabolism in all non-target organisms, including plants, is essential. The present study was designed to identify the metabolic pathway of ABZ and to test potential ABZ phytotoxicity in fodder plant alfalfa, with seeds and in vitro regenerants used for these purposes. Alfalfa was chosen, as it may meet manure from ABZ-treated animals in pastures and fields. Alfalfa is often used as a feed of livestock, which might already be infected with helminths. The obtained results showed that ABZ did not inhibit alfalfa seed germination and germ growth, but evoked stress and a toxic effect in alfalfa regenerants. Alfalfa regenerants were able to uptake ABZ and transform it into 21 metabolites. UHPLC-MS/MS analysis revealed three new ABZ metabolites that have not been described yet. The discovery of the parent compound ABZ together with the anthelmintically active and instable metabolites in alfalfa leaves shows that the contact of fodder plants with ABZ-containing manure might represent not only a danger for herbivorous invertebrates, but also may cause the development of ABZ resistance in helminths.
CpG Site-Specific Regulation of Metallothionein-1 Gene Expression
Authors: Ogushi Shoko , Yoshida Yuya , Nakanishi Tsuyoshi , Kimura Tomoki
Published: August 2020

Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter contains 5 MREs (a–e), and MTF1 has the highest affinity to MREd. Epigenetic changes like DNA methylation might affect transcription and, therefore, the cytoprotective function of MT genes. To reveal the CpG site(s) critical for Mt1 transcription, we analyzed the methylation status of CpG dinucleotides in the Mt1 gene promoter through bisulfite sequencing in P1798 mouse lymphosarcoma cells, with high or low MT expression. We found demethylated CpG sites near MREd and MREe, in cells with high expression. Next, we compared Mt1 gene-promoter-driven Lucia luciferase gene expression in unmethylated and methylated reporter vectors. To clarify the effect of complete and partial CpG methylation, we used M.SssI (CG→5mCG) and HhaI (GCGC→G5mCGC)-methylated reporter vectors. Point mutation analysis revealed that methylation of a CpG site near MREd and MREe strongly inhibited Mt1 gene expression. Our results suggest that the methylation status of this site is important for the regulation of Mt1 gene expression.
Genome-Wide Systematic Characterization of the NPF Family Genes and Their Transcriptional Responses to Multiple Nutrient Stresses in Allotetraploid Rapeseed
Authors: Zhang Hao , Li Shuang , Shi Mengyao , Wang Sheliang , Shi Lei , Xu Fangsen , Ding Guangda
Published: August 2020

NITRATE TRANSPORTER 1 (NRT1)/PEPTIDE TRANSPORTER (PTR) family (NPF) proteins can transport various substrates, and play crucial roles in governing plant nitrogen (N) uptake and distribution. However, little is known about the NPF genes in Brassica napus. Here, a comprehensive genome-wide systematic characterization of the NPF family led to the identification of 193 NPF genes in the whole genome of B. napus. The BnaNPF family exhibited high levels of genetic diversity among sub-families but this was conserved within each subfamily. Whole-genome duplication and segmental duplication played a major role in BnaNPF evolution. The expression analysis indicated that a broad range of expression patterns for individual gene occurred in response to multiple nutrient stresses, including N, phosphorus (P) and potassium (K) deficiencies, as well as ammonium toxicity. Furthermore, 10 core BnaNPF genes in response to N stress were identified. These genes contained 6–13 transmembrane domains, located in plasma membrane, that respond discrepantly to N deficiency in different tissues. Robust cis-regulatory elements were identified within the promoter regions of the core genes. Taken together, our results suggest that BnaNPFs are versatile transporters that might evolve new functions in B. napus. Our findings benefit future research on this gene family.
Reciprocal Dysregulation of MiR-146b and MiR-451 Contributes in Malignant Phenotype of Follicular Thyroid Tumor
Authors: Knyazeva Margarita , Korobkina Ekaterina , Karizky Alexey , Sorokin Maxim , Buzdin Anton , Vorobyev Sergey , Malek Anastasia
Published: August 2020

Over the last few years, incidental thyroid nodules are being diagnosed with increasing frequency with the use of highly sensitive imaging techniques. The ultrasound thyroid gland examination, followed by the fine-needle aspiration cytology is the standard diagnostic approach. However, in cases of the follicular nature of nodules, cytological diagnosis is not enough. Analysis of miRNAs in the biopsy presents a promising approach. Increasing our knowledge of miRNA’s role in follicular carcinogenesis, and development of the appropriate the miRNA analytical technologies are required to implement miRNA-based tests in clinical practice. We used material from follicular thyroid nodes (n.84), grouped in accordance with their invasive properties. The invasion-associated miRNAs expression alterations were assayed. Expression data were confirmed by highly sensitive two-tailed RT-qPCR. Reciprocally dysregulated miRNAs pair concentration ratios were explored as a diagnostic parameter using receiver operation curve (ROC) analysis. A new bioinformatics method (MiRImpact) was applied to evaluate the biological significance of the observed expression alterations. Coupled experimental and computational approaches identified reciprocal dysregulation of miR-146b and miR-451 as important attributes of follicular cell malignant transformation and follicular thyroid cancer progression. Thus, evaluation of combined dysregulation of miRNAs relevant to invasion and metastasis can help to distinguish truly malignant follicular thyroid cancer from indolent follicular adenoma.
4,4′-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor
Authors: Lee Jong-hoon , An Ha Kyeu , Sohn Mun-Gi , Kivela Paul , Oh Sangsuk
Published: August 2020

The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1β, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer’s disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4′-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen’s disease, also diagnosed as Alzheimer’s disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson’s disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.
Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem
Authors: Infante Barbara , Rossini Michele , Leo Serena , Troise Dario , Netti Giuseppe Stefano , Ranieri Elena , Gesualdo Loreto , Castellano Giuseppe , Stallone Giovanni
Published: August 2020

Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.
Diversity and Antimicrobial Activity of Endophytic Fungi Isolated from Chloranthus japonicus Sieb in Qinling Mountains, China
Authors: An Chao , Ma Saijian , Shi Xinwei , Xue Wenjiao , Liu Chen , Ding Hao
Published: August 2020

The plant Chloranthus japonicus Sieb is known for its anticancer properties and mainly distributed in China, Japan, and Korea. In this study, we firstly investigated the diversity and antimicrobial activity of the culturable endophytic fungi from C. japonicus. A total of 332 fungal colonies were successfully isolated from 555 tissue segments of the medicinal plant C. japonicus collected from Qinling Mountains, China. One hundred and thirty representative morphotype strains were identified according to ITS rDNA sequence analyses and were grouped into three phyla (Ascomycota, Basidiomycota, Mucoromycota), five classes (Dothideomycetes, Sordariomycetes, Eurotiomycetes, Agaricomycetes, Mucoromycetes), and at least 30 genera. Colletotrichum (RA, 60.54%) was the most abundant genus, followed by Aspergillus (RA, 11.75%) and Diaporthe (RA, 9.34%). The Species Richness Index (S, 56) and the Shannon-Wiener Index (H′, 2.7076) indicated that C. japonicus harbored abundant fungal resources. Thirteen out of 130 endophytic fungal ethyl acetate extracts exhibited inhibitory activities against at least one pathogenic bacterium or fungus. Among of these, F8158, which was identified as Trichoderma cf. harzianum, exhibited good antagonistic capacities (the percent inhibition of mycelial growth ranged from 47.72~88.18) for different pathogens and has a potential application in biological control. In addition, it is noteworthy that the strain F8157 (Thanatephorus cucumeris, an opportunistic pathogen) showed antibacterial and antifungal activity, which is reported firstly in this study, and should be investigated further. Taken together, these results indicated that the endophytic fungi from C. japonicus may be of potential interest in screening bio-control agents and discovering of new bioactive compounds.
Carbon Fibers as a New Type of Scaffold for Midbrain Organoid Development
Authors: Tejchman Anna , Znój Agnieszka , Chlebanowska Paula , Frączek-Szczypta Aneta , Majka Marcin
Published: August 2020

The combination of induced pluripotent stem cell (iPSC) technology and 3D cell culture creates a unique possibility for the generation of organoids that mimic human organs in in vitro cultures. The use of iPS cells in organoid cultures enables the differentiation of cells into dopaminergic neurons, also found in the human midbrain. However, long-lasting organoid cultures often cause necrosis within organoids. In this work, we present carbon fibers (CFs) for medical use as a new type of scaffold for organoid culture, comparing them to a previously tested copolymer poly-(lactic-co-glycolic acid) (PLGA) scaffold. We verified the physicochemical properties of CF scaffolds compared to PLGA in improving the efficiency of iPSC differentiation within organoids. The physicochemical properties of carbon scaffolds such as porosity, microstructure, or stability in the cellular environment make them a convenient material for creating in vitro organoid models. Through screening several genes expressed during the differentiation of organoids at crucial brain stages of development, we found that there is a correlation between PITX3, one of the key regulators of terminal differentiation, and the survival of midbrain dopaminergic (mDA) neurons and tyrosine hydroxylase (TH) gene expression. This makes organoids formed on carbon scaffolds an improved model containing mDA neurons convenient for studying midbrain-associated neurodegenerative diseases such as Parkinson’s disease.
Repositioning Dequalinium as Potent Muscarinic Allosteric Ligand by Combining Virtual Screening Campaigns and Experimental Binding Assays
Authors: Mazzolari Angelica , Gervasoni Silvia , Pedretti Alessandro , Fumagalli Laura , Matucci Rosanna , Vistoli Giulio
Published: August 2020

Structure-based virtual screening is a truly productive repurposing approach provided that reliable target structures are available. Recent progresses in the structural resolution of the G-Protein Coupled Receptors (GPCRs) render these targets amenable for structure-based repurposing studies. Hence, the present study describes structure-based virtual screening campaigns with a view to repurposing known drugs as potential allosteric (and/or orthosteric) ligands for the hM2 muscarinic subtype which was indeed resolved in complex with an allosteric modulator thus allowing a precise identification of this binding cavity. First, a docking protocol was developed and optimized based on binding space concept and enrichment factor optimization algorithm (EFO) consensus approach by using a purposely collected database including known allosteric modulators. The so-developed consensus models were then utilized to virtually screen the DrugBank database. Based on the computational results, six promising molecules were selected and experimentally tested and four of them revealed interesting affinity data; in particular, dequalinium showed a very impressive allosteric modulation for hM2. Based on these results, a second campaign was focused on bis-cationic derivatives and allowed the identification of other two relevant hM2 ligands. Overall, the study enhances the understanding of the factors governing the hM2 allosteric modulation emphasizing the key role of ligand flexibility as well as of arrangement and delocalization of the positively charged moieties.
Merged Tacrine-Based, Multitarget-Directed Acetylcholinesterase Inhibitors 2015–Present: Synthesis and Biological Activity
Authors: Eckroat Todd J. , Manross Danielle L. , Cowan Seth C.
Published: August 2020

Acetylcholinesterase is an important biochemical enzyme in that it controls acetylcholine-mediated neuronal transmission in the central nervous system, contains a unique structure with two binding sites connected by a gorge region, and it has historically been the main pharmacological target for treatment of Alzheimer’s disease. Given the large projected increase in Alzheimer’s disease cases in the coming decades and its complex, multifactorial nature, new drugs that target multiple aspects of the disease at once are needed. Tacrine, the first acetylcholinesterase inhibitor used clinically but withdrawn due to hepatotoxicity concerns, remains an important starting point in research for the development of multitarget-directed acetylcholinesterase inhibitors. This review highlights tacrine-based, multitarget-directed acetylcholinesterase inhibitors published in the literature since 2015 with a specific focus on merged compounds (i.e., compounds where tacrine and a second pharmacophore show significant overlap in structure). The synthesis of these compounds from readily available starting materials is discussed, along with acetylcholinesterase inhibition data, relative to tacrine, and structure activity relationships. Where applicable, molecular modeling, to elucidate key enzyme-inhibitor interactions, and secondary biological activity is highlighted. Of the numerous compounds identified, there is a subset with promising preliminary screening results, which should inspire further development and future research in this field.
The Regulatory Network of CMPG1-V in Wheat–Blumeria graminis f. sp. tritici Interaction Revealed by Temporal Profiling Using RNA-Seq
Authors: Liu Jia , Sun Li , Chen Yiming , Wei Luyang , Hao Yongli , Yu Zhongyu , Wang Zongkuan , Zhang Heng , Zhang Xu , Li Mengli , Wang Haiyan , Xiao Jin , Wang Xiue
Published: August 2020

Wheat powdery mildew (Pm), caused by Blumeria graminis f. sp. tritici (Bgt), is a prevalent fungal disease. The diploid wheat relative Haynaldia villosa (H. villosa) showed broad-spectrum resistance (BSR) to Pm. A previous study reported an E3 ligase gene, CMPG1-V from H. villosa, showing BSR to Pm. To elucidate the regulatory network mediated by CMPG1-V, in this study, gene expression profiling of CMPG1-V transgenic plant (CMPG1-VOE) and its receptor Yangmai 158 was analyzed and compared after Bgt inoculation at four infection stages. GO and KEGG analysis revealed obvious reprogramming of SA and ABA signaling, starch/sucrose metabolism, and photosynthesis in CMPG1-VOE, compared with those in Yangmai 158. Transcripts of SA synthesis genes SARD1 and UGT, signaling factors TGA and PRs, and SnRKs in ABA signaling were specifically upregulated in CMPG1-VOE rather than Yangmai 158. Transcripts of LHCII in photosynthesis, GLUC and TPP in starch/sucrose metabolism were also induced distinctly in CMPG1-VOE. WGCNA analysis showed crucial regulatory candidates of CMPG1-V, involving serine/threonine-protein kinase in phosphorylation, glucosyltransferase in flavonoid biosynthesis, defense factor WRKYs, and peroxidase in oxidative stress. Our results facilitate the deciphering of the resistant regulatory network of CMPG1-V and the identification of key candidates which might be employed in breeding programs.
Solution Structures and Dynamic Assembly of the 24-Meric Plasmodial Pdx1–Pdx2 Complex
Authors: Ullah Najeeb , Andaleeb Hina , Mudogo Celestin Nzanzu , Falke Sven , Betzel Christian , Wrenger Carsten
Published: August 2020

Plasmodium species are protozoan parasites causing the deadly malaria disease. They have developed effective resistance mechanisms against most antimalarial medication, causing an urgent need to identify new antimalarial drug targets. Ideally, new drugs would be generated to specifically target the parasite with minimal or no toxicity to humans, requiring these drug targets to be distinctly different from the host’s metabolic processes or even absent in the host. In this context, the essential presence of vitamin B6 biosynthesis enzymes in Plasmodium, the pyridoxal phosphate (PLP) biosynthesis enzyme complex, and its absence in humans is recognized as a potential drug target. To characterize the PLP enzyme complex in terms of initial drug discovery investigations, we performed structural analysis of the Plasmodium vivax PLP synthase domain (Pdx1), glutaminase domain (Pdx2), and Pdx1–Pdx2 (Pdx) complex (PLP synthase complex) by utilizing complementary bioanalytical techniques, such as dynamic light scattering (DLS), X-ray solution scattering (SAXS), and electron microscopy (EM). Our investigations revealed a dodecameric Pdx1 and a monodispersed Pdx complex. Pdx2 was identified in monomeric and in different oligomeric states in solution. Interestingly, mixing oligomeric and polydisperse Pdx2 with dodecameric monodisperse Pdx1 resulted in a monodispersed Pdx complex. SAXS measurements revealed the low-resolution dodecameric structure of Pdx1, different oligomeric structures for Pdx2, and a ring-shaped dodecameric Pdx1 decorated with Pdx2, forming a heteromeric 24-meric Pdx complex.
A Study of Consumer Repurchase Behaviors of Smartphones Using Artificial Neural Network
Authors: Lee Hong Joo
Published: August 2020

This study analyzed consumer intention to repurchase a smartphone, using an analysis of previous research and suggesting this as a research model. To this end, factors influencing “intention to repurchase” the smartphone were derived as social influence, consumer satisfaction, emotional loyalty, and habit. In addition, statistical analysis was conducted to investigate consumer repurchase intentions and the causal relationships. It is also possible to investigate whether consumer habits are linked to repurchases by analyzing their psychological inclinations; therefore, in this study, 390 people who repurchased a smartphone over the past two years were surveyed, and data were collected. This study analyzed the causal relationships among the factors using SPSS 24.0. Moreover, the causal relationship analysis was enhanced using the artificial neural network (ANN) algorithm. With multiple regression analysis and the ANN algorithm, consumer satisfaction (0.71), emotional loyalty (0.108), and social influence (0.062) were determined to affect the intention to repurchase. This means that the ANN algorithm can be used over multiple regression analysis and improve the results of the analysis. In addition, this study also provided practitioners with a way to improve their understanding of consumer behavior intention to repurchase smartphones.
Maternal Exposure to Ozone Modulates the Endophyte-Conferred Resistance to Aphids in Lolium multiflorum Plants
Authors: Bubica Bustos Ludmila M. , Ueno Andrea C. , Di Leo Tara D. , Crocco Carlos D. , Martínez-Ghersa M. Alejandra , Molina-Montenegro Marco A. , Gundel Pedro E.
Published: August 2020

Plants are challenged by biotic and abiotic stress factors and the incidence of one can increase or decrease resistance to another. These relations can also occur transgenerationally. For instance, progeny plants whose mothers experienced herbivory can be more resistant to herbivores. Certain fungal endophytes that are vertically transmitted endow plants with alkaloids and resistance to herbivores. However, endophyte-symbiotic plants exposed to the oxidative agent ozone became susceptible to aphids. Here, we explored whether this effect persists transgenerationally. We exposed Lolium multiflorum plants with and without fungal endophyte Epichloë occultans to ozone (120 or 0 ppb), and then, challenged the progeny with aphids (Rhopalosiphum padi). The endophyte was the main factor determining the resistance to aphids, but its importance diminished in plants with ozone history. This negative ozone effect on the endophyte-mediated resistance was apparent on aphid individual weights. Phenolic compounds in seeds were increased by the symbiosis and diminished by the ozone. The endophyte effect on phenolics vanished in progeny plants while the negative ozone effect persisted. Independently of ozone, the symbiosis increased the plant biomass (≈24%). Although ozone can diminish the importance of endophyte symbiosis for plant resistance to herbivores, it would be compensated by host growth stimulation.
How Effective Are Citizen Scientists at Contributing to Government Tree Health Public Engagement and Surveillance Needs—An Analysis of the UK Open Air Laboratories (OPAL) Survey Model
Authors: Slawson David D. , Moffat Andy J.
Published: August 2020

The incidence of tree disease has been increasing in the UK in recent years as a result of a range of alien tree pests and pathogens new to the country. In the early 2010s government staff resources to monitor, identify and eradicate these pathogens were limited, so we tested the efficacy of “citizen scientists” to support these needs. The Open Air Laboratories (OPAL) is a successful citizen science programme launched in 2007, which at that time of launch involved over 650 thousand people in a range of environmental surveys. In 2012–2013, the Food and Environment Research Agency (Fera) and Forest Research staff worked with OPAL and its partners to launch a citizen science tree health survey in Great Britain and this was extended to cover Northern Ireland until it closed in 2019. Over 2800 surveys were completed including records on more than 4500 trees, the majority from urban areas. This paper discusses the results of the survey and their value for the assessment of tree health. It also considers the implications of engagement with the general public for the future of tree health surveillance. Recommendations are made for further development of the OPAL “model” and more generally for the role of citizen science in this important area.
Inheritance, Fitness Cost, and Management of Lambda-Cyhalothrin Resistance in a Laboratory-Selected Strain of Ceratitis capitata (Wiedemann)
Authors: Guillem-Amat Ana , López-Errasquín Elena , Sánchez Lucas , González-Guzmán Miguel , Ortego Félix
Published: August 2020

The management of the medfly, Ceratitis capitata, in Spanish citrus crops relies mainly on the use of insecticides and the release of sterile males. However, the development of resistance to different insecticides in field populations, including lambda-cyhalothrin, implies a threat for the sustainable control of this pest. The inheritance, fitness cost, and management of lambda-cyhalothrin resistance were examined in the laboratory-selected W-1Kλ strain. We have demonstrated that lambda-cyhalothrin resistance in W-1Kλ is autosomic, completely dominant, and polygenic. In addition, individuals from W-1Kλ showed a lower embryo to pupal viability, a slower developmental time from egg to pupae, and an increase in adults’ weight and longevity. We did not find significant trade-offs in the activity of digestive hydrolytic enzymes, with the exception of higher α-amylase activity in W-1Kλ females. A comparative study with different insecticide treatment strategies showed that lambda-cyhalothrin resistance increased when several consecutive treatments with this insecticide were applied. However, the alternation of this insecticide with spinosad was enough to delay the development of resistance. Our results indicate that the rotation of lambda-cyhalothrin with spinosad—a practice already used in some fields—may contribute to prevent the development of resistance.
Novel Polyvinyl Butyral/Monoacylglycerol Nanofibrous Membrane with Antifouling Activity
Authors: Peer Petra , Sedlaříková Jana , Janalíková Magda , Kučerová Liliana , Pleva Pavel
Published: August 2020

Monoacylglycerols (MAGs) have proven of great interest to the foodstuffs industry due to the promising antibacterial activity they show for controlling microbial contamination. Prior to this paper, this antibacterial agent had not been incorporated in a nanofibrous membrane. This study details convenient fabrication of nanofibrous membranes based on polyvinyl butyral (PVB) containing various concentrations of monocaprin (MAG 10) by an electrospinning process. Increasing the concentration of MAG 10 caused differences to appear in the shape of the nanofibers, in addition to which the level of wettability was heightened. Besides exhibiting antibacterial properties, the functional membranes demonstrated especially good antifouling activity. The novel and efficient nanofibrous membranes described have the potential to find eventual application in medical or environmental fields.
Joining of Dissimilar Alloys Ti-6Al-4V and Ti-6Al-2Sn-4Zr-2Mo-0.1Si Using Linear Friction Welding
Authors: Rajan Sidharth , Wanjara Priti , Gholipour Javad , Kabir Abu Syed
Published: August 2020

Dissimilar joints between Ti-6Al-4V (Ti-64) and Ti-6Al-2Sn-4Zr-2Mo-0.1Si (Ti-6242) were manufactured using linear friction welding. The weld quality, in terms of the microstructure and mechanical properties, was investigated after stress relief annealing (SRA) at 750 °C for 2 h and compared with the as-welded (AWed) results. The central weld zone (CWZ) microstructure in the AWed condition consisted of recrystallized prior-β grains with α’ martensite, which transformed into an acicular α+β structure after SRA. The hardness in the AWed condition was highest in the CWZ and decreased sharply through the thermomechanically affected zones (TMAZ) to the parent materials (PMs). After SRA, the hardness of the CWZ decreased, mainly due to tempering of the α’ martensite microstructure. Static tensile testing of the dissimilar welds in both the AWed and stress relief annealed (SRAed) conditions resulted in ductile fracture occurring exclusively in the Ti-6Al-4V side of the joint. The promising results on joining of Ti-64 to Ti-6242 provide valuable insight for tailoring performance of next-generation aero-engine products.
Controlled Synthesis of Visible Light Active CuxS Photocatalyst: The Effect of Heat Treatment on Their Adsorption Capacity and Photoactivity
Authors: Fodor Szilvia , Baia Lucian , Hernádi Klára , Pap Zsolt
Published: August 2020

The effects of different precursor salts, stabilizing agents, and heat treatment parameters are already known to have an influence on the synthesis of nano-sized semiconductors in heterogenous photocatalysis. In the present work, CuxS materials were prepared by using different precursors (copper (II) chloride dihydrate or copper (II) acetate monohydrate) and shape tailoring/stabilizing agents, such as ethylenediaminetetraacetic acid/polyvinylpyrrolidone, and thiourea as the sulfur source. The polyvinylpyrrolidone (PVP) kinetically controlled the growth rate of the nanoplates, while ethylenediaminetetraacetic acid (EDTA) adjusted the nucleation process through the complexation of copper. A one-step hydrothermal method was used for the synthesis, and the materials were characterized by means of morphological and structural complementary investigation methods. Furthermore, the adsorption capacity and photocatalytic activity were also measured for these materials. It was found that the vacancy sites formed by changing the precursor salt, as confirmed by Raman measurements, affect the photocatalytic activity. The rise of the specific surface area was achieved by heat treatment, and concomitantly, the adsorption capacity of the treated samples was found to increase likewise.