bluuebunny/crossref_metadata_2025_split huggingface dataset:
Purified anacardic acids exert multiple neuroprotective effects in pesticide model of Parkinson's disease: in vivo and in silico analysis
Authors: Augusto Ricielle L. , Mendonça Ingrid P. , de Albuquerque Rego Gabriel N. , Pereira Danielle D. , da Penha Gonçalves Lílian V. , dos Santos Maria L. , de Souza Raphael F. , Moreno Giselle M. M. , Cardoso Pablo R. G. , de Souza Andrade Daniele , da Silva‐Júnior José C. , Pereira Michelly C. , Peixoto Christina A. , Medeiros‐Linard Cybelle F. B. , de Souza Ivone A. , Andrade‐da‐Costa Belmira L. da Silveira 
Published: May 2020

AbstractParkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF‐kB‐p65, pro‐IL‐1β, cleaved IL‐1β, metalloproteinase‐9, Tissue Inhibitory Factor‐1 (TIMP‐1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF‐kB‐p65, pro, and cleaved IL‐1β, MMP‐9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro‐IL‐1β in the striatum while they augmented TIMP1 and reduced MMP‐9 amounts in both regions. AAs reversed rotenone‐induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro‐IL‐1β and MMP‐9 levels in both regions, NF‐kB‐p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.
Alchemical free energy calculations via metadynamics: Application to the theophylline‐RNA aptamer complex
Authors: Tanida Yoshiaki , Matsuura Azuma 
Published: May 2020

AbstractWe propose a computational workflow for robust and accurate prediction of both binding poses and their affinities at early stage in designing drug candidates. Small, rigid ligands with few intramolecular degrees of freedom, for example, fragment‐like molecules, have multiple binding poses, even at a single binding site, and their affinities are often close to each other. We explore various structures of ligand binding to a target through metadynamics using a small number of collective variables, followed by reweighting to obtain the atomic coordinates. After identifying each binding pose by cluster analysis, we perform alchemical free energy calculations on each structure to obtain the overall value. We applied this protocol in computing free energy of binding for the theophylline‐RNA aptamer complex. Of the six (meta)stable structures found, the most favorable binding structure is consistent with the structure obtained by NMR. The overall free energy of binding reproduces the experimental values very well.
Phospholipase‐A2 receptor antibody, 24 hours proteinuria, and serum albumin as indicators of cyclophosphamide efficacy in idiopathic membranous nephropathy
Authors: Xiao Chunying , Liu Yong , Zhang Xinpeng , Luo Lin , Li Xiaoying , Wang Tingting , Tian Zhe , Qin Xiaosong , Liu Jianhua 
Published: May 2020

AbstractBackgroundWe aimed to evaluate cyclophosphamide efficacy in the treatment of idiopathic membranous nephropathy (IMN) and explore the efficacy of phospholipase‐A2 receptor antibody (PLA2R‐Ab), 24 hours proteinuria, and serum albumin in predicting 6‐ and 12‐month treatment effects.MethodsA retrospective analysis was performed on 135 patients with IMN who followed up after treatment. The observation points were before, and after 3, 6, and 12 months of treatment. We collected clinical indicator data at each observation point and measured PLA2R‐Ab levels before and after 3‐month treatment.ResultsThe remission rates at 3, 6, and 12 months of cyclophosphamide therapy for patients with IMN were 41.4, 74.8, and 76.1%, respectively. Patients in whom PLA2R‐Ab turned negative within 3 months had high remission rates at 3, 6, and 12 months after treatment (P < .05). PLA2R‐Ab change at 3 months had a strong correlation with 24 hours proteinuria change at 6 months. The change in albumin concentration before and after 3‐month treatment was an independent variable related to remission rate at 6 months, and 24 hours proteinuria change before and after 6‐month treatment was an independent variable related to remission rate at 12 months after treatment.ConclusionCyclophosphamide showed good efficacy at 3, 6, and 12 months for patients with IMN. Serum albumin change and PLA2R‐Ab change at 3 months can be used as indicators to predict remission at 6 months, respectively. Moreover, 24 hours proteinuria change at 6 months can predict remission at 12 months.
CCL5 persists in RSV stocks following sucrose-gradient purification
Authors: Ajamian Farnam , Ilarraza Ramses , Wu Yingqi , Morris Katherine , Odemuyiwa Solomon O , Moqbel Redwan , Adamko Darryl J 
Published: May 2020

Abstract
Respiratory syncytial virus (RSV) is associated with bronchiolitis in infancy and the later development of asthma. Research on RSV in vitro requires preparation of a purified RSV stock. The objective for this work was to develop best methods for RSV purification, while monitoring the samples for potential contaminating proinflammatory mediators. Using polyethylene glycol concentration, and sucrose-gradient ultracentrifugation, we collected samples at each step of purification and measured the values of RSV titer, total protein (µg/mL), and proinflammatory cytokines (ELISA). We analyzed the efficacy of each step in the purification procedure. In so doing, we also determined that despite optimal purification methods, a well-known chemokine in the field of allergic disease, CCL5 (RANTES), persisted within the virus preparations, whereas other cytokines did not. We suggest that researchers should be aware that CCL5 appears to co-purify with RSV. Despite reasonable purification methods, a significant level of CCL5 (RANTES) persists in the virus preparation. This is relevant to the study of RSV-induced allergic disease.
Skull osteology and osteological phylogeny of the Western whip snake Hierophis viridiflavus (Squamata, Colubridae)
Authors: Racca Luca , Villa Andrea , Wencker Lukardis C. M. , Camaiti Marco , Blain Hugues‐Alexandre , Delfino Massimo 
Published: May 2020

AbstractThe skull osteology of Hierophis viridiflavus is here described and figured in detail on the basis of 18 specimens. The sample includes specimens from the ranges of both H. viridiflavus viridiflavus and H. viridiflavus carbonarius as well as specimens not identified at sub‐specific level. The main characters that define H. viridiflavus in comparison to the parapatric congeneric species Hierophis gemonensis are wide maxillary diastema, basioccipital crest well distinct in three lobes and basioccipital process well marked. The foramina of the otoccipital and prootic, and the basioccipital process of the basioccipital are among the most ontogenetically variable characters, as indicated by two juvenile specimens included in the sample. A specimen‐level phylogenetic analysis including H. gemonensis and other outgroups (overall 6 species, 26 specimens, 64 skull characters) recovered all H. viridiflavus specimens in one clade, indicating the presence of a clear phylogenetic signal in the applied characters. However, the resolution within the H. viridiflavus clade is poor the monophyly of H. viridiflavus carbonarius was retrieved, but not that of Hierophis v. viridiflavus. Probably due to the relatively high variability, the skull morphology does not support the recently proposed specific status of the two subspecies.
Finding ways to support radiographers as teachers
Authors: Thompson Andrea , Taylor Darci 
Published: May 2020

AbstractIntroductionTeaching and supervision of medical imaging students are part of the role of many radiographers, yet they are frequently unsupported in the development of their role as a teacher. This study explores radiographers’ experiences and level of confidence in teaching and establishes the areas of support they require to be more effective in their clinical teaching role.MethodsSixty radiographers from across Australia completed an anonymous questionnaire, and nine radiographers participated in focus groups. Thematic analysis was conducted on the qualitative data, whilst quantitative data were analysed using one‐way ANOVA and reported as descriptive statistics.ResultsThe findings demonstrate that radiographers were mostly confident in the domains of familiarising students to the practice environment, supervising students and assisting students to integrate into the practice environment, but were less confident in facilitating students’ learning. Radiographers have identified the teaching skills and attributes they currently possess and the areas in which they need further development.ConclusionsThis study calls for support for radiographers in their teaching role and provides guidance for education providers wanting to design education to support radiographers’ learning needs for teaching.
Evaluation of tyrosol and farnesol as inducer in pigment production by Monascus purpureus ATCC16365
Authors: Erkaya Seval , Arslan Nazli Pinar , Orak Tugba , Esim Nevzat , Taskin Mesut 
Published: May 2020

AbstractThis study focused on investigating the effect of exogenously applied two quorum sensing molecules (tyrosol and farnesol) on the synthesis of bioactive metabolites (pigments, lactic acid, ethanol, and citric acid) in Monascus purpureus ATCC16365. None of the tested concentrations (62.5, 125, 250, and 500 µl/L) of farnesol affected the synthesis of metabolites as well as cell growth. As with farnesol application, none of the tested concentrations (3.45, 6.9, 13.8, and 27.6 mg/L) of tyrosol caused a significant change in the synthesis of lactic acid and citric acid as well as cell growth. Conversely, all of the tested concentrations of tyrosol increased pigment synthesis but reduced ethanol synthesis, compared with the control. Maximum increases (3.16‐, 2.68‐, and 2.87‐fold increase, respectively) in yellow, orange, and red pigment production were achieved, especially when 6.9‐mg/L tyrosol was added to the culture on day 3. On the contrary, 6.9‐mg/L tyrosol reduced the content of citrinin by approximately 51.5%. This is the first report on the effect of tyrosol and farnesol on the synthesis of Monascus metabolites. Due to potential properties, such as low price, nonhuman toxicity, promotion of pigment synthesis, and reduction in citrinin synthesis, tyrosol can be used as a novel inducer in the fermentative production of Monascus pigments.
Increased Cd2+ biosorption capability of Aspergillus nidulans elicited by crpA deletion
Authors: Boczonádi Imre , Török Zsófia , Jakab Ágnes , Kónya Gábor , Gyurcsó Klaudia , Baranyai Edina , Szoboszlai Zoltán , Döncző Boglárka , Fábián István , Leiter Éva , Lee Mi‐Kyung , Csernoch László , Yu Jae‐Hyuk , Kertész Zsófia , Emri Tamás , Pócsi István 
Published: May 2020

AbstractThe P‐type ATPase CrpA is an important Cu2+/Cd2+ pump in the Aspergilli, significantly contributing to the heavy metal stress tolerance of these ascomycetous fungi. As expected, the deletion of crpA resulted in Cu2+/Cd2+‐sensitive phenotypes in Aspergillus nidulans on stress agar plates inoculated with conidia. Nevertheless, paradoxical growth stimulations were observed with the ΔcrpA strain in both standard Cu2+ stress agar plate experiments and cellophane colony harvest (CCH) cultures, when exposed to Cd2+. These observations reflect efficient compensatory mechanisms for the loss of CrpA operating under these experimental conditions. It is remarkable that the ΔcrpA strain showed a 2.7 times higher Cd biosorption capacity in CCH cultures, which may facilitate the development of new, fungal biomass‐based bioremediation technologies to extract harmful Cd2+ ions from the environment. The nullification of crpA also significantly changed the spatial distribution of Cu and Cd in CCH cultures, as demonstrated by the combined particle‐induced X‐ray emission and scanning transmission ion microscopy technique. Most important, the centers of gravity for Cu and Cd accumulations of the ΔcrpA colonies shifted toward the older regions as compared with wild‐type surface cultures.
Periodontal disease classifications and incident coronary heart disease in the Atherosclerosis Risk in Communities study
Authors: Beck James D. , Philips Kamaira , Moss Kevin , Sen Souvik , Morelli Thiago , Preisser John , Pankow James 
Published: May 2020

AbstractBackgroundPeriodontal disease has been linked to coronary heart disease (CHD), but studies have been inconclusive. This study investigates the link between periodontal disease and incident CHD.MethodsBaseline periodontal data from a full‐mouth periodontal exam (N = 6,300) and CHD outcomes through 2017 were obtained from the Atherosclerosis Risk in Communities Study. Periodontitis was defined by the Periodontal Profile Class System adapted to Stages (PPC stages) and the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) index. Competing risk models were used to determine hazard ratios (HR) for incident CHD, congestive heart failure (CHF), and other causes of death. Secondary analysis included myocardial infarction (MI) and fatal CHD.ResultsFemales comprised 56% of participants and males 44% with a combined mean age of 62.3 years (range: 52 to 74). Participants were followed for an average of 16.7 (SD: 5.5) years. In a fully adjusted model, PPC stage VII (Severe Tooth Loss) was moderately significantly related to incident CHD, (HR 1.51 [1.11 to 2.09]). PPC stage V (Mild Tooth Loss/High Gingival Inflammation) was significant for fatal CHD (HR, 5.27 [1.80 to 15.4]) and PPC stage VII was significant for incident MI (HR, 1.59 [1.13 to 2.23]). The CDC/AAP definition was not significantly associated with incident CHD.ConclusionsIncident CHD was moderately significantly associated with a specific stage of periodontal disease characterized by severe tooth loss, while none of the categories of the CDC/AAP were significantly associated. Thus, while periodontal therapy may improve oral health, it may be effective at impacting CHD incidence in only certain groups of people.
High Molecular Weight Poly(ethylenimine)‐Based Water‐Soluble Lipopolymer for Transfection of Cancer Cells
Authors: Abd Elhameed Heba Alaa Hosiny , Ungor Ditta , Igaz Nóra , Gopisetty Mohana Krishna , Kiricsi Mónika , Csapó Edit , Gyurcsik Béla 
Published: May 2020

AbstractOver the past decade, search for novel materials for nucleic acid delivery has prompted a special interest in polymeric nanoparticles (NPs). In this study, the biological applicability of a water‐soluble cationic lipopolymer (WSLP) obtained by the modification of high molecular weight branched poly(ethylenimine) (PEI) with cholesteryl chloroformate is characterized and assessed for better cellular membrane permeability. To test the delivery efficiency of the produced lipopolymer, plasmid DNA (pDNA) encoding the enhanced green fluorescent protein and WSLP are mixed at different charge ratios. WSLP and WSLP/pDNA complexes are characterized by dynamic and static light scattering, particle charge detection, scanning electron microscopy, and transmission electron microscopy. The pDNA loading of WSLP is also verified by agarose gel electrophoresis. Cytotoxicity of PEI, WSLP, and of WSLP/pDNA is evaluated on human A549 and HeLa cells. A remarkable dependence of the toxicity on the dose, cholesterylation, and charge ratio is detected. Transfection is monitored by flow cytometry and by fluorescence microscopy. Importantly, cholesterylation decreases the toxicity of the polymer, while promoting high transfection efficiency in both cell lines. This work indicates a possible optimization mode of the high molecular weight PEI‐based WSLP rendering it a promising candidate for gene delivery.
Semi‐Interpenetrated Hydrogels‐Microfibers Electroactive Assemblies for Release and Real‐Time Monitoring of Drugs
Authors: Moghimiardekani Ali , Molina Brenda G. , Enshaei Hamidreza , del Valle Luis J. , Pérez‐Madrigal Maria M. , Estrany Francesc , Alemán Carlos 
Published: May 2020

AbstractSimultaneous drug release and monitoring using a single polymeric platform represents a significant advance in the utilization of biomaterials for therapeutic use. Tracking drug release by real‐time electrochemical detection using the same platform is a simple way to guide the dosage of the drug, improve the desired therapeutic effect, and reduce the adverse side effects. The platform developed in this work takes advantage of the flexibility and loading capacity of hydrogels, the mechanical strength of microfibers, and the capacity of conducting polymers to detect the redox properties of drugs. The engineered platform is prepared by assembling two spin‐coated layers of poly‐γ‐glutamic acid hydrogel, loaded with poly(3,4‐ethylenedioxythiophene) (PEDOT) microparticles, and separated by a electrospun layer of poly‐ε‐caprolactone microfibers. Loaded PEDOT microparticles are used as reaction nuclei for the polymerization of poly(hydroxymethyl‐3,4‐ethylenedioxythiophene) (PHMeDOT), that semi‐interpenetrate the whole three layered system while forming a dense network of electrical conduction paths. After demonstrating its properties, the platform is loaded with levofloxacin and its release monitored externally by UV–vis spectroscopy and in situ by using the PHMeDOT network. In situ real‐time electrochemical monitoring of the drug release from the engineered platform holds great promise for the development of multi‐functional devices for advanced biomedical applications.
Targeting Inhibition of Foxp3 by MMP2/9 Sensitive Short Peptide Linked P60 Fusion Protein 6(P60‐MMPs) to Enhance Antitumor Immunity
Authors: Ding Xiuli , Peng Chen , Li Yongkui , Liu Jia , Song Yu , Cai Bo , Xiang Mengxi , Zhang Jian , Wang Zheng , Wang Lin 
Published: May 2020

AbstractRegulatory T‐cells (Tregs) play an important role in tumor immunosuppressive network, thus Tregs‐targeted strategy is expected to enhance antitumor immunity and improve the effect of immunotherapy. Short peptide P60 can bind to the forkhead box protein P3 (Foxp3), a crucial transcriptional regulator for the development and inhibitory function of Tregs, and inhibit Foxp3 nuclear translocation in Tregs. However, its treatment effect in cancer is limited due to nonspecificity. Therefore, realizing the specific delivery of P60 in tumor microenvironment will greatly facilitate its Treg‐suppressing effect for tumor therapeutics. Herein, utilizing the unique matrix metallase protease 2/9 (MMP2/9) overexpressing feature in tumor tissues, a fusion protein 6(P60‐MMPs) containing six segments of P60 linked by MMP2/9‐sensitive peptides is constructed for antitumor targeting immunotherapy. The fusion protein 6(P60‐MMPs) specifically degrades into short peptide P60 in tumor, and then binds to Foxp3 to inhibit Foxp3 nuclear translocation in Tregs, thus impairing Tregs’ activity. This fusion protein efficiently inhibits murine breast cancer 4T1 transplanted tumor growth and decreases lung metastasis through down‐regulating tumor‐infiltrated Tregs and up‐regulating CD8+ T cells in tumor tissue. The study develops a Treg‐targeted anticancer fusion protein with effective therapeutic activity, suggesting its potential in clinical translation.
On 4‐dimensional Lorentzian affine hypersurfaces with an almost symplectic form
Authors: Szancer Michal , Szancer Zuzanna 
Published: May 2020

AbstractIn this paper we study 4‐dimensional affine hypersurfaces with a Lorentzian second fundamental form additionally equipped with an almost symplectic structure ω. We prove that the rank of the shape operator is at most one if or for some positive integer k. This result is the final step in a classification of Lorentzian affine hypersurfaces with higher order parallel almost symplectic forms.
Inter‐rater reliability of activity measure for post‐acute care ‘6‐Clicks’ inpatient mobility short form in the intensive care unit
Authors: Hiser Stephanie , Toonstra Amy , Friedman Lisa A. , Colantuoni Elizabeth , Needham Dale M. 
Published: May 2020

AbstractObjectiveExamine the inter‐rater reliability of the activity measure for post‐acute care (AM‐PAC) inpatient mobility short form (IMSF) when completed by physical therapists (PTs), during routine clinical practice, in a variety of patients with critical illness.MethodsA prospective observational evaluation at single, large academic hospital in the United States. Patients (n = 76) in surgical, medical and neurological intensive care units (ICUs) were evaluated as part of routine clinical practice using the AM‐PAC IMSF administered by eight PTs with at least 6 months of experience using this tool. One of two reference rater PTs observed the physical therapy session, and simultaneously scored the AM‐PAC IMSF. The reference rater and clinical PTs were blinded to each other's scores with a minimum of 10 assessments completed by each clinical PT. Bland–Altman plots were constructed and intra‐class correlation coefficients (ICC) were computed using a random intercept (physical therapy session) model.ResultsEighty one assessments (five patients assessed twice) were scored by both a clinical PT and reference rater PT (total assessments = 162). Bland–Altman plots revealed a mean difference in AM‐PAC IMSF scoring of 0.0 (95% limits of agreement: −3.0 to +3.0), with an ICC (95% confidence interval) of 0.957 (0.947–0.964). The ICC (95% confidence interval) for patients in surgical, medical and neurological ICUs was very similar: 0.949 (0.927–0.959), 0.963 (0.946–0.971) and 0.936 (0.886–0.955), respectively.ConclusionsThe AM‐PAC IMSF demonstrates excellent reliability compared with reference rater PTs when performed by PTs during clinical care across surgical, medical and neurological ICUs.
Isolation, identification and structural interpretation of degradation impurities in idelalisib
Authors: Bommuluri Vijay , Vajjha Soujanya , Rumalla Chidananda Swamy , Doddipalla Raju , Kaliyaperumal Muralidharan , Korupolu Raghu Babu , Choppela Vidyasagar 
Published: May 2020

AbstractIdelalisib is a Quinazolinone derivative, phosphatidylinositol‐3‐kinase delta inhibitor that has been approved for the treatment of hematological malignancies. A liquid chromatography method was developed to study the degradation of Idelalisib. As per the International Conference on Harmonisation guidelines, Idelalisib was exposed to acid, base, oxidative, photolytic, and thermal degradation studies. Idelalisib was labile to acidic, basic, and oxidative stress conditions. It was stable in remaining conditions. Three degradation products were observed that were not yet reported in the literature. Degradation products are isolated by using preparative‐scale high‐pressure liquid chromatography apparatus with C18 column using gradient elution. Structural characterization done by using fragmentation pattern of high‐resolution mass spectroscopy and further confirmed by using extensive NMR spectroscopic studies. Degradation studies were performed to determine the intrinsic stability of a drug substance in formulation and to generate more stable formulation.