bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid arterial mechanics as useful biomarker of extracellular matrix turnover and preserved ejection fraction heart failure
Authors: Zhou Kevin Ning , Sung Kuo‐Tzu , Yen Chih‐Hsuan , Su Cheng‐Huang , Lee Ping‐Ying , Hung Ta‐Chuan , Huang Wen‐Hung , Chien Shih‐Chieh , Tsai Jui‐Peng , Yun Chun‐Ho , Chang Shun‐Chuan , Yeh Hung‐I , Hung Chung‐Lieh
Published: May 2020

Aims

We aimed to investigate the functional alterations, diagnostic utilization, and prognostic implication of carotid arterial deformations in subjects with cardiovascular risk factors and heart failure (HF) with preserved ejection fraction (HFpEF).

Methods and results

Among 251 prospectively participants (mean age 66.0 ± 9.8 years, 65.7% female) in a single centre between December 2011 and September 2014, carotid artery deformations including circumferential strain (CCS)/strain rate and radial strain were analysed by two‐dimensional speckle tracking. We further related these carotid artery deformation indices to HF biomarkers and cardiac structure and function by echocardiography and explored their prognostic values. Significant reductions of CCS, circumferential strain rate, and circumferential radial strain were observed across control (n = 52), high risk (n = 147), and HFpEF (n = 52) (trend P ≤ 0.001). Aging, hypertension, HFpEF, and higher pulse rate showed independent associations with reduced CCS by stepwise multivariate regressions (all P < 0.05). Higher CCS was inversely associated with better cardiac remodelling and functional indices, and lower multiple HF biomarkers (all P ≤ 0.005). After adjustment, higher CCS was independently associated with better global ventricular longitudinal strain/early diastolic strain rate, lower matrix metalloproteinase‐2, and N‐terminal propeptide of procollagen type III levels (adjusted coef: −0.08 and −19.9, all P < 0.05). During a median follow‐up of 1406 days (interquartile range: 1342‑1720 days), CCS less than 3.28% as a cut‐off had markedly higher HF events [Harrell's C: 0.72, adjusted HR: 2.20 (95% confidence interval: 1.24, 3.16), P = 0.008]. CCS also showed significantly improved risk prediction for HF over global ventricular longitudinal strain (net reclassification index: 48%, P = 0.001; integrated discrimination improvement: 1.8%, P < 0.001).

Conclusions

Carotid artery deformations using two‐dimensional speckle‐tracking imaging showed novel mechanistic insights on functional arterial alterations reflecting coupled arterial‐ventricular pathophysiology. Utilization of such measure may further provide additive prognostic value to advanced myocardial functional assessment.
Does lack of control lead to conspiracy beliefs? A meta‐analysis
Authors: Stojanov Ana , Halberstadt Jamin
Published: May 2020

Perceived lack of control is widely believed to motivate, at least partly, belief in conspiracy theories. We question the theoretical foundations of this belief and meta‐analyze existing published and unpublished studies to assess the overall effect of lack of control on conspiracy beliefs. The overall effect was small and not statistically significant (d = −0.05), and was not moderated by comparison group (baseline vs. control affirmation), type of manipulation used to threaten control, inclusion of a manipulation check, or sample type. However, the predicted effect of control was more likely to be observed when beliefs were measured in terms of specific conspiracy theories, rather than as general or abstract claims. Overall, the present studies to date offer limited support for the hypothesis that conspiracy beliefs arise as a compensatory control.
Detection of olive oil adulteration with vegetable oils by ultra‐performance convergence chromatography‐quadrupole time‐of‐flight mass spectrometry (UPC2‐QTOF MS) coupled with multivariate data analysis based on the differences of triacylglycerol compositions
Authors: Luo Yinghua , Gao Boyan , Zhang Yaqiong , Yu Liangli (Lucy)
Published: May 2020

Three different vegetable oils, including soybean, corn, and sunflower oils, were differentiated from olive oil by using ultra‐performance convergence chromatography coupled with quadrupole time‐of‐flight (UPC2‐QTOF MS) and multivariate data analysis based on their differences in triacylglycerol compositions. Then, olive oil was adulterated by adding these three vegetable oils in 1%, 0.75%, and 0.5% (v/v), and the adulterated olive oils were differentiated from the pure olive oils using the similar analytical strategies but different data processing approaches. After that, the representative markers in differentiating the adulterations were selected, and a mathematical model was created to detect the olive oil adulteration based on these specific markers. These results indicated that UPC2‐QTOF MS coupled with multivariate data analysis is a sensitive and accurate method in detecting olive oil adulteration, even in 0.5% adulteration level (v/v). This method could be applied in olive oil adulteration detection, and potentially beneficial to the oil industry.
Doping amino acids with classical gas hydrate inhibitors to facilitate the hydrate inhibition effect at low dosages
Authors: Qureshi M Fahed , Khraisheh Majeda , Almomani Fares
Published: May 2020

The formation of gas hydrates in offshore subsea lines is a major flow assurance concern for the oil and gas industry. In this work, the thermodynamic hydrate inhibition (THI) effect of doping amino acids (AA) such as glycine (Gly), l‐alanine (Ala), and histidine (His) with classical gas hydrate inhibitors (CHI) such as methanol (Me), ethylene glycol (EG), and sodium chloride (NaCl) have been examined at diverse operating conditions. The experimental tests were carried out using rocking cell assembly [RC‐5] on pure methane gas at different pressure conditions (40–120 bars) using an equal ratio mixture (1:1) of AA and CHI at a low dosage (2 wt%). The computational three‐dimensional molecular models of AA and CHI were generated to examine electric charge distribution within these molecules and cognize the interaction mechanism between methane hydrates and AA. The experimental results indicate that Me and EG can synergize the THI effect of AA at a low dosage of 1 wt%. The AA doped with Me tend to provide better THI effect compared to AA doped with EG and NaCl. The experimental results also show that the doped AA Ala mixtures provide THI effect similar to pure CHI such as Me, EG, and NaCl at low dosage (2 wt%). © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls
Authors: Pearlman Eric M. , Wilbraham Darren , Dennehy Ellen B. , Berg Paul H. , Tsai Max , Doty Erin G. , Kay Gary G.
Published: May 2020

Objective

To evaluate the impact of lasmiditan, an oral, centrally‐penetrant, selective serotonin 1F (5‐HT1F) receptor agonist developed for the acute treatment of migraine, on simulated driving.

Methods

Healthy adult volunteers enrolled in two randomized, placebo and active comparator‐controlled, crossover studies. Study 1 (N= 90) tested lasmiditan (50‐, 100‐, 200‐mg), alprazolam (1‐mg), and placebo at 1.5 hr post‐dose. Study 2 (N= 68) tested lasmiditan (100‐, 200‐mg), diphenhydramine (50‐mg, administered 2 hr pre‐assessments), and placebo at 8, 12 and 24 hr post‐dose. Driving performance was assessed using a validated driving simulator employing a 100 km driving scenario. Standard deviation of lateral position (SDLP), a measure of lane position control, was the primary endpoint.

Results

Assay sensitivity was confirmed by increased SDLP for active comparators at 1.5‐ and 8‐hr time points. Lasmiditan doses showed significant driving impairment versus placebo at 1.5 hr post‐dose. Lasmiditan doses were non‐inferior to placebo at 8 hr. Driving impairment was concentration‐dependent at 1.5 hr but not at 8 hr. Common adverse events were central nervous system‐related and mild‐to‐moderate in severity.

Conclusions

Lasmiditan was associated with impaired simulated driving performance at 1.5 hr post‐dose, but showed no clinically meaningful impairment at 8 hr post‐dose.
Water uptake of riparian plants in the lower Lhasa River Basin, South Tibetan Plateau using stable water isotopes
Authors: Rao Wenbo , Chen Xi , Meredith Karina T. , Tan Hongbing , Gao Man , Liu Jintao
Published: May 2020

Riparian plants can adapt their water uptake strategies based on climatic and hydrological conditions within a river basin. The response of cold‐alpine riparian trees to changes in water availability is poorly understood. The Lhasa River is a representative cold‐alpine river in South Tibet and an under‐studied environment. Therefore, a 96 km section of the lower Lhasa River was selected for a study on the water‐use patterns of riparian plants. Plant water, soil water, groundwater and river water were measured at three sites for δ18O and δ2H values during the warm‐wet and cold‐dry periods in 2018. Soil profiles differed in isotope values between seasons and with the distance along the river. During the cold‐dry period, the upper parts of the soil profiles were significantly affected by evaporation. During the warm‐wet period, the soil profile was influenced by precipitation infiltration in the upper reaches of the study area and by various water sources in the lower reaches. Calculations using the IsoSource model indicated that the mature salix and birch trees (Salix cheilophila Schneid. and Betula platyphylla Suk.) accessed water from multiple sources during the cold‐dry period, whereas they sourced more than 70% of their requirement from the upper 60–80 cm of the soil profile during the warm‐wet period. The model indicated that the immature rose willow tree (Tamarix ramosissima Ledeb) accessed 66% of its water from the surface soil during the cold‐dry period, but used the deeper layers during the warm‐wet period. The plant type was not the dominant factor driving water uptake patterns in mature plants. Our findings can contribute to strategies for the sustainable development of cold‐alpine riparian ecosystems. It is recommended that reducing plantation density and collocating plants with different rooting depths would be conducive to optimal plant growth in this environment.
UBC12‐mediated SREBP‐1 neddylation worsens metastatic tumor prognosis
Authors: Heo Mi Jeong , Kang Sung Hyun , Kim Yun Seok , Lee Jung Min , Yu Jinha , Kim Hong‐Rae , Lim Hyesol , Kim Kyoung Mee , Jung Joohee , Jeong Lak Shin , Moon Aree , Kim Sang Geon
Published: May 2020

Activation of sterol regulatory element‐binding protein 1 (SREBP‐1), a master lipogenic transcription factor, is associated with cancer metabolism and metabolic disorders. Neddylation, the process of adding NEDD8 to its substrate, contributes to diverse biological processes. Here, we identified SREBP‐1 as a substrate for neddylation by UBC12 and explored its impact on tumor aggressiveness. In cell‐based assays, SREBP‐1 neddylation prolonged SREBP‐1 stability with a decrease in ubiquitination. Consequently, NEDD8 overexpression facilitated proliferation, migration, and invasion of SK‐Hep1 liver tumor cells. MLN4924 (an inhibitor of the NEDD8‐activating enzyme‐E1) treatment or UBC12 knockdown prevented SREBP‐1 neddylation and tumor cell phenotype change. This effect was corroborated in an in vivo xenograft model. In human specimens, SREBP‐1, UBC12, and NEDD8 were all upregulated in hepatocellular carcinoma (HCC) compared to nontumorous regions. Moreover, SREBP‐1 levels positively correlated with UBC12. In GEO database analyses, SREBP‐1 levels were greater in metastatic HCC samples accompanying UBC12 upregulation. In HCC analysis, tumoral SREBP‐1 and UBC12 levels discriminated overall patient survival rates. Additionally, MLN4924 treatment destabilized SREBP‐1 in MDA‐MB‐231 breast cancer cells and in the tumor cell xenograft. SREBP‐1 and UBC12 were also highly expressed in human breast cancer tissues. Moreover, most breast cancers with lymph node metastasis displayed predominant SREBP‐1 and UBC12 expressions, which compromised overall patient survival rates. In summary, SREBP‐1 is neddylated by UBC12, which may contribute to HCC and breast cancer aggressiveness through SREBP‐1 stabilization, and these events can be intervented by MLN4924 therapy. Our findings may also provide potential reliable prognostic markers for tumor metastasis.
First‐principles Studies of Band Gap Engineering in Ferroelectric Oxides
Authors: Grinberg Ilya
Published: May 2020

In the last decade there has been a resurgence of activity in the field of photoferroelectrics with a focus on the studies of oxides. Ferroelectric (FE) materials have a spontaneous switchable polarization that can lead to interesting light‐matter interactions such as the bulk photovoltaic effect. While a wide range of compositions has been explored for ferroelectrics, until recently, FE oxides were considered to be capable of absorbing UV light only. Playing a key role in the advance of the field, first‐principles calculations have guided the experimental materials discovery efforts that have identified a wide variety of visible‐light‐absorbing oxides. First‐principles research efforts have also achieved considerable progress in revealing the interplay between the composition, structure and light absorption properties in these materials, and it is now understood that even small changes in the local environment can lead to large changes in band gap character and magnitude. Here, we survey the first‐principles efforts following different band‐gap engineering strategies and the advances in the computational methods that have been driven by these studies.
Treated Oil Shale Ashes as a Substitute for Natural Aggregates, Sand, and Cement in Concrete
Authors: Nov Sarit , Cohen Haim , Knop Yaniv
Published: May 2020

Oil shales are rocks that contain organic matter and are used as a low‐grade fuel for energy production. The oil shale combustion process produces large quantities of ash as combustion wastes. These residues contain a high concentration of calcium anhydrite (CaSO4) and calcium carbonate (CaCO3), which can be utilized to neutralize acidic wastes (e. g., wastes from the phosphate industry) .Using untreated oil shale bottom ash as partial substitutes for aggregates, natural sand, and cement in concrete mixtures has resulted in a significantly decreased performance of the concrete mixtures. However, by blending the oil shale with acidic materials, the concrete properties improved, as manifested by the development of compressive strength and the workability of the concrete mixtures. In the current study, it was shown that treatment of the oil shale ash with the acidic waste of the Israeli phosphate industry or with phosphoric acid significantly improves the properties of the concrete mixtures, by partial replacement of the natural aggregates and sand by the treated oil shale ash.
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

Parkinson'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

We 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

Background

We 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.

Methods

A 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.

Results

The 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.

Conclusion

Cyclophosphamide 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

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

The 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

Introduction

Teaching 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.

Methods

Sixty 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.

Results

The 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.

Conclusions

This 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

This 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

The 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

Background

Periodontal 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.

Methods

Baseline 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.

Results

Females 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.

Conclusions

Incident 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

Over 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

Simultaneous 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

Regulatory 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.
Isometric immersions of space forms into Sp×R
Authors: Canevari S. , Tojeiro Ruy
Published: May 2020

In this article we classify isometric immersions of Riemannian manifolds of dimension n and constant sectional curvature into the product space , , where denotes the m‐dimensional unit sphere.
On 4‐dimensional Lorentzian affine hypersurfaces with an almost symplectic form
Authors: Szancer Michal , Szancer Zuzanna
Published: May 2020

In 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

Objective

Examine 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.

Methods

A 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.

Results

Eighty 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.

Conclusions

The AM‐PAC IMSF demonstrates excellent reliability compared with reference rater PTs when performed by PTs during clinical care across surgical, medical and neurological ICUs.
Anticancer molecular mechanisms of oleocanthal
Authors: El Haouari Mohammed , Quintero Juan E. , Rosado Juan A.
Published: May 2020

Cancer is among the leading causes of mortality worldwide. Current cancer therapies are associated with serious side effects, which further damage patients' health. Therefore, the search for new anticancer agents with no toxic effects on normal and healthy cells is of great interest. Recently, we and other groups have demonstrated that oleocanthal (OLC), a phenolic compound from extra virgin olive oil, exhibits antitumor activity in various tumor models. However, the underlying mechanisms and intracellular targets of OLC remain to be completely elucidated. This review summarizes the current advancers concerning the anticancer activity of OLC, with particular emphasis on the molecular signaling pathways modulated by this compound in different tumor cell types. The major mechanisms of action of OLC include modulation of the apoptotic pathway, the HGF/c‐Met pathway, and the signal transducer and activator of transcription 3 signaling pathway, among others. Furthermore, OLC has synergistic effects with anticancer drugs in vitro. Also discussed are OLC bioavailability and its concentration in olive oil. Data summarized here will represent a database for more extensive studies aimed at providing information on molecular mechanisms against cancer induced by OLC.
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

Idelalisib 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.
Bioactive nanomaterials for ion‐interference therapy
Authors: Liu Yanyan , Zhang Meng , Bu Wenbo
Published: May 2020

Ions with biological actions have been exploited to perform a wide range of tasks, including antitumor therapy, termed ion‐interference therapy (IIT). However, single ions or ion‐containing small molecules possess serious limitations for in vivo therapeutic applications due to their short circulation duration, weak discrimination between healthy and tumor tissues, and dose‐limiting systemic toxicity. Bioactive nanomaterials, not only successful targeting tumors but also sufficient generation/release of active species for cell death induction, have attracted enormous interest in IIT due to their potential to tackle the challenges, and are largely the focus of this review.
A description of the likelihood ratios in the probabilistic genotyping software STRmix™
Authors: Kelly Hannah , Bright Jo‐Anne , Coble Michael D. , Buckleton John S.
Published: May 2020

Probabilistic methods of DNA profile interpretation are being adopted by forensic laboratories worldwide. One commonality to all probabilistic genotyping software is an assignment of the strength of evidence using the likelihood ratio (LR). The probabilistic genotyping software STRmix™ reports a number of LRs that differ based on the propositions considered and the level within the hierarchy of propositions considered. Within this paper, we describe the different LRs assigned in a STRmix™ software report.

This article is categorized under:

Forensic Biology > Interpretation of Biological Evidence

Forensic Biology > Forensic DNA Technologies
Legislation-driven development of a Gift Aid system using Event-B
Authors: Williams David M. , Darwish Salaheddin , Schneider Steve , Michael David R.
Published: May 2020

This work presents our approach to formally model the Swiftaid system design, a digital platform that enables donors to automatically add Gift Aid to donations made via card payments. Following principles of Behaviour-Driven Development, we use Gherkin to capture requirements specified in legislation, specifically the UK Charity (Gift Aid Declarations) Regulations 2016. The Gherkin scenarios provide a basis for subsequent formal modelling and analysis using Event-B, Rodin and ProB. Interactive model simulations assist communication between domain experts, software architects and other stakeholders during requirements capture and system design, enabling the emergent system behaviour to be validated. Our approach was employed within the development of the real Swiftaid product, launched by Streeva in February 2019. Our analysis helped conclude that there was not a strong enough business case for one of the features, whichwas shown to provide nominal user convenience at the expense of increased complexity. This work provides a case study in allying formal and agile software development to enable rapid development of robust software.
Suicide by air embolism introduced by means of a bicycle pump
Authors: Falk Jens , Fischer Victoria , Riepert Thomas , Rothschild Markus A.
Published: May 2020

A 64-year-old man was found dead in bed in his flat. In his right hand he held a bicycle pump to which a small-gauge cannula was attached and two fresh puncture wounds were found on his left hand. During the autopsy an air embolism of ca. 50 ml air was detected in the right ventricle of the heart by means of an aspirometer. The air embolism could not be reliably detected in a thorax radiograph taken prior to autopsy. Blood in the right ventricle was foamy. Pathological changes to organs were not found. Aside from the puncture wounds, there were no signs of externally applied mechanical force. The results of the toxicological analyses were negative.
Schrubber als Tatwaffe
Authors: Wirth I. , Schulz R. , Schmidt S. , Schmeling A.
Published: May 2020

Es wird über einen Fall häuslicher Gewalt berichtet, bei dem die 86-jährige Ehefrau ihren gleichaltrigen, an Demenz leidenden Ehemann durch vielfache stumpfe Gewalteinwirkungen tötete. Als Tatwerkzeug kam ein Schrubber zum Einsatz. Richtungweisend für die Identifizierung des Schrubbers als Tatwaffe waren die zahlreichen gruppiert angeordneten, rundlichen, kleinfleckigen Hautabschürfungen sowie die gruppiert angeordneten, kleinfleckigen Hautunterblutungen, die sich den Borstenbüscheln eines Schrubbers zuordnen ließen. Todesursächlich war ein Verbluten in die Weichteile. Eine Fettembolie wurde histologisch ausgeschlossen. In einem Sicherungsverfahren wurde für die Ehefrau aufgrund einer Alzheimer-Demenz mit dadurch bedingter mangelnder Steuerungsfähigkeit die Unterbringung in einem psychiatrischen Krankenhaus angeordnet.
Clinical and cost-effectiveness of physiotherapy interventions following total hip replacement: a systematic review and meta-analysis
Authors: Fatoye Francis , Wright J. M. , Yeowell G. , Gebrye T.
Published: May 2020

To examine the reported clinical and cost-effectiveness of physiotherapy interventions following total hip replacement (THR). A systematic review was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, CINAHL, AMED, Scopus, DARE, HTA, and NHS EED databases were searched for studies on clinical and cost-effectiveness of physiotherapy in adults with THR published up to March 2020. Studies meeting the inclusion criteria were identified and key data were extracted. Risk of bias was assessed using the Cochrane Risk of Bias Tool and a Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Data were summarised and combined using random-effect meta-analysis. A total of 1263 studies related to the aim of the review were identified, from which 20 studies met the inclusion criteria and were included in the review. These studies were conducted in Australia (n = 3), Brazil (n = 1), United States of America (USA) (n = 2), France (n = 2), Italy (n = 2), Germany (n = 3), Ireland (n = 1), Norway (n = 2), Canada (n = 1), Japan (n = 1), Denmark (n = 1), and United Kingdom (UK) (n = 1). The duration of follow-up of the included studies was ranged from 2 weeks to 12 months. Physiotherapy interventions were found to be clinically effective for functional performance, hip muscle strength, pain, and range of motion flexion. From the National Health Service perspective, an accelerated physiotherapy programme following THR was cost-effective. The findings of the review suggest that physiotherapy interventions were clinically effective for people with THR. However, questions remain on the pooled cost-effectiveness of physiotherapy interventions, and further research is required to examine this in patients with THR. Future studies are required to examine the cost-effectiveness of these interventions from patients, caregivers, and societal perspectives.

Registration Prospero(ID: CRD42018096524).
Ratio F test for testing simultaneous hypotheses in models with blocked compound symmetric covariance structure
Authors: Zmyślony Roman , Kozioł Arkadiusz
Published: May 2020

This article deals with testing simultaneous hypotheses about the mean structure and the covariance structure in models with blocked compound symmetric (BCS) covariance structure. Considered models are used for double multivariate data, which means that m-variate vector of observation is measured repeatedly over u levels of some factor on each of n individual. Additionally, the assumption of multivariate normality for this type of data is made. We use framework of ratio of positive and negative parts of best unbiased estimators to obtain simultaneous F test. The test statistic is constructed as a ratio of test statistics for testing single hypotheses about the mean vector and the covariance matrix. In simulation study power of obtained test is compared with powers of three other F tests—two for testing single hypotheses and one for testing simultaneous hypotheses, whose test statistic is convex combination of test statistics of these two single F tests. The problem of simultaneous testing of the mean vector and covariance matrix was also consider in paper (Hyodo and Nishiyama, Commun Stat Theory Methods, 10.1080/03610926.2019.1639751, 2019).