bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Cell Lung Cancer Therapeutic Responses Through Fractal Measurements: From Radiology to Mitochondrial Biology
Authors: Mambetsariev Isa , Mirzapoiazova Tamara , Lennon Frances , Jolly Mohit Kumar , Li Haiqing , Nasser Mohd W. , Vora Lalit , Kulkarni Prakash , Batra Surinder K. , Salgia Ravi
Published: July 2019

Small cell lung cancer (SCLC) is an aggressive neuroendocrine disease with an overall 5 year survival rate of ~7%. Although patients tend to respond initially to therapy, therapy-resistant disease inevitably emerges. Unfortunately, there are no validated biomarkers for early-stage SCLC to aid in early detection. Here, we used readouts of lesion image characteristics and cancer morphology that were based on fractal geometry, namely fractal dimension (FD) and lacunarity (LC), as novel biomarkers for SCLC. Scanned tumors of patients before treatment had a high FD and a low LC compared to post treatment, and this effect was reversed after treatment, suggesting that these measurements reflect the initial conditions of the tumor, its growth rate, and the condition of the lung. Fractal analysis of mitochondrial morphology showed that cisplatin-treated cells showed a discernibly decreased LC and an increased FD, as compared with control. However, treatment with mdivi-1, the small molecule that attenuates mitochondrial division, was associated with an increase in FD as compared with control. These data correlated well with the altered metabolic functions of the mitochondria in the diseased state, suggesting that morphological changes in the mitochondria predicate the tumor’s future ability for mitogenesis and motogenesis, which was also observed on the CT scan images. Taken together, FD and LC present ideal tools to differentiate normal tissue from malignant SCLC tissue as a potential diagnostic biomarker for SCLC.
Electrospun Polyethylene Terephthalate Nanofibers Loaded with Silver Nanoparticles: Novel Approach in Anti-Infective Therapy
Authors: Grumezescu Alexandru Mihai , Stoica Alexandra Elena , Dima-Bălcescu Mihnea-Ștefan , Chircov Cristina , Gharbia Sami , Baltă Cornel , Roșu Marcel , Herman Hildegard , Holban Alina Maria , Ficai Anton , Vasile Bogdan Stefan , Andronescu Ecaterina , Chifiriuc Mariana Carmen , Hermenean Anca
Published: July 2019

Polyethylene terephthalate (PET) is a major pollutant polymer, due to its wide use in food packaging and fiber production industries worldwide. Currently, there is great interest for recycling the huge amount of PET-based materials, derived especially from the food and textile industries. In this study, we applied the electrospinning technique to obtain nanostructured fibrillary membranes based on PET materials. Subsequently, the recycled PET networks were decorated with silver nanoparticles through the chemical reduction method for antimicrobial applications. After the characterization of the materials in terms of crystallinity, chemical bonding, and morphology, the effect against Gram-positive and Gram-negative bacteria, as well as fungal strains, was investigated. Furthermore, in vitro and in vivo biocompatibility tests were performed in order to open up potential biomedical applications, such as wound dressings or implant coatings. Silver-decorated fibers showed lower cytotoxicity and inflammatory effects and increased antibiofilm activity, thus highlighting the potential of these systems for antimicrobial purposes.
Novel SFRP2 DNA Methylation Profile Following Neoadjuvant Therapy in Colorectal Cancer Patients with Different Grades of BMI
Authors: Cabrera-Mulero Amanda , Crujeiras Ana , Izquierdo Andrea , Torres Esperanza , Ayers Duncan , Casanueva Felipe , Tinahones Francisco , Morcillo Sonsoles , Macias-Gonzalez Manuel
Published: July 2019

The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant SFRP2 methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of SFRP2 in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI < 25.0 kg/m2 and BMI > 25.0 kg/m2. SFRP2 DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between SFRP2 methylation levels and BMI in CRC tumor samples. The correlation of SFRP2 hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor SFRP2 hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for SFRP2 in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary results.
Nutritional Management and Outcomes in Malnourished Medical Inpatients: Anorexia Nervosa
Authors: Cuerda Cristina , Vasiloglou Maria F. , Arhip Loredana
Published: July 2019

Background: Anorexia Nervosa (AN) is a psychiatric disorder characterised by a physical and psychosocial deterioration due to an altered pattern on the intake and weight control. The severity of the disease is based on the degree of malnutrition. The objective of this article is to review the scientific evidence of the refeeding process of malnourished inpatients with AN; focusing on the clinical outcome. Methods: We conducted an extensive search in Medline and Cochrane; on April 22; 2019; using different search terms. After screening all abstracts; we identified 19 papers that corresponded to our inclusion criteria. Results: The article focuses on evidence on the characteristics of malnutrition and changes in body composition; energy and protein requirements; nutritional treatment; physical activity programmes; models of organisation of the nutritional treatment and nutritional support related outcomes in AN patients. Conclusion: Evidence-based standards for clinical practice with clear outcomes are needed to improve the management of these patients and standardise the healthcare process.
Water Uptake in PHBV/Wollastonite Scaffolds: A Kinetics Study
Authors: Ribas Renata G. , Montanheiro Thaís L. A. , Montagna Larissa S. , Prado Renata Falchete do , Lemes Ana Paula , Bastos Campos Tiago M. , Thim Gilmar P.
Published: July 2019

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a widely studied polymer and it has been found that porous PHBV materials are suitable for substrates for cell cultures. A crucial factor for scaffolds designed for tissue engineering is the water uptake. This property influences the transport of water and nutrients into the scaffold, which promotes cell growth. PHBV has significant hydrophobicity, which can harm the production of cells. Thus, the addition of α-wollastonite (WOL) can modify the PHBV scaffold’s water uptake. To our knowledge, a kinetics study of water uptake of α-wollastonite phase powder and the PHBV matrix has not been reported. In this work, PHBV and WOL, (PHBV/WOL) films were produced with 0, 5, 10, and 20 wt % of WOL. Films were characterized, and the best concentrations were chosen to produce PHBV/WOL scaffolds. The addition of WOL in concentrations up to 10 wt % increased the cell viability of the films. MTT analysis showed that PHBV/5%WOL and PHBV/10%WOL obtained cell viability of 80% and 98%, respectively. Therefore, scaffolds with 0, 5 and 10 wt % of WOL were fabricated by thermally induced phase separation (TIPS). Scaffolds were characterized with respect to morphology and water uptake in assay for 65 days. The scaffold with 10 wt % of WOL absorbed 44.1% more water than neat PHBV scaffold, and also presented a different kinetic mechanism when compared to other samples. Accordingly, PHBV/WOL scaffolds were shown to be potential candidates for biological applications.
Longitudinal Changes in CD4+, CD8+ T Cell Phenotype and Activation Marker Expression Following Antiretroviral Therapy Initiation among Patients with Cryptococcal Meningitis
Authors: Bayiyana Alice , Okurut Samuel , Nabatanzi Rose , Zziwa Godfrey , Boulware David R. , Lutwama Fredrick , Meya David
Published: July 2019

Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.
Determination of Risk Factors for Venous Thromboembolism by an Adapted Caprini Scoring System in Surgical Patients
Authors: Hanh Bui My , Cuong Le Quang , Son Nguyen Truong , Duc Duong Tuan , Hung Tran Tien , Hung Duong Duc , Giang Tran Binh , Hiep Nguyen Hoang , Xuyen Hoang Thi Hong , Nga Nguyen Thi , Chu Dinh-Toi
Published: July 2019

Venous thromboembolism (VTE) is a frequent preventable complication among surgical patients. Precise risk assessment is a necessary step for providing appropriate thromboprophylaxis and reducing mortality as well as morbidity caused by VTE. We carried out this work to define the rate of VTE postoperatively, following a Caprini score, and to determine VTE risk factors through a modified Caprini risk scoring system. This multicenter, observational, cohort study involved 2,790,027 patients who underwent surgery in four Vietnamese hospitals from 01/2017 to 12/2018. All patients who were evaluated before surgery by using a Caprini risk assessment model (RAM) and monitored within 90 days after surgery. The endpoint of the study was ultrasound-confirmed VTE. Our data showed that the 90-day postoperative VTE was found in 3068 patients. Most of VTE (46.97%) cases were found in the highest risk group (Caprini score > 5). A total of 37.19% were observed in the high risk group, while the rest (15.84%) were from low to moderate risk groups. The likelihood of occurring VTE was heightened 2.83 times for patients with a Caprini score of 3–4, 4.83 times for a Caprini score of 5–6, 8.84 times for a score of 7–8, and 11.42 times for a score of >8, comparing to ones with a score of 0 to 2 (all p values < 0.05). Thus, the frequency of postoperative VTE rises substantially, according to the advanced Caprini score. Further categorizing patients among the highest risk group need delivering more appropriate thromboprophylaxis.
Dealing with Low Interest Rates in Life Insurance: An Analysis of Additional Reserves in the German Life Insurance Industry
Authors: Eckert Christian
Published: July 2019

Interest rates have been very low for several years, which is particularly challenging for life insurers. Since 2001, German life insurers have had to set an additional reserve due to low interest rates to ensure the protection of policyholders. However, the method introduced at that time to calculate these reserves was criticized, therefore, the German Federal Ministry of Finance replaced it with a new approach. In this article, we investigated the effects of the different methods on a typical German life insurer in various future interest rate scenarios and from various perspectives. For this purpose, we modelled such a life insurer holistically, considered its asset liability management and projected its future development in different interest rate scenarios using simulation techniques. Taking into account dependencies between assets, liabilities and interest rates, we analyzed and discussed our results from the life insurer’s, equity holders’, policyholders’ and regulators’ perspectives. The results show that the new method eliminated the weaknesses of the previous one and seems to be a suitable alternative to determine the additional reserve.
Operationalizing Vulnerability: Land System Dynamics in a Transfrontier Conservation Area
Authors: Gaughan Andrea Elizabeth , Stevens Forrest Robert , Pricope Narcisa Gabriela , Hartter Joel , Cassidy Lin , Salerno Jonathan
Published: July 2019

Understanding how individuals, communities, and populations vary in their vulnerability requires defining and identifying vulnerability with respect to a condition, and then developing robust methods to reliably measure vulnerability. In this study, we illustrate how a conceptual model translated via simulation can guide the real-world implementation of data collection and measurement of a model system. We present a generalizable statistical framework that specifies linkages among interacting social and biophysical components in complex landscapes to examine vulnerability. We use the simulated data to present a case study in which households are vulnerable to conditions of land function, which we define as the provision of goods and services from the surrounding environment. We use an example of a transboundary region of Southern Africa and apply a set of hypothesized, simulated data to illustrate how one might use the framework to assess vulnerability based on empirical data. We define vulnerability as the predisposition of being adversely affected by environmental variation and its impacts on land uses and their outcomes as exposure (E), mediated by sensitivity (S), and mitigated by adaptive capacity (AC). We argue that these are latent, or hidden, characteristics that can be measured through a set of observable indicators. Those indicators and the linkages between latent variables require model specification prior to data collection, critical for applying the type of modeling framework presented. We discuss the strength and directional pathways between land function and vulnerability components, and assess their implications for identifying potential leverage points within the system for the benefit of future policy and management decisions.
Design and Analysis of a Lightweight Composite Shipping Container Made of Carbon Fiber Laminates
Authors: Yildiz Turkay
Published: July 2019

The literature indicates that a 20% reduction in the weight of empty 40-foot shipping containers would result in $28 billion of fuel savings, along with a 3.6 exajoule reduction in the energy demand over containers’ 15-year lifetime. Decreasing the energy demand and thereby greenhouse gas emissions by utilizing lightweight shipping containers has been an unexplored strategy. In this regard, this study investigates the possibility of further reducing the weight of an empty container without compromising the structural integrity, strength, and function of a traditional steel container. This research finds that up to an 80% reduction in weight is possible by producing shipping containers with composite materials. This research presents the new design of a 40-foot container made of carbon fiber laminates. The tare weight of a traditional 40-foot shipping container is around 3750 kg. On the contrary, in this research, the weight of a composite design of the same container is calculated to be around 822 kg. Additional tests with various loads, such as lifting the container and stacking loads onto the composite container, are performed to explore the strength and buckling issues of the design presented in this study. The analyses reveal that the composite shipping container is a highly promising candidate for reducing greenhouse gas emissions, providing fuel savings and thus reducing the operational costs of transportation.
Inspection Plan Based on the Process Capability Index Using the Neutrosophic Statistical Method
Authors: Aslam Muhammad , Albassam Mohammed
Published: July 2019

The Process Capability Index (PCI) has been widely used in industry to advance the quality of a product. Neutrosophic statistics is the more generalized form of classical statistics and is applied when the data from the production process or a product lot is incomplete, incredible, and indeterminate. In this paper, we will originally propose a variable sampling plan for the PCI using neutrosophic statistics. The neutrosophic operating function will be given. The neutrosophic plan parameters will be determined using the neutrosophic optimization solution. A comparison between plans based on neutrosophic statistics and classical statistics is given. The application of the proposed neutrosophic sampling plan will be given using company data.
Analytical Solution for Multi-Energy Groups of Neutron Diffusion Equations by a Residual Power Series Method
Authors: Shqair Mohammed , El-Ajou Ahmad , Nairat Mazen
Published: July 2019

In this paper, a multi-energy groups of a neutron diffusion equations system is analytically solved by a residual power series method. The solution is generalized to consider three different geometries: slab, cylinder and sphere. Diffusion of two and four energy groups of neutrons is specifically analyzed through numerical calculation at certain boundary conditions. This study revels sufficient analytical description for radial flux distribution of multi-energy groups of neutron diffusion theory as well as determination of each nuclear reactor dimension in criticality case. The generated results are compatible with other different methods data. The generated results are practically efficient for neutron reactors dimension.
Effects of Physical Exercise Intervention on Psychological and Physical Fitness in Lymphoma Patients
Authors: Fischetti Francesco , Greco Gianpiero , Cataldi Stefania , Minoia Carla , Loseto Giacomo , Guarini Attilio
Published: July 2019

Background and objectives: Lymphoma patients experience a psychological and physiological decline that could be reversed by exercise. However, little is known about the effects of the exercise on psychological and physical fitness variables. Therefore, the purpose of this longitudinal study was to assess self-efficacy, fatigue and physical fitness before and after an eight-week exercise intervention. Materials and Methods: Thirty-six participants (54.4 ± 19.1 years) performed a supervised exercise program (~60 min, 2d·wk−1). Each session included a combined progressive training of cardiorespiratory, resistance, flexibility and postural education exercises. Self-efficacy and fatigue were measured with the Regulatory Emotional Self-Efficacy scale and 0–10 rating scale, respectively. Physical fitness was assessed with the body mass index, lower back flexibility, static balance, muscle strength and functional mobility. Results: Adherence to exercise was high (91.2% ± 4.8%) and no major health problems were noted in the patients over the intervention period. At baseline, significant differences were found between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma patients by age and all dependent measures (p < 0.05). Fatigue significantly decreased and the perceived capability to regulate negative affect and to express positive emotions improved after exercise (p < 0.001). Significant improvements were found for body mass index, trunk lateral flexibility, monopodalic balance, isometric handgrip force and functional mobility (p < 0.001). Fatigue was significantly correlated with handgrip force (r = −0.56, p < 0.001) and functional mobility (r = −0.69, p < 0.001). Conclusions: The supervised exercise program improved psychological and physical fitness without causing adverse effects and health problems. Therefore, exercise to improve fitness levels and reduce perceived fatigue should be considered in the management of lymphoma patients.
Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach
Authors: Bonino Barbara , Leoncini Giovanna , De Cosmo Salvatore , Greco Eulalia , Russo Giuseppina T. , Giandalia Annalisa , Viazzi Francesca , Pontremoli Roberto
Published: July 2019

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin–angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin–angiotensin–aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype.
Symmetrical Peripheral Gangrene Associated with Low Output Cardiac Failure
Authors: Basnet Sijan , Rajagopalan Priya , Dhital Rashmi , Qureshi Ataul
Published: July 2019

Symmetrical peripheral gangrene (SPG) is a rare entity characterized by ischemic changes of the distal extremities with maintained vascular integrity. We present the case of a 64-year-old man with bilateral necrotic toes and deranged liver function tests. This was thought to be related to severely depressed ejection fraction from non-ischemic etiology, presumably chronic alcohol ingestion. We hope that awareness of SPG and association with a low output state will aid in early detection and prevention.
Key Molecular Events in Cervical Cancer Development
Authors: Balasubramaniam Shandra Devi , Balakrishnan Venugopal , Oon Chern Ein , Kaur Gurjeet
Published: July 2019

Cervical cancer is the fourth most common cancer among women. Infection by high-risk human papillomavirus (HPV) is the main aetiology for the development of cervical cancer. Infection by high-risk human papillomavirus (HPV) and the integration of the HPV genome into the host chromosome of cervical epithelial cells are key early events in the neoplastic progression of cervical lesions. The viral oncoproteins, mainly E6 and E7, are responsible for the initial changes in epithelial cells. The viral proteins inactivate two main tumour suppressor proteins, p53, and retinoblastoma (pRb). Inactivation of these host proteins disrupts both the DNA repair mechanisms and apoptosis, leading to rapid cell proliferation. Multiple genes involved in DNA repair, cell proliferation, growth factor activity, angiogenesis, as well as mitogenesis genes become highly expressed in cervical intraepithelial neoplasia (CIN) and cancer. This genomic instability encourages HPV-infected cells to progress towards invasive carcinoma. The key molecular events involved in cervical carcinogenesis will be discussed in this review.
Effects of Boron Addition on the Microstructure and Mechanical Properties of (Ti,Ta)(C,N)-Co Based Cermets
Authors: Chicardi Ernesto , Gotor Martínez Francisco José
Published: July 2019

In this work, a titanium–tantalum carbonitride based cermet, with cobalt as the binder phase and boron as a sintering additive, was developed by a mechanically induced self-sustaining reaction process using two different methodologies. The boron additive was added to prevent the formation of brittle intermetallic compounds generally formed during the liquid phase sintering step due to the excessive ceramic dissolution into the molten binder phase. A systematic study was carried out to understand the effects of boron addition on the nature of the phases, microstructure, and mechanical properties of cermets. With the boron addition, the formation of two different boride solid solutions, i.e., (Ti,Ta)B2 and (Ti,Ta)3B4, was observed. Moreover, the nature of the binder was also modified, from the (Ti,Ta)Co2 brittle intermetallic compound (for cermets without boron addition) to ductile and tough (Ti,Ta)Co3 and α-Co phases (for cermets with boron addition). These modifications caused, as a general trend, the increase of hardness and toughness in cermets.
Hot Rolling Simulation System for Steel Based on Advanced Meshless Solution
Authors: Hanoglu Umut , Šarler Božidar
Published: July 2019

In this work, a rolling simulation system for the hot rolling of steel is elaborated. The system is capable of simulating rolling of slabs and blooms, as well as round or square billets, in different symmetric or asymmetric forms in continuous, reversing, or combined rolling. Groove geometries are user-defined and an arbitrary number of rolling stands and distances between them may be used. A slice model assumption is considered, which allows the problem to be efficiently coped with. The related large-deformation thermomechanical problem is solved by the novel meshless Local Radial Basis Function Collocation Method. A compression test is used to compare the simulation results with the Finite Element Method. A user-friendly rolling simulation application has been created for the industrial use based on C# and .NET framework. Results of the simulation, directly taken from the system, are shown for each type of the rolling mill configurations.
Carbon Redistribution Process in Austempered Ductile Iron (ADI) During Heat Treatment—APT and Synchrotron Diffraction Study
Authors: Li Xiaohu , Wagner Julia N. , Stark Andreas , Koos Robert , Landesberger Martin , Hofmann Michael , Fan Guohua , Gan Weimin , Petry Winfried
Published: July 2019

In-situ synchrotron diffraction and atom probe tomography (APT) have been used to study the carbon diffusion and redistribution process in austempered ductile iron (ADI) during austempering. The process of carbon content change in bainitic ferrite during different austempering temperatures has been determined quantitatively. The transformation in ADI is controlled by decarburization of supersaturated ferrite and carbide precipitation and has been found to be divided into three stages based on a model developed for bainitic steels by Takahashi and Bhadeshia. The formation, morphology and composition of carbides and carbon clusters in ferrite after austempering have been identified unequivocally by APT. Finally, the relationships of carbon content in ferrite, carbon gap values, and austempering temperatures in the ADI alloy were expressed using empirical equations.
Extraction of Carotenoids and Fat-Soluble Vitamins from Tetradesmus Obliquus Microalgae: An Optimized Approach by Using Supercritical CO2
Authors: Chronopoulou Laura , Dal Bosco Chiara , Di Caprio Fabrizio , Prosini Letizia , Gentili Alessandra , Pagnanelli Francesca , Palocci Cleofe
Published: July 2019

In recent years, great attention has been focused on rapid, selective, and environmentally friendly extraction methods to recover pigments and antioxidants from microalgae. Among these, supercritical fluid extraction (SFE) represents one of the most important alternatives to traditional extraction methods carried out with the use of organic solvents. In this study, the influence of parameters such as pressure, temperature, and the addition of a polar co-solvent in the SFE yields of carotenoids and fat-soluble vitamins from T. obliquus biomass were evaluated. The highest extraction of alpha-tocopherol, gamma-tocopherol, and retinol was achieved at a pressure of 30 MPa and a temperature of 40 °C. It was observed that overall, the extraction yield increased considerably when a preliminary step of sample pre-treatment, based on a matrix solid phase dispersion, was applied using diatomaceous earth as a dispersing agent. The use of ethanol as a co-solvent, under certain conditions of pressure and temperature, resulted in selectively increasing the yields of only some compounds. In particular, a remarkable selectivity was observed if the extraction was carried out in the presence of ethanol at 10 MPa and 40 °C: under these conditions, it was possible to isolate menaquinone-7, a homologous of vitamin K2, which, otherwise, cannot not recovered by using traditional extraction procedures.
Potential Photoprotective Effect of Dietary Corn Silk Extract on Ultraviolet B-Induced Skin Damage
Authors: Kim Yeon-hee , Cho Amy , Kwon Sang-Ah , Kim Minju , Song Mina , Han Hye won , Shin Eun-Ji , Park Eunju , Lee Seung-Min
Published: July 2019

Ultraviolet B (UVB) irradiation causes adverse effects on the skin. Corn silk contains flavonoids and other bioactive compounds and antioxidants, which may prevent skin photoaging through antioxidant and anti-inflammatory effects. We aimed to investigate the potential photoprotective effects of dietary corn silk on UVB-induced skin damage in mice and the mechanisms behind these effects on human skin cells. Oral administration of corn silk water extract (CS) (2 or 4 g/kg/day) for 19 weeks decreased epidermal thickness, wrinkle formation, and positive staining for PCNA, Ki67, and 8-OHdG, and increased collagen staining in UVB-irradiated SKH-1 hairless mice compared with controls. The pro-inflammatory NF-κB target genes (IL-1β, iNOS, and COX-2) and MMP-9 expressions were lower in the CS groups, and TGF-β/Smad signaling increased. Low skin lipid peroxidation and blood DNA oxidation levels and high blood glutathione were detected. Antioxidant transcription factor Nrf2-related catalase and SOD1 proteins and glutaredoxin mRNA levels increased. The results of CS extract treatment and UVB irradiation in HaCaT cells showed the same results in Nrf2 and NF-κB target genes. An LC-MS/MS analysis showed that the CS extract contained potential antioxidants, which might have contributed to its anti-photoaging effects in tissues and cells. CS extract may reduce UVB-induced skin damage through antioxidant and anti-inflammatory mechanisms.
Discovery of Immunoproteasome Inhibitors Using Large-Scale Covalent Virtual Screening
Authors: Scarpino Andrea , Bajusz Dávid , Proj Matic , Gobec Martina , Sosič Izidor , Gobec Stanislav , Ferenczy György G. , Keserű György M.
Published: July 2019

Large-scale virtual screening of boronic acid derivatives was performed to identify nonpeptidic covalent inhibitors of the β5i subunit of the immunoproteasome. A hierarchical virtual screening cascade including noncovalent and covalent docking steps was applied to a virtual library of over 104,000 compounds. Then, 32 virtual hits were selected, out of which five were experimentally confirmed. Biophysical and biochemical tests showed micromolar binding affinity and time-dependent inhibitory potency for two compounds. These results validate the computational protocol that allows the screening of large compound collections. One of the lead-like boronic acid derivatives identified as a covalent immunoproteasome inhibitor is a suitable starting point for chemical optimization.
Use of 1H NMR to Detect the Percentage of Pure Fruit Juices in Blends
Authors: Marchetti Lucia , Pellati Federica , Benvenuti Stefania , Bertelli Davide
Published: July 2019

The consumption of high-nutritional-value juice blends is increasing worldwide and, considering the large market volume, fraud and adulteration represent an ongoing problem. Therefore, advanced anti-fraud tools are needed. This study aims to verify the potential of 1H NMR combined with partial least squares regression (PLS) to determine the relative percentage of pure fruit juices in commercial blends. Apple, orange, pineapple, and pomegranate juices were selected to set up an experimental plan and then mixed in different proportions according to a central composite design (CCD). NOESY (nuclear Overhauser enhancement spectroscopy) experiments that suppress the water signal were used. Considering the high complexity of the spectra, it was necessary to pretreat and then analyze by chemometric tools the large amount of information contained in the raw data. PLS analysis was performed using venetian-blind internal cross-validation, and the model was established using different chemometric indicators (RMSEC, RMSECV, RMSEP, R2CAL, R2CV, R2PRED). PLS produced the best model, using five factors explaining 94.51 and 88.62% of the total variance in X and Y, respectively. The present work shows the feasibility and advantages of using 1H NMR spectral data in combination with multivariate analysis to develop and optimize calibration models potentially useful for detecting fruit juice adulteration.
Overexpression of Pear (Pyrus pyrifolia) CAD2 in Tomato Affects Lignin Content
Authors: Li Mingtong , Cheng Chenxia , Zhang Xinfu , Zhou Suping , Li Lixia , Yang Shaolan
Published: July 2019

PpCAD2 was originally isolated from the ‘Wangkumbae’ pear (Pyrus pyrifolia Nakai), and it encodes for cinnamyl alcohol dehydrogenase (CAD), which is a key enzyme in the lignin biosynthesis pathway. In order to verify the function of PpCAD2, transgenic tomato (Solanum lycopersicum) ‘Micro-Tom’ plants were generated using over-expression constructs via the agrobacterium-mediated transformation method. The results showed that the PpCAD2 over-expression transgenic tomato plant had a strong growth vigor. Furthermore, these PpCAD2 over-expression transgenic tomato plants contained a higher lignin content and CAD enzymatic activity in the stem, leaf and fruit pericarp tissues, and formed a greater number of vessel elements in the stem and leaf vein, compared to wild type tomato plants. This study clearly indicated that overexpressing PpCAD2 increased the lignin deposition of transgenic tomato plants, and thus validated the function of PpCAD2 in lignin biosynthesis.
Divergent Effects of Resveratrol on Rat Cardiac Fibroblasts and Cardiomyocytes
Authors: Lieben Louis Xavier , Meikle Zach , Chan Laura , DeGagne Garret , Cummer Rebecca , Meikle Shannon , Krishnan Sampath , Yu Liping , Netticadan Thomas , Wigle Jeffrey T.
Published: July 2019

In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling.
Influence of Zn+2 Doping on Ni-Based Nanoferrites; (Ni1−x ZnxFe2O4)
Authors: Khan Sadaf Bashir , Irfan Syed , Lee Shern-Long
Published: July 2019

Nickel zinc nanoferrites (Ni1−xZnxFe2O4) were synthesized via a chemical co-precipitation method having stoichiometric proportion (x) altering from 0.00 to 1.00 in steps of 0.25. The synthesized nanoparticles were sintered at 800 °C for 12 h. X-ray diffraction patterns illustrate that the nanocrystalline cubic spinel ferrites have been obtained after sintering. The Scherrer formula is used to evaluate the particle size using the extreme intense peak (311). The experimental results demonstrate that precipitated particles’ size was in the range of 20–60 nm. Scanning electron microscopy (SEM) is used to investigate the elemental configuration and morphological characterizations of all the prepared samples. FTIR spectroscopy data for respective sites were examined in the range of 300–1000 cm−1. The higher frequency band ν1 were assigned due to tetrahedral complexes while lower frequency band ν2 were allocated due to octahedral complexes. Our experimental results demonstrate that the lattice constant a0 increases while lattice strain decreases with increasing zinc substitution in nickel zinc nanoferrites.
Non-Milk Extrinsic Sugars Intake and Food and Nutrient Consumption Patterns among Adolescents in the UK National Diet and Nutrition Survey, Years 2008–16
Authors: Lai Heidi T. , Hutchinson Jayne , Evans Charlotte E. L.
Published: July 2019

The revised guidelines from the Department of Health (DoH) in the UK state that mean population intakes of free sugars should be below 5% of the total energy (TE) consumption of the British population. However, very few studies have assessed the impact of this recommendation on diet quality in the UK. We explored the dietary patterns and intakes of micronutrients of British adolescents with low intakes of non-milk extrinsic sugars (NMES) (similar to free sugars but not equal, with slight differences in the categorisation of fruit sugars from dried, stewed or canned fruit and smoothies), using the National Diet and Nutrition Survey Rolling Programme, years 1–8 (NDNS RP). The sample included 2587 adolescents aged 11–18 years. Four percent (112) of adolescents reported consuming 5% or lower NMES as a proportion of TE. The odds of being categorised as a low-sugar consumer in adolescents (≤5% TE from NMES) were significantly lower with higher intakes of sweetened drinks, fruit juice, cakes, biscuits, sugar and sweet spreads, chocolate confectionery and sugar confectionery, and significantly higher with higher intakes of pasta and rice, wholemeal and brown bread, and fish. Across the five categories of NMES intakes, micronutrient intakes were lowest for those consuming either ≤5% TE or more than 20% TE from NMES, and optimal for those consuming between 10–15% of energy from NMES. These findings confirm the difficulties of meeting the free sugars recommended intake for adolescents. Care needs to be taken to ensure that an adequate consumption of micronutrients is achieved in those adhering to the revised guidelines on free sugars.
A Standardized Extract of Asparagus officinalis Stem (ETAS®) Ameliorates Cognitive Impairment, Inhibits Amyloid β Deposition via BACE-1 and Normalizes Circadian Rhythm Signaling via MT1 and MT2
Authors: Chan Yin-Ching , Wu Ci-Sian , Wu Tsai-Chen , Lin Yu-Hsuan , Chang Sue-Joan
Published: July 2019

The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer’s disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS® on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS® consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS® groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS® significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid β (Aβ) in the brain. ETAS® also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS® enhances the cognitive ability, inhibits Aβ deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.
Managing Medical Emergencies in Hungarian Pharmacies
Authors: Felkai Peter P. , Iván Zsolt
Published: July 2019

To amass a body of knowledge for managing emergency situations in pharmacies, we surveyed the occurrence and nature of medical problems in Hungarian pharmacies. The occurrence of real or suspected emergencies in pharmacies was markedly different and varied from 1–52 per year, with five cases per year on average. The most frequent problems were bleeding (69%) and dizziness (55%), but other more serious problems (allergic reaction (32%), collapse (23%), and chest pain (25%)) also occurred. Sometimes more than one symptom was reported by a patient. People appear to consider pharmacies to be an appropriate site for receiving first aid for minor ailments, including common medical problems (e.g., fever (12%)). Unfortunately, the range of interventions was very limited because of local legal regulations and the lack of appropriate guidelines for emergencies in pharmacies. The most frequent interventions were wound treatment, control of bleeding (78%), alleviation of anxiety (68%), and providing patients with a glass of water (55%). Very often, more than one intervention was reported for the same case. Whereas 76.3% of pharmacists provided interventions only for adults, 21% of pharmacists provided interventions for all types of patients (adults, co-workers in pharmacies, and children). Pharmacists appeared to be reluctant to treat children, owing to the special issues related to pediatrics. This poor range of intervention should encourage responsible officials to develop guidelines for pharmacists to ensure pharmacists’ familiarity with the appropriate interventions in emergency situations. Such knowledge could also provide a good basis for preparing pharmacists to perform vaccinations in the future. The pharmacists had a positive attitude toward providing first aid, and 88% of respondents requested more postgraduate education on medical first aid issues.
Growth and Physiological Responses of Temperate Pasture Species to Consecutive Heat and Drought Stresses
Authors: Perera Ruchika S. , Cullen Brendan R. , Eckard Richard J.
Published: July 2019

Heat and drought are two major limiting factors for perennial pasture production in south eastern Australia. Although previous studies have focused on the effects of prolonged heat and drought stresses on pasture growth and physiology, the effects of short term recurring combined heat and drought stresses and the recovery from them have not been studied in detail. A controlled environment experiment was conducted to investigate the growth and physiological responses of perennial ryegrass (Lolium perenne L.), cocksfoot (Dactylis glomerata L.), tall fescue (Festuca arundinacea Schreb.) and chicory (Cichorium intybus L.) plants exposed to two consecutive seven day heat (control = 25/15 °C day/night; moderate = 30/20 °C day/night and severe = 35/30 °C day/night) and/or drought stresses each followed by a seven day recovery period. During the first moderate and severe heat and drought treatments, maximum photochemical efficiency of photosystem II (Fv/Fm), cell membrane permeability and relative leaf water content decreased in chicory and tall fescue compared to perennial ryegrass and cocksfoot. However, during the second moderate heat and drought treatment, all species showed less reduction in the same parameters suggesting that these species acclimated to consecutive moderate heat and drought stresses. Chicory was the only species that was not affected by the second severe heat and drought stress while physiological parameters of all grass species were reduced closer to minimum values. Irrigation mitigated the negative effects of heat stress by cooling the canopies 1–3 °C below air temperatures with the most cooling observed in chicory. All the species exposed to moderate heat and drought were fully recovered and those exposed to severe heat and drought recovered partially at the end of the experiment. These findings suggest that chicory may be a potential species for areas subject to frequent heat and drought stress.
Diversion of Carbon Flux from Sugars to Lipids Improves the Growth of an Arabidopsis Starchless Mutant
Authors: Fan Jilian , Zhou Chao , Yu Linhui , Li Ping , Shanklin John , Xu Changcheng
Published: July 2019

Inactivation of ADP-glucose pyrophosphorylase1 (ADG1) causes a starchless phenotype in Arabidopsis. Mutants defective in ADG1 show severe growth retardation in day/night conditions but exhibit similar growth to wild type under continuous light, implying that starch plays an important role in supporting respiration, metabolism and growth at night. In addition to carbohydrates, lipids and proteins can serve as alternative respiratory substrates for the energy production in mature plants. To test the role of lipids in plant growth, we generated transgenic plants overexpressing phospholipid:diacylglycerol acyltransferase1 (PDAT1) in adg1. We found that PDAT1 overexpression caused an increase in both fatty acid synthesis and turnover and increased the accumulation of triacylglycerol (TAG) at the expense of sugars, and enhanced the growth of adg1. We demonstrated that unlike sugars, which were metabolized within a few hours of darkness, TAG breakdown was slow, occurring throughout the entire dark period. The slow pace of TAG hydrolysis provided a sustained supply of fatty acids for energy production, thereby alleviating energy deficiency at night and thereby improving the growth of the starchless mutants. We conclude that lipids can contribute to plant growth by providing a constant supply of fatty acids as an alternative energy source in mature starchless mutant plants.