bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Risk and Resilient Profiles for Functional Impairment and Baseline Predictors in a 2-Year Follow-Up First-Episode Psychosis Cohort Using Latent Class Growth Analysis
Authors: Salagre Estela , Grande Iria , Solé Brisa , Mezquida Gisela , Cuesta Manuel , Díaz-Caneja Covadonga , Amoretti Silvia , Lobo Antonio , González-Pinto Ana , Moreno Carmen , Pina-Camacho Laura , Corripio Iluminada , Baeza Immaculada , Bergé Daniel , Verdolini Norma , Carvalho André , Vieta Eduard , Bernardo Miquel ,   PEPs Group
Published: December 2020

Being able to predict functional outcomes after First-Episode Psychosis (FEP) is a major goal in psychiatry. Thus, we aimed to identify trajectories of psychosocial functioning in a FEP cohort followed-up for 2 years in order to find premorbid/baseline predictors for each trajectory. Additionally, we explored diagnosis distribution within the different trajectories. A total of 261 adults with FEP were included. Latent class growth analysis identified four distinct trajectories: Mild impairment-Improving trajectory (Mi-I) (38.31% of the sample), Moderate impairment-Stable trajectory (Mo-S) (18.39%), Severe impairment-Improving trajectory (Se-I) (12.26%), and Severe impairment-Stable trajectory (Se-S) (31.03%). Participants in the Mi-I trajectory were more likely to have higher parental socioeconomic status, less severe baseline depressive and negative symptoms, and better premorbid adjustment than individuals in the Se-S trajectory. Participants in the Se-I trajectory were more likely to have better baseline verbal learning and memory and better premorbid adjustment than those in the Se-S trajectory. Lower baseline positive symptoms predicted a Mo-S trajectory vs. Se-S trajectory. Diagnoses of Bipolar disorder and Other psychoses were more prevalent among individuals falling into Mi-I trajectory. Our findings suggest four distinct trajectories of psychosocial functioning after FEP. We also identified social, clinical, and cognitive factors associated with more resilient trajectories, thus providing insights for early interventions targeting psychosocial functioning.
The Bioengineered Combo Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent in Patients with Chronic Total Occlusion Evaluated by Clinical Outcome and Optical Coherence Tomography Imaging Analysis
Authors: Blessing Recha , Ahoopai Majid , Geyer Martin , Brandt Moritz , Zeiher Andreas M. , Münzel Thomas , Wenzel Philip , Gori Tommaso , Dimitriadis Zisis
Published: December 2020

We sought to determine the effects of the use of a Bioengineered Combo Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Coronary Stent (Combo® DTS) in patients with chronic total occlusion (CTO) by evaluating clinical outcomes and by performing an optical coherence tomography (OCT) analysis. We retrospectively analyzed data from 39 patients who had successfully undergone OCT-guided revascularization of a CTO being treated with a Combo® DTS. Clinical assessment, angiography (with quantitative coronary angiography analysis) and OCT examination were performed at baseline and at follow-up. The median follow-up period was 189 days, ranging from 157 to 615 days. At follow-up, revascularization was required due to angiographic restenosis in 40% (14 of 35) of patients. OCT analysis detected neointima proliferation in 23 (76.6%) patients. Neointima formation was often associated with microvessels in 18 patients (60%). Neoatheroslcerosis was observed in 2 (6.6%) patients. Malapposition was found in 4 patients (13.3%), and stent fractures were found in 11 patients (36.6%). Rate of strut coverage was 96.3% at follow-up. In conclusion, the implantation of a Combo® DTS after successful CTO recanalization was associated with a restenosis rate of 40% despite good stent implantation at baseline, proven by OCT. Neointima formation was found as a main contributor to restenosis. Nevertheless, we observed a low rate of major cardiovascular events in our follow-up.
Cerebellar GABA Levels and Cognitive Interference in Parkinson’s disease and Healthy Comparators
Authors: Piras Federica , Vecchio Daniela , Assogna Francesca , Pellicano Clelia , Ciullo Valentina , Banaj Nerisa , Edden Richard A. E. , Pontieri Francesco E. , Piras Fabrizio , Spalletta Gianfranco
Published: December 2020

The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.
The Impact of Working Capital Management on Firm Profitability: Empirical Evidence from the Polish Listed Firms
Authors: Anton Sorin , Afloarei Nucu Anca
Published: December 2020

The purpose of this study is to investigate the relationship between working capital and firm profitability for a sample of 719 Polish listed firms over the period of 2007–2016. The scarcity of empirical evidence for emerging economies and the importance of working capital efficiency motivate the research on the working capital–financial performance relationship. The paper adopts a quantitative approach using different panel data techniques (ordinary least squares, fixed effects, and panel-corrected standard errors models). The empirical results report an inverted U-shape relationship between working capital level and firm profitability, meaning that working capital has a positive effect on the profitability of Polish firms to a break-even point (optimum level). After the break-even point, working capital starts to negatively affect firm profitability. The study brings theoretical and practical contributions. It extends and complements the literature on the field by highlighting new evidence on the non-linear interrelation between working capital management (WCM) and corporate performance in Poland. From the practitioners’ perspective, the results highlight the importance of WCM for firm profitability.
Assessing Architecture-and-Landscape Integration as a Basis for Evaluating the Impact of Construction Projects on the Cultural Landscape of Tourist Seaside Resorts
Authors: Bal Wojciech , Czalczynska-Podolska Magdalena
Published: December 2020

The coastline of Western Pomerania has natural and cultural assets that have promoted the development of tourism, but also require additional measures to ensure the traditional features and characteristics are protected. This is to ensure that new developments conform to a more uniform set of spatial structures which are in line with the original culture. Today, seaside resorts are characterized by a rapid increase in development with a clear trend towards non-physiognomic architectural forms which continually expand and encroach on land closer to the coastline. This results in a blurring of the original concepts that characterized the founding seaside resort. This study evaluates 11 development projects (including a range of hotels, luxury residential buildings and hotel suites) built in 2009–2020 in the coastal area of Western Pomerania. An assessment of architecture-and-landscape integration for each development project was made, using four groups of evaluation criteria: aesthetic, socio-cultural, functional and locational factors. The study methodology included a historical and interpretative study (iconology, iconography, historiography) and an examination of architecture-and-landscape integration using a pre-prepared evaluation form. Each criterion was first assessed using both field surveys and desk research (including the analysis of construction plans and developer materials), and then compared with the original, traditional qualities of the town. This study demonstrates that it is possible to clearly identify the potential negative impact of tourism development on the cultural landscape of seaside resorts, and provides recommendations for future shaping, management and conservation of the landscape.
Analysis of the Effect of the Slip-Pocket in Single and Double Parallel Bearing Considering Cavitation: A Theoretical Approach
Authors: Muchammad M. , Tauviqirrahman Mohammad , Jamari J. , Schipper D. J.
Published: December 2020

In this paper, based on an analytical approach, the effect of pockets and boundary slip on the hydrodynamic performance of parallel sliding surfaces considering cavitation is investigated. A modified Reynolds theory is developed for solving two kinds of bearings: a single and a double pocket bearing. The performance is compared with respect to the variation of the pocket depth, pocket length, slip, and no-slip situation. The results show that the maximum pressure and load support increases with the reduction in pocket length. The main finding is that the pocket depth reduces the cavitation area. However, in the case of a single pocket, the role of pocket depth is more significant in reducing the cavitation effect than that in the case of a double pocket bearing.
Sign, Wilcoxon and Mann-Whitney Tests for Functional Data: An Approach Based on Random Projections
Authors: Meléndez Rafael , Giraldo Ramón , Leiva Víctor
Published: December 2020

Sign, Wilcoxon and Mann-Whitney tests are nonparametric methods in one or two-sample problems. The nonparametric methods are alternatives used for testing hypothesis when the standard methods based on the Gaussianity assumption are not suitable to be applied. Recently, the functional data analysis (FDA) has gained relevance in statistical modeling. In FDA, each observation is a curve or function which usually is a realization of a stochastic process. In the literature of FDA, several methods have been proposed for testing hypothesis with samples coming from Gaussian processes. However, when this assumption is not realistic, it is necessary to utilize other approaches. Clustering and regression methods, among others, for non-Gaussian functional data have been proposed recently. In this paper, we propose extensions of the sign, Wilcoxon and Mann-Whitney tests to the functional data context as methods for testing hypothesis when we have one or two samples of non-Gaussian functional data. We use random projections to transform the functional problem into a scalar one, and then we proceed as in the standard case. Based on a simulation study, we show that the proposed tests have a good performance. We illustrate the methodology by applying it to a real data set.
Calculation and Prediction of Crushing Process of Al–Mg–Si Alloy Thin-Walled Components
Authors: Guo Hui , Deng Yunlai , Fan Shitong , Pan Renjie
Published: December 2020

Crushing performance is being widely investigated because it is the key performance indicator of the thin-walled beam structure in automobile safety components. In this study, five kinds of ageing state with different yield strengths were prefabricated with a self-developed KHC63 alloy. Using a rectangular tube profile, the physical relationship between crushing properties and mechanical properties, and the structure of the profile, were studied. According to variation characteristics, the crushing curve was divided into four typical stages: elastic stage, bending stage, compaction stage and folding stage. In the elastic stage, the peak load of the component is related to material elasticity and structure elasticity, and the relationship is approximately linear. In the bending stage, the driving factor of plastic hinge deformation is the bending moment, and it is always constant. In the compaction stage, the crushing curve correlates well with the cosine function. In the folding stage, the crushing process begins to lose stability and is hard to predict. The mathematical relationships between force and displacement were established according to the characteristics of each stage, and the calculated results were close to the measured results except for the folding stage. The deviation of the calculated energy absorption from the measured data in the first three stages is only 4.3%, but it is 10.6% in the folding stage. The calculation method used for the first three stages is, therefore, suitable.
Microstructure and Mechanical Properties of 6061 Al/AZ31 Mg Joints Friction Stir Lap Welded by a Tool with Variable-Pitch Thread Pin
Authors: He Changshu , Qiu Chengpeng , Zhang Zhiqiang , Wei Jingxun , Zhang Hao , Tian Ni , Qin Gaowu
Published: December 2020

Sheets of 6061-T6 aluminum alloy (thickness = 3 mm) and AZ31 magnesium alloy were friction stir lap welded by a tool with a variable-pitch thread pin (coarse-threaded in the upper part and fine-threaded in the lower part). For the same rotation speed and welding speed, the heat input was higher in joints with an upper Al alloy (Configuration Al-Mg) than in those with an upper Mg alloy (Configuration Mg-Al). In Configuration Al-Mg, these two dissimilar metals were poorly mixed and Al dominated the stirred zone (SZ). Many intermetallic compounds (IMCs) of Al3Mg2 formed inside the SZ. In Configuration Mg-Al, Mg alloy bands, flocculent Al12Mg17 bands, and minor Al alloy bands intersected in the SZ, forming a complex onion-ring structure. Moreover, a complex mechanical interlocking structure developed at the bottom interface of the SZ. The maximum tensile shear strengths of the Al-Mg and Mg-Al lap configurations were 160.3 and 217 N/mm, respectively, at 700 rpm. The higher tensile shear strength of the Mg-Al configuration primarily represented less IMCs and complex mechanical interlocking structures in the SZ.
Influence of Addition of Al and Ti Solutes and Variable Processing Conditions on Mechanical and Electrical Properties of Cu-Cr Alloys
Authors: Cho Chang-Hee , Shin Jesik , Kim Dongearn , Cho Hoon
Published: December 2020

To apply the electric component with high efficiency, the softening problem of material should be improved. Cu-Cr alloys are recognized to be proper materials to be applied. However, the softening problem has not been solved yet. In this study, the effect of Ti and Al on mechanical property and electrical conductivity in Cu-Cr alloy was investigated. Cr content is designed to up to 0.25 wt.% in order to be expected to improve electrical conductivity. During fabrication processing, microstructure identification, Cr concentration, lattice parameter, and micro-hardness in copper matrix were measured. Then, aging condition was investigated. Resistance about over-aging is increased compared to Cu-Cr and Cu-Cr-Al alloy added to Ti. The hardness and electrical conductivity are discussed by the working conditions and heat treatment, such as rolling, solid-solution treatment, and aging process, which improve the formability also at the optimum condition. Moreover, the role of Ti contents is studied. In the Cu-Cr alloys, the addition of both Al and Ti contents keeps the hardness from being reduced. As a result, the precipitation of Cr particles and the obstacle by Al and Ti contents to be softened are observed in this study.
Application of Type-2 Fuzzy AHP-ARAS for Selecting Optimal WEDM Parameters
Authors: Sen Binayak , Hussain Syed Abou Iltaf , Gupta Archisman Das , Gupta Munish Kumar , Pimenov Danil Yurievich , Mikołajczyk Tadeusz
Published: December 2020

Machining of the nickel-based alloy is very demanding due to its extreme mechanical properties, for example, higher fatigue strength, better corrosion and creep resistance feature, substantial work hardening capability, and appreciable tensile and shear strength. Owing to these properties, the selection of machining parameters is a major challenge for modern machining industries. Therefore, the present experimental work is carried out to select the best parametric combination of the wire electrical discharge machining (WEDM) machine for reducing machining cost and human effort. The Trapezoidal Interval Type-2 fuzzy number (T2FS) integrated Analytical Hierarchy Process (AHP)-based Additive Ratio Assessment (ARAS) method is used for selecting the best WEDM process parameters of Inconel-800 superalloy. Finally, the results were compared with some existing multi-criteria decision-making methods to confirm the validity of the adopted method. The comparison shows that Type-2 Fuzzy AHP-ARAS synergy can help to formulate the problem and facilitate the assessment and ranking of WEDM process parameters when multiple criteria are jointly considered.
Study of Microchannels Fabricated Using Desktop Fused Deposition Modeling Systems
Authors: Rehmani Muhammad Asif Ali , Jaywant Swapna A. , Arif Khalid Mahmood
Published: December 2020

Microfluidic devices are used to transfer small quantities of liquid through micro-scale channels. Conventionally, these devices are fabricated using techniques such as soft-lithography, paper microfluidics, micromachining, injection moulding, etc. The advancement in modern additive manufacturing methods is making three dimensional printing (3DP) a promising platform for the fabrication of microfluidic devices. Particularly, the availability of low-cost desktop 3D printers can produce inexpensive microfluidic devices in fast turnaround times. In this paper, we explore fused deposition modelling (FDM) to print non-transparent and closed internal micro features of in-plane microchannels (i.e., linear, curved and spiral channel profiles) and varying cross-section microchannels in the build direction (i.e., helical microchannel). The study provides a comparison of the minimum possible diameter size, the maximum possible fluid flow-rate without leakage, and absorption through the straight, curved, spiral and helical microchannels along with the printing accuracy of the FDM process for two low-cost desktop printers. Moreover, we highlight the geometry dependent printing issues of microchannels, pressure developed in the microchannels for complex geometry and establish that the profiles in which flowrate generates 4000 Pa are susceptible to leakages when no pre or post processing in the FDM printed parts is employed.
Preparation of Microneedle Array Mold Based on MEMS Lithography Technology
Authors: Wang Jie , Wang Huan , Lai Liyan , Li Yigui
Published: December 2020

As a transdermal drug delivery technology, microneedle array (MNA) has the characteristics of painless, minimally invasive, and precise dosage. This work discusses and compares the new MNA mold prepared by our group using MEMS technology. First, we introduced the planar pattern-to-cross-section technology (PCT) method using LIGA (Photolithography, Galvanogormung, Abformung) technology to obtain a three-dimensional structure similar to an X-ray mask pattern. On this basis, combined with polydimethylsiloxane (PDMS) transfer technology and electroplating process, metal MNA can be prepared. The second method is to use silicon wet etching combined with the SU-8 process to obtain a PDMS quadrangular pyramid MNA using PDMS transfer technology. Third method is to use the tilting rotary lithography process to obtain PDMS conical MNA on SU-8 photoresist through PDMS transfer technology. All three processes utilize parallel subtractive manufacturing methods, and the error range of reproducibility and accuracy is 2–11%. LIGA technology produces hollow MNA with an aspect ratio of up to 30, which is used for blood extraction and drug injection. The height of the MNA prepared by the engraving process is about 600 μm, which can achieve a sustained release effect together with a potential systemic delivery. The height of the MNA prepared by the ultraviolet exposure process is about 150 μm, which is used to stimulate the subcutaneous tissue.
Metabolic Engineering of Extremophilic Bacterium Deinococcus radiodurans for the Production of the Novel Carotenoid Deinoxanthin
Authors: Jeong Sun-Wook , Kim Jun-Ho , Kim Ji-Woong , Kim Chae Yeon , Kim Su Young , Choi Yong Jun
Published: December 2020

Deinoxanthin, a xanthophyll derived from Deinococcus species, is a unique organic compound that provides greater antioxidant effects compared to other carotenoids due to its superior scavenging activity against singlet oxygen and hydrogen peroxide. Therefore, it has attracted significant attention as a next-generation organic compound that has great potential as a natural ingredient in a food supplements. Although the microbial identification of deinoxanthin has been identified, mass production has not yet been achieved. Here, we report, for the first time, the development of an engineered extremophilic microorganism, Deinococcus radiodurans strain R1, that is capable of producing deinoxanthin through rational metabolic engineering and process optimization. The genes crtB and dxs were first introduced into the genome to reinforce the metabolic flux towards deinoxanthin. The optimal temperature was then identified through a comparative analysis of the mRNA expression of the two genes, while the carbon source was further optimized to increase deinoxanthin production. The final engineered D. radiodurans strain R1 was able to produce 394 ± 17.6 mg/L (102 ± 11.1 mg/g DCW) of deinoxanthin with a yield of 40.4 ± 1.2 mg/g sucrose and a productivity of 8.4 ± 0.2 mg/L/h from 10 g/L of sucrose. The final engineered strain and the strategies developed in the present study can act as the foundation for the industrial application of extremophilic microorganisms.
Interaction of Styrylpyridinium Compound with Pathogenic Candida albicans Yeasts and Human Embryonic Kidney HEK-293 Cells
Authors: Vaitkienė Simona , Bekere Laura , Duburs Gunars , Daugelavičius Rimantas
Published: December 2020

Candida albicans-caused local and systemic diseases are a serious health issue worldwide, leading to high mycosis-associated morbidity and mortality. Efficient combinations of novel compounds with commonly used antifungals could be an important tool for fighting infections. The aim of this study was to evaluate the interaction of synthesized 4-(4-cyanostyryl)-1-dodecylpyridin-1-ium (CSDP+) bromide alone or in combination with fluconazole with yeast and mammalian cells. We investigated cytotoxicity of the tested agents to mammalian HEK-293 cells and the influence of CSDP+ on the ability of C. albicans wt and a clinical isolate to adhere to HEK-293. Accumulation of lipophilic cation ethidium (Et+) was used to monitor the activity of efflux pumps in HEK-293 cells. The effect of CSDP+ on the expression of the main efflux transporter genes and transcription factors in C.albicans cells as well as HEK-293 efflux pump gene ABCB1 was determined. The study showed that CSDP+ alone and in combination with fluconazole was nontoxic to HEK-293 cells and was able to reduce C.albicans adhesion. The treatment of C.albicans cells with CSDP+ in combination with fluconazole resulted in a considerable overexpression of the MDR1 and MRR1 genes. The findings suggest that these genes could be associated with efflux-related resistance to fluconazole. Measurements of Et+ fluorescence and analysis of ABCB1 gene expression demonstrated that mammalian cells were not sensitive to concentrations of CSDP+ affecting C. albicans.
Azole-Resistant Aspergillus fumigatus Harboring the TR34/L98H Mutation: First Report in Portugal in Environmental Samples
Authors: Gonçalves Paulo , Melo Aryse , Dias Marta , Almeida Beatriz , Caetano Liliana Aranha , Veríssimo Cristina , Viegas Carla , Sabino Raquel
Published: December 2020

Introduction: The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010. In Portugal, the section Fumigati is one of the most frequent, and resistant strains to have been found in clinical and environmental contexts. Although several cryptic species within the Fumigati section show intrinsic resistance to azoles, one factor driving (acquired) resistance is selective pressure deriving from the extensive use of azoles. This is particularly problematic in occupational environments where high fungal loads are expected, and where there is an increased risk of human exposure and infection, with impact on treatment success and disease outcome. The mechanisms of resistance are diverse, but mainly associated with mutations in the cyp51A gene. Despite TR34/L98H being the most frequent mutation described, it has only been detected in clinical specimens in Portugal. Methods: We analyzed 99 A. fumigatus isolates from indoor environments (healthcare facilities, spas, one dairy and one waste sorting unit) collected from January 2018 to February 2019 in different regions of Portugal. Isolates were screened for resistance to itraconazole, voriconazole and posaconazole by culture, and resistance was confirmed by broth microdilution. Sequencing of the cyp51A gene and its promoter was performed to detect mutations associated with resistance. Results: Overall, 8.1% of isolates were able to grow in the presence of at least one azole, and 3% (isolated from the air in a dairy and from filtering respiratory protective devices in a waste sorting industry) were pan-azole-resistant, bearing the TR34/L98H mutation. Conclusion: For the first time in Portugal, we report environmental isolates bearing the TR34/L98H mutation, isolated from occupational environments. Environmental surveillance of the emergence of azole-resistant A. fumigatus sensu stricto strains is needed, to ensure proper and timely implementation of control policies that may have a positive impact on public and occupational health.
Separation of Radionuclides from a Rare Earth-Containing Solution by Zeolite Adsorption
Authors: Talan Deniz , Huang Qingqing
Published: December 2020

The increasing industrial demand for rare earths requires new or alternative sources to be found. Within this context, there have been studies validating the technical feasibility of coal and coal byproducts as alternative sources for rare earth elements. Nonetheless, radioactive materials, such as thorium and uranium, are frequently seen in the rare earths’ mineralization, and causes environmental and health concerns. Consequently, there exists an urgent need to remove these radionuclides in order to produce high purity rare earths to diversify the supply chain, as well as maintain an environmentally-favorable extraction process for the surroundings. In this study, an experimental design was generated to examine the effect of zeolite particle size, feed solution pH, zeolite amount, and contact time of solid and aqueous phases on the removal of thorium and uranium from the solution. The best separation performance was achieved using 2.50 g of 12-µm zeolite sample at a pH value of 3 with a contact time of 2 h. Under these conditions, the adsorption recovery of rare earths, thorium, and uranium into the solid phase was found to be 20.43 wt%, 99.20 wt%, and 89.60 wt%, respectively. The Freundlich adsorption isotherm was determined to be the best-fit model, and the adsorption mechanism of rare earths and thorium was identified as multilayer physisorption. Further, the separation efficiency was assessed using the response surface methodology based on the development of a statistically significant model.
Geochemical Variation of Miocene Basalts within Shikoku Basin: Magma Source Compositions and Geodynamic Implications
Authors: Chen Shuang-Shuang , Hou Tong , Liu Jia-Qi , Zhang Zhao-Chong
Published: December 2020

Shikoku Basin is unique as being located within a trench-ridge-trench triple junction. Here, we report mineral compositions, major, trace-element, and Sr-Nd-Pb isotopic compositions of bulk-rocks from Sites C0012 (>18.9 Ma) and 1173 (13–15 Ma) of the Shikoku Basin. Samples from Sites C0012 and 1173 are tholeiitic in composition and display relative depletion in light rare earth elements (REEs) and enrichment in heavy REEs, generally similar to normal mid-ocean ridge basalts (N-MORB). Specifically, Site C0012 samples display more pronounced positive anomalies in Rb, Ba, K, Pb and Sr, and negative anomalies in Th, U, Nb, and Ta, as well as negative Nb relative to La and Th. Site 1173 basalts have relatively uniform Sr-Nd-Pb isotopic compositions, close to the end member of depleted mantle, while Site C0012 samples show slightly enriched Sr-Nd-Pb isotopic signature, indicating a possible involvement of enriched mantle 1 (EM1) and EM2 sources, which could be attributed to the metasomatism of the fluids released from the dehydrated subduction slab, but with the little involvement of subducted slab-derived sedimentary component. Additionally, the Shikoku Basin record the formation of the back-arc basin was a mantle conversion process from an island arc to a typical MORB. The formation of the Shikoku Basin is different from that of the adjacent Japan Sea and Parece Vela Basin, mainly in terms of the metasomatized subduction-related components, the nature of mantle source, and partial melting processes.
Predictive Quantitative Structure–Activity Relationship Modeling of the Antifungal and Antibiotic Properties of Triazolothiadiazine Compounds
Authors: Appell Michael , Compton David L. , Evans Kervin O.
Published: December 2020

Predictive models were developed using two-dimensional quantitative structure activity relationship (QSAR) methods coupled with B3LYP/6-311+G** density functional theory modeling that describe the antimicrobial properties of twenty-four triazolothiadiazine compounds against Aspergillus niger, Aspergillus flavus and Penicillium sp., as well as the bacteria Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. B3LYP/6-311+G** density functional theory calculations indicated the triazolothiadiazine derivatives possess only modest variation between the frontier orbital properties. Genetic function approximation (GFA) analysis identified the topological and density functional theory derived descriptors for antimicrobial models using a population of 200 models with one to three descriptors that were crossed for 10,000 generations. Two or three descriptor models provided validated predictive models for antifungal and antibiotic properties with R2 values between 0.725 and 0.768 and no outliers. The best models to describe antimicrobial activities include descriptors related to connectivity, electronegativity, polarizability, and van der Waals properties. The reported method provided robust two-dimensional QSAR models with topological and density functional theory descriptors that explain a variety of antifungal and antibiotic activities for structurally related heterocyclic compounds.
Homogeneous Incorporation of Gallium into Layered Double Hydroxide Lattice for Potential Radiodiagnostics: Proof-of-Concept
Authors: Jeung Do-Gak , Kim Tae-Hyun , Oh Jae-Min
Published: December 2020

Trivalent gallium ion was successfully incorporated into chemically well-defined MgAl-layered double hydroxide (LDH) frameworks through postsynthetic hydrothermal treatment. Quantitative analysis with inductively coupled plasma-mass spectroscopy exhibited that Ga3+ was first incorporated into LDH through partial dissolution-precipitation at the edge of LDH particle and homogeneously distributed throughout the particle by substitution of Ga3+ for Al3+ in LDH frame works. The powder X-ray diffraction patterns showed that the Ga3+ incorporation did not affect the crystal structure without evolution of unexpected impurities. The morphology and surface property of LDH evaluated by scanning electron microscopy and light scattering showed the preservation of physicochemical properties throughout 24 h of hydrothermal reaction. The distribution of incorporated Ga3+ was visualized with energy dispersive spectroscopy-assisted transmission electron microscopy, suggesting the homogeneous location of Ga3+ in an LDH particle. The X-ray absorption near-edge structure and extended X-ray absorption fine structure suggested that the Ga moiety was immobilized in LDH from 0.5 h and readily crystallized upon reaction time.
Design and Assessment of a Polyurethane Carrier Used for the Transmembrane Transfer of Acyclovir
Authors: Borcan Florin , Len Adél , Dehelean Cristina A. , Dudás Zoltán , Ghiulai Roxana , Iftode Andrada , Racoviceanu Roxana , Soica Codruta M.
Published: December 2020

The Herpes simplex viruses (HSV-1, HSV-2) are responsible for a wide variety of conditions, from cutaneous-mucosal to central nervous system (CNS) infections and occasional infections of the visceral organs, some of them with a lethal end. Acyclovir is often used intravenously, orally, or locally to treat herpetic infections but it must be administered with caution to patients with kidney disease and to children of early age. The main objectives of this study were to synthesize and evaluate new polyurethane nanoparticles that might be used as proper transmembrane carriers for acyclovir. Polyurethane particles were obtained by a polyaddition process: a mixture of two aliphatic diisocyanates used as organic phase was added to a mixture of butanediol and polyethylene glycol used as aqueous phase. Two different samples (with and without acyclovir, respectively) were synthesized and characterized by UV-Vis spectra in order to assess the encapsulation efficacy and the release profile, FT-IR, DSC, SEM, and SANS for structural characterization, as well as skin irritation tests. Nearly homogeneous samples with particle sizes between 78 and 91 nm have been prepared and characterized revealing a medium tendency to form clusters and a high resistance to heat up to 300 °C. The release profile of these nanoparticles is characteristic to a drug delivery system with a late discharge of the loaded active agents. Very slight increases in the level of transepidermal water loss and erythema were found in a 15-day evaluation on human skin. The results suggest the synthesis of a non-irritative carrier with a high encapsulation efficacy that can be successfully used for the transmembrane transfer of acyclovir.
Nutritional Support in Head and Neck Radiotherapy Patients Considering HPV Status
Authors: Brewczyński Adam , Jabłońska Beata , Mrowiec Sławomir , Składowski Krzysztof , Rutkowski Tomasz
Published: December 2020

Malnutrition is a common problem in patients with head and neck cancer (HNC), including oropharyngeal cancer (OPC). It is caused by insufficient food intake due to dysphagia, odynophagia, and a lack of appetite caused by the tumor. It is also secondary to the oncological treatment of the basic disease, such as radiotherapy (RT) and chemoradiotherapy (CRT), as a consequence of mucositis with the dry mouth, loss of taste, and dysphagia. The severe dysphagia leads to a definitive total impossibility of eating through the mouth in 20–30% of patients. These patients usually require enteral nutritional support. Feeding tubes are a commonly used nutritional intervention during radiotherapy, most frequently percutaneous gastrostomy tube. Recently, a novel HPV-related type of OPC has been described. Patients with HPV-associated OPC are different from the HPV− ones. Typical HPV− OPC is associated with smoking and alcohol abuse. Patients with HPV+ OPC are younger and healthy (without comorbidities) at diagnosis compared to HPV− ones. Patients with OPC are at high nutritional risk, and therefore, they require nutritional support in order to improve the treatment results and quality of life. Some authors noted the high incidence of critical weight loss (CWL) in patients with HPV-related OPC. Other authors have observed the increased acute toxicities during oncological treatment in HPV+ OPC patients compared to HPV− ones. The aim of this paper is to review and discuss the indications for nutritional support and the kinds of nutrition, including immunonutrition (IN), in HNC, particularly OPC patients, undergoing RT/CRT, considering HPV status.
Cultural Influences on the Regulation of Energy Intake and Obesity: A Qualitative Study Comparing Food Customs and Attitudes to Eating in Adults from France and the United States
Authors: Dao Maria Carlota , Thiron Sophie , Messer Ellen , Sergeant Camille , Sévigné Anne , Huart Camille , Rossi Melinda , Silverman Ilyssa , Sakaida Kylie , Bel Lassen Pierre , Sarrat Charlotte , Arciniegas Laura , Das Sai Krupa , Gausserès Nicolas , Clément Karine , Roberts Susan B.
Published: December 2020

(1) Background: The influence of food culture on eating behavior and obesity risk is poorly understood. (2) Methods: In this qualitative study, 25 adults in France with or without overweight/obesity participated in semi-structured interviews (n = 10) or focus groups (n = 15) to examine attitudes to food consumption and external pressures that influence eating behavior and weight management. Results were compared to an equivalent study conducted in the United States, thereby contrasting two countries with markedly different rates of obesity. Emerging key themes in the French data were identified through coding using a reflexive approach. (3) Results: The main themes identified were: (1) influence of commensality, social interactions, and pleasure from eating on eating behavior, (2) having a balanced and holistic approach to nutrition, (3) the role of environmental concerns in food consumption, (4) relationship with “natural” products (idealized) and food processing (demonized), (5) perceptions of weight status and management. Stress and difficulties in hunger cue discernment were viewed as important obstacles to weight management in both countries. External pressures were described as a major factor that explicitly influences food consumption in the U.S., while there was an implicit influence of external pressures through eating-related social interactions in France. In France, products considered “natural” where idealized and juxtaposed against processed and “industrial” products, whereas this was not a salient aspect in the U.S. (4) Conclusions: This first comparative qualitative study assessing aspects of food culture and eating behaviors across countries identifies both common and divergent attitudes to food and eating behavior. Further studies are needed to inform the development of effective behavioral interventions to address obesity in different populations.
Nutritional Status and Indicators of 2-Year Mortality and Re-Hospitalizations: Experience from the Internal Clinic Departments in Tertiary Hospital in Croatia
Authors: Miličević Tanja , Kolčić Ivana , Đogaš Tina , Živković Piero Marin , Radman Maja , Radić Josipa
Published: December 2020

We aimed to provide insight into nutritional and clinical indicators of malnutrition risk and their influence on two-year mortality and re-hospitalization rate among patients hospitalized in internal clinic departments in the tertiary hospital in Croatia. Initially, data on 346 participants were obtained, while 218 of them where followed-up two years later. At baseline, the majority of participants were old and polymorbid (62.1% suffered from arterial hypertension, 29.5% from cancer, and 29.2% from diabetes). Even apparently presenting with satisfying anthropometric indices, 38.4% of them were at-risk for malnutrition when screened with the Nutritional Risk Screening-2002 (NRS-2002) questionnaire (NRS-2002 ≥ 3). More importantly, only 15.3% of all participants were prescribed an oral nutritional supplement during hospitalization. Those that were at-risk for malnutrition suffered significantly more often from cancer (54.9% vs. 20.6%; p < 0.001) and died more often in the follow-up period (42.7% vs. 23.5%; p < 0.003). Their anthropometric indices were generally normal and contradictory 46.3% were overweight and obese (body mass index (BMI) > 25 kg/m2). Only 36.6% of nutritionally endangered participants used an oral supplement in the follow-up period. NRS-2002 ≥ 3 correlated with anthropometric indices, glomerular filtration rate, age, and length of the initial hospital stay. Unlike other studies, NRS-2002 ≥ 3 was not an independent predictor of mortality and re-hospitalizations; other clinical, rather than nutritional parameters proved to be better predictors. Patients in our hospital are neither adequately nutritionally assessed nor managed. There is an urgent need to develop strategies to prevent, identify, and treat malnutrition in our hospital and post-discharge.
Oral Gel Loaded by Fluconazole‒Sesame Oil Nanotransfersomes: Development, Optimization, and Assessment of Antifungal Activity
Authors: Alkhalidi Hala M. , Hosny Khaled M. , Rizg Waleed Y.
Published: December 2020

Candidiasis is one of the frequently encountered opportunistic infections in the oral cavity and can be found in acute and chronic presentations. The study aimed to develop fluconazole-loaded sesame oil containing nanotransfersomes (FS-NTF) by the thin-layer evaporation technique to improve the local treatment of oral candidiasis. Optimization of the formulation was performed using the Box‒Behnken statistical design to determine the variable parameters that influence the vesicle size, entrapment efficiency, zone of inhibition, and ulcer index. Finally, the formulated FS-NTF was embedded within the hyaluronic acid‒based hydrogel (HA-FS-NTF). The rheological behavior of the optimized HA-FS-NTF was assessed and the thixotropic behavior with the pseudoplastic flow was recorded; this is desirable for an oral application. An in vitro release study revealed the rapid release of fluconazole from the HA-FS-NTF. This was significantly higher when compared with the fluconazole suspension and hyaluronic acid hydrogel containing fluconazole. Correspondingly, the ex vivo permeation was also found to be higher in HA-FS-NTF in sheep buccal mucosa (400 μg/cm2) when compared with the fluconazole suspension (122 μg/cm2) and hyaluronic acid hydrogel (294 μg/cm2). The optimized formulation had an inhibition zone of 14.33 ± 0.76 mm and enhanced antifungal efficacy for the ulcer index (0.67 ± 0.29) in immunocompromised animals with Candida infection; these findings were superior to those of other tested formulations. Hence, it can be summarized that fluconazole can effectively be delivered for the treatment of oral candidiasis when it is entrapped in a nanotransfersome carrier and embedded into cross-linked hyaluronic acid hydrogel.
Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions
Authors: Rahić Ognjenka , Tucak Amina , Omerović Naida , Sirbubalo Merima , Hindija Lamija , Hadžiabdić Jasmina , Vranić Edina
Published: December 2020

Glaucoma is considered to be one of the biggest health problems in the world. It is the main cause of preventable blindness due to its asymptomatic nature in the early stages on the one hand and patients’ non-adherence on the other. There are several approaches in glaucoma treatment, whereby this has to be individually designed for each patient. The first-line treatment is medication therapy. However, taking into account numerous disadvantages of conventional ophthalmic dosage forms, intensive work has been carried out on the development of novel drug delivery systems for glaucoma. This review aims to provide an overview of formulation solutions and strategies in the development of in situ gel systems, nanosystems, ocular inserts, contact lenses, collagen corneal shields, ocular implants, microneedles, and iontophoretic devices. The results of studies confirming the effectiveness of the aforementioned drug delivery systems were also briefly presented.
Lactoferrin-Anchored Tannylated Mesoporous Silica Nanomaterials for Enhanced Osteo-Differentiation Ability
Authors: Noh Sung Hyun , Jo Han-Saem , Choi Somang , Song Hee Gyeong , Kim Hak-Jun , Kim Keung Nyun , Kim Sung Eun , Park Kyeongsoon
Published: December 2020

In the present study, we created lactoferrin-anchored mesoporous silica nanomaterials with absorbed tannic acid (LF/TA-MSNs) and evaluated the effect of these LF/TA-MSNs on the in vitro osteo-differentiation ability of adipose-derived stem cells (ADSCs) by testing alkaline phosphatase (ALP) level, calcium accumulation, and expression of osteo-differentiation-specific genes, including osteocalcin (OCN) and osteopontin (OPN). Both bare MSNs and LF/TA-MSNs exhibited round nano-particle structures. The LF/TA-MSNs demonstrated prolonged LF release for up to 28 days. Treatment of ADSCs with LF (50 μg)/TA-MSNs resulted in markedly higher ALP level and calcium accumulation compared to treatment with LF (10 μg)/TA-MSNs or bare MSNs. Furthermore, LF (50 μg)/TA-MSNs remarkably increased mRNA levels of osteo-differentiation-specific genes, including OCN and OPN, compared to MSNs or LF (10 μg)/TA-MSNs. Together, these data suggest that the ability of LF/TA-MSNs to enhance osteo-differentiation of ADSCs make them a possible nanovehicle for bone healing and bone regeneration in patients with bone defect or disease.
Better Medicines for Older Patients: Considerations between Patient Characteristics and Solid Oral Dosage Form Designs to Improve Swallowing Experience
Authors: Drumond Nélio , Stegemann Sven
Published: December 2020

Oral drug administration provided as solid oral dosage forms (SODF) remains the major route of drug therapy in primary and secondary care. There is clear evidence for a growing number of clinically relevant swallowing issues (e.g., dysphagia) in the older patient population, especially when considering the multimorbid, frail, and polymedicated patients. Swallowing impairments have a negative impact on SODF administration, which leads to poor adherence and inappropriate alterations (e.g., crushing, splitting). Different strategies have been proposed over the years in order to enhance the swallowing experience with SODF, by using conventional administration techniques or applying swallowing aids and devices. Nevertheless, new formulation designs must be considered by implementing a patient centric approach in order to efficiently improve SODF administration by older patient populations. Together with appropriate SODF size reductions, innovative film coating materials that can be applied to SODF and provide swallowing safety and efficacy with little effort being required by the patients are still needed. With that in mind, a literature review was conducted in order to identify the availability of patient centric coating materials claiming to shorten esophageal transit times and improve the overall SODF swallowing experience for older patients. The majority of coating technologies were identified in patent applications, and they mainly included well-known water soluble polymers that are commonly applied into pharmaceutical coatings. Nevertheless, scientific evidence demonstrating the benefits of given SODF coating materials in the concerned patient populations are still very limited. Consequently, the availability for safe, effective, and clinically proven solutions to address the increasing prevalence of swallowing issues in the older patient population is still limited.