bluuebunny/crossref_metadata_2025 huggingface dataset:
A High Accurate and Stable Legendre Transform Based on Block Partitioning and Butterfly Algorithm for NWP
Authors: Yin Fukang , Wu Jianping , Song Junqiang , Yang Jinhui
Published: October 2019

In this paper, we proposed a high accurate and stable Legendre transform algorithm, which can reduce the potential instability for a very high order at a very small increase in the computational time. The error analysis of interpolative decomposition for Legendre transform is presented. By employing block partitioning of the Legendre-Vandermonde matrix and butterfly algorithm, a new Legendre transform algorithm with computational complexity O(Nlog2N /loglogN) in theory and O(Nlog3N) in practical application is obtained. Numerical results are provided to demonstrate the efficiency and numerical stability of the new algorithm.
Multi Fractals of Generalized Multivalued Iterated Function Systems in b-Metric Spaces with Applications
Authors: Kumari Sudesh , Chugh Renu , Cao Jinde , Huang Chuangxia
Published: October 2019

In this paper, we obtain multifractals (attractors) in the framework of Hausdorff b-metric spaces. Fractals and multifractals are defined to be the fixed points of associated fractal operators, which are known as attractors in the literature of fractals. We extend the results obtained by Chifu et al. (2014) and N.A. Secelean (2015) and generalize the results of Nazir et al. (2016) by using the assumptions imposed by Dung et al. (2017) to the case of ciric type generalized multi-iterated function system (CGMIFS) composed of ciric type generalized multivalued G-contractions defined on multifractal space C ( U ) in the framework of a Hausdorff b-metric space, where U = U 1 × U 2 × ⋯ × U N , N being a finite natural number. As an application of our study, we derive collage theorem which can be used to construct general fractals and to solve inverse problem in Hausdorff b-metric spaces which are more general spaces than Hausdorff metric spaces.
Coefficient Bounds for Certain Subclasses of q-Starlike Functions
Authors: Fan Lin-Lin , Wang Zhi-Gang , Khan Shahid , Hussain Saqib , Naeem Muhammad , Mahmood Tahir
Published: October 2019

By making use of q-calculus, we define and investigate several new subclasses of bi-univalent mappings related to the q-Noor integral operator. The coefficient bounds | u 2 | , | u 3 | and the Fekete–Szegő problem u 3 − μ u 2 2 for mappings belonging to these classes are derived.
The Invariant Two-Parameter Function of Algebras ψ
Authors: Escobar José María , Núñez-Valdés Juan , Pérez-Fernández Pedro
Published: October 2019

At present, the research on invariant functions for algebras is very extended since Hrivnák and Novotný defined in 2007 the invariant functions ψ and φ as a tool to study the Inönü–Wigner contractions (IW-contractions), previously introduced by those authors in 1953. In this paper, we introduce a new invariant two-parameter function of algebras, which we call ψ ¯ , as a tool which makes easier the computations and allows researchers to deal with contractions of algebras. Our study of this new function is mainly focused in Malcev algebras of the type Lie, although it can also be used with any other types of algebras. The main goal of the paper is to prove, by means of this function, that the five-dimensional classical-mechanical model built upon certain types of five-dimensional Lie algebras cannot be obtained as a limit process of a quantum-mechanical model based on a fifth Heisenberg algebra. As an example of other applications of the new function obtained, its computation in the case of the Lie algebra induced by the Lorentz group S O ( 3 , 1 ) is shown and some open physical problems related to contractions are also formulated.
Glycol Chitosan-Docosahexaenoic Acid Liposomes for Drug Delivery: Synergistic Effect of Doxorubicin-Rapamycin in Drug-Resistant Breast Cancer
Authors: Kim Min Woo , Niidome Takuro , Lee Ruda
Published: October 2019

Marine ecosystems are the most prevalent ecosystems on the planet, providing a diversity of living organisms and resources. The development of nanotechnology may provide solutions for utilizing these thousands of potential compounds as marine pharmaceuticals. Here, we designed a liposomal glycol chitosan formulation to load both doxorubicin (DOX) and rapamycin (RAPA), and then evaluated its therapeutic potential in a prepared drug-resistant cell model. We explored the stability of the drug delivery system by changing the physiological conditions and characterized its physicochemical properties. The electrostatic complexation between DOX-glycol chitosan and docosahexaenoic acid RAPA-liposomes (GC-DOX/RAPA ω-liposomes) was precisely regulated, resulting in particle size of 131.3 nm and zeta potential of −14.5 mV. The well-characterized structure of GC-DOX/RAPA ω-liposomes led to high loading efficiencies of 4.1% for DOX and 6.2% for RAPA. Also, GC-DOX/RAPA ω-liposomes exhibited high colloidal stability under physiological conditions and synergistic anti-cancer effects on DOX-resistant MDA-MB-231 cells, while showing pH-sensitive drug release behavior. Our results provided a viable example of marine pharmaceuticals with therapeutic potential for treating drug-resistant tumors using an efficient and safe drug delivery system.
Foreign Body Ingestion in Pediatrics: Distribution, Management and Complications
Authors: Khorana Jiraporn , Tantivit Yaowaret , Phiuphong Chanitsara , Pattapong Saranchana , Siripan Suparat
Published: October 2019

Background and Objectives: Foreign body (FB) ingestion is a common problem in children, causing serious complications. This study aimed to identify the distribution of types and locations of these foreign bodies and create Chiang Mai University (CMU) Guidelines. Materials and Methods: A retrospective descriptive study was conducted. All patients under 15 years old with foreign body ingestion (International Statistical Classification of Diseases and Related Health Problems; ICD-10 codes T18) treated in CMU Hospital from January 2006 to December 2017 were included. The data were analyzed using descriptive statistics. The guidelines were created, which paralleled the standard guidelines. Results: In total, 194 episodes of FB ingestion were recorded. These included 53.6% males and 46.4% females with a median age of 43.5 months. A history of foreign body ingestion complaints occurred in 77.8% of cases. Presentation was divided into asymptomatic (44.3%) and symptomatic (55.7%). The most common symptom was vomiting (23.2%). In the majority of cases, foreign bodies were located in the esophagus (37%). The most common type of foreign body was a coin (41.2%). Management included spontaneous passing (60.3%), endoscopy (35.6%), and others (3.1%). Complications before treatment were recorded in 9.3% of cases and after treatment in 2.1% of cases. Conclusions: Foreign body ingestion is common among children younger than four years old. Coins are the most common foreign body found, and the esophagus is the most common location. We recommend our created CMU Guidelines for management.
Targeting Aberrant Sialylation to Treat Cancer
Authors: Munkley Jennifer , Scott Emma
Published: October 2019

Cell surface carbohydrates (known as glycans) are often aberrantly expressed or found at atypical levels in cancer. Glycans can impact all steps in tumour progression, from malignant transformation to metastasis, and have roles in all the cancer hallmarks. An increased understanding of glycans in the metastatic cascade offers exciting new therapeutic opportunities. Glycan-based targeting strategies are currently being tested in clinical trials and are a rich and untapped frontier for development. As we learn more about cancer glycobiology, new targets will continue to emerge for drug design. One key change in tumour glycosylation is the upregulation of cancer-associated sialylated glycans. Abnormal sialylation is integral to tumour growth, metastasis and immune evasion; therefore, targeting sialic acid moieties in cancer could be of high therapeutic value. Here, we summarise the changes to sialic acid biology in cancer and discuss recent advances and technologies bringing sialic-acid targeting treatments to the forefront of cancer therapeutics.
Molecular Dynamics Simulation Study of Solid Vibration Permeation in Microporous Amorphous Silica Network Voids
Authors: Yoshioka Tomohisa , Nakata Akihiro , Tung Kuo-Lun , Kanezashi Masakoto , Tsuru Toshinori
Published: October 2019

Microporous silica membranes have silica polymer network voids smaller than 3 Å where only small gas molecules such as helium (2.6 Å) and hydrogen (2.89 Å) can be transported. These silica membranes are highly expected to be available for H2 separation. In order to examine gas permeation mechanisms in the silica polymer network voids, factors such as membrane porous structures, gas diffusivity, and gas permeability were studied via membrane permeation molecular dynamics simulation. The thermal motions of silica membrane constituent atoms were examined according to classic harmonic oscillation potential using a suitable amorphous silica structure and non-equilibrium molecular dynamics (NEMD) simulations of gas permeation. The dynamic model successfully simulated the gas permeation characteristics in an amorphous silica membrane with a suitable Hooke’s potential parameter. The introduction of the oscillative thermal motion of the membrane atoms enhanced gas diffusivity. Helium and hydrogen diffusivity and permeability were analyzed using gas translation (GT) and solid vibration (SV) models. The diffusion distance of gas molecules between adsorption sites was around 5.5–7 Å. The solid-type vibration frequencies of gas molecules in the site were on the order of 1013 and were reasonably smaller for heavier helium than for hydrogen. Both the GT and SV models could explain the temperature dependency of helium and hydrogen gas diffusivities, but the SV model provided a more realistic geometrical representation of the silica membrane. The SV model also successfully explained gas permeability in an actual silica membrane as well as the virtual amorphous silica membrane.
Notch Stress Intensity Factor (NSIF)-Based Fatigue Design to Assess Cast Steel Porosity and Related Artificially Generated Imperfections
Authors: Schuscha Manuel , Horvath Michael , Leitner Martin , Stoschka Michael
Published: October 2019

Shrinkage porosities and non-metallic inclusions are common manufacturing process based defects that are present within cast materials. Conventional fatigue design recommendations, such as the FKM guideline (“Forschungskuratorium Maschinenbau”), therefore propose general safety factors for the fatigue assessment of cast structures. In fact, these factors mostly lead to oversized components and do not facilitate a lightweight design process. In this work, the effect of shrinkage porosities on the fatigue strength of defect-afflicted large-scale specimens manufactured from the cast steel G21Mn5 is studied by means of a notch stress intensity factor-based (NSIF-based) generalized Kitagawa diagram. Additionally, the mean stress sensitivity of the material is taken into account and establishes a load stress ratio enhanced diagram. Thereby, the fatigue assessment approach is performed by utilizing the defects sizes taken either from the fracture surface of the tested specimens or from non-destructive X-ray investigations. Additionally, a numerical algorithm invoking cellular automata, which enables the generation of artificial defects, is presented. Conclusively, a comparison to the results of the experimental investigations reveals a sound agreement to the generated spatial pore geometries. To sum up, the generalized Kitagawa diagram, as well as a concept utilizing artificially generated defects, is capable of assessing the local fatigue limit of cast steel G21Mn5 components and features the mapping of imperfection grades to their corresponding fatigue strength limit.
Comparative Transcriptome and Metabolic Profiling Analysis of Buckwheat (Fagopyrum Tataricum (L.) Gaertn.) under Salinity Stress
Authors: Ma Weibo , Kim Jae Kwang , Jia Caihua , Yin Feifan , Kim Hyo Jin , Akram Waheed , Hu Xuebo , Li Xiaohua
Published: October 2019

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a nutritional crop, which has high flavonoid content. However, buckwheat is a salt sensitive glycophyte cereal crop and the growth and grain yield of buckwheat are significantly affected by soil salinity. In this study, we performed a comprehensive analysis of the transcriptome and metabolome of salt treated-buckwheat to understand the effects of salinity on buckwheat. A total of 50,681,938 clean reads were acquired from all samples. We acquired 94,950 unigenes with a mean length of 1133 bp and N50 length of 1900 bp assembly. Of these, 63,305 unigenes (66.7%) were matched in public databases. Comparison of the transcriptome expression patterns between control and salt treated groups showed that 4098 unigenes were up-regulated and 3292 unigenes were down-regulated significantly. Further, we found that genes involved with amino acid, lipid and nucleotide metabolism were most responsive to salt stress. Additionally, many genes involved in secondary metabolite biosynthesis changed significantly following treatment. Those affected included phenylpropanoid biosynthesis and flavonoid biosynthesis. Chromatographic analysis was used to examine the differences in concentration of flavonoids, carotenoids, amino acids and organic acids in the samples following treatment. There was a significant increase in rutin (12.115 mg/g dry weight), following salt stress; whereas, six carotenoids (lutein, zeaxanthin, 13Z-β-carotene, α-carotene, E-β-carotene and 9Z-β-carotene) did not significantly respond to salt stress. Ultimately, our data acts as a valuable resource for future research on buckwheat and can be used as the basis for future analysis focused on gene-to-metabolite networks in buckwheat.
Korean Traditional Medicine (Jakyakgamcho-tang) Ameliorates Colitis by Regulating Gut Microbiota
Authors: Seo Seung-Ho , Unno Tatsuya , Park Seong-Eun , Kim Eun-Ju , Lee Yu-Mi , Na Chang-Su , Son Hong-Seok
Published: October 2019

The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT or 5-aminosalicylic acid (5-ASA) alleviated the severity of colitis symptoms by suppressing inflammatory cytokine levels of IL-6, IL-12, and IFN-γ. The non-metric multidimensional scaling analysis of gut microbiome revealed that JGT groups were clearly separated from the DSS group, suggesting that JGT administration altered gut microbiota. The operational taxonomic units (OTUs) that were decreased by DSS but increased by JGT include Akkermansia and Allobaculum. On the other hand, OTUs that were increased by DSS but decreased by 5-ASA or JGT treatments include Bacteroidales S24-7, Ruminococcaceae, and Rikenellaceae, and the genera Bacteroides, Parabacteroides, Oscillospira, and Coprobacillus. After JGT administration, the metabolites, including most amino acids and lactic acid that were altered by colitis induction, became similar to those of the control group. This study demonstrates that JGT might have potential to effectively treat colitis by restoring dysbiosis of gut microbiota and host metabolites.
A Cancer Spheroid Array Chip for Selecting Effective Drug
Authors: Choi Jae Won , Lee Sang-Yun , Lee Dong Woo
Published: October 2019

A cancer spheroid array chip was developed by modifying a micropillar and microwell structure to improve the evaluation of drugs targeting specific mutations such as phosphor-epidermal growth factor receptor (p-EGFR). The chip encapsulated cells in alginate and allowed cancer cells to grow for over seven days to form cancer spheroids. However, reagents or media used to screen drugs in a high-density spheroid array had to be replaced very carefully, and this was a tedious task. Particularly, the immunostaining of cancer spheroids required numerous steps to replace many of the reagents used for drug evaluation. To solve this problem, we adapted a micropillar and microwell structure to a spheroid array. Thus, culturing cancer spheroids in alginate spots attached to the micropillar allowed us to replace the reagents in the microwell chip with a single fill of fresh medium, without damaging the cancer spheroids. In this study, a cancer spheroid array was made from a p-EGFR-overexpressing cell line (A549 lung cancer cell line). In a 12 by 36 column array chip (25 mm by 75 mm), the spheroid over 100 µm in diameter started to form at day seven and p-EGFR was also considerably overexpressed. The array was used for p-EGFR inhibition and cell viability measurement against seventy drugs, including ten EGFR-targeting drugs. By comparing drug response in the spheroid array (spheroid model) with that in the single-cell model, we demonstrated that the two models showed different responses and that the spheroid model might be more resistant to some drugs, thus narrowing the choice of drug candidates.
A Study on the Trimming Effects on the Quality Factor of Micro-Shell Resonators Vibrating in Wineglass Modes
Authors: Lu Kun , Xi Xiang , Xiao Dingbang , Shi Yan , Zhuo Ming , Wu Xuezhong , Wu Yulie
Published: October 2019

Frequency trimming based on mass and stiffness modification is an important post-fabrication process for micro-shell resonators (MSRs). However, the trimming effects on the quality factor are seldom studied, although they may have great influence on the performance of the resonator. This paper presents a study on the quality factor (Q-factor) variation of trimmed micro-shell resonators (MSR). Thermoelastic damping (QTED) and anchor loss (Qanchor) are found to be the dominant energy loss mechanisms resulting in the reduction of the overall Q-factor, according to finite element method (FEM). The effects of different trimming methods on QTED and Qanchor are studied here, respectively. It is found that trimming grooves ablated in the rim of the resonator can cause a ~1–10% reduction of QTED, and the length of trimming groove is positively related to the reduction of QTED. The reduction of QTED caused by the mass adding process is mainly related to the thermal expansion coefficient and density of the additive and contact area between the resonator and additive masses. Besides, the first and second harmonic errors caused by asymmetrical trimming can cause a 10–90% reduction of Qanchor. Finally, trimming experiments were conducted on different resonators and the results were compared with FEM simulation. The work presented in this paper could help to optimize the trimming process of MSRs.
A Diverse Repertoire of Exopolysaccharide Biosynthesis Gene Clusters in Lactobacillus Revealed by Comparative Analysis in 106 Sequenced Genomes
Authors: Deo Dipti , Davray Dimple , Kulkarni Ram
Published: October 2019

Production of exopolysaccharides (EPS) is one of the unique features of Lactobacillus genus. EPS not only have many physiological roles such as in stress tolerance, quorum sensing and biofilm formation, but also have numerous applications in the food and pharmaceutical industries. In this study, we identified and compared EPS biosynthesis gene clusters in 106 sequenced Lactobacillus genomes representing 27 species. Of the 146 identified clusters, only 41 showed the typical generic organization of genes as reported earlier. Hierarchical clustering showed highly varied nature of the clusters in terms of the gene composition; nonetheless, habitat-wise grouping was observed for the gene clusters from host-adapted and nomadic strains. Of the core genes required for EPS biosynthesis, epsA, B, C, D and E showed higher conservation, whereas gt, wzx and wzy showed high variability in terms of the number and composition of the protein families. Analysis of the distribution pattern of the protein families indicated a higher proportion of mutually exclusive families in clusters from host-adapted and nomadic strains, whereas those from the free-living group had very few unique families. Taken together, this analysis highlights high variability in the EPS gene clusters amongst Lactobacillus with some of their properties correlated to the habitats.
Diversity, Distribution, and Ecology of Fungi in the Seasonal Snow of Antarctica
Authors: de Menezes Graciéle C.A. , Amorim Soraya S. , Gonçalves Vívian N. , Godinho Valéria M. , Simões Jefferson C. , Rosa Carlos A. , Rosa Luiz H.
Published: October 2019

We characterized the fungal community found in the winter seasonal snow of the Antarctic Peninsula. From the samples of snow, 234 fungal isolates were obtained and could be assigned to 51 taxa of 26 genera. Eleven yeast species displayed the highest densities; among them, Phenoliferia glacialis showed a broad distribution and was detected at all sites that were sampled. Fungi known to be opportunistic in humans were subjected to antifungal minimal inhibition concentration. Debaryomyces hansenii, Rhodotorula mucilaginosa, Penicillium chrysogenum, Penicillium sp. 3, and Penicillium sp. 4 displayed resistance against the antifungals benomyl and fluconazole. Among them, R. mucilaginosa isolates were able to grow at 37 °C. Our results show that the winter seasonal snow of the Antarctic Peninsula contains a diverse fungal community dominated by cosmopolitan ubiquitous fungal species previously found in tropical, temperate, and polar ecosystems. The high densities of these cosmopolitan fungi suggest that they could be present in the air that arrives at the Antarctic Peninsula by air masses from outside Antarctica. Additionally, we detected environmental fungal isolates that were resistant to agricultural and clinical antifungals and able to grow at 37 °C. Further studies will be needed to characterize the virulence potential of these fungi in humans and animals.
Cell Cycle, Division Rate, and Feeding of the Heterotroph Phalacroma rotundatum in a Chilean Fjord
Authors: Díaz Patricio A. , Pérez-Santos Iván , Álvarez Gonzalo , Araya Michael , Álvarez Francisco , Reguera Beatriz
Published: October 2019

Phalacroma rotundatum is a rare cosmopolitan heterotrophic dinoflagellate. This species, included in the IOC-UNESCO Taxonomic Reference List of Harmful Microalgae, may be a diarrhetic shellfish poisoning (DSP) toxin vector, but little is known about its ecophysiology and behavior. A vertical net haul collected during the austral summer of 2018 in Reloncaví Sound (Chilean Patagonia) revealed an unusually abundant population of P. rotundatum and prompted intensive 24 h sampling on 16–17 January to study the cell cycle and feeding behavior of this species. Hydrographic measurements from a buoy revealed the local characteristic estuarine circulation, with a brackish surface layer (salinity 26–28) separated from saltier, colder bottom waters by a pycnocline at a depth modulated by the tidal regime. A high proportion of P. rotundatum cells were packed with digestive vacuoles (peak of 70% at 14:00), and phased cell division (µ = 0.46 d−1) occurred 3 h after sunrise. The division time (TD) was 2 h. This is the first cell cycle study of P. rotundatum. The results here disagree with those of previous field studies that considered asynchronous division in some Dinophysis species to be related to heterotrophic feeding. They also question the very specific prey requirements, Tiarina fusus, reported for P. rotundatum in northern Europe.
Characterization of INS-15, A Metalloprotease Potentially Involved in the Invasion of Cryptosporidium parvum
Authors: Xu Rui , Guo Yaqiong , Li Na , Zhang Qiang , Wu Haizhen , Ryan Una , Feng Yaoyu , Xiao Lihua
Published: October 2019

Cryptosporidium parvum is a protozoan parasite that can cause moderate-to-severe diarrhea. Insulinase-like proteases (INS) are one of the largest protein families within the small proteome of the pathogen. However, their roles in C. parvum biology remain un-elucidated. In this study, a member of the protein family, INS-15 of C. parvum encoded by cgd3_4260, was cloned, expressed and characterized to understand its function. INS-15 and its domain I were expressed in Escherichia coli and polyclonal antibodies against the domain I and one specific polypeptide were prepared in rabbits. The role of INS-15 protein in the C. parvum invasion was preliminarily studied. Recombinant INS-15 protein and its domain I were successfully expressed in E. coli, together with various degraded products. The cgd3_4260 gene had a peak expression at 2 h of in vitro C. parvum culture, while the INS-15 protein was expressed in the mid-anterior region of sporozoites and the area of merozoites opposite to the nucleus. Anti-INS-15 domain I antibodies reduced the invasion of C. parvum sporozoites by over 40%. The anterior location of INS-15 in invasion stages and partial reduction of in vitro growth indicate that INS-15 plays some roles in the invasion or early development of C. parvum.
Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma
Authors: Oliveira Pinho Jacinta , Matias Mariana , Gaspar Maria Manuela
Published: October 2019

Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosinase. In addition, the role of nanotechnology as a valuable strategy to effectively deliver selective drugs is emphasized, either incorporating/encapsulating synthetic molecules or natural-derived compounds in lipid-based nanosystems such as liposomes. Nanoformulated compounds have been explored for their improved anticancer activity against melanoma and promising results have been obtained. Indeed, they displayed improved physicochemical properties and higher accumulation in tumoral tissues, which potentiated the efficacy of the compounds in pre-clinical experiments. Overall, these experiments opened new doors for the discovery and development of more effective drug formulations for melanoma treatment.
Metagenomic Insights into the Effects of Fructooligosaccharides (FOS) on the Composition of Luminal and Mucosal Microbiota in C57BL/6J Mice, Especially the Bifidobacterium Composition
Authors: Gu Jiayu , Mao Bingyong , Cui Shumao , Liu Xuemei , Zhang Hao , Zhao Jianxin , Chen Wei
Published: October 2019

Fructooligosaccharides (FOS) are considered prebiotics and have been proven to selectively promote the growth of Bifidobacterium in the gut. This study aimed to clarify the effects of FOS intake on the composition of luminal and mucosal microbiota in mice. Briefly, mice were fed a 0% or 25% FOS (w/w)-supplemented diet for four weeks, and the composition of luminal and mucosal microbiota, especially the Bifidobacterium, was analyzed by sequencing the V3–V4 region of 16S rRNA and groEL gene, respectively. After FOS intervention, there were significant increases in the total and wall weights of the cecum and the amount of total short-chain fatty acids (SCFAs) in the cecal contents of the mice. At the phylum level, the results showed a significant increase in the relative abundance of Actinobacteria in the contents and mucosa from the cecum to the distal colon in the FOS group. Besides Bifidobacterium, a significant increase was observed in the relative abundance of Coprococcus in all samples at the genus level, which may be partially related to the increase in butyric acid levels in the luminal contents. Furthermore, groEL sequencing revealed that Bifidobacterium pseudolongum was almost the sole bifidobacterial species in the luminal contents (>98%) and mucosa (>89%). These results indicated that FOS can selectively promote B. pseudolongum proliferation in the intestine, either in the lumen or the mucosa from the cecum to the distal colon. Further studies are required to reveal the competitive advantage of B. pseudolongum over other FOS-metabolizing bacteria and the response mechanisms of B. pseudolongum to FOS.
Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training
Authors: Evans Parker L. , McMillin Shawna L. , Weyrauch Luke A. , Witczak Carol A.
Published: October 2019

Aerobic exercise training and resistance exercise training are both well-known for their ability to improve human health; especially in individuals with type 2 diabetes. However, there are critical differences between these two main forms of exercise training and the adaptations that they induce in the body that may account for their beneficial effects. This article reviews the literature and highlights key gaps in our current understanding of the effects of aerobic and resistance exercise training on the regulation of systemic glucose homeostasis, skeletal muscle glucose transport and skeletal muscle glucose metabolism.
Identification of Dietary Patterns Related to Metabolic Diseases and Their Association with Cardiovascular Disease: From the Korean Genome and Epidemiology Study
Authors: Lee Hye Ah , An Hyoin , Park Hyesook
Published: October 2019

Using data from the community-based cohort of the Korean Genome and Epidemiology Study (KoGES), we evaluated the dietary patterns (DPs) related to metabolic diseases and their associations with the incidence of non-fatal cardiovascular disease (CVD). After excluding those with a history of CVD or cancer, we analyzed the data of 8352 subjects aged 40–69 years. Based on their daily intake of 26 food groups at baseline, the DPs of the subjects with metabolic diseases (n = 1679, 20.1%) were analyzed using principal component analysis. Due to regional differences in the effect of DPs on CVD, we performed analyses stratified by region. The association between DPs and the incidence of non-fatal CVD was evaluated by calculating the hazard ratio (HR) and 95% confidence interval (CI) using the Cox proportional hazards model. During the 12-year follow-up, the incidence of non-fatal CVD was 5.4 per 1000 person-years (n = 431). An animal-based DP made the greatest contribution to the total variance and was characterized by a high intake of pork, beef, chicken, fish, and shellfish. The effect of DP on CVD differed by region (industrial/rural regions, p < 0.05) and was dominant in industrial regions, irrespective of metabolic disease status. In industrial regions, subjects in the top quintile of DP had a 0.42-fold (95% CI = 0.24–0.74) lower risk of incident CVD than those in the bottom quintile, even after adjusting for various covariates. In addition, the risk of CVD was high in individuals with a history of metabolic disease in both regions (HR = 1.74, 95% CI = 1.24–2.43 in industrial regions; HR = 1.88, 95% CI = 1.42–2.48 in rural regions). DP and a history of metabolic diseases, but not their interaction, were independently associated with incident CVD. In our study, an animal-based DP related to metabolic disease was independently associated with incident CVD, and this effect was noticeable only in industrial regions.
Circulating Folate Concentrations and Risk of Peripheral Neuropathy and Mortality: A Retrospective Cohort Study in the U.K
Authors: Taverner Tom , Crowe Francesca L. , Thomas G. Neil , Gokhale Krishna , Thayakaran Rasiah , Nirantharakumar Krishnarajah , Rajabally Yusuf A.
Published: October 2019

Background: Folate deficiency may increase the risk of peripheral neuropathy but there is a paucity of data from large prospective studies examining this association. Methods: Longitudinal analysis of electronic health records in The Health Improvement Network (THIN), a U.K. primary care database including 594,338 patients aged 18–70 years with a folate measurement and without a history of peripheral neuropathy. Results: After a mean follow-up of 3.71 (standard deviation (SD) = 3.14) years, 1949 patients were diagnosed with peripheral neuropathy and 20,679 patients died. In those <40 years, compared to patients with folate ≥13.6 nmol/L, those with folate <6.8 (deficient) and 6.8–13.5 nmol/L (insufficient) had a hazard ratio (HR) for peripheral neuropathy of 1.83 (95% confidence intervals (CI) = 1.16–2.91) and 1.48 (95% CI = 1.04–2.08), respectively. There was no significant association between folate and peripheral neuropathy among those aged 41–70 years. Compared to patients with folate ≥ 13.6 nmol/L, folate <6.8 nmol/L was associated with a greater risk of death among all ages. Conclusion: Folate deficiency and insufficiency was associated with a greater risk of peripheral neuropathy among younger patients. This investigation should be replicated in other large datasets and it may be important to monitor peripheral neuropathy incidence after the introduction of mandatory folic acid fortification of flour in the U.K.
Intervention Study on the Efficacy and Safety of Platycodon grandiflorus Ethanol Extract in Overweight or Moderately Obese Adults: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Kim Ye Jin , Kwon Eun-Young , Kim Ji-Won , Lee Youngmi , Ryu Ri , Yun Jongbok , Kim Manheun , Choi Myung-Sook
Published: October 2019

Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20–60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.
Preconception Lifestyle and Cardiovascular Health in the Offspring of Overweight and Obese Women
Authors: van Elten Tessa , van de Beek Cornelieke , Geelen Anouk , Gemke Reinoud , Groen Henk , Hoek Annemieke , Mol Ben , van Poppel Mireille , Roseboom Tessa
Published: October 2019

Women’s lifestyle has important implications for the development and health of their offspring. Yet little is known about the association between women’s preconception dietary intake and physical activity with cardiovascular health of the offspring. We therefore examined this association in a group of Dutch women with overweight or obesity (BMI ≥ 29 kg/m2) and infertility, who participated in a 6-month randomized preconception lifestyle intervention trial, and their offspring (n = 46). Preconception dietary intake and physical activity were assessed during the 6-month intervention using a food frequency questionnaire and the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH), respectively. Offspring cardiovascular health (i.e., BMI, waist:height ratio, systolic and diastolic blood pressure, fat and fat free mass, and pulse wave velocity) was measured at age 3–6 years. Multivariable linear regression analyses were used to examine the associations between preconception lifestyle and offspring cardiovascular health. Higher preconception vegetable intake (per 10 g/day) was associated with lower offspring diastolic blood pressure (Z-score: −0.05 (−0.08; −0.01); p = 0.007) and higher preconception fruit intake (per 10 g/day) was associated with lower offspring pulse wave velocity (−0.05 m/s (−0.10; −0.01); p = 0.03). Against our expectations, higher preconception intake of sugary drinks was associated with a higher offspring fat free mass (0.54 kg (0.01; 1.07); p = 0.045). To conclude, preconception dietary intake is associated with offspring health.
Controversies in Diagnosing Sarcopenia in Cirrhosis—Moving from Research to Clinical Practice
Authors: Sinclair Marie
Published: October 2019

Sarcopenia, defined as loss of muscle mass and function, is increasingly recognized as a common consequence of advanced cirrhosis that is associated with adverse clinical outcomes. Despite the recent proliferation in publications pertaining to sarcopenia in end-stage liver disease, there remains no single ‘best method’ for its diagnosis. The inability to identify a gold standard is common to other specialties, including geriatrics from which many diagnostic tools are derived. Controversies in diagnosis have implications for the accuracy and reproducibility of cohort studies in the field, largely prohibit the introduction of sarcopenia measurement into routine patient care and impede the development of clinical trials to identify appropriate therapies. Difficulties in diagnosis are partly driven by our ongoing limited understanding of the pathophysiology of sarcopenia in cirrhosis, the mechanisms by which it impacts on patient outcomes, the heterogeneity of patient populations, and the accuracy, availability and cost of assessments of muscle mass and function. This review discusses the currently studied diagnostic methods for sarcopenia in cirrhosis, and outlines why reaching a consensus on sarcopenia diagnosis is important and suggests potential ways to improve diagnostic criteria to allow us to translate sarcopenia research into improvements in clinical care.
Cortical Visual Evoked Potentials and Growth in Infants Fed with Bioactive Compounds-Enriched Infant Formula: Results from COGNIS Randomized Clinical Trial
Authors: Nieto-Ruiz Ana , García-Santos José Antonio , Bermúdez Mercedes G. , Herrmann Florian , Diéguez Estefanía , Sepúlveda-Valbuena Natalia , García Salomé , Miranda Maria Teresa , De-Castellar Roser , Rodríguez-Palmero María , Catena Andrés , Campoy Cristina
Published: October 2019

Postnatal nutrition is essential for growth and neurodevelopment. We analyzed the influence of a new enriched-infant formula with bioactive compounds on growth, neurodevelopment, and visual function (VF) in healthy infants during their first 18 months of life. A total of 170 infants were randomized in the COGNIS randomized clinical trial (RCT) to receive a standard infant formula (SF = 85) or a new experimental infant formula supplemented with functional nutrients (EF = 85). As a control, 50 breastfed infants (BF) were enrolled. Growth patterns were evaluated up to 18 months of life; neurodevelopment was assessed by general movements at 2, 3, and 4 months; VF was measured by cortical visual evoked potentials at 3 and 12 months. No differences in growth and neurodevelopment were found between groups. Regarding VF, SF and EF infants presented prolonged latencies and lower amplitudes in the P100 wave than BF infants. In the EF group, a higher percentage of infants presented response at 7½′ of arc at 12 months compared to 3 months of age; a similar proportion of BF and EF infants presented responses at 7½′ of arc at 12 months of age. Early nutritional intervention with bioactive compounds could narrow the gap in growth and neurodevelopment between breastfed and formula-fed infants.
Soluble Extracts from Chia Seed (Salvia hispanica L.) Affect Brush Border Membrane Functionality, Morphology and Intestinal Bacterial Populations In Vivo (Gallus gallus)
Authors: Pereira da Silva Bárbara , Kolba Nikolai , Stampini Duarte Martino Hércia , Hart Jonathan , Tako Elad
Published: October 2019

This study assessed and compared the effects of the intra-amniotic administration of various concentrations of soluble extracts from chia seed (Salvia hispanica L.) on the Fe and Zn status, brush border membrane functionality, intestinal morphology, and intestinal bacterial populations, in vivo. The hypothesis was that chia seed soluble extracts will affect the intestinal morphology, functionality and intestinal bacterial populations. By using the Gallus gallus model and the intra-amniotic administration approach, seven treatment groups (non-injected, 18 Ω H2O, 40 mg/mL inulin, non-injected, 5 mg/mL, 10 mg/mL, 25 mg/mL and 50 mg/mL of chia seed soluble extracts) were utilized. At hatch, the cecum, duodenum, liver, pectoral muscle and blood samples were collected for assessment of the relative abundance of the gut microflora, relative expression of Fe- and Zn-related genes and brush border membrane functionality and morphology, relative expression of lipids-related genes, glycogen, and hemoglobin levels, respectively. This study demonstrated that the intra-amniotic administration of chia seed soluble extracts increased (p < 0.05) the villus surface area, villus length, villus width and the number of goblet cells. Further, we observed an increase (p < 0.05) in zinc transporter 1 (ZnT1) and duodenal cytochrome b (Dcytb) proteins gene expression. Our results suggest that the dietary consumption of chia seeds may improve intestinal health and functionality and may indirectly improve iron and zinc intestinal absorption.
Can Ciprofloxacin be Used for Precision Treatment of Gonorrhea in Public STD Clinics? Assessment of Ciprofloxacin Susceptibility and an Opportunity for Point-of-Care Testing
Authors: Melendez Johan H. , Hsieh Yu-Hsiang , Barnes Mathilda , Hardick Justin , Gilliams Elizabeth A. , Gaydos Charlotte A.
Published: October 2019

Background: Given the lack of new antimicrobials to treat Neisseria gonorrhoeae (NG) infections, reusing previously recommended antimicrobials has been proposed as a strategy to control the spread of multi-drug-resistant NG. We assessed ciprofloxacin susceptibility in a large sample set of NG isolates and identified correlates associated with ciprofloxacin-resistant NG infections. Methods: NG isolates collected in Baltimore, Maryland between 2014 and 2016 were evaluated by Gyrase A (gyrA) PCR and E-test for susceptibility to ciprofloxacin. Clinical characteristics and demographics were evaluated by multivariate regression analysis to identify correlates of ciprofloxacin-resistant NG infections. Results: 510 NG isolates from predominately African American (96.5%), heterosexual (85.7%), and HIV-negative (92.5%) male subjects were included in the study. The overall percentage of isolates with mutant gyrA sequences, indicative of ciprofloxacin resistance, was 32.4%, and significantly increased from 24.7% in 2014 to 45.2% in 2016 (p < 0.001). Participants older than 35 years of age were 2.35 times more likely to have a gyrA mutant NG infection than younger participants (p < 0.001). Race, sexual orientation, symptomology, or co-infection the HIV or syphilis were not associated with a particular NG gyrA genotype. Conclusions: Resistance to ciprofloxacin in Baltimore is lower than other regions and indicates that in this environment, use of ciprofloxacin may be appropriate for targeted treatment provided utilization of enhanced surveillance tools. The targeted use of ciprofloxacin may be more beneficial for individuals under 35 years of age. Point-of-care tests for NG diagnosis and susceptibility testing are urgently needed to identify individuals who can be treated with this targeted approach.
Myristic Acid Coated Protein Immobilised Mesoporous Silica Particles as pH Induced Oral Delivery System for the Delivery of Biomolecules
Authors: Trivedi Vivek , Bhomia Ruchir , Mitchell John C
Published: October 2019

Solid core drug delivery systems (SCDDS) were prepared for the oral delivery of biomolecules using mesoporous silica as core, bovine haemoglobin (bHb) as model drug and supercritical fluid (SCF) processing as encapsulation technique. The use of organic solvents or harsh processing conditions in the development of drug delivery systems for biomolecules can be detrimental for the structural integrity of the molecule. Hence, the coating on protein-immobilised particles was performed via supercritical carbon dioxide (scCO2) processing at a temperature lower than the melting point of myristic acid (MA) to avoid any thermal degradation of bHb. The SCDDS were prepared by bHb immobilisation on mesoporous silica followed by myristic acid (MA) coating at 43 °C and 100 bar in scCO2. bHb-immobilised silica particles were also coated via solvent evaporation (SE) to compare the protein release with scCO2 processed formulations. In both cases, MA coating provided required enteric protection and restricted the bHb release for the first two hours in simulated gastric fluid (SGF). The protein release was immediate upon the change of media to simulated intestinal fluid (SIF), reaching 70% within three hours. The release from SCF processed samples was slower than SE formulations, indicating superior surface coverage of MA on particles in comparison to the SE method. Most importantly, the protein conformation remained unchanged after the release from SCDDS as confirmed by circular dichroism. This study clearly demonstrates that the approach involving protein immobilisation on silica and scCO2 assisted melt-coating method can protect biomolecules from gastric environment and provide the required release of a biologic in intestine without any untoward effects on protein conformation during processing or after release.
Role of the Metal Center in the Modulation of the Aggregation Process of Amyloid Model Systems by Square Planar Complexes Bearing 2-(2′-pyridyl)benzimidazole Ligands
Authors: Florio Daniele , Iacobucci Ilaria , Ferraro Giarita , Mansour Ahmed M. , Morelli Giancarlo , Monti Maria , Merlino Antonello , Marasco Daniela
Published: October 2019

The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring 2-(2′-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from Aβ and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of aggregation were evaluated using thioflavin binding assays, whereas the interactions of the compounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. The results indicate that the compounds modulate the aggregation of the investigated peptides using different mechanisms, suggesting that the reactivity of the metal center and the physicochemical properties of the metals (rather than those of the ligands and the geometry of the metal compounds) play a crucial role in determining the anti-aggregation properties.
Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin
Authors: Rancan Fiorenza , Contardi Marco , Jurisch Jana , Blume-Peytavi Ulrike , Vogt Annika , Bayer Ilker S. , Schaudinn Christoph
Published: October 2019

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds.