bluuebunny/crossref_metadata_2025 huggingface dataset:
Location-Specific Comparison Between a 3D In-Stent Restenosis Model and Micro-CT and Histology Data from Porcine In Vivo Experiments
Authors: Zun P. S. , Narracott A. J. , Chiastra C. , Gunn J. , Hoekstra A. G.
Published: September 2019

Background

Coronary artery restenosis is an important side effect of percutaneous coronary intervention. Computational models can be used to better understand this process. We report on an approach for validation of an in silico 3D model of in-stent restenosis in porcine coronary arteries and illustrate this approach by comparing the modelling results to in vivo data for 14 and 28 days post-stenting.

Methods

This multiscale model includes single-scale models for stent deployment, blood flow and tissue growth in the stented vessel, including smooth muscle cell (SMC) proliferation and extracellular matrix (ECM) production. The validation procedure uses data from porcine in vivo experiments, by simulating stent deployment using stent geometry obtained from micro computed tomography (micro-CT) of the stented vessel and directly comparing the simulation results of neointimal growth to histological sections taken at the same locations.

Results

Metrics for comparison are per-strut neointimal thickness and per-section neointimal area. The neointimal area predicted by the model demonstrates a good agreement with the detailed experimental data. For 14 days post-stenting the relative neointimal area, averaged over all vessel sections considered, was 20 ± 3% in vivo and 22 ± 4% in silico. For 28 days, the area was 42 ± 3% in vivo and 41 ± 3% in silico.

Conclusions

The approach presented here provides a very detailed, location-specific, validation methodology for in silico restenosis models. The model was able to closely match both histology datasets with a single set of parameters. Good agreement was obtained for both the overall amount of neointima produced and the local distribution. It should be noted that including vessel curvature and ECM production in the model was paramount to obtain a good agreement with the experimental data.
The experimental approach into the influence of external inductance on the discharge characteristic of HiPIMS
Authors: Ghasemi Saeed , Seyfi Pourya , Farhadizadeh Alireza , Ghomi Hamid
Published: September 2019

The main objective of the current paper is to describe the effect of external inductance (EI) on the current discharge waveforms of HiPIMS at different pulse-on time (Pon) and its relation with static deposition rate and topographical properties of deposited titanium thin films, which is investigated by scanning electron microscope and atomic force microscope. It has shown that the higher the EI, independent of the Pon, the higher the peak power is. The delay time also extensively increases when an EI is implemented into the circuit. However, the rise time does not have a linear dependency with the EI and its behavior changes to some extent at different Pon. By increasing the EI from zero to 30 mH at Pon = 60 μs, the peak power subsequently rises from 11 to 32 kW at constant time-average power. Meanwhile, the deposition rate decreases from 8.5 to 1.5 nm/min, which is mainly attributed to the metal ions return to the target surface and nonlinear dependency of sputtering yield with applied voltage. It was also revealed that the higher peak power has no special effect on the surface roughness of titanium thin films deposited by HiPIMS.
Gaucher Disease in Fetus: The Usual and the Unusual Presentations in a Family
Authors: Mishra Ranjana , Bijarnia-Mahay Sunita , Sharma Nidhish , Dimri Nandita , Saxena Renu , Puri Ratna Dua , Verma I. C.
Published: September 2019

Gaucher disease is the most common of the lysosomal storage disorders, with a continuum of clinical features ranging from a perinatal lethal form to an asymptomatic form. Perinatal lethal Gaucher disease (PLGD), also known as fetal Gaucher disease is a distinct, severe form of type II Gaucher disease and typically presents as non- immune hydrops fetalis, hepatosplenomegaly and ichthyosiform abnormalities in the fetal life. We herein report a family with a spectrum of usual (i.e. hepatosplenomegaly) and unusual (i.e. absence of hydrops and presence of significant intrauterine growth restriction) features of PLGD with a genetic diagnosis of homozygous RecNciI mutation in the GBA gene.
On a problem of Pillai with Fibonacci numbers and powers of 3
Authors: Ddamulira Mahadi
Published: September 2019

Consider the sequence $$ \{{F}_{n}\}_{n \ge 0} $${Fn}n≥0 of Fibonacci numbers defined by $${F}_0=0$$F0=0, $${F}_1 =1$$F1=1, and $${F}_{{n}+2}= {F}_{{n}+1}+ {F}_{n} $$Fn+2=Fn+1+Fn for all $$ n\ge 0 $$n≥0. In this paper, we find all integers c having at least two representations as a difference between a Fibonacci number and a power of 3.
Educational handbook for healthcare professionals: Preventing complications and treating peristomal skin
Authors: Salomé Geraldo Magela , Cunha André Luiz da , Pereira Antônio Pedro , Miranda Flávio Dutra , Alves José Ronaldo
Published: September 2019

Objective To create and validate a handbook for the prevention of peristomal skin complications.

Methods For the elaboration of the handbook, a literature review was conducted in the following databases: Cochrane Library, SciELO, LILACS, and MEDLINE. The handbook “Preventing and treating the complications of intestinal peristomal skin” was elaborated in nine steps. The first step addressed the concepts of ostomy, stoma type, and ostomy classification. In the second step, the following were described: definition of the collection equipment, type of collection equipment, and technique of changing one- and two-piece equipment. In the third step, the peristomal skin cleansing technique was described. In the fourth step, the types of complications of the peristomal skin were listed. In the fifth step, preventive approaches to avoid complications with the peristomal skin were described. In the sixth step, the therapeutic approaches in the treatment of aforementioned peristomal skin complications were addressed. In the seventh step, the handbook layout was created by an Information Technology professional. In the eighth step, the handbook was validated by 25 nurses. In the ninth step, the final version of the instrument was laid out.

Results The final version of the “Preventing and treating the complications of intestinal peristomal skin” handbook has 37 pages. It was registered in the International Standard Book Number: 978-85-67647-46-3, standard format size (21
cm high by 15 cm wide), totaling 50 illustrations. In the first evaluation, the evaluators assessed the manual as partially adequate to completely adequate. In the first evaluation, the content validity index ranged between 0.88 to 1.0; no 100% agreement was observed among the evaluators' answers. In the second evaluation, as an agreement was observed in all items, the content validity index was 1.0.

Conclusion The handbook “Preventing and treating the complications of intestinal peristomal skin” was elaborated based on scientific principles and had its content, language, and design validated by specialists in the field.
Critically examining virtual history curriculum
Authors: McBean Tiffany Rae , Feinberg Joseph R.
Published: September 2019

With a notable growth in the number of students accessing online education and virtual schools, social studies educators and researchers should evaluate these educational platforms. This study involves a critical evaluation of U.S. History curriculum of Georgia Virtual School through Critical Race Theory, and contributes to the nascent literature on social studies online instruction. The results from this study illustrate a picture of Georgia Virtual School (GAVS) that coincides with research on race and racism in social studies education. In particular, analysis of the U.S. History course from GAVS shows race and racism are not addressed to the degree that Georgia Standards of Excellence require. In addition, traditionally marginalized groups, such as LatinX, Asian Americans and Native Americans, are given significantly less curricular coverage than African Americans. Racism is also presented as an overarching systemic problem. Overall, the data shows that GAVS U.S. History curriculum inadequately addresses the significance of race and racism in United States history.
Experimental and numerical investigation of a viscoseal: part I
Authors: Mohamed Jarray , Yann Henry , Aurelian Fatu , Dominique Souchet
Published: September 2019

This article, which is published in two parts, describes research that focuses on the analysis – through an experimental study – of the sealing behaviour of a non-contact dynamic sealing device known as a viscoseal (or sometimes called a helical groove seal). Despite its reliability and its advantageous characteristics, compared with other types of sealing devices, the viscoseal is still under-researched because of its complex characteristics. The experimental apparatus used in this work is equipped with two different test cells. This first, made from acrylic glass, is transparent and is used for the visualisation of the liquid–air interface within the viscoseal. The second cell, used for pressure measurement, is composed of bronze. The experimental results are compared with numerical results obtained using the Reynolds model and also with computational fluid dynamics code. The first instalment, which appears here, includes a general introduction and covers the experimental set-up and relevant references. Part II will be published in the September issue.
National Cyber Governance Awareness Policy and Framework
Authors: Alwan Hala Bou
Published: September 2019

Despite an ongoing drive by governments and law enforcers around the world to improve the sophistication of their risk mitigation measures, cyber-attacks are continually increasing. A study from Computer Crime and Intellectual Property Section (CCIPS) shows more than 4,000 ransomware attacks occurred daily in 2016. That's a 300 percent increase over 2015, where 1,000 ransomware attacks were seen per day. Cyber criminals are successfully penetrating even the most high-profile companies and governmental agencies. The breach at the NSA was truly alarming and just one recent example of the dire situation the country, and world, face as cybercrime intensifies and the cyber security talent shortage becomes more serious.

Accordingly, the purpose of this research is to focus on cyber education at the national, government, and law enforcement level examining the methodology to set the tone from the top ensuring alignment between governments, law enforcers, private sector, and academic level. It also examines the gaps in cyber laws and educational governance initiatives and their impact on efficient execution of cyber policies for various regions of the world with a focus on the United Arab Emirates and the United States of America.

Finally, this article recommends policy guidelines and a compliance manual framework for governments and law enforcers to consider ensuring that cyber risks are properly addressed and mitigated in a structured and coherent way.
Liouville theorem for fractional Hénon–Lane–Emden systems on a half space
Authors: Le Phuong
Published: September 2019

This paper is concerned with the fractional system
\begin{cases} (-\Delta)^{\frac{\alpha}{2}} u(x) = \vert x \vert ^a v^p(x), &x\in\mathbb{R}^n_+,\\ (-\Delta)^{\frac{\beta}{2}} v(x) = \vert x \vert ^b u^q(x), &x\in\mathbb{R}^n_+,\\ u(x)=v(x)=0, &x\in\mathbb{R}^n{\setminus}\mathbb{R}^n_+, \end{cases}where n ⩾ 2, 0 < α, β < 2, a > −α, b > −β and p, q ⩾ 1. By exploiting a direct method of scaling spheres for fractional systems, we prove that if $p \leqslant \frac {n+\alpha +2a}{n-\beta }$, $q \leqslant \frac {n+\beta +2b}{n-\alpha }$, $p+q<\frac {n+\alpha +2a}{n-\beta }+\frac {n+\beta +2b}{n-\alpha }$ and (u, v) is a nonnegative strong solution of the system, then u ≡ v ≡ 0.
Bee Venom Stimulates Hormone Secretion in Rat Somatotroph and Corticotroph Cells: Digital Image Analysis of Secretory Granules
Authors: Florea Adrian , El Hof Fares Abu , Hazi Georgeta Maria , Oprea Marius Cristian
Published: September 2019

In this study, we characterized secretory granules in somatotroph (STCs) and corticotroph (CTCs) cells from the anterior pituitary of rats, in conjunction with different experimental treatments with bee venom (BV). In the rats injected for 30 days with daily BV doses equivalent to one sting, we found significant changes in secretory granules' diameter: reduced by 48.15% in STCs and increased by 5.09% in CTCs, and especially a shift to gray into their intensity profile: increased by 237.04% in STCs and by 212.38% in CTCs. In the rats injected with a single high BV dose, the granules' diameter was reduced in both STCs (by 7.14%) and CTCs (by 4.67%—significant) and their gray intensity profile increased by 200% in STCs and by 51.71% in CTCs (both are significant). The changes in the gray profile reflected a reduced content of granules in the cells, consistent with an increase of the plasma levels of GH and ACTH in all cases. We concluded that the reduced hormone cargo of granules in STCs and CTCs resulted from an accelerated cell secretion. The results obtained for the two types of cells correlated, indicating a similar reaction of these secretory cells to the prolonged and acute presence of BV in the organism.
Ambient black carbon particles reach the fetal side of human placenta
Authors: Bové Hannelore , Bongaerts Eva , Slenders Eli , Bijnens Esmée M. , Saenen Nelly D. , Gyselaers Wilfried , Van Eyken Peter , Plusquin Michelle , Roeffaers Maarten B. J. , Ameloot Marcel , Nawrot Tim S.
Published: September 2019

Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 104 (0.66 × 104) and 2.09 × 104 (0.9 × 104) particles per mm3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers’ residential BC exposure during pregnancy (0.63–2.42 µg per m3). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards.
Evolutionary and functional impact of common polymorphic inversions in the human genome
Authors: Giner-Delgado Carla , Villatoro Sergi , Lerga-Jaso Jon , Gayà-Vidal Magdalena , Oliva Meritxell , Castellano David , Pantano Lorena , Bitarello Bárbara D. , Izquierdo David , Noguera Isaac , Olalde Iñigo , Delprat Alejandra , Blancher Antoine , Lalueza-Fox Carles , Esko Tõnu , O’Reilly Paul F. , Andrés Aida M. , Ferretti Luca , Puig Marta , Cáceres Mario
Published: September 2019

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based on probe hybridization and amplification, and we perform a complete study of 45 common human inversions of 0.1–415 kb. Most inversions promoted by homologous recombination occur recurrently in humans and great apes and they are not tagged by SNPs. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.
A chromosome-level genome assembly of Cydia pomonella provides insights into chemical ecology and insecticide resistance
Authors: Wan Fanghao , Yin Chuanlin , Tang Rui , Chen Maohua , Wu Qiang , Huang Cong , Qian Wanqiang , Rota-Stabelli Omar , Yang Nianwan , Wang Shuping , Wang Guirong , Zhang Guifen , Guo Jianyang , Gu Liuqi , Chen Longfei , Xing Longsheng , Xi Yu , Liu Feiling , Lin Kejian , Guo Mengbo , Liu Wei , He Kang , Tian Ruizheng , Jacquin-Joly Emmanuelle , Franck Pierre , Siegwart Myriam , Ometto Lino , Anfora Gianfranco , Blaxter Mark , Meslin Camille , Nguyen Petr , Dalíková Martina , Marec František , Olivares Jérôme , Maugin Sandrine , Shen Jianru , Liu Jinding , Guo Jinmeng , Luo Jiapeng , Liu Bo , Fan Wei , Feng Likai , Zhao Xianxin , Peng Xiong , Wang Kang , Liu Lang , Zhan Haixia , Liu Wanxue , Shi Guoliang , Jiang Chunyan , Jin Jisu , Xian Xiaoqing , Lu Sha , Ye Mingli , Li Meizhen , Yang Minglu , Xiong Renci , Walters James R. , Li Fei
Published: September 2019

The codling moth Cydia pomonella, a major invasive pest of pome fruit, has spread around the globe in the last half century. We generated a chromosome-level scaffold assembly including the Z chromosome and a portion of the W chromosome. This assembly reveals the duplication of an olfactory receptor gene (OR3), which we demonstrate enhances the ability of C. pomonella to exploit kairomones and pheromones in locating both host plants and mates. Genome-wide association studies contrasting insecticide-resistant and susceptible strains identify hundreds of single nucleotide polymorphisms (SNPs) potentially associated with insecticide resistance, including three SNPs found in the promoter of CYP6B2. RNAi knockdown of CYP6B2 increases C. pomonella sensitivity to two insecticides, deltamethrin and azinphos methyl. The high-quality genome assembly of C. pomonella informs the genetic basis of its invasiveness, suggesting the codling moth has distinctive capabilities and adaptive potential that may explain its worldwide expansion.
Tunable assembly of truncated nanocubes by evaporation-driven poor-solvent enrichment
Authors: Lv Zhong-Peng , Kapuscinski Martin , Bergström Lennart
Published: September 2019

Self-assembly of nanocrystals is extensively used to generate superlattices with long-range translational order and atomic crystallographic orientation, i.e. mesocrystals, with emergent mesoscale properties, but the predictability and tunability of the assembly methods are poorly understood. Here, we report how mesocrystals produced by poor-solvent enrichment can be tuned by solvent composition, initial nanocrystal concentration, poor-solvent enrichment rate, and excess surfactant. The crystallographic coherence and mesoscopic order within the mesocrystal were characterized using techniques in real and reciprocal spaces, and superlattice growth was followed in real time by small-angle X-ray scattering. We show that formation of highly ordered superlattices is dominated by the evaporation-driven increase of the solvent polarity and particle concentration, and facilitated by excess surfactant. Poor-solvent enrichment is a versatile nanoparticle assembly method that offers a promising production route with high predictability to modulate and maximize the size and morphology of nanocrystal metamaterials.
The influence of initial developmental status on the life-history of sea trout (Salmo trutta)
Authors: del Villar-Guerra Diego , Larsen Martin H. , Baktoft Henrik , Koed Anders , Aarestrup Kim
Published: September 2019

Spring migrating sea trout juveniles can be classified as parr, pre-smolt or smolt based on body morphology and osmoregulatory capacity. In this respect, parr are assumed to be less prepared for a marine life and to have lower survival at sea than pre-smolts and smolts. However, the behaviour and survival of these trout phenotypes upon entering the sea is not well known. Using passive integrated transponder telemetry, this study found that the return rate from the sea to the natal river was higher for parr compared to pre-smolts and smolts. Additionally, trout classified as parr generally migrated earlier to the sea and a larger proportion returned to the river after less than one year at sea. The daily mortality rate at sea was comparable among the different phenotypes of trout, suggesting that the higher proportion of returning parr to the river was linked to their shorter duration at sea. These results provide evidence of different life-history strategies for seaward-migrating juvenile sea trout, ultimately affecting their return rate to the natal river. Investigations failing to consider downstream migrating parr and pre-smolts risks neglecting a large part of the anadromous population and may result in inaccurate assessments of sea trout stocks in rivers.
Resistance to anticoagulant rodenticides in Martinique could lead to inefficient rodent control in a context of endemic leptospirosis
Authors: Marquez Aurélie , Khalil Rami Abi , Fourel Isabelle , Ovarbury Teddy , Pinot Adrien , Rosine Armand , Thalmensi Gérard , Jaffory Georges , Kodjo Angeli , Benoit Etienne , Lattard Virginie
Published: September 2019

Leptospirosis is a re-emergent worldwide zoonosis. It is endemic in Martinique where transmission conditions are favourable. Humans are usually infected through contact with water contaminated with urine of rodents. Recent human leptospirosis outbreaks in Martinique require today effective rodent management to prevent leptospirosis transmission. Nowadays, use of anticoagulant rodenticides (AR) is the main method implemented to control rodent populations. Nevertheless, intensive use of these AR has selected worldwide many VKORC1-based resistant rodent strains to AR. Our aim was to characterize the sensitivity of Martinique commensal rodents to AR to better prevent leptospirosis transmission. Resistance of house mice to first-generation and in rare cases even to second-generation ARs were clearly demonstrated in Martinique with the detection of the Y139C mutation with a very high allelic frequency of 40% and the A26T/Y139C double-mutation with an allelic frequency of 0.9%. In black rat, the most prevalent rodent in Martinique, 3 new Vkorc1 coding mutations were detected, the H68N, A115T and S149N mutations associated with moderate resistance to first generation AR. Therefore, rodent management in Martinique must be carried carefully to avoid resistance diffusion and maintain long-term effective rodent management, to be able to efficiently prevent leptospirosis transmission.
Anthropogenic impact is negatively related to coral health in Sicily (Mediterranean Sea)
Authors: Prada Fiorella , Musco Luigi , Alagna Adriana , Agnetta Davide , Beccari Eleonora , D’Anna Giovanni , Giacalone Vincenzo Maximiliano , Pipitone Carlo , Vega Fernández Tomás , Goffredo Stefano , Badalamenti Fabio
Published: September 2019

Shallow-water marine organisms are among the first to suffer from combined effects of natural and anthropogenic drivers. The orange coralAstroides calycularisis a shallow-water bioconstructor species endemic to the Mediterranean Sea. Although raising conservation interest, also given its special position within the Dendrophylliidae, information about the threats to its health is scant. We investigated the health status ofA. calycularisat five locations in northwestern Sicily along a gradient of cumulative human impact and the most probable origin of the threats to this species, including anthropogenic land-based and sea-based threats. Cumulative human impact appeared inversely related to the performance ofA. calycularisat population, colony, and polyp levels. Sea-based human impacts appeared among the most likely causes of the variation observed. The reduction in polyp length can limit the reproductive performance ofA. calycularis, while the decrease of percent cover and colony area is expected to impair its peculiar feeding behaviour by limiting the exploitable dimensional range of prey and, ultimately, reef functioning. This endangered habitat-forming species appeared susceptible to anthropogenic pressures, suggesting the need to re-assess its vulnerability status. Creating microprotected areas with specific restrictions to sea-based human impacts could be the best practice preserve these bioconstructions.
Deciphering the microbiome shift during fermentation of medicinal plants
Authors: Köberl Martina , Erschen Sabine , Etemadi Mohammad , White Richard Allen , El-Arabi Tarek F. , Berg Gabriele
Published: September 2019

The importance of the human-microbiome relationship for positive health outcomes has become more apparent over the last decade. Influencing the gut microbiome via modification of diet represents a possibility of maintaining a healthy gut flora. Fermented food and lactic acid bacteria (LAB) display a preventive way to inhibit microbial dysbioses and diseases, but their ecology on plants is poorly understood. We characterized the microbiome of medicinal plants (Matricaria chamomilla L. and Calendula officinalis L.) using 16S rRNA gene profiling from leaves that were fermented over a six-week time course. The unfermented samples were characterized by a distinct phyllosphere microbiome, while the endosphere revealed a high similarity. During fermentation, significant microbial shifts were observed, whereby LAB were enhanced in all approaches but never numerically dominated. Among the LAB, Enterococcaceae were identified as the most dominant family in both plants. M. chamomilla community had higher relative abundances of Lactobacillaceae and Carnobacteriaceae, while C. officinalis showed a higher presence of Leuconostocaceae and Streptococcaceae. The natural leaf microbiome and the indigenous LAB communities of field-grown Asteraceae medicinal plants are plant-specific and habitat-specific and are subjected to significant shifts during fermentation. Leaf surfaces as well as leaf endospheres were identified as sources for biopreservative LAB.
Detection of dengue using PAMAM dendrimer integrated tapered optical fiber sensor
Authors: Mustapha Kamil Yasmin , Al-Rekabi Sura H. , Yaacob Mohd Hanif , Syahir Amir , Chee Hui Yee , Mahdi Mohd Adzir , Abu Bakar Muhammad Hafiz
Published: September 2019

The exponential escalation of dengue cases has indeed become a global health crisis. This work elaborates on the development of a biofunctionalized tapered optical fiber (TOF) based sensor with the integration of polyamidoamine (PAMAM) dendrimer for the detection of dengue E protein. The dimension of the TOF generated an evanescent field that was sensitive to any changes in the external medium while the integration of PAMAM promoted more adhesion of bio-recognition molecules; anti-DENV II E protein antibodies; that were complementary to the targeted protein. This in return created more active sites for the absorption of DENV II E proteins onto the tapered region. The resolution and detection limit of the sensor are 19.53 nm/nM and 1 pM, respectively with Kd = 1.02 × 10−10 M.
Quantification of wild-type and radiation attenuated Plasmodium falciparum sporozoite motility in human skin
Authors: Winkel Béatrice M. F. , de Korne Clarize M. , van Oosterom Matthias N. , Staphorst Diego , Meijhuis Mark , Baalbergen Els , Ganesh Munisha S. , Dechering Koen J. , Vos Martijn W. , Chevalley-Maurel Séverine C. , Franke-Fayard Blandine , van Leeuwen Fijs W. B. , Roestenberg Meta
Published: September 2019

Given the number of global malaria cases and deaths, the need for a vaccine against Plasmodium falciparum (Pf) remains pressing. Administration of live, radiation-attenuated Pf sporozoites can fully protect malaria-naïve individuals. Despite the fact that motility of these attenuated parasites is key to their infectivity and ultimately protective efficacy, sporozoite motility in human tissue (e.g. skin) remains wholly uncharacterized to date. We show that the ability to quantitatively address the complexity of sporozoite motility in human tissue provides an additional tool in the development of attenuated sporozoite vaccines. We imaged Pf movement in the skin of its natural host and compared wild-type and radiation-attenuated GFP-expressing Pf sporozoites. Using custom image analysis software and human skin explants we were able to quantitatively study their key motility features. This head-to-head comparison revealed that radiation attenuation impaired the capacity of sporozoites to vary their movement angle, velocity and direction, promoting less refined movement patterns. Understanding and overcoming these changes in motility will contribute to the development of an efficacious attenuated parasite malaria vaccine.
The association between airflow limitation and blood eosinophil levels with treatment outcomes in patients with chronic obstructive pulmonary disease and prolonged mechanical ventilation
Authors: Huang Wei-Chang , Huang Chen-Cheng , Wu Pi-Chu , Chen Chao-Jung , Cheng Ya-Hua , Chen Hui-Chen , Lee Ching-Hsiao , Wu Ming-Feng , Hsu Jeng-Yuan
Published: September 2019

The clinical implications of airflow limitation severity and blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and prolonged mechanical ventilation (PMV) are unknown. Thus, this study aimed to identify whether or not these two indicators were significantly associated with short-term in-respiratory care center (RCC) treatment outcomes in this population. Of all participants (n = 181) in this retrospective cross-sectional study, 41.4%, 40.9%, 8.3%, and 52.5% had prolonged RCC admission (RCC length of stay >21 days), failed weaning, death, and any adverse outcomes of interest, respectively. Compared to participants without any adverse outcomes of interest, moderate (the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II) and/or severe (GOLD III) airflow limitation were significantly associated with short-term in-RCC adverse outcomes in terms of failed weaning (for III versus I, OR = 15.06, p = 0.003) and having any adverse outcomes of interest (for II versus I, OR = 17.66, p = 0.002; for III versus I, OR = 37.07, p = 0.000) though the severity of airflow limitation did not have associations with prolonged RCC admission and death after adjustment. Meanwhile, blood eosinophilia defined by various cut-off values was not associated with any adverse outcomes. The findings have significant clinical implications and are useful in the management of patients with COPD and PMV.
VX-770-mediated potentiation of numerous human CFTR disease mutants is influenced by phosphorylation level
Authors: Cui Guiying , Stauffer Brandon B. , Imhoff Barry R. , Rab Andras , Hong Jeong S. , Sorscher Eric J. , McCarty Nael A.
Published: September 2019

VX-770 (ivacaftor) is approved for clinical use in CF patients bearing multiple CFTR mutations. VX-770 potentiated wildtype CFTR and several disease mutants expressed in oocytes in a manner modulated by PKA-mediated phosphorylation. Potentiation of some other mutants, including G551D-CFTR, was less dependent upon the level of phosphorylation, likely related to the severe gating defects in these mutants exhibited in part by a shift in PKA sensitivity to activation, possibly due to an electrostatic interaction of D551 with K1250. Phosphorylation-dependent potentiation of wildtype CFTR and other variants also was observed in epithelial cells. Hence, the efficacy of potentiators may be obscured by a ceiling effect when drug screening is performed under strongly phosphorylating conditions. These results should be considered in campaigns for CFTR potentiator discovery, and may enable the expansion of VX-770 to CF patients bearing ultra-orphan CFTR mutations.
Circulating microRNA profile as a potential biomarker for obstructive sleep apnea diagnosis
Authors: Santamaria-Martos Fernando , Benítez Iván , Ortega Francisco , Zapater Andrea , Giron Cristina , Pinilla Lucía , Pascual Lydia , Cortijo Anunciación , Dalmases Mireia , Fernandez-Real Jose M. , Barbé Ferran , Sánchez-de-la-Torre Manuel
Published: September 2019

Evaluation of microRNAs (miRNAs) could allow characterization of the obstructive sleep apnea (OSA) and help diagnose it more accurately. We aimed to examine circulating miRNA profiles to establish the differences between non-OSA and OSA patients. Additionally, we aimed to analyse the effect of continuous positive airway pressure (CPAP) treatment on the miRNA profile. This observational, longitudinal study included 230 subjects referred to the Sleep Unit due to suspected OSA. Expression profiling of 188 miRNAs in plasma was performed in 27 subjects by TaqMan-Low-Density-Array. OSA-related miRNAs were selected for validation by RT-qPCR in 203 patients. Prediction models were built to discriminate between non-OSA and OSA: 1) NoSAS-score, 2) differentially expressed miRNAs, and 3) combination of NoSAS-score plus miRNAs. The differentially expressed miRNAs were measured after 6 months of follow-up. From the 14 miRNAs selected for validation, 6 were confirmed to be differentially expressed. The areas under the curve were 0.73 for the NoSAS-score, 0.81 for the miRNAs and 0.86 for the combination. After 6 months of CPAP treatment, miRNA levels in the OSA group seem to approximate to non-OSA levels. A cluster of miRNAs was identified to differentiate between non-OSA and OSA patients. CPAP treatment was associated with changes in the circulating miRNA profile.
Impact of systemic therapy on circulating leukocyte populations in patients with metastatic breast cancer
Authors: Larsson Anna-Maria , Roxå Anna , Leandersson Karin , Bergenfelz Caroline
Published: September 2019

Tumors affect the immune system, locally and systemically. The frequencies of specific circulating immune cell populations correlate with disease progression as well as prognosis of the patients. Although largely neglected, conventional antitumoral therapies often possess immunomodulatory properties and affect the levels of specific immune cell populations. Most information, however, derive from animal or in vitro studies. As this could impact prognosis as well as response to therapy, further studies of the effects of treatment on circulating immune cells in patients are warranted. In this pilot study, we evaluated a wide panel of circulating immune cells over time (up to six months) in ten patients with metastatic breast cancer receiving standard antitumoral regimens. Overall, endocrine therapy tends to enrich for natural killer (NK) and natural killer T (NKT) cells in the circulation, whereas both chemotherapy and endocrine therapy reduce the levels of circulating monocytic myeloid-derived suppressor cells (Mo-MDSCs). This indicates that the systemic immunosuppressive profile observed in patients tends to revert over the course of systemic therapy and holds promise for future combination treatment with standard antitumoral agents and immunotherapy.
Safety of transcutaneous electrical sensory stimulation of the neck in terms of vital parameters in dysphagia rehabilitation
Authors: Nagami Shinsuke , Maeda Keisuke , Fukunaga Shinya , Ikeno Masahiro , Oku Yoshitaka
Published: September 2019

Transcutaneous electrical sensory stimulation (TESS) devices are approved for use in Japan, but their safety when used through the neck skin for dysphagia rehabilitation has not been reported. This study aimed to verify the safety of TESS use through the neck skin. Twenty patients (mean age 86.5 ± 5.1 years) with aspiration pneumonia undergoing dysphagia rehabilitation were included in this retrospective observational and matched control study. We compared vital signs in 10 subjects who underwent swallowing rehabilitation with the TESS device, and matched control patients over 7 days. The results were the following: tachycardia, 0.60 ± 1.07 vs. 0.70 ± 0.67 days; high blood pressure, 0.40 ± 0.70 vs. 0.50 ± 1.08 days; low blood pressure, 0.40 ± 0.70 vs. 0.10 ± 0.32 days; low oxygen saturation, 0.60 ± 1.58 vs. 0.50 ± 1.08 days, p = 0.870; oxygen administration, 0.80 ± 2.20 vs. 1.20 ± 2.15 days; tachypnea, 0.50 ± 0.71 vs. 0.50 ± 0.53 days; elevated body temperature, 2.00 ± 1.41 vs. 1.60 ± 1.96 days. There were no significant differences in clinical stability between the TESS and control groups of patients with aspiration pneumonia. TESS through the neck appears safe as an intervention in dysphagia rehabilitation.
Embedding topography enables fracture guidance in soft solids
Authors: Maiorana Christopher H. , Erbe Mitchell , Blank Travis , Lipsky Zachary , German Guy K.
Published: September 2019

The natural topographical microchannels in human skin have recently been shown to be capable of guiding propagating cracks. In this article we examine the ability to guide fracture by incorporating similar topographical features into both single, and dual layer elastomer membranes that exhibit uniform thickness. In single layer membranes, crack guidance is achieved by minimizing the nadir thickness of incorporated v-shaped channels, maximizing the release of localized strain energy. In dual layer membranes, crack guidance along embedded channels is achieved via interfacial delamination, which requires less energy to create a new surface than molecular debonding. In both membrane types, guided crack growth is only temporary. However, utilizing multiple embedded channels, non-contiguous crack control can be maintained at angles up to 45° from the mode I fracture condition. The ability to control and deflect fracture holds great potential for improving the robustness and lifespan of flexible electronics and stretchable sensors.
Diversity and geochemical community assembly processes of the living rare biosphere in a sand-and-gravel aquifer ecosystem in the Midwestern United States
Authors: Yamamoto Kyosuke , Hackley Keith C. , Kelly Walton R. , Panno Samuel V. , Sekiguchi Yuji , Sanford Robert A. , Liu Wen-Tso , Kamagata Yoichi , Tamaki Hideyuki
Published: September 2019

Natural microbial communities consist of a limited number of abundant species and an extraordinarily diverse population of rare species referred to as the rare biosphere. Recent studies have revealed that the rare biosphere is not merely an inactive dormant population but may play substantial functional roles in the ecosystem. However, structure, activity and community assembly processes of the rare biosphere are poorly understood. In this study, we evaluated the present and living microbial community structures including rare populations in an aquifer ecosystem, the Mahomet Aquifer, USA, by both 16S rDNA and rRNA amplicon deep sequencing. The 13 groundwater samples formed three distinct groups based on the “entire” community structure, and the same grouping was obtained when focusing on the “rare” subcommunities (<0.1% of total abundance), while the “abundant” subcommunities (>1.0%) gave a different grouping. In the correlation analyses, the observed grouping pattern is associated with several geochemical factors, and structures of not only the entire community but also the rare subcommunity are correlated with geochemical profiles in the aquifer ecosystem. Our findings first indicate that the living rare biosphere in the aquifer system has the metabolic potential to adapt to local geochemical factors which dictate the community assembly processes.
Effects of cannabinoids on the development of chick embryos in ovo
Authors: Gustafsson Sofia B. , Jacobsson Stig O. P.
Published: September 2019

We have examined the effects of the synthetic cannabinoids HU 210 and HU 211, the plant-derived cannabidiol and the endogenous cannabinoid anandamide on the viability and development of chick embryos. Fertilized White Leghorn chicken eggs were injected with the test compounds or carrier vehicle, via a drilled small hole in the egg, directly into the egg yolk. After nine days of exposure, the embryonal viability, length and wet weight of embryos, and wet weight of brains were measured, and the development stages were assessed according to the Hamburger and Hamilton (HH) scale. The potent synthetic cannabinoid receptor agonist HU 210 and the non-psychotropic cannabidiol were embryotoxic at the highest concentrations examined (10 µM and 50 µM, respectively), with no viable embryos after the HU 210 injection, and 20% viability after the cannabidiol injections. The effects of HU 210 on the chick embryo were attenuated by α-tocopherol and the cannabinoid receptor antagonist AM251, whereas only α-tocopherol gave a statistically significant protection against the embryotoxic effects of cannabidiol. This study shows that exposure to plant-derived or synthetic cannabinoids during early embryonal development decreases embryonal viability. Extrapolation of data across species is of course difficult, but the data would argue against the use of cannabinoids, be it recreationally or therapeutically, during pregnancy.
TET2 catalyzes active DNA demethylation of the Sry promoter and enhances its expression
Authors: Okashita Naoki , Kuroki Shunsuke , Maeda Ryo , Tachibana Makoto
Published: September 2019

SRY is the master regulator of male sex determination in eutherian mammals. In mice, Sry expression is transcriptionally and epigenetically controlled in a developmental stage-specific manner. The Sry promoter undergoes demethylation in embryonic gonadal somatic cells at the sex-determining period. However, its molecular mechanism and in vivo significance remain unclear. Here, we report that the Sry promoter is actively demethylated during gonadal development, and TET2 plays a fundamental role in Sry demethylation. Tet2-deficient mice showed absence of 5-hydroxymethylcytosine in the Sry promoter. Furthermore, Tet2 deficiency diminished Sry expression, indicating that TET2-mediated DNA demethylation regulates Sry expression positively. We previously showed that the deficiency of the H3K9 demethylase Jmjd1a compromises Sry expression and induces male-to-female sex reversal. Tet2 deficiency enhanced the sex reversal phenotype of Jmjd1a-deficient mice. Thus, TET2-mediated active DNA demethylation and JMJD1A-mediated H3K9 demethylation contribute synergistically to sex determination.
High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity
Authors: Zhu Wen , Radadiya Ashish , Bisson Claudine , Wenzel Sabine , Nordin Brian E. , Martínez-Márquez Francisco , Imasaki Tsuyoshi , Sedelnikova Svetlana E. , Coricello Adriana , Baumann Patrick , Berry Alexandria H. , Nomanbhoy Tyzoon K. , Kozarich John W. , Jin Yi , Rice David W. , Takagi Yuichiro , Richards Nigel G. J.
Published: September 2019

Expression of human asparagine synthetase (ASNS) promotes metastatic progression and tumor cell invasiveness in colorectal and breast cancer, presumably by altering cellular levels of L-asparagine. Human ASNS is therefore emerging as a bona fide drug target for cancer therapy. Here we show that a slow-onset, tight binding inhibitor, which exhibits nanomolar affinity for human ASNS in vitro, exhibits excellent selectivity at 10 μM concentration in HCT-116 cell lysates with almost no off-target binding. The high-resolution (1.85 Å) crystal structure of human ASNS has enabled us to identify a cluster of negatively charged side chains in the synthetase domain that plays a key role in inhibitor binding. Comparing this structure with those of evolutionarily related AMP-forming enzymes provides insights into intermolecular interactions that give rise to the observed binding selectivity. Our findings demonstrate the feasibility of developing second generation human ASNS inhibitors as lead compounds for the discovery of drugs against metastasis.
Oligonucleotide-templated lateral flow assays for amplification-free sensing of circulating microRNAs
Authors: Pavagada Suraj , Channon Robert B. , Chang Jason Y. H. , Kim Sung Hye , MacIntyre David , Bennett Phillip R. , Terzidou Vasso , Ladame Sylvain
Published: September 2019

Low-cost detection of miRNA biomarkers from maternal blood is achieved via a highly sequence-specific templated reaction on nitrocellulose paper strips to enable early prediction of preterm birth in a minimally invasive manner.
Tetrahedral iron featuring an appended Lewis acid: distinct pathways for the reduction of hydroxylamine and hydrazine
Authors: Kiernicki John J. , Norwine Emily E. , Zeller Matthias , Szymczak Nathaniel K.
Published: September 2019

A tetrahedral iron complex bearing an appended Lewis acid is capable of effecting hydrazine and hydroxylamine reduction.
The influence of disorder on the exciton spectra in two-dimensional structures
Authors: Kirichenko E. V. , Stephanovich V. A.
Published: September 2019

We mimic the disorder in the 2D excitons spectra by introduction of fractional Laplacian into the Schrödinger equation.
When cobalt-mediated [2 + 2 + 2] cycloaddition reaction dares go astray: synthesis of unprecedented cobalt(iii)-complexes
Authors: Delorme Marion , Punter Alexander , Oliveira Raquel , Aubert Corinne , Carissan Yannick , Parrain Jean-Luc , Amatore Muriel , Nava Paola , Commeiras Laurent
Published: September 2019

The cobalt-mediated cycloaddition with γ-alkylidenebutenolide diverges dramatically from what is expected, leading to unprecedented polycyclic scaffold cobalt(iii)-complexes. The mechanism of this reaction has been studied by DFT calculations.
Three peroxidovanadium(v) compounds mediated by transition metal cations for enhanced anticancer activity
Authors: Chen Fanghui , Gao Zhiguo , You Chaoqun , Wu Hongshuai , Li Yaojia , He Xiaotong , Zhang Yuchen , Zhang Yaan , Sun Baiwang
Published: September 2019

The mediation of transition metal cations leads to superior antiproliferative activity and cell-type selectivity of peroxidovanadium(v) compounds.
Spontaneous self-assembly of amyloid β (1–40) into dimers
Authors: Hashemi Mohtadin , Zhang Yuliang , Lv Zhengjian , Lyubchenko Yuri L.
Published: September 2019

Aβ40 dimer structure was identified by MD and validated using force spectroscopy data.
Tracking the DNA complexation state of pBAE polyplexes in cells with super resolution microscopy
Authors: Riera Roger , Feiner-Gracia Natalia , Fornaguera Cristina , Cascante Anna , Borrós Salvador , Albertazzi Lorenzo
Published: September 2019

The future of gene therapy relies on the development of efficient and safe delivery vectors.
One-pot synthesis of high molar activity 6-[18F]fluoro-l-DOPA by Cu-mediated fluorination of a BPin precursor
Authors: Mossine Andrew V. , Tanzey Sean S. , Brooks Allen F. , Makaravage Katarina J. , Ichiishi Naoko , Miller Jason M. , Henderson Bradford D. , Skaddan Marc B. , Sanford Melanie S. , Scott Peter J. H.
Published: September 2019

A one-pot two-step synthesis of 6-[18F]fluoro-l-DOPA has been developed, involving Cu-mediated radiofluorination of the corresponding pinacol boronate ester precursor, and validated for production of doses for human use.
Evaluation of plasmid DNA stability against ultrasonic shear stress and its in vitro delivery efficiency using ionic liquid [Bmim][PF6]
Authors: Sarker Satya Ranjan , Ball Andrew S. , Bhargava Suresh K. , Soni Sarvesh K.
Published: September 2019

The hydrophobic ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate [Bmim][PF6] forms ultrasonically stable and functional nanostructures with negatively charged plasmid DNA through electrostatic interactions.
Erythrocyte membrane affinity chromatography, solid-phase extraction and UPLC-QTOF-MS/MS to screen active ingredients of Buyang Huanwu decoction
Authors: Yu Aiming , Zheng Huazhu , Yan Xiangli , Wang Shengxin , Shen Xiao , Zheng Haozhen , Meng Yingjiao , Wang Lisheng
Published: September 2019

A method that uses erythrocyte membrane and solid-phase extraction to isolate the specific compounds of Buyang Huanwu decoction was developed.
Property improvement of multi-walled carbon nanotubes/polypropylene composites with high filler loading via interfacial modification
Authors: Wang Hongqing , Li Zewen , Hong Kailiang , Chen Mengna , Qiao Zhen , Yuan Zhijuan , Wang Zhe
Published: September 2019

The graphical illustrated the synthesis route to PP-g-MWNTs.
Fenton's reagent-enhanced supercritical water oxidation of wastewater released from 3-hydroxypyridine production
Authors: Bu Junru , Liu Huan , Lin Chunmian
Published: September 2019

A study on Fenton's reagent-enhanced supercritical water oxidation (SCFO) of wastewater released from 3-hydroxypyridine production was carried out in this paper.