bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased plasma β‐amyloid in the Alzheimer's disease APPA673T variant carriers
Authors: Martiskainen Henna , Herukka Sanna‐Kaisa , Stančáková Alena , Paananen Jussi , Soininen Hilkka , Kuusisto Johanna , Laakso Markku , Hiltunen Mikko
Published: May 2017

We investigated the association of Alzheimer's disease (AD)‐related rare variants APP A673T and ABCA7 rs200538373‐C with the levels of β‐amyloid (Aβ) and parameters of metabolic and cardiovascular health in a population‐based cohort of healthy middle‐aged and elderly men. Carriers of protective APP A673T variant had, on average, 28% lower levels of Aβ40 and Aβ42 in plasma as compared to the controls and the carriers of ABCA7 rs200538373‐C. This is the first report to show decreased Aβ levels in plasma in APP A673T carriers and thus provides evidence that lower Aβ levels throughout life may be protective against AD. Ann Neurol 2017;82:128–132
A simple blood test expedites the diagnosis of glucose transporter type 1 deficiency syndrome
Authors: Gras Domitille , Cousin Christelle , Kappeler Caroline , Fung Cheuk‐Wing , Auvin Stéphane , Essid Nouha , Chung Brian Hy , Da Costa Lydie , Hainque Elodie , Luton Marie‐Pierre , Petit Vincent , Vuillaumier‐Barrot Sandrine , Boespflug‐Tanguy Odile , Roze Emmanuel , Mochel Fanny
Published: May 2017

Glucose transporter type 1 (GLUT1) deficiency syndrome (GLUT1‐DS) leads to a wide range of neurological symptoms. Ketogenic diets are very efficient to control epilepsy and movement disorders. We tested a novel simple and rapid blood test in 30 patients with GLUT1‐DS with predominant movement disorders, 18 patients with movement disorders attributed to other genetic defects, and 346 healthy controls. We detected significantly reduced GLUT1 expression only on red blood cells from patients with GLUT1‐DS (23 patients; 78%), including patients with inconclusive genetic analysis. This test opens perspectives for the screening of GLUT1‐DS in children and adults with cognitive impairment, movement disorder, or epilepsy. Ann Neurol 2017;82:133–138
Fabrication of elastomeric silk fibers
Authors: Bradner Sarah A. , Partlow Benjamin P. , Cebe Peggy , Omenetto Fiorenzo G. , Kaplan David L.
Published: May 2017

Methods to generate fibers from hydrogels, with control over mechanical properties, fiber diameter, and crystallinity, while retaining cytocompatibility and degradability, would expand options for biomaterials. Here, we exploited features of silk fibroin protein for the formation of tunable silk hydrogel fibers. The biological, chemical, and morphological features inherent to silk were combined with elastomeric properties gained through enzymatic crosslinking of the protein. Postprocessing via methanol and autoclaving provided tunable control of fiber features. Mechanical, optical, and chemical analyses demonstrated control of fiber properties by exploiting the physical cross‐links, and generating double network hydrogels consisting of chemical and physical cross‐links. Structure and chemical analyses revealed crystallinity from 30 to 50%, modulus from 0.5 to 4 MPa, and ultimate strength 1–5 MPa depending on the processing method. Fabrication and postprocessing combined provided fibers with extensibility from 100 to 400% ultimate strain. Fibers strained to 100% exhibited fourth order birefringence, revealing macroscopic orientation driven by chain mobility. The physical cross‐links were influenced in part by the drying rate of fabricated materials, where bound water, packing density, and microstructural homogeneity influenced cross‐linking efficiency. The ability to generate robust and versatile hydrogel microfibers is desirable for bottom‐up assembly of biological tissues and for broader biomaterial applications.
Activity of synthetic peptides against Chlamydia
Authors: Donati Manuela , Cenacchi Giovanna , Biondi Roberta , Papa Valentina , Borel Nicole , Vecchio Nepita Edoardo , Magnino Simone , Pasquinelli Gianandrea , Levi Aurora , Franco Octavio L.
Published: May 2017

The in vitro activity of six synthetic peptides against 36 strains of Chlamydia from different origins was investigated. Clavanin MO (CMO) proved to be the most active peptide, reducing the inclusion number of all Chlamydia strains from eight different species tested by ≥50% at 10 µg mL−1. Mastoparan L showed an equal activity against C. trachomatis, C. pneumoniae, C. suis, and C. muridarum, but did not exert any inhibitory effect against C. psittaci, C. pecorum, C. abortus, and C. avium even at 80 µg mL−1. These data suggest that CMO could be a promising compound in the prevention and treatment of chlamydial infections.
Development of a 3‐step straight‐through purification strategy combining membrane adsorbers and resins
Authors: Hughson Michael D. , Cruz Thayana A. , Carvalho Rimenys J. , Castilho Leda R.
Published: May 2017

The pressures to efficiently produce complex biopharmaceuticals at reduced costs are driving the development of novel techniques, such as in downstream processing with straight‐through processing (STP). This method involves directly and sequentially purifying a particular target with minimal holding steps. This work developed and compared six different 3‐step STP strategies, combining membrane adsorbers, monoliths, and resins, to purify a large, complex, and labile glycoprotein from Chinese hamster ovary cell culture supernatant. The best performing pathway was cation exchange chromatography to hydrophobic interaction chromatography to affinity chromatography with an overall product recovery of up to 88% across the process and significant clearance of DNA and protein impurities. This work establishes a platform and considerations for the development of STP of biopharmaceutical products and highlights its suitability for integration with single‐use technologies and continuous production methods. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:931–940, 2017
Characterizing the impact of pressure on virus filtration processes and establishing design spaces to ensure effective parvovirus removal
Authors: Strauss Daniel , Goldstein Joshua , Hongo‐Hirasaki Tomoko , Yokoyama Yoshiro , Hirotomi Naokatsu , Miyabayashi Tomoyuki , Vacante Dominick
Published: May 2017

Virus filtration provides robust removal of potential viral contaminants and is a critical step during the manufacture of biotherapeutic products. However, recent studies have shown that small virus removal can be impacted by low operating pressure and depressurization. To better understand the impact of these conditions and to define robust virus filtration design spaces, we conducted multivariate analyses to evaluate parvovirus removal over wide ranges of operating pressure, solution pH, and conductivity for three mAb products on Planova™ BioEX and 20N filters. Pressure ranges from 0.69 to 3.43 bar (10.0–49.7 psi) for Planova BioEX filters and from 0.50 to 1.10 bar (7.3 to 16.0 psi) for Planova 20N filters were identified as ranges over which effective removal of parvovirus is achieved for different products over wide ranges of pH and conductivity. Viral clearance at operating pressure below the robust pressure range suggests that effective parvovirus removal can be achieved at low pressure but that Minute virus of mice (MVM) logarithmic reduction value (LRV) results may be impacted by product and solution conditions. These results establish robust design spaces for Planova BioEX and 20N filters where high parvovirus clearance can be expected for most antibody products and provide further understanding of viral clearance mechanisms. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1294–1302, 2017
Synbiotic Fermentation for the Co‐Production of Lactic and Lactobionic Acids from Residual Dairy Whey
Authors: García Cristina , Rendueles Manuel , Díaz Mario
Published: May 2017

Besides its properties as an antioxidant, stabilizer, or acidifier, lactobionic acid has emerged as a potential prebiotic compound, raising the possibility of being included together with the probiotic microorganism Lactobacillus casei in novel functional fermented foods with synbiotic characteristics. Their manufacturing strategy could benefit from the recently implemented microbial synthesis of lactobionic acid by the strong producer Pseudomonas taetrolens, employing residual dairy whey as raw material. The phenomenon of amensalism established between Pseudomonas and Lactobacillus makes simultaneous fermentation unfeasible. A novel sequential process has been developed in which L. casei is inoculated in a second step. Its ability to utilize lactobionic acid as a carbon and energy source was previously tested. Experimental results showed the capacity of L. casei to work efficiently on the residual substrate fermented by P. taetrolens, producing lactic acid by degrading the remaining lactose, with a lactic acid yield on substrate and productivity of 0.95 g g−1 and 0.20 g L−1 h−1, respectively. Lactobionic acid was barely consumed in this complex growth medium, thus ensuring its presence in the resulting fermented product. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1250–1256, 2017
Confocal microscopy as an early relapse marker for acanthamoeba keratitis
Authors: Daas Loay , Viestenz Arne , Schnabel Philipp Albert , Fries Fabian N. , Hager Tobias , SzentmÁry Nora , Seitz Berthold
Published: May 2017

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision‐threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow‐up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60–63, 2018. © 2017 Wiley Periodicals, Inc.
Microsurgical anatomy of the maxillary artery for extracranial‐intracranial bypass in the pterygopalatine segment of the maxillary artery
Authors: Akiyama Osamu , Güngör Abuzer , Middlebrooks Erik H. , Kondo Akihide , Arai Hajime
Published: May 2017

The extracranial‐intracranial (EC‐IC) bypass using the maxillary artery (MA) has been successfully completed using a radial artery (RA) graft but the complicated anatomy and narrow exposure make it difficult. The purpose of this article is to define the microsurgical exposure of the MA through the middle fossa and describe the branches, diameter, and length of the MA available for the EC‐IC bypass in the sphenopalatine fossa and anterior part of the infratemporal fossa. 5 cadaveric specimens were dissected bilaterally (10 MA dissections) to define the microsurgical anatomy of the MA through an intracranial approach. The exposable branches of the MA at the level of the infratemporal and sphenopalatine fossae were the anterior deep temporal, posterior superior alveolar, and infraorbital arteries. The origin of each branch could be exposed. The available section of the MA for use as a donor vessel is between the origin of the anterior deep temporal artery and the infraorbital artery. The mean exposable length of the MA was 19.4 mm. The mean outer diameter of the donor MA was 3.2 mm. Tension‐free EC‐IC bypass was possible using a RA graft between the MA and the middle cerebral artery, the MA and the supraclinoid internal carotid artery (ICA), or the MA and the petrous ICA. Exposure of the MA at the infratemporal and sphenopalatine fossae is complicated but provides length and diameter suitable as a donor artery for the EC‐IC bypass. Clin. Anat. 31:724–733, 2018. © 2017 Wiley Periodicals, Inc.
Anatomical study of the internal nasal branch of the infraorbital nerve
Authors: Iwanaga Joe , Watanabe Koichi , Henry Brandon , Tomaszewski Krzysztof A. , Walocha Jerzy A. , Oskouian Rod J. , Shane Tubbs R.
Published: May 2017

The internal nasal branch of the infraorbital nerve (ION) runs down the nose and around the ala to be distributed to the nasal septum and vestibule. The aim of this study was to measure the internal nasal branch around the ala of the nose and discuss its possible relevance in clinical/surgical practice. Twelve sides from seven specimens derived from fresh frozen and embalmed Caucasian cadaveric heads were dissected. The specimens included three males and four females. The ages of the cadavers at death ranged from 65 to 84 years. The diameter of the internal nasal branch, horizontal distance from the lateral contour of the ala (Point A) to the branch (distance H) and vertical distance from the bottom part of the ala (Point B) to the branch (distance V) were recorded. Distance H ranged from −1.6 to 1.5 mm on right sides and −1.0 to 1.5 mm on left sides. The diameter of the nerves at Point A ranged from 1.3 to 1.8 mm on right sides and 1.3 to 1.6 mm on left sides. Distance V ranged from −1.5 to 1.0 mm on right sides and −2.3 to 1.1 mm on left sides. The diameter of the nerves at Point B ranged from 0.7 to 1.3 mm on right sides and 0.8 to 1.2 mm on left sides. The results of this study are the first to detail the topography of the internal nasal branch of the ION. Clin. Anat. 30:817–820, 2017. © 2017Wiley Periodicals, Inc.
Influence of Environmental Factors on Essential Oil Variability in Origanum compactum Benth. Growing Wild in Morocco
Authors: Aboukhalid Kaoutar , Al Faiz Chaouki , Douaik Ahmed , Bakha Mohamed , Kursa Karolina , Agacka‐Mołdoch Monika , Machon Nathalie , Tomi Félix , Lamiri Abdeslam
Published: May 2017

The present study aimed to evaluate the influence of environmental factors on essential oils (EOs) composition of Origanum compactum populations sampled all over the distribution area of the species in Morocco, and to determine the extent of the chemical profiles throughout the geographical distribution of the species. The chemical compositions were submitted to canonical correlation analysis and canonical discriminant analysis that indicated a significant relationship between oil components and some environmental factors. According to their chemical composition and edapho‐climatic characteristics, two major groups of populations were differentiated. The first group was composed of samples growing in regions with humid climate, clayey, sandy, and alkaline soils. These samples showed high thymol, α‐terpineol, linalool, and carvacryl methyl oxide content. The second group consisted of plants belonging to semi‐arid climate, and growing at high altitudes and silty soils. These samples were characterized by high carvacrol, α‐thujene, α‐terpinene, and myrcene content. However, populations exposed to sub‐humid climate, appeared less homogeneous and belong mainly either to the first or second group. A significant correlation between some edaphic factors (pH, K2O content, soil texture) and the EOs yield of O. compactum plants was evidenced. In spite of the correlation obtained for the oil composition with edapho‐climatic factors and the variance explained by the environmental data set, the observed EO diversity might be also genetically determined.
Induction of Necroptosis in Cancer Stem Cells using a Nickel(II)‐Dithiocarbamate Phenanthroline Complex
Authors: Flamme Marie , Cressey Paul B. , Lu Chunxin , Bruno Peter M. , Eskandari Arvin , Hemann Michael T. , Hogarth Graeme , Suntharalingam Kogularamanan
Published: May 2017

The cytotoxic properties of a series of nickel(II)‐dithiocarbamate phenanthroline complexes is reported. The complexes 1–6 kill bulk cancer cells and cancer stem cells (CSCs) with micromolar potency. Two of the complexes, 2 and 6, kill twice as many breast cancer stem cell (CSC)‐enriched HMLER‐shEcad cells as compared to breast CSC‐depleted HMLER cells. Complex 2 inhibits mammosphere formation to a similar extent as salinomycin (a CSC‐specific toxin). Detailed mechanistic studies suggest that 2 induces CSC death by necroptosis, a programmed form of necrosis. Specifically, 2 triggers MLKL phosphorylation, oligomerization, and translocation to the cell membrane. Additionally, 2 induces necrosome‐mediated propidium iodide (PI) uptake and mitochondrial membrane depolarisation, as well as morphological changes consistent with necroptotosis. Strikingly, 2 does not evoke necroptosis by intracellular reactive oxygen species (ROS) production or poly(ADP) ribose polymerase (PARP‐1) activation.
Retinal pigment epithelium expansion around the neural retina occurs in two separate phases with distinct mechanisms
Authors: Cechmanek Paula Bernice , McFarlane Sarah
Published: May 2017

Background: The retinal pigment epithelium (RPE) is a specialized monolayer of epithelial cells that forms a tight barrier surrounding the neural retina. RPE cells are indispensable for mature photoreceptor renewal and survival, yet how the initial RPE cell population expands around the neural retina during eye development is poorly understood. Results: Here we characterize the differentiation, proliferation, and movements of RPE progenitors in the Zebrafish embryo over the period of optic cup morphogenesis. RPE progenitors are present in the dorsomedial eye vesicle shortly after eye vesicle evagination. We define two separate phases that allow for full RPE expansion. The first phase involves a previously uncharacterized antero‐wards expansion of the RPE progenitor domain in the inner eye vesicle leaflet, driven largely by an increase in cell number. During this phase, RPE progenitors start to express differentiation markers. In the second phase, the progenitor domain stretches in the dorsoventral and posterior axes, involving cell movements and shape changes, and coinciding with optic cup morphogenesis. Significantly, cell division is not required for RPE expansion. Conclusions: RPE development to produce the monolayer epithelium that covers the back of the neural retina occurs in two distinct phases driven by distinct mechanisms. Developmental Dynamics 246:598–609, 2017. © 2017 Wiley Periodicals, Inc.
Demographics, reproduction, growth, and abundance of Jollyville Plateau salamanders (Eurycea tonkawae)
Authors: Bendik Nathan F.
Published: June 2017

Insights into the ecology and natural history of the neotenic salamander, Eurycea tonkawae, are provided from eight years of capture‐recapture data from 10,041 captures of 7,315 individuals at 16 sites. Eurycea tonkawae exhibits seasonal reproduction, with peak gravidity occurring in the fall and winter. Size frequency data indicated recruitment occurred in the spring and summer. Open‐population capture‐recapture models revealed a similar seasonal pattern at two of three sites, while recruitment was dependent on flow at the third site. Females can reach sexual maturity within one year, and oviposition likely takes place below ground. The asymptotic body length of 1,290 individuals was estimated as 31.73 mm (at ca. two years of age), although there was substantial heterogeneity among growth trajectories. Longevity was approximately eight years, and the median age for a recaptured adult was 2.3 years. Abundance estimated from closed‐population and robust‐design capture‐recapture models varied widely within and among sites (range 41–834), although, surprisingly, dramatic changes in abundance were not observed following prolonged dry periods. Seasonal migration patterns of second‐year and older adults may help explain lower ratios of large individuals and higher temporary emigration during the latter half of the year, but further study is required. Low numbers of captures and recaptures precluded the use of open‐population models to estimate demographic parameters at several sites; therefore, closed‐population (or robust‐design) methods are generally recommended. Based on observations of their life history and population demographics, E. tonkawae seems well adapted to conditions where spring flow is variable and surface habitat periodically goes dry.
Vector population growth and condition‐dependent movement drive the spread of plant pathogens
Authors: Shaw Allison K. , Peace Angela , Power Alison G. , Bosque‐Pérez Nilsa A.
Published: May 2017

Plant viruses, often spread by arthropod vectors, impact natural and agricultural ecosystems worldwide. Intuitively, the movement behavior and life history of vectors influence pathogen spread, but the relative contribution of each factor has not been examined. Recent research has highlighted the influence of host infection status on vector behavior and life history. Here, we developed a model to explore how vector traits influence the spread of vector‐borne plant viruses. We allowed vector life history (growth rate, carrying capacity) and movement behavior (departure and settlement rates) parameters to be conditional on whether the plant host is infected or healthy and whether the vector is viruliferous (carrying the virus) or not. We ran simulations under a wide range of parameter combinations and quantified the fraction of hosts infected over time. We also ran case studies of the model for Barley yellow dwarf virus, a persistently transmitted virus, and for Potato virus Y, a non‐persistently transmitted virus. We quantified the relative importance of each parameter on pathogen spread using Latin hypercube sampling with the statistical partial rank correlation coefficient technique. We found two general types of mechanisms in our model that increased the rate of pathogen spread. First, increasing factors such as vector intrinsic growth rate, carrying capacity, and departure rate from hosts (independent of whether these factors were condition‐dependent) led to more vectors moving between hosts, which increased pathogen spread. Second, changing condition‐dependent factors such as a vector's preference for settling on a host with a different infection status than itself, and vector tendency to leave a host of the same infection status, led to increased contact between hosts and vectors with different infection statuses, which also increased pathogen spread. Overall, our findings suggest that vector population growth rates had the greatest influence on rates of virus spread, but rates of vector dispersal from infected hosts and from hosts of the same infection status were also very important. Our model highlights the importance of simultaneously considering vector life history and behavior to better understand pathogen spread. Although developed for plant viruses, our model could readily be utilized with other vector‐borne pathogen systems.
Intraspecific variation in growth rate is a poor predictor of fitness for reef corals
Authors: Edmunds Peter J.
Published: May 2017

Genetic variation underlying differences in organism performance is subject to natural selection, and organisms with high values of genetically determined phenotypic measures of fitness should perform better than those that do not. Using small scleractinian corals (i.e., ≤40‐mm diameter), this principle was tested with 20 yr of census data from St. John, US Virgin Islands. Using growth rate (change in diameter) as a measure of fitness, growth in one year was tested for association with growth and survivorship in the following two years, and this process was repeated over 20 yr using a 3‐yr sliding window. Virtually all variation in growth was independent of colony size, and growth among pairs of years was highly variable, with corals that grew fast in one year rarely growing fast in the next 2 yr. While growth in some pairs of years was positively correlated, ≤4% of the growth variance was explained by growth in the preceding 2 yr. Survivorship was related positively to growth in the preceding year, but the association was weak, it did not extend over 3 yr, and was inconsistent over the study. These results demonstrate the importance of the environment in translating phenotypic measures of fitness into future performance, and for small Caribbean corals, they suggest that environmental conditions may preempt genotype in determining short‐term success.
Redox Equilibration Observed for the Reduction of a Ruthenium(III) Complex by Ascorbate under Low‐Driving‐Force Conditions
Authors: Impert Olga , Katafias Anna , Chrzanowska Marta , Muzioł Tadeusz , Wrzeszcz Grzegorz , van Eldik Rudi
Published: May 2017

A detailed kinetic study of the reduction of trans‐[RuCl2(dipicOEt)2]–, where dipicOEt = dipicolinate mono ethyl ester anion, by l‐ascorbic acid that leads to the formation of the corresponding RuII complex, was carried out spectrophotometrically using the stopped‐flow technique. The reaction was studied as a function of [AscH2]T and pH. The observed kinetic traces could only be fitted by a three‐exponential function, characteristic of three parallel reaction paths. The complex was isolated as {[Na(H2O)2][trans‐RuCl2(dipicOEt)2]}n, of which a single‐crystal X‐ray diffraction structure was determined. Detailed spectroscopic studies on the complex in aqueous solution showed that, under the selected experimental conditions, only a single complex species is present in solution. The observed complication is suggested to arise from the low driving force of the reaction during which the reoxidation of RuII by the semioxidized l‐ascorbic acid, that is, ascorbyl radical Asc·–, accounts for the apparent three‐exponential behavior of the reaction. The results are in excellent agreement with those of a recent study on the same reaction for cis‐dichloridobispicolinatoruthenate(III) (Eur. J. Inorg. Chem. 2016, 5380–5386).
“All‐Water” Synthesis of β‐Amino α,α‐Difluoro Ketones from Fluorinated Enol Silyl Ethers and Imines
Authors: Wu Ye‐bin , Wan Li , Lu Guo‐ping , Cai Chun
Published: May 2017

A one‐pot synthesis of β‐amino α,α‐difluoro ketones without any additives was developed. Through a series of control experiments we found that water played a crucial and indispensable role. The hydrogen bond between water and fluorinated enol silyl ether had a significant impact on the addition reaction.
Differential responses of the dorsomedial prefrontal cortex and right posterior superior temporal sulcus to spontaneous mentalizing
Authors: Moessnang Carolin , Otto Kristina , Bilek Edda , Schäfer Axel , Baumeister Sarah , Hohmann Sarah , Poustka Luise , Brandeis Daniel , Banaschewski Tobias , Tost Heike , Meyer‐Lindenberg Andreas
Published: May 2017

Previous research suggests a role of the dorsomedial prefrontal cortex (dmPFC) in metacognitive representation of social information, while the right posterior superior temporal sulcus (pSTS) has been linked to social perception. This study targeted these functional roles in the context of spontaneous mentalizing. An animated shapes task was presented to 46 subjects during functional magnetic resonance imaging. Stimuli consisted of video clips depicting animated shapes whose movement patterns prompt spontaneous mentalizing or simple intention attribution. Based on their differential response during spontaneous mentalizing, both regions were characterized with respect to their task‐dependent connectivity profiles and their associations with autistic traits. Functional network analyses revealed highly localized coupling of the right pSTS with visual areas in the lateral occipital cortex, while the dmPFC showed extensive coupling with instances of large‐scale control networks and temporal areas including the right pSTS. Autistic traits were related to mentalizing‐specific activation of the dmPFC and to the strength of connectivity between the dmPFC and posterior temporal regions. These results are in good agreement with the hypothesized roles of the dmPFC and right pSTS for metacognitive representation and perception‐based processing of social information, respectively, and further inform their implication in social behavior linked to autism. Hum Brain Mapp 38:3791–3803, 2017. © 2017 Wiley Periodicals, Inc.
Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
Authors: Arbelaiz Ander , Azkargorta Mikel , Krawczyk Marcin , Santos‐Laso Alvaro , Lapitz Ainhoa , Perugorria Maria J. , Erice Oihane , Gonzalez Esperanza , Jimenez‐Agüero Raul , Lacasta Adelaida , Ibarra Cesar , Sanchez‐Campos Alberto , Jimeno Juan P. , Lammert Frank , Milkiewicz Piotr , Marzioni Marco , Macias Rocio I.R. , Marin Jose J.G. , Patel Tushar , Gores Gregory J. , Martinez Ibon , Elortza Félix , Falcon‐Perez Juan M. , Bujanda Luis , Banales Jesus M.
Published: May 2017

Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions, such as primary sclerosing cholangitis (PSC), are risk factors. Noninvasive differential diagnosis between intrahepatic CCA and hepatocellular carcinoma (HCC) is sometimes difficult. Accurate noninvasive biomarkers for PSC, CCA, and HCC are not available. In the search for novel biomarkers, serum extracellular vesicles (EV) were isolated from CCA (n = 43), PSC (n = 30), or HCC (n = 29) patients and healthy individuals (control, n = 32); and their protein content was characterized. By using nanoparticle tracking analysis, serum EV concentration was found to be higher in HCC than in all the other groups. Round morphology (by transmission electron microscopy), size (∼180 nm diameter by nanoparticle tracking analysis), and markers (clusters of differentiation 9, 63, and 81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed multiple differentially expressed proteins among groups. Several of these proteins showed high diagnostic values with maximum area under the receiver operating characteristic curve of 0.878 for CCA versus control, 0.905 for CCA stage I‐II versus control, 0.789 for PSC versus control, 0.806 for noncirhottic PSC versus control, 0.796 for CCA versus PSC, 0.956 for CCA stage I‐II versus PSC, 0.904 for HCC versus control, and 0.894 for intrahepatic CCA versus HCC. Proteomic analysis of EV derived from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by normal human cholangiocytes. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release to serum of EV containing some similar human oncogenic proteins. Conclusion: Proteomic signatures found in serum EV of CCA, PSC, and HCC patients show potential usefulness as diagnostic tools. (Hepatology 2017;66:1125‐1143).
Recommendations on the use of magnetic resonance imaging in PSC‐A position statement from the International PSC Study Group
Authors: Schramm Christoph , Eaton John , Ringe Kristina I. , Venkatesh Sudhakar , Yamamura Jin ,   for the MRI working group of the IPSCSG
Published: May 2017

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder characterized by inflammation and fibrosis of the intra‐ and/or extrahepatic bile ducts. Magnetic resonance imaging (MRI) is a noninvasive imaging modality that can be used to diagnose PSC and detect disease related complications. Quantitative MRI technologies also have the potential to provide valuable prognostic information. Despite the potential of this imaging technology, the clinical application of MRI in the care of PSC patients and imaging standards vary across institutions. Moreover, a unified position statement about the role of MRI in the care of PSC patients, quality imaging standards, and its potential as a research tool is lacking. Conclusion: Members of the International PSC Study Group and radiologists from North America and Europe have compiled the following position statement to provide guidance regarding the application of MRI in the care of PSC patients, minimum imaging standards, and future areas of research. (Hepatology 2017;66:1675–1688).
Reconstruction of a clinician training system in China—A successful “5 + 3” model from Shanghai
Authors: Chen Zhaojun , Wang Ling
Published: June 2017

To promote medical educational reforms and improve the quality of health care services in China, Shanghai has embarked on a pilot reform programme to combine 3‐year graduate education with standardized residency training, which is called the 5 + 3 model and consists of 5 years of undergraduate studies plus 3 years of graduate studies integrated with standardized residency training. In the current review, we present the reconstruction and practice of the model in China.
Recent advancements in electrospinning design for tissue engineering applications: A review
Authors: Kishan Alysha P. , Cosgriff‐Hernandez Elizabeth M.
Published: May 2017

Electrospinning, a technique used to fabricate fibrous scaffolds, has gained popularity in recent years as a method to produce tissue engineered grafts with architectural similarities to the extracellular matrix. Beyond its versatility in material selection, electrospinning also provides many tools to tune the fiber morphology and scaffold geometry. Recent efforts have focused on extending the capabilities of electrospinning to produce scaffolds that better recapitulate tissue properties and enhance regeneration. This review highlights these advancements by providing an overview of the processing variables and setups used to modulate scaffold architecture, discussing strategies to improve cellular infiltration and guide cell behavior, and providing a summary of electrospinning applications in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2892–2905, 2017.
VEGF release from a polymeric nanofiber scaffold for improved angiogenesis
Authors: Zigdon‐Giladi Hadar , Khutaba Alaa , Elimelech Rina , Machtei Eli E. , Srouji Samer
Published: May 2017

Angiogenesis plays a pivotal role in tissue engineering and regenerative medicine. This study aimed to develop an electrospun fiber scaffold that supports release of recombinant human vascular endothelial growth factor (rhVEGF) to enhance angiogenesis. Scaffolds composed of core–shell fibers were fabricated using co‐electrospinning. The core solution was composed of polyethylene oxide and mixed with rhVEGF. The shell solution was composed of polycarpolactone, with 0.25, 1, and 3% of polyethylene glycol (PEG) to manipulate pore size on the shell. Pore size and density increased with higher PEG concentrations. Similarly, rhVEGF release was affected by PEG concentration: initial burst release was found in all scaffolds, followed by continuous 4 h release in 3% PEG and 18 h release in the 0.25 and 1% PEG polymeric scaffolds. Endothelial cell migration toward rhVEGF‐incorporated polymeric scaffold was 80‐fold higher as compared to VEGF‐free polymeric scaffold. In a subcutaneous mouse model, VEGF‐incorporated polymeric scaffold stimulated cell migration into the scaffold within three days and significantly enhanced blood vessels formation within 14 days, whereas control scaffolds contained few vessels. In conclusion, the described novel scaffold represents a promising device for vascular tissue engineering, which may be of clinical significance in treating vascular deficient wounds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2712–2721, 2017.
Functionalization promotes pathogen‐mimicking characteristics of polyanhydride nanoparticle adjuvants
Authors: Phanse Yashdeep , Carrillo‐Conde Brenda R. , Ramer‐Tait Amanda E. , Roychoudhury Rajarshi , Broderick Scott , Pohl Nicola , Rajan Krishna , Narasimhan Balaji , Wannemuehler Michael J. , Bellaire Bryan H.
Published: May 2017

Rational design of adjuvants and delivery systems will promote development of next‐generation vaccines to control emerging and re‐emerging diseases. To accomplish this, understanding the immune‐enhancing properties of new adjuvants relative to those induced by natural infections can help with the development of pathogen‐mimicking materials that will effectively initiate innate immune signaling cascades. In this work, the surfaces of polyanhydride nanoparticles composed of sebacic acid (SA) and 1,6‐bis(p‐carboxyphenoxy) hexane were decorated with an ethylene diamine spacer partially modified with either a glycolic acid linker or an α‐1,2‐linked di‐mannopyranoside (di‐mannose) to confer “pathogen‐like” properties and enhance adjuvanticity. Co‐incubation of linker‐modified nanoparticles with dendritic cells (DCs) elicited significant increases in surface expression of MHC I, MHC II, CD86, and CD40, and enhanced secretion of IL‐6, IL‐12p40, and TNF‐α. An 800% increase in uptake of ethylene‐diamine‐spaced, linker and di‐mannose functionalized polyanhydride nanoparticles was also observed. Together, our data showed that linker‐functionalized polyanhydride nanoparticles demonstrate similar patterns of uptake, intracellular trafficking, particle persistence, and innate activation as did DCs exposed to Yersinia pestis or Escherichia coli. These results set the stage for rational selection of adjuvant chemistries to induce pathogen‐mimicking immune responses. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2762–2771, 2017.
A quantitative analysis of light‐driven charge transfer processes using voronoi partitioning of time dependent DFT‐derived electron densities
Authors: Rombouts Jeroen A. , Ehlers Andreas W. , Lammertsma Koop
Published: May 2017

An analytical method is presented that provides quantitative insight into light‐driven electron density rearrangement using the output of standard time‐dependent density functional theory (TD‐DFT) computations on molecular compounds. Using final and initial electron densities for photochemical processes, the subtraction of summed electron density in each atom‐centered Voronoi polyhedron yields the electronic charge difference, QVECD. This subtractive method can also be used with Bader, Mulliken and Hirshfeld charges. A validation study shows QVECD to have the most consistent performance across basis sets and good conservation of charge between electronic states. Besides vertical transitions, relaxation processes can be investigated as well. Significant electron transfer is computed for isomerization on the excited state energy surface of azobenzene. A number of linear anilinepyridinium donor‐bridge‐acceptor chromophores was examined using QVECD to unravel the influence of its pi‐conjugated bridge on charge separation. Finally, the usefulness of the presented method as a tool in optimizing charge transfer is shown for a homologous series of organometallic pigments. The presented work allows facile calculation of a novel, relevant quantity describing charge transfer processes at the atomic level. © 2017 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
Simple modification of arm position improves B1+ and signal homogeneity in the thoracolumbar spine at 3T
Authors: Ishizaka Kinya , Kudo Kohsuke , Harada Kuniaki , Shirai Toru , Fujiwara Taro , Aoike Suzuko , Takamori Sayaka , Shirato Hiroki
Published: May 2017

Purpose

To evaluate the homogeneity of the radiofrequency magnetic field (B1+) and signal intensity using different arm positions during 3T thoracolumbar spinal imaging.

Materials and Methods

Twenty volunteers were scanned with a four‐channel radiofrequency (RF) transmit coil at 3T, with arms on the bed (conventional), arms elevated by 100 mm (arm lift), or with the arms‐up position (elevated arm). Axial B1+ maps and sagittal T1‐weighted image (T1WI)‐performed RF shimming were obtained for each arm position. The mean and standard deviation (SD) of the flip angle (FA) at the center of the vertebra on each B1+ map, and contrast noise ratios (CNRs) between the spinal cord and cerebrospinal fluid of sagittal T1WI, were calculated and compared among the different arm positions.

Results

Mean FA values (degrees) for the arm lift and elevated arm positions were significantly larger than for the conventional position (P < 0.001 for both) at the twelfth thoracic vertebra (Th12). FA SD values for the arm lift and elevated arm position were significantly smaller than for the conventional position (P < 0.001 for both) at Th12. CNR for the arm lift and elevated arm position were significantly higher than for the conventional position (P = 0.007 and 0.002, respectively). The mean and SD of the FA and the CNR did not differ significantly for the arm lift and elevated arm positions (P = 0.591, 0.958, and 0.927, respectively).

Conclusion

Inhomogeneities of B1+ and signal intensities were improved by simply changing the arm position in 3T thoracolumbar spinal imaging.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;47:123–130.
Physico‐chemical properties, rheology and degree of esterification of passion fruit (Passiflora edulis f. flavicarpa) peel flour
Authors: Coelho Emanuela M , de Azevêdo Luciana C , Viana Arão C , Ramos Ingrid G , Gomes Raquel G , Lima Marcos dos S , Umsza‐Guez Marcelo A
Published: May 2017

BACKGROUND

The peel of yellow passion fruit is as an agro‐industrial waste of great environmental impact, representing more than 50% of the total weight of the fruit. For this reason, and also considering its importance as a source of functional components such as pectin, this organic waste is increasingly attracting the attention of researchers. The aim of this study was to investigate the physico‐chemical composition and physical properties of this material, which may be of interest to the food industry.

RESULTS

We obtained two samples of passion fruit peel flour applying different processes: flour without treatment (FWOT) and flour with treatment by maceration (FWT). It was found that the flour samples contain, respectively, 372.4 g kg−1 and 246.7 kg−1 of soluble fiber and, according to the FTIR analysis, this material corresponds to high and low methoxyl pectins, respectively.

CONCLUSION

The flour obtained by maceration (FWT) offers greater benefits for industrial use, with 60% fewer tannins and greater thermal stability. In addition, this sample does not reabsorb moisture as easily, although FWOT also shows potential for use in dietary products. Considering the pseudoplastic properties of the flours, the application of both samples could be expanded to many industrial sectors. © 2017 Society of Chemical Industry
Simple, rapid, and environmentally friendly method for the separation of isoflavones using ultra‐high performance supercritical fluid chromatography
Authors: Wu Wenjie , Zhang Yuan , Wu Hanqiu , Zhou Weie , Cheng Yan , Li Hongna , Zhang Chuanbin , Li Lulu , Huang Ying , Zhang Feng
Published: May 2017

Isoflavones are natural substances that exhibit hormone‐like pharmacological activities. The separation of isoflavones remains an analytical challenge because of their similar structures. We show that ultra‐high performance supercritical fluid chromatography can be an appropriate tool to achieve the fast separation of 12 common dietary isoflavones. Among the five tested columns the Torus DEA column was found to be the most effective column for the separation of these isoflavones. The impact of individual parameters on the retention time and separation factor was evaluated. These parameters were optimized to develop a simple, rapid, and green method for the separation of the 12 target analytes. It only took 12.91 min using gradient elution with methanol as an organic modifier and formic acid as an additive. These isoflavones were determined with limit of quantitation ranging from 0.10 to 0.50 μg/mL, which was sufficient for reliable determination of various matrixes.
Preparation of magnetic molecularly imprinted polymers for the rapid and selective separation and enrichment of perfluorooctane sulfonate
Authors: Du Lingling , Wu Yongqiong , Zhang Xiaoli , Zhang Fang , Chen Xianping , Cheng Zhen , Wu Fei , Tan Kejun
Published: May 2017

As a persistent organic pollutant, perfluorooctane sulfonate has drawn a great worldwide attention. In this contribution, a novel material of magnetic molecularly imprinted polymers, based on perfluorooctane sulfonate, as a template, molecule was prepared. The magnetic molecularly imprinted polymers were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, and vibrating sample magnetometry. The adsorption isotherm was measured, and adsorption kinetic tests were conducted. The adsorbents possess high recognition ability (2.460 mg/g) and short adsorption equilibration time (60 min). Besides, they show good specificity and good reusability with the adsorption capacities of adsorbent toward perfluorooctane sulfonate decreasing less than 3% after five adsorption–desorption cycles. The magnetic molecularly imprinted polymers were used successfully in the separation and enrichment of perfluorooctane sulfonate in real water sample and exhibited good prospects in environmental treatment and monitoring.
Physical Injury and Somatic Complaints: The Mediating Role of Posttraumatic Stress Symptoms in Young Survivors of a Terror Attack
Authors: Bugge Ingrid , Dyb Grete , Stensland Synne Øien , Ekeberg Øivind , Wentzel‐Larsen Tore , Diseth Trond H.
Published: May 2017

Physically injured trauma survivors have particularly high risk for later somatic complaints and posttraumatic stress symptoms (PTSS). However, the potential mediating role of PTSS linking injury to later somatic complaints has been poorly investigated. In this study, survivors (N = 255) were interviewed longitudinally at 2 timepoints after the terror attack on Utøya Island, Norway, in 2011. Assessments included injury sustained during the attack, PTSS (after 4–5 months), somatic complaints (after 14–15 months), and background factors. Causal mediation analysis was conducted to evaluate the potential mediating role of PTSS in linking injury to somatic complaints comparing 2 groups of injured survivors with noninjured survivors. For the nonhospitalized injured versus the noninjured survivors, the mediated pathway was significant (average causal mediation effect; ACME = 0.09, p = .028, proportion = 55.8%). For the hospitalized versus the noninjured survivors, the mediated pathway was not significant (ACME = 0.04, p = .453, proportion = 11.6%). PTSS may play a significant mediating role in the development of somatic complaints among nonhospitalized injured trauma survivors. Intervening health professionals should be aware of this possible pathway to somatic complaints.
Diagnostic Performance of Sonographic Features in Patients With Biliary Atresia: A Systematic Review and Meta‐analysis
Authors: Yoon Hee Mang , Suh Chong Hyun , Kim Jeong Rye , Lee Jin Seong , Jung Ah Young , Cho Young Ah
Published: May 2017

Objectives

To evaluate the diagnostic performance of sonographic features of biliary atresia in patients with infantile cholestasis.

Methods

The Ovid‐MEDLINE and EMBASE databases were searched for studies of the diagnostic performance of sonographic features of biliary atresia in patients with infantile cholestasis. A meta‐analysis was performed to evaluate the diagnostic performance of the triangular cord sign and other sonographic features in patients with biliary atresia.

Results

Seventeen eligible studies with 1444 patients were included. The triangular cord sign had high accuracy for diagnosing biliary atresia: the meta‐analytic summary sensitivity and specificity were 85% (95% confidence interval, 77%–90%) and 97% (95% confidence interval, 94%–99%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.97. Meta‐regression analysis revealed that the cutoff thickness of the triangular cord sign (3 or 4 mm) was a significant factor affecting study heterogeneity (P < .01). The proportions of nonidentification of the gallbladder (GB) ranged from 0% to 53%. Abnormal GB morphologic characteristics, nonvisualization of the common bile duct, and the presence of hepatic subcapsular flow showed relatively high sensitivities and specificities.

Conclusions

The triangular cord sign and other sonographic features, including abnormal GB morphologic characteristics, nonvisualization of the common bile duct, and the presence of hepatic subcapsular flow, had high diagnostic performance for the diagnosis of biliary atresia.