bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial
Authors: Poddubnyy Denis , Listing Joachim , Sieper Joachim
Published: March 2016

Objective

To investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone.

Methods

A total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions.

Results

After 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score −2.9 ± 5.1, versus −2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score −4.3 ± 5.2 in the infliximab plus naproxen group versus −3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86]).

Conclusion

These findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti‐TNF.
The Effect of Comedication With a Conventional Synthetic Disease‐Modifying Antirheumatic Drug on Drug Retention and Clinical Effectiveness of Anti–Tumor Necrosis Factor Therapy in Patients With Axial Spondyloarthritis
Authors: Nissen Michael J. , Ciurea Adrian , Bernhard Jürg , Tamborrini Giorgio , Mueller Ruediger , Weiss Bettina , Toniolo Martin , Exer Pascale , Gabay Cem , Finckh Axel ,   for the physicians of the Swiss Clinical Quality Management Cohort
Published: March 2016

Objective

To explore the effect of comedication with conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) on drug retention and clinical effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (SpA).

Methods

The study included all patients starting treatment with a TNFi in a large prospective cohort of axial SpA patients (Swiss Clinical Quality Management in axial SpA). Crude drug retention was analyzed using the Kaplan‐Meier method, and in adjusted analyses, Cox proportional hazards regression was used to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time.

Results

A total of 2,765 TNFi treatment courses were included from 1,914 patients with axial SpA, 20.4% in combination with a conventional synthetic DMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months) compared to the cotherapy group (39.1 months) (P = 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95% confidence interval [95% CI] 1.01–1.35). This effect was even larger when only infliximab‐treated patients were considered, with an HR for monotherapy of 1.36 (95% CI 1.06–1.74). Clinical response rates were almost identical at 1 year, with a change in the Bath Ankylosing Spondylitis Disease Activity Index of −2.02 and −2.00 (P = 0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using C‐reactive protein of −1.14 and −1.12 (P = 0.45) in the monotherapy and cotherapy groups, respectively.

Conclusion

We demonstrate an association between the combination of a TNFi with conventional synthetic DMARDs and improved drug retention in patients with axial SpA, particularly in the subgroup of patients with infliximab.
Rapid screening and identification of lycodine‐type alkaloids in Lycopodiaceae and Huperziaceae plants by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Shan Si‐Ming , Luo Jian‐Guang , Pan Ke , Zou Hong‐yan , Kong Ling‐Yi
Published: March 2016

Lycodine‐type alkaloids have gained significant interest owing to their unique skeletal characteristics and acetylcholinesterase activity. This study established a rapid and reliable method using ultra‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐ESI‐Q/TOF‐MS/MS) for comprehensive characterization of lycodine‐type alkaloids for the first time. The lycodine‐type alkaloids were detected successfully from Lycopodiastrum casuarinoides, Huperzia serrata and Phlegmarirus carinatus in seven plants of the Lycopodiaceae and Huperziaceae families, based on the established characteristic MS fragmentation of five known alkaloids. Furthermore, a total of 13 lycodine‐type alkaloids were identified, of which three pairs of isomers were structurally characterized and differentiated. This study further improves mass analysis of lycodine‐type alkaloids and demonstrates the superiority of UPLC with a high‐resolution mass spectrometer for the rapid and sensitive structural elucidation of other trace active compounds. Copyright © 2016 John Wiley & Sons, Ltd.
Development and validation of a sensitive LC–MS/MS assay for quantification of bruceine D in rat plasma
Authors: Zhang Yining , Zhen Yong , Zhang Ying , Liu Shouyue
Published: March 2016

A sensitive LC–MS/MS method for the determination of bruceine D in rat plasma was developed. The analyte and IS were separated on a Luna C18 column (2.1 × 50 mm, 1.7 μm) using a mobile phase of acetonitrile and 0.1% formic acid in water (40:60, v/v) at a flow rate of 0.25 mL/min. The selected reaction monitoring mode was chosen to monitor the precursor‐to‐product ion transitions of m/z 409.2 → 373.2 for bruceine D and m/z 469.2 → 229.3 for IS using a negative ESI mode. The method was validated over a concentration range of 0.5–2000 ng/mL for bruceine D. Total chromatography time for each run was 3.5 min. The method was successfully applied to a pharmacokinetic study of bruceine D in rats. Copyright © 2016 John Wiley & Sons, Ltd.
A self‐contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P‐glycoprotein‐mediated digoxin transport activity
Authors: Yang Bei , Ma Li‐Ping , Ma Wei , Wei Shi‐Jie , Ji Hong‐Yan , Li Hou‐Gang , Dang Hong‐Wan , Liu Cheng , Wu Xiu‐Li , Chen Jing
Published: March 2016

In this study, we used a self‐contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P‐glycoprotein (P‐gp) transport activity. A sensitive and rapid UHPLC–MS/MS method was applied for quantification of digoxin, a P‐gp‐specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09 mg/kg (first period), followed by a 20‐day wash‐out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0–24, Cmax, tmax, and Clz/F of the negative control and ART alone groups showed no difference. However, the AUC0–24 and Cmax in the CHR alone, CHR–ART (1:2) and verapamil (positive control) groups showed 2.34‐, 3.04‐, 1.79‐, and 1.81‐, 1.99‐, 2.06‐fold increases along with 3.50‐, 3.84‐ and 4.76‐fold decreases for CLz/F, respectively. The tmax in the CHR–ART (1:2) group increased 3.73‐fold. In conclusion, our self‐contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P‐gp activity while ART alone has no effect. Copyright © 2016 John Wiley & Sons, Ltd.
Autism and chromosome abnormalities—A review
Authors: Bergbaum Anne , Ogilvie Caroline Mackie
Published: March 2016

The neuro‐behavioral disorder of autism was first described in the 1940s and was predicted to have a biological basis. Since that time, with the growth of genetic investigations particularly in the area of pediatric development, an increasing number of children with autism and related disorders (autistic spectrum disorders, ASD) have been the subject of genetic studies both in the clinical setting and in the wider research environment. However, a full understanding of the biological basis of ASDs has yet to be achieved. Early observations of children with chromosomal abnormalities detected by G‐banded chromosome analysis (karyotyping) and in situ hybridization revealed, in some cases, ASD associated with other features arising from such an abnormality. The introduction of higher resolution techniques for whole genome screening, such as array comparative genome hybridization (aCGH), allowed smaller imbalances to be detected, some of which are now considered to represent autism susceptibility loci. In this review, we describe some of the work underpinning the conclusion that ASDs have a genetic basis; a brief history of the developments in genetic analysis tools over the last 50 years; and the most common chromosome abnormalities found in association with ASDs. Introduction of next generation sequencing (NGS) into the clinical diagnostic setting is likely to provide further insights into this complex field but will not be covered in this review. Clin. Anat. 29:620–627, 2016. © 2016 Wiley Periodicals, Inc.
Frankincense Revisited, Part II: Volatiles in Rare Boswellia Species and Hybrids
Authors: Niebler Johannes , Eslamieh Jason , Buettner Andrea
Published: March 2016

In this second part of the investigation of volatiles and semivolatiles in Boswellia gum resins, an additional five less common species were analyzed by (SPME‐)GC/MS, namely B. ameero, B. elongata, B. neglecta, B. popoviana, and B. rivae. Moreover, the results of hybridization experiments are reported in combination with the volatile composition of their gum resins. Our study shows that B. sacra benefits from an intraspecific cross‐pollination, as the resulting hybrid B. sacra var. supersacra has a far higher seed germination rate and viability.
Cracking a tricuspid perimount bioprosthesis to optimize a second transcatheter sapien valve‐in‐valve placement
Authors: Brown Stephen C. , Cools Bjorn , Gewillig Marc
Published: March 2016

Bioprosthetic valves degenerate over time. Transcatheter valve‐in‐valve procedures have become an attractive alternative to surgery. However, every valve increasingly diminishes the diameter of the valvar orifice. We report a 12‐year‐old female who had a previous transcatheter tricuspid valve‐in‐valve procedure; cracking the ring of a Carpentier Edwards Perimount valve by means of an ultrahigh pressure balloon allowed implantation of a further larger percutaneous valve. The advantage of this novel approach permits enlarging the inner valve diameter and may facilitate future interventions and prolong time to surgery. © 2016 Wiley Periodicals, Inc.
Pump and pipeline performance when pumping slurries with different particle gradings
Authors: Sellgren Anders , Visintainer Robert , Furlan John , Matoušek Václav
Published: March 2016

A pipeline slurry friction loss model consisting of three regimes was initially proposed by Wilson then extended to four components consisting of fluid, pseudo‐homogeneous, heterogeneous, and fully stratified regimes. The weighting technique using up to four regime‐related components often works well for friction loss estimations based on simple input data and model parameters. This also holds for the Hydraulic Institute's pump performance derating procedure for settling slurries. The comparisons and discussion focus on coarse particle slurries and some cases where the modelling estimations for pipeline and pump performance were not particularly accurate.
Flow of non‐Newtonian fluids in pipes with large roughness
Authors: Graham Lachlan J. W. , Pullum Lionel , Wu Jie
Published: March 2016

Pipes with large roughnesses can occur due to erosion, corrosion, and scale. These roughnesses can be much larger than are accounted for in the Moody diagram. Experimental tests have shown that laminar flow of non‐Newtonian fluids in pipes with large roughnesses can be accurately predicted by using a constricted diameter, where the diameter measurement is taken as the typical minimum of the rough pipe. Turbulent flows of non‐Newtonian fluids are less accurately predicted by available methods and it is suggested that test work be performed if it is required to account for large pipe roughness.
Inhibiting Smad2/3 signaling in pluripotent mouse embryonic stem cells enhances endoderm formation by increasing transcriptional priming of lineage‐specifying target genes
Authors: Dahle Øyvind , Kuehn Michael R.
Published: March 2016

Background: Pluripotent embryonic stem cells (ESCs) offer great potential for regenerative medicine. However, efficient in vitro generation of specific desired cell types is still a challenge. We previously established that Smad2/3 signaling, essential for endoderm formation, regulates target gene expression by counteracting epigenetic repression mediated by Polycomb Repressive Complex 2 (PRC2). Although this mechanism has been demonstrated during differentiation and reprogramming, little is known of its role in pluripotent cells. Results: Chromatin immunoprecipitation‐deep sequencing of undifferentiated mouse ESCs inhibited for Smad2/3 signaling identified Prdm14, important for protecting pluripotency, as a target gene. Although Prdm14 accumulates the normally repressive PRC2 deposited histone modification H3K27me3 under these conditions, surprisingly, expression increases. Analysis indicates that increased H3K27me3 leads to increased binding of PRC2 accessory component Jarid2 and recruitment of RNA polymerase II. Similar increases were found at the Nodal endoderm target gene Eomes but it remained unexpressed in pluripotent cells as normal. Upon differentiation, however, Eomes expression was significantly higher than in cells that had not been inhibited for signaling before differentiation. In addition, endoderm formation was markedly increased. Conclusions: Blocking Smad2/3 signaling in pluripotent stem cells results in epigenetic changes that enhance the capacity for endoderm differentiation. Developmental Dynamics 245:807–815, 2016. © 2016 Wiley Periodicals, Inc.
Exclusive transmission of the embryonic stem cell‐derived genome through the mouse germline
Authors: Koentgen Frank , Lin Jiangwei , Katidou Markella , Chang Isabelle , Khan Mona , Watts Jacqui , Mombaerts Peter
Published: March 2016

Gene targeting in embryonic stem (ES) cells remains best practice for introducing complex mutations into the mouse germline. One aspect in this multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency of germline transmission: the transmission of the ES cell‐derived genome through the germline of chimeras to their offspring. A method whereby male chimeras transmit exclusively the genome of the injected ES cells to their offspring has been developed. The new technology, referred to as goGermline, entails injecting ES cells into blastocysts produced by superovulated homozygous Tsc22d3 floxed females mated with homozygous ROSA26‐Cre males. This cross produces males that are sterile due to a complete cell‐autonomous defect in spermatogenesis. The resulting male chimeras can be sterile but when fertile, they transmit the ES cell‐derived genome to 100% of their offspring. The method was validated extensively and in two laboratories for gene‐targeted ES clones that were derived from the commonly used parental ES cell lines Bruce4, E14, and JM8A3. The complete elimination of the collateral birth of undesired, non‐ES cell‐derived offspring in goGermline technology fulfills the reduction imperative of the 3R principle of humane experimental technique with animals. genesis 54:326–333, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.
Phylogenies and traits provide distinct insights about the historical and contemporary assembly of aquatic insect communities
Authors: Saito Victor S. , Cianciaruso Marcus Vinicius , Siqueira Tadeu , Fonseca‐Gessner Alaide A. , Pavoine Sandrine
Published: March 2016

The assumption that traits and phylogenies can be used as proxies of species niche has faced criticisms. Evidence suggested that phylogenic relatedness is a weak proxy of trait similarity. Moreover, different processes can select different traits, giving opposing signals in null model analyses. To circumvent these criticisms, we separated traits of stream insects based on the concept of α and β niches, which should give clues about assembling pressures expected to act independently of each other. We investigated the congruence between the phylogenetic structure and trait structure of communities using all available traits and all possible combinations of traits (4095 combinations). To account for hierarchical assembling processes, we analyzed patterns on two spatial scales with three pools of genera. Beta niche traits selected a priori – i.e., traits related to environmental variation (e.g., respiration type) – were consistently clustered on the smaller scale, suggesting environmental filtering, while α niche traits – i.e., traits related to resource use (e.g., trophic position) – did not display the expected overdispersion, suggesting a weak role of competition. Using all traits together provided random patterns and the analysis of all possible combinations of traits provided scenarios ranging from strong clustering to overdispersion. Communities were phylogenetically overdispersed, a pattern previously interpreted as phylogenetic limiting similarity. However, our results likely reflect the co‐occurrence of ancient clades due to the stability of stream habitats along the evolutionary scale. We advise ecologists to avoid using combinations of all available traits but rather carefully traits based on the objective under consideration. Both trait and phylogenetic approaches should be kept in the ecologist toolbox, but phylogenetic distances should not be used as proxies of traits differences. Although the phylogenetic structure revealed processes operating at the evolutionary scale, only specific traits explained local processes operating in our communities.
The land‐potential knowledge system (landpks): mobile apps and collaboration for optimizing climate change investments
Authors: Herrick Jeffrey E. , Beh Adam , Barrios Edmundo , Bouvier Ioana , Coetzee Marina , Dent David , Elias Emile , Hengl Tomislav , Karl Jason W. , Liniger Hanspeter , Matuszak John , Neff Jason C. , Ndungu Lilian Wangui , Obersteiner Michael , Shepherd Keith D. , Urama Kevin C. , Bosch Rik , Webb Nicholas P.
Published: March 2016

Massive investments in climate change mitigation and adaptation are projected during coming decades. Many of these investments will seek to modify how land is managed. The return on both types of investments can be increased through an understanding of land potential: the potential of the land to support primary production and ecosystem services, and its resilience. A Land‐Potential Knowledge System (LandPKS) is being developed and implemented to provide individual users with point‐based estimates of land potential based on the integration of simple, geo‐tagged user inputs with cloud‐based information and knowledge. This system will rely on mobile phones for knowledge and information exchange, and use cloud computing to integrate, interpret, and access relevant knowledge and information, including local knowledge about land with similar potential. The system will initially provide management options based on long‐term land potential, which depends on climate, topography, and relatively static soil properties, such as soil texture, depth, and mineralogy. Future modules will provide more specific management information based on the status of relatively dynamic soil properties such as organic matter and nutrient content, and of weather. The paper includes a discussion of how this system can be used to help distinguish between meteorological and edaphic drought.
Assessing impact of land use and climate change on regulating ecosystem services in the czech republic
Authors: Krkoška lorencová Eliška , Harmáčková Zuzana V. , Landová Lucie , Pártl Adam , Vačkář David
Published: March 2016

Ecosystem services, defined as benefits provided by ecosystem functioning to society, are essential to human well‐being. Due to global environmental change and related anthropogenic drivers, ecosystems are often degraded, which hinders the delivery of ecosystem services. This study aims to quantify the impacts of land use and climate change on two regulating ecosystem services—carbon sequestration and water purification in terms of nitrogen retention in the Czech Republic. While employing approaches of scenarios and modeling, we illustrate current and potential future status of these ecosystem services. Our results show that among the ecosystem change drivers, one of the dominant domestic land‐use change of (Business‐As‐Might‐Be‐Usual) scenario is change of arable land and grassland to forest area that increases by 4.5% in 2080 compared to 2000. The results of ecosystem service modeling based on scenario for the years 2050 and 2080 indicate that the highest yearly carbon sequestration rate occurred in 2000–2050, reaching 640 GgC·yr
−1
, 2000–2080 shows decline in this regulating service by 16%. Average nitrogen leaching to water streams reached 0.75 kgN·ha
−1
·yr
−1
for in 2050 scenario and 0.80 kgN·ha
−1
·yr
−1
for in 2080 scenario as a result of decreasing nitrogen load, which suggested a decrease in nitrogen pollution compared to 2000. Since ecosystem services have not been extensively mainstreamed into research and policies in eastern European countries, we aim to contribute to improvement of knowledge on current status and potential future pathways of the provision of regulating ecosystem services in the Czech Republic.
Reef to island sediment connections on a Maldivian carbonate platform: using benthic ecology and biosedimentary depositional facies to examine island‐building potential
Authors: Morgan Kyle M. , Kench Paul S.
Published: March 2016

Reef islands are low‐lying accumulations of unconsolidated sediment formed from the skeletal remains of carbonate‐producing reef organisms and are therefore perceived as highly vulnerable to environmental change. However, basic elements of island composition are not well described and given their high inter‐ and intra‐basinal variability a better understanding of reef and island sedimentary environments (and the connections between them) are needed to predict future morphological response. Here, we use detailed ecological and sedimentological datasets to delineate key sediment production zones and biosedimentary depositional facies across the surface of Vabbinfaru platform, Maldives. Field measurements of platform hydrodynamics are applied to sedimentary deposits to determine the potential mobility of grains and identify transport pathways. Carbonate production was dominated by coral framework (mean: 52%) within a narrow zone on the outer reef rim (22% of platform area) resulting in coral‐rich detrital sediments (reef: 51%, island: 64%) that closely resemble living assemblages. The net transfer of sediment occurred lagoonward by wave‐driven processes leading to a decrease in grain size towards the island (R2 = 0.502) which acts as a major control on depositional facies development within the lagoon. Island sediments were distinct from reefal deposits, comprising a restricted suite of durable sands (mean: 1.34ϕ) throughout long‐term development. Our findings suggest that the production, breakdown and redistribution of coral‐derived sediment by platform currents is fundamental to future island stability at Vabbinfaru, and although alterations away from current ecological states may reduce sediment supply, the timescales over which island morphological response will occur depends upon phase lags between initial coral mortality and the conversion of this material into island‐grade sand. Copyright © 2016 John Wiley & Sons, Ltd.
A variable‐fidelity aerodynamic model using proper orthogonal decomposition
Authors: Mifsud M. J. , MacManus D. G. , Shaw S.T.
Published: March 2016

A variable‐fidelity aerodynamic model based on proper orthogonal decomposition (POD) of an ensemble of computational fluid dynamics (CFD) solutions at different parameters is presented in this article. The ensemble of CFD solutions consists of two subsets of numerical solutions or snapshots computed at two different nominal orders of accuracy or discretization. These two subsets are referred to as the low‐fidelity and high‐fidelity solutions or data, whereby the low fidelity corresponds with computations made at the lower nominal order of accuracy or coarser discretization. In this model, the relatively inexpensive low‐fidelity data and the more accurate but expensive high‐fidelity data are considered altogether to devise an efficient prediction methodology involving as few high‐fidelity analyses as possible, while obtaining the desired level of detail and accuracy. The POD of this set of variable‐fidelity data produces an optimal linear set of orthogonal basis vectors that best describe the ensemble of numerical solutions altogether. These solutions are projected onto this set of basis vectors to provide a finite set of scalar coefficients that represent either the low‐fidelity or high‐fidelity solutions. Subsequently, a global response surface is constructed through this set of projection coefficients for each basis vector, which allows predictions to be made at parameter combinations not in the original set of observations. This approach is used to predict supersonic flow over a slender configuration using Navier–Stokes solutions that are computed at two different levels of nominal accuracy as the low‐fidelity and high‐fidelity solutions. The numerical examples show that the proposed model is efficient and sufficiently accurate. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of electro‐activated brine solution on the migration of metallic ions from the cans to the product in sterilized canned sweet corn
Authors: Liato Viacheslav , Labrie Steve , Benali Marzouk , Aider Mohammed
Published: March 2016

Tinplate cans were used to study if electro‐activated brine solution (EAS) is more corrosive than conventional one by ICP analysis. The results showed different effects of EAS on cans, alone or filled with product. Acidic EAS (pH 2–3) and Redox +900 to +1200 mV highly reacted with the cans. The concentrations of Zn, Fe, and Cu in the solution were 0.028, 28.81, and 0.022 ppm, respectively. No Sn migration was observed in this case. When neutral or acidic chlorine‐free EAS was used, no significant difference was observed in comparison with the corrosivity of standard NaCl brine. Alkaline EAS with pH>10 and negative E (≤−966 mV) did not affect Zn, Fe, and Cu migration. However, it affected tin migration. Nevertheless, it is important to mention that even if some corrosion was observed, it was in the limit of the permitted level of concentration when the cans were filled with a product.
Excision margins and sentinel lymph node status as prognostic factors in thick melanoma of the head and neck: A retrospective analysis
Authors: Ruskin Olivia , Sanelli Alexandra , Herschtal Alan , Webb Angela , Dixon Ben , Pohl Miklos , Donahoe Simon , Spillane John , Henderson Michael A. , Gyorki David E.
Published: March 2016

Background

Recommended margins for thick cutaneous melanoma (Breslow thickness >4 mm; T4) have decreased over recent decades. Optimal margins and the role of sentinel node biopsy (SNB) in thick head and neck melanoma remain controversial.

Methods

A single‐center review was conducted of patients treated between 2002 and 2012 assessing the impact of excision margins and sentinel lymph node status on locoregional recurrence and melanoma‐specific survival (MSS).

Results

One hundred eight patients were identified. Median age was 71.1 years and median Breslow thickness was 6.0 mm. Median follow‐up was 40 months. Locoregional recurrence occurred in 27% and there was no significant reduction in recurrence with margins ≥2 cm (p = .17). Increasing margins did not improve survival (p = .58). Fifty‐nine patients (55%) underwent SNB, of which 27% were positive. There was a trend toward longer survival for patients who were sentinel lymph node‐negative (p = .097).

Conclusion

Wider margins do not significantly improve locoregional recurrence or MSS. Sentinel lymph node involvement reflects a poor prognosis. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1373–1379, 2016
Retracted: Immunoglobulin G4+ B‐cell receptor clones distinguish immunoglobulin G 4‐related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies
Authors: Doorenspleet Marieke E. , Hubers Lowiek M. , Culver Emma L. , Maillette de Buy Wenniger Lucas J. , Klarenbeek Paul L. , Chapman Roger W. , Baas Frank , van de Graaf Stan F. , Verheij Joanne , van Gulik Thomas M. , Barnes Eleanor , Beuers Ulrich , de Vries Niek
Published: March 2016

Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B‐cell receptor (BCR) clones determined by next‐generation sequencing accurately distinguish patients with IgG4‐associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4‐RD of the biliary tree and pancreas. (Hepatology 2016;64:501‐507)
Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis
Authors: Sun Xiaofang , Niu Xiaohua , Chen Ruochan , He Wenyin , Chen De , Kang Rui , Tang Daolin
Published: March 2016

Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death worldwide and currently has the fastest rising incidence of all cancers. Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the only approved systemic therapy for advanced HCC. However, acquired resistance to sorafenib has been found in HCC patients, which results in poor prognosis. Here, we show that metallothionein (MT)‐1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. The expression of MT‐1G messenger RNA and protein is remarkably induced by sorafenib but not other clinically relevant kinase inhibitors (e.g., erlotinib, gefitinib, tivantinib, vemurafenib, selumetinib, imatinib, masitinib, and ponatinib). Activation of the transcription factor nuclear factor erythroid 2‐related factor 2, but not p53 and hypoxia‐inducible factor 1‐alpha, is essential for induction of MT‐1G expression following sorafenib treatment. Importantly, genetic and pharmacological inhibition of MT‐1G enhances the anticancer activity of sorafenib in vitro and in tumor xenograft models. The molecular mechanisms underlying the action of MT‐1G in sorafenib resistance involve the inhibition of ferroptosis, a novel form of regulated cell death. Knockdown of MT‐1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib‐induced ferroptosis. Conclusion: These findings demonstrate a novel molecular mechanism of sorafenib resistance and suggest that MT‐1G is a new regulator of ferroptosis in HCC cells. (Hepatology 2016;64:488‐500)
Ice‐jam flood risk assessment and mapping
Authors: Lindenschmidt Karl‐Erich , Das Apurba , Rokaya Prabin , Chu Thuan
Published: March 2016

In northern regions, river ice‐ jam flooding can be more severe than open‐water flooding causing property and infrastructure damages, loss of human life and adverse impacts on aquatic ecosystems. Very little has been performed to assess the risk induced by ice‐related floods because most risk assessments are limited to open‐water floods. The specific objective of this study is to incorporate ice‐jam numerical modelling tools (e.g. RIVICE, Monte‐Carlo simulation) into flood hazard and risk assessment along the Peace River at the Town of Peace River (TPR) in Alberta, Canada. Adequate historical data for different ice‐jam and open‐water flooding events were available for this study site and were useful in developing ice‐affected stage‐frequency curves. These curves were then applied to calibrate a numerical hydraulic model, which simulated different ice jams and flood scenarios along the Peace River at the TPR. A Monte‐Carlo analysis was then carried out to acquire an ensemble of water level profiles to determine the 1 : 100‐year and 1 : 200‐year annual exceedance probability flood stages for the TPR. These flood stages were then used to map flood hazard and vulnerability of the TPR. Finally, the flood risk for a 200‐year return period was calculated to be an average of $32/m2/a ($/m2/a corresponds to a unit of annual expected damages or risk). Copyright © 2016 John Wiley & Sons, Ltd.
The Novel NF‐κB Inhibitor, MTI‐II Peptide Anti‐Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast‐Like Cells
Authors: Nakayama Kouhei , Hirata‐Tsuchiya Shizu , Okamoto Kazuki , Morotomi Takahiko , Jimi Eijiro , Kitamura Chiaki
Published: March 2016

Regulation of inflammation is important for pulp wound healing, including protective responses by odontoblast‐like cells. However, methods for directly regulating pulp inflammation have not yet been described. The inflammatory response is mediated by a transcription factor, nuclear factor‐κB (NF‐κB), which activates inflammatory cytokines including tumor necrosis factor (TNF)‐α. Macromolecular translocation inhibitor II (MTI‐II) was previously demonstrated as an enhancer of the transcriptional activity of glucocorticoid‐bound glucocorticoid receptor. Recently, a MTI‐II peptide anti‐inflammatory drug (MPAID) was bioengineered from the structure of MTI‐II as an inhibitor of NF‐κB transactivation. Here, we examined the effects of MTI‐II and MPAID on the inflammatory responses of odontoblast‐like cells. TNF‐α inhibited alkaline phosphatase (ALP) activity, a marker of odontoblast/osteogenic differentiation, and induced NF‐κB transcriptional activity in KN‐3 cells, which are odontoblast‐like cells derived from dental papilla cells of rat incisors, without affecting their viability. Exogenous expression of MTI‐II suppressed the NF‐κB transcriptional activity induced by TNF‐α or overexpression of p65 (a main subunit of NF‐κB) in the cells, whereas it failed to inhibit degradation of IκBα and nuclear translocation of p65 after TNF‐α treatment, suggesting that MTI‐II inhibits NF‐κB transcriptional activity by modulating the duration of DNA binding by p65. MPAID also inhibited TNF‐α‐induced NF‐κB transcriptional activity, the mRNA expression of IL‐6 and IL‐8, and IL‐6 production. Furthermore, pretreatment of the cells with MPAID restored the inhibitory effect of TNF‐α on ALP activity. These results suggest that MPAID may be able to regulate the inflammatory response and maintain a protective response of dental pulp. J. Cell. Biochem. 117: 2552–2558, 2016. © 2016 Wiley Periodicals, Inc.
HMGB1 Osteo‐Modulatory Action on Osteosarcoma SaOS‐2 Cell Line: An Integrated Study From Biochemical and ‐Omics Approaches
Authors: Martinotti Simona , Patrone Mauro , Manfredi Marcello , Gosetti Fabio , Pedrazzi Marco , Marengo Emilio , Ranzato Elia
Published: March 2016

High mobility group box protein‐1 (HMGB1) is released from cells under various pathological conditions and it plays a pivotal role as an alarmin signaling tissue damage. Little is known about the impact of HMGB1 in bone repair and remodeling. To this aim, we focused on HMGB1‐induced effects on the in vitro osteoblast model SaOS‐2. Cell proliferation was stimulated with a maximum at concentration of 2.5 nM, and such a dose also stimulated cell migration and scratch wound healing. We then characterized the modulatory effect of HMGB1 on bone biology, by using osteogenesis/mineralization assays, a PCR array, and the analysis of a series of osteogenic markers. We performed also a proteomic screening using SWATH‐MS on SaOS‐2 cell exposed to HMGB1 and we provide evidence for proteins modulated in HMGB1 exposed cells. Taken together, our data demonstrate that SaOS‐2 cell proliferation, migration, and osteogenic differentiation were increased by HMGB1. We, therefore, propose that HMGB1 could be a potent bone‐remodeling signal but the physiological meaning of this property remains to be more ascertained. J. Cell. Biochem. 117: 2559–2569, 2016. © 2016 Wiley Periodicals, Inc.
Highly efficient implementation of pseudospectral time‐dependent density‐functional theory for the calculation of excitation energies of large molecules
Authors: Cao Yixiang , Hughes Thomas , Giesen Dave , Halls Mathew D. , Goldberg Alexander , Vadicherla Tati Reddy , Sastry Madhavi , Patel Bhargav , Sherman Woody , Weisman Andrew L. , Friesner Richard A.
Published: March 2016

We have developed and implemented pseudospectral time‐dependent density‐functional theory (TDDFT) in the quantum mechanics package Jaguar to calculate restricted singlet and restricted triplet, as well as unrestricted excitation energies with either full linear response (FLR) or the Tamm–Dancoff approximation (TDA) with the pseudospectral length scales, pseudospectral atomic corrections, and pseudospectral multigrid strategy included in the implementations to improve the chemical accuracy and to speed the pseudospectral calculations. The calculations based on pseudospectral time‐dependent density‐functional theory with full linear response (PS‐FLR‐TDDFT) and within the Tamm–Dancoff approximation (PS‐TDA‐TDDFT) for G2 set molecules using B3LYP/6‐31G** show mean and maximum absolute deviations of 0.0015 eV and 0.0081 eV, 0.0007 eV and 0.0064 eV, 0.0004 eV and 0.0022 eV for restricted singlet excitation energies, restricted triplet excitation energies, and unrestricted excitation energies, respectively; compared with the results calculated from the conventional spectral method. The application of PS‐FLR‐TDDFT to OLED molecules and organic dyes, as well as the comparisons for results calculated from PS‐FLR‐TDDFT and best estimations demonstrate that the accuracy of both PS‐FLR‐TDDFT and PS‐TDA‐TDDFT. Calculations for a set of medium‐sized molecules, including Cn fullerenes and nanotubes, using the B3LYP functional and 6‐31G** basis set show PS‐TDA‐TDDFT provides 19‐ to 34‐fold speedups for Cn fullerenes with 450–1470 basis functions, 11‐ to 32‐fold speedups for nanotubes with 660–3180 basis functions, and 9‐ to 16‐fold speedups for organic molecules with 540–1340 basis functions compared to fully analytic calculations without sacrificing chemical accuracy. The calculations on a set of larger molecules, including the antibiotic drug Ramoplanin, the 46‐residue crambin protein, fullerenes up to C540 and nanotubes up to 14×(6,6), using the B3LYP functional and 6‐31G** basis set with up to 8100 basis functions show that PS‐FLR‐TDDFT CPU time scales as N2.05 with the number of basis functions. © 2016 Wiley Periodicals, Inc.
Atomic force microscopy as a tool to study the adsorption of DNA onto lipid interfaces
Authors: Luque‐Caballero Germán , Maldonado‐Valderrama Julia , Quesada‐Pérez Manuel , Martín‐Molina Alberto
Published: March 2016

The Atomic Force Microscopy (AFM) technique appears as a central tool for the characterization of DNA adsorption onto lipid interfaces. Regardless of the huge number of surveys devoted to this issue, there are still fascinating phenomena in this field that have not been explored in detail by AFM. For instance, adsorption of DNA onto like‐charged lipid surfaces mediated by cations is still not fully understood even though it is gaining popularity nowadays in gene therapy and nanotechnology. Studies related to the complexation of DNA with anionic lipids as a non‐viral gene delivery vehicle as well as the formation of self‐assembled nanoscale DNA constructs (DNA origami) are two of the most attractive systems. Unfortunately, molecular mechanisms underlying the adsorption of DNA onto anionic lipid interfaces remain unclear so far. In view of that, AFM becomes an appropriate technique to provide valuable information to understand the adsorption of DNA to anionic lipid surfaces. As a second part of this review we provide an illustrative example of application of the AFM technique to probe the DNA adsorption onto a model lipid monolayer negatively charged. Microsc. Res. Tech. 80:11–17, 2017. © 2016 Wiley Periodicals, Inc.
Comparative study on fermentation performance in the genome shuffled Candida versatilis and wild‐type salt tolerant yeast strain
Authors: Qi Wei , Guo Hong‐Lian , Wang Chun‐Ling , Hou Li‐Hua , Cao Xiao‐Hong , Liu Jin‐Fu , Lu Fu‐Ping
Published: March 2016

BACKGROUND

The fermentation performance of a genome‐shuffled strain of Candida versatilis S3‐5, isolated for improved tolerance to salt, and wild‐type (WT) strain were analysed. The fermentation parameters, such as growth, reducing sugar, ethanol, organic acids and volatile compounds, were detected during soy sauce fermentation process.

RESULTS

The results showed that ethanol produced by the genome shuffled strain S3‐5 was increasing at a faster rate and to a greater extent than WT. At the end of the fermentation, malic acid, citric acid and succinic acid formed in tricarboxylic acid cycle after S3‐5 treatment elevated by 39.20%, 6.85% and 17.09% compared to WT, respectively. Moreover, flavour compounds such as phenethyl acetate, ethyl vanillate, ethyl acetate, isoamyl acetate, ethyl myristate, ethyl pentadecanoate, ethyl palmitate and phenylacetaldehyde produced by S3‐5 were 2.26, 2.12, 2.87, 34.41, 6.32, 13.64, 2.23 and 78.85 times as compared to WT.

CONCLUSIONS

S3‐5 exhibited enhanced metabolic ability as compared to the wild‐type strain, improved conversion of sugars to ethanol, metabolism of organic acid and formation of volatile compounds, especially esters, Moreover, S3‐5 might be an ester‐flavour type salt‐tolerant yeast. © 2016 Society of Chemical Industry
Functional, bioactive and antigenicity properties of blue whiting protein hydrolysates: effect of enzymatic treatment and degree of hydrolysis
Authors: García‐Moreno Pedro J , Pérez‐Gálvez Raúl , Espejo‐Carpio F Javier , Ruiz‐Quesada Cristina , Pérez‐Morilla Ana I , Martínez‐Agustín Olga , Guadix Antonio , Guadix Emilia M
Published: March 2016

BACKGROUND

Fish discards represent an important under‐utilisation of marine resources. This study evaluated the up‐grading of the protein fraction of blue whiting (Micromesistius poutassou) discards by the production of fish protein hydrolysates (FPHs) exhibiting functional, antioxidant, angiotensin‐I converting enzyme (ACE)‐inhibitory and antigenicity properties.

RESULTS

FPHswith lowDH(4%) showed better emulsifying, foaming and oil binding capacities, particularly those obtained using only trypsin.FPHswithDH4% exhibited also the stronger antioxidant activity, especially the one obtained using only subtilisin (IC50= 1.36 mg proteinmL−1). The presence of hydrophobic residues at the C‐terminal of theFPHproduced using subtilisin also led to the strongerACE‐inhibitory activity. However,FPHswith highDH(12%), which implies a higher proportion of short peptides, was required to enhanceACE‐inhibition (IC50= 172 µg proteinmL−1). The antigenic levels of theFPHwere also reduced withDHindependently of the enzymatic treatment. Nevertheless, the highest degradation of fish allergens (e.g. parvalbumin) was also obtained when using only subtilisin.

CONCLUSION

These results suggest that added‐value products for food applications can be produced from the protein fraction of discards. © 2016 Society of Chemical Industry
Influence of gas–liquid two‐phase flow on angiotensin‐I converting enzyme inhibitory peptides separation by ultra‐filtration
Authors: Charoenphun Narin , Youravong Wirote
Published: March 2016

BACKGROUND

Membrane fouling is a major problem in ultra‐filtration systems and two‐phase flow is a promising technique for permeate flux enhancement. The objective of this research was to study the use of an ultra‐filtration (UF) system to enrich angiotensin‐I converting enzyme (ACE) inhibitory peptides from tilapia protein hydrolysate. To select the most appropriate membrane and operating condition, the effects of membrane molecular weight cut‐off (MWCO), transmembrane pressure (TMP) and cross‐flow velocity (CFV) on permeate flux and ACE inhibitory peptide separation were studied. Additionally, the gas–liquid two‐phase flow technique was applied to investigate its effect on the process capability.

RESULTS

The results showed that the highest ACE inhibitory activity was obtained from permeate of the 1 kDa membrane. In terms of TMP and CFV, the permeate flux tended to increase with TMP and CFV. The use of gas–liquid two‐phase flow as indicated by shear stress number could reduce membrane fouling and increase the permeate flux up to 42%, depending on shear stress number. Moreover, the use of a shear stress number of 0.039 led to an augmentation in ACE inhibitory activity of permeates.

CONCLUSIONS

Operating conditions using a shear stress number of 0.039 were recommended for enrichment of ACE inhibitory peptides. © 2016 Society of Chemical Industry
Novel technologies for monitoring the in‐line quality of virgin olive oil during manufacturing and storage
Authors: Beltrán Ortega Julio , Martínez Gila Diego M , Aguilera Puerto Daniel , Gámez García Javier , Gómez Ortega Juan
Published: March 2016

The quality of virgin olive oil is related to the agronomic conditions of the olive fruits and the process variables of the production process. Nowadays, food markets demand better products in terms of safety, health and organoleptic properties with competitive prices. Innovative techniques for process control, inspection and classification have been developed in order to to achieve these requirements. This paper presents a review of the most significant sensing technologies which are increasingly used in the olive oil industry to supervise and control the virgin olive oil production process. Throughout the present work, the main research studies in the literature that employ non‐invasive technologies such as infrared spectroscopy, computer vision, machine olfaction technology, electronic tongues and dielectric spectroscopy are analysed and their main results and conclusions are presented. These technologies are used on olive fruit, olive slurry and olive oil to determine parameters such as acidity, peroxide indexes, ripening indexes, organoleptic properties and minor components, among others. © 2016 Society of Chemical Industry