bluuebunny/crossref_metadata_2025 huggingface dataset:
A snapshot of the evolving epidemiology of oropharynx cancers
Authors: Chaturvedi Anil K. , Zumsteg Zachary S.
Published: April 2018

The trajectory of the human papillomavirus–positive oropharyngeal cancer epidemic in the United States reveals that “what's past is prologue” (William Shakespeare, The Tempest): birth cohorts that previously experienced rises in incidence at younger ages do so now at older ages. Trials to determine the optimal clinical management of this increasingly older patient population are needed.

See also pages 2993‐9.
An efficient CPU‐GPU hybrid parallel implementation for DVB‐RCS2 receiver
Authors: Wang Yueqing , Wang Fang , Li Rongchun , Dou Yong
Published: April 2018

The second‐generation digital video broadcasting return channel via satellite (DVB‐RCS2) is a promising real‐time wireless protocol that has been widely used in many applications, such as video conferences, video feeds, and video multicasting. However, the receiver end of DVB‐RCS2 is time consuming and should be accelerated by high‐performance processing systems. Today, graphic processing units (GPUs) have been applied in communication systems due to high parallel capability and processing throughput. In this study, we design a novel pipeline of the receiver on the CPU‐GPU platform. Moreover, we propose a CPU‐GPU hybrid strategy to fully utilize resources and reduce communication latency. Compared with the parallel turbo decoder proposed in other work on the same platform, our parallel implementation achieves higher throughput. For the entire DVB‐RCS2 receiver, compared with the non‐pipelined serial and non‐pipelined parallel algorithms, our proposed pipeline obtains 20 times and 6 times speedup, respectively. In addition, the latency of our implementation is lower than that of non‐pipelined CPU‐GPU implementation, which is equal to 1.06 ms.
Coordination of Be and Mg Centres by HCN Ligands – Be…N and Mg…N Interactions
Authors: Grabowski Sławomir J.
Published: April 2018

ωB97XD/aug‐cc‐pVTZ calculations were performed for clusters of Z2+cations (Z=Be and Mg) and HCN molecules (up to six molecules). The clusters of Be(CH3)2and Mg(CH3)2with HCN species were also calculated to analyse the influence of the Be/Mg−C formally covalent bonds on interactions of Be or Mg centre with ligands. The beryllium and magnesium centres possess different areas of a positive electrostatic potential that depend on a number of HCN ligands in the cluster considered. Numerous correlations between geometrical, energetic and topological parameters of the clusters considered are discussed since various theoretical approaches are applied; Quantum Theory of ‘Atoms in Molecules’, Natural Bond Orbital method and decomposition of the energy of interaction. The Be/Mg…N interactions classified as beryllium and magnesium bonds possess numerous characteristics which are known for the hydrogen bonds. Different types of coordination of Be and Mg centres analysed here exist also in crystal structures.
An In Vitro Model of Hematotoxicity: Differentiation of Bone Marrow–Derived Stem/Progenitor Cells into Hematopoietic Lineages and Evaluation of Lineage‐Specific Hematotoxicity
Authors: Mahalingaiah Prathap Kumar , Palenski Tammy , Van Vleet Terry R.
Published: April 2018

Hematotoxicity is a significant issue for drug safety and can result from direct cytotoxicity toward circulating mature blood cell types as well as targeting of immature blood‐forming stem cells/progenitor cells in the bone marrow. In vitro models for understanding and investigating the hematotoxicity potential of new test items/drugs are critical in early preclinical drug development. The traditional method, colony forming unit (CFU) assay, is commonly used and has been validated as a method for hematotoxicity screening. The CFU assay has multiple limitations for its application in investigative work. In this paper, we describe a detailed protocol for a liquid‐culture, microplate‐based in vitro hematotoxicity assay to evaluate lineage‐specific (myeloid, erythroid, and megakaryocytic) hematotoxicity at different stages of differentiation. This assay has multiple advantages over the traditional CFU assay, including being suitable for high‐throughput screening and flexible enough to allow inclusion of additional endpoints for mechanistic studies. Therefore, it is an extremely useful tool for scientists in pharmaceutical discovery and development. © 2018 by John Wiley & Sons, Inc.
Quantification of Serum Voriconazole, Isavuconazole, and Posaconazole by Liquid Chromatography Tandem Mass Spectrometry (LC‐MS/MS)
Authors: Smith Andrew , Dowis Justin , French Deborah
Published: April 2018

Voriconazole, isavuconazole, and posaconazole are triazole anti‐fungal drugs commonly used to treat invasive fungal infections. Therapeutic drug monitoring is commonly carried out when patients are prescribed these drugs to ensure that the serum concentrations are sufficiently high for efficacy, but do not reach toxic concentrations. Mass spectrometric (MS) assays have been successfully utilized to determine the serum concentrations of these drugs. This protocol describes a sample preparation procedure and a liquid chromatography‐tandem mass spectrometry assay for quantifying serum voriconazole, isavuconazole, and posaconazole in a single method. © 2018 by John Wiley & Sons, Inc.
Determining Food Allergens by Skin Sensitization in Mice
Authors: Tamehiro Norimasa , Adachi Reiko , Kimura Yoshie , Sakai Shinobu , Teshima Reiko , Kondo Kazunari
Published: April 2018

A food allergy is a chronic inflammatory disease against dietary antigens with high prevalence in industrialized countries. Because there is currently no cure for food allergies, avoiding the allergen is crucial for the prevention of an allergic reaction. Therefore, a further understanding of the pathogenesis and risk factors that augment the sensitization to food allergens is required. We have previously developed a food allergy mouse model using transdermal sensitization, which influences the susceptibility to food allergies. In this model, mice sensitized with partially hydrolyzed wheat protein (HWP) successfully resembled the major features of HWP‐sensitized and wheat allergy–induced patients. In this article, we describe transdermal sensitization of food allergens and induction of immediate‐type food allergies in mice. The methodology detailed here was mainly adapted from an original work by Adachi and colleagues with some modifications to the dressing methods to reduce stress. © 2018 by John Wiley & Sons, Inc.
Analysis of the Canadian national corporate social responsibility strategy: Insights and implications
Authors: Idemudia Uwafiokun , Kwakyewah Cynthia
Published: April 2018

Incidences of corporate–community conflict and human rights violation associated with the activities of Canadian extractive companies (CECs) abroad have led to debates at home about the social responsibility of CECs overseas and the role of the Canadian government in corporate social responsibility (CSR). In response to these debates, the Canadian government launched the Canadian national CSR strategy to steer the CSR agenda of CECs. This paper questions and problematizes governmental discourses within the national strategies as a basis for contributing to the debate on the role of government in CSR. We show that the Canadian national CSR strategy embodies the same neoliberal tendencies as the European governmental approach to CSR. However, while the Canadian government's approach to CSR emerged with an emphasis on self‐regulation, it has now morphed into a form of enforced self‐regulation. Hence, the Canadian government adopts both collaborative and confrontation strategies in its efforts to make self‐regulation effective.
Automatic current‐sharing extendable two‐channel LED driver with non‐pulsating input current and zero dc flux
Authors: Hwu K.I. , Jiang W.Z. , Chen W.H.
Published: April 2018

A 2‐channel LED driver is presented herein, which possesses non‐pulsating input current and automatic current sharing. There are 4 features in the proposed LED driver. First, due to an input inductor, the input current is non‐pulsating, which makes the life of the renewable energy module or input capacitor longer. Second, each coupled inductor winding has a capacitor connected in series. Therefore, the dc magnetizing bias current is zero, and this can improve the iron core utilization, making the core loss and size reduced. Third, the number of LED channels can be extended by increasing windings. Fourth, the LED currents can be almost identical even if there are different LED numbers in LED strings. Eventually, the proposed LED driver is verified by simulation and experiment.
A new single‐phase multilevel converter topology with reduced power electronic devices, voltage rating on switches, and power losses
Authors: Alishah Rasoul Shalchi , Hosseini Seyed Hossein , Babaei Ebrahim , Sabahi Mehran
Published: April 2018

In this paper, a new extended single‐phase structure for multilevel converter is presented which consists of several bidirectional and unidirectional switches along with dc voltage sources. To generate all possible levels at output voltage waveform, 2 methods are presented for determination of the amplitudes of dc voltage sources. The proposed structure is compared with traditional cascade H‐bridge multilevel converter and other recently proposed structures in terms of the number of power electronic components, voltage rating on switches, and power losses. Based on the comparison results, it is demonstrated that the proposed structure needs minimum number of IGBTs, gate drivers, and anti‐parallel diodes. Moreover, the voltage rating on bidirectional and unidirectional switches in the proposed structure is less than other similar topologies. Also, power losses analysis on the proposed topology is investigated. It is shown that the power loss of proposed topology is less than H‐bridge multilevel converter topology. The number of on‐state switches in the current path of proposed topology is much lower than other topologies which lead to the reduction of voltage drop on the switches and power losses. Both experimental and simulation works are provided to verify the performance of the presented structure.
Grazing disturbance increases transient but decreases persistent soil seed bank
Authors: Ma Miaojun , Walck Jeffrey l. , Ma Zhen , Wang Lipei , Du Guozhen
Published: April 2018

Very few studies have examined whether the impacts of grazing disturbance on soil seed banks occur directly or indirectly through aboveground vegetation and soil properties. The potential role of the seed bank in alpine wetland restoration is also unknown. We used SEM (structural equation modeling) to explore the direct effect of grazing disturbance on the seed bank and the indirect effect through aboveground vegetation and soil properties. We also studied the role of the seed bank on the restoration potential in wetlands with various grazing intensities: low (fenced, winter grazed only), medium (seasonally grazed), and high (whole‐year grazed). For the seed bank, species richness and density per plot showed no difference among grazing intensities for each depth (0–5, 5–10, 10–15 cm) and for the whole depth (0–15 cm) in spring and summer. There was no direct effect of grazing disturbance on seed bank richness and density both in spring and summer, and also no indirect effect on the seed bank through its direct effect on vegetation richness and abundance. Grazing disturbance indirectly increased spring seed bank density but decreased summer seed bank density through its direct effect (negative correlation) on soil moisture and total nitrogen and its indirect effect on vegetation abundance. Species composition of the vegetation changed with grazing regime, but that of the seed bank did not. An increased trend of similarity between the seed bank and aboveground vegetation with increased grazing disturbance was found in the shallow depth and in the whole depth only in spring. Although there was almost no change in seed bank size with grazing intensities, grazing disturbance increased the quantity of transient seeds but decreased persistent seeds. Persistent seeds stored in the soil could play a crucial role in vegetation regeneration and in restoration of degraded wetland ecosystems. The seed bank should be an integral part of alpine wetland restoration programs.
Recent Advances in Effective Reduction of Graphene Oxide for Highly Improved Performance Toward Electrochemical Energy Storage
Authors: Zhang Peng , Li Zhi , Zhang Shijie , Shao Guosheng
Published: April 2018

The demand for high‐quality graphene from various applications promotes the exploration of various synthesis methods such as chemical vapor deposition, chemical reduction of graphite oxide, liquid‐phase exfoliation, and electrochemical exfoliation. Among those, chemical treatments for the production of reduced graphene oxide (RGO) dictate the current technologies for mass production of graphene powder. However, such conventional chemical reduction methods are rather ineffective in removing oxygen‐containing functional groups from graphene oxide (GO), with resultant RGO products containing high level of structural defects. This leads to significantly damaged crystallinity and drastically lowered electric and thermal conductivity, which is probably the main bottleneck to limit the performance of RGO‐based materials. Great efforts such as thermal reduction, microwave‐irradiation reduction, or other novel reduction methods (e.g., photoreduction) have been developed to repair defects in RGO materials. This perspective review is to outline the latest advances toward effective reduction of GO for significantly enhanced properties. We demonstrate that effectively repaired RGO with large specific surface area and highly improved crystallinity is key to highly improved electric and thermal conductivity, thus leading to significantly enhanced properties essential for chemical energy storage devices.
Advances in Understanding Materials for Rechargeable Lithium Batteries by Atomic Force Microscopy
Authors: Wang Shuwei , Liu Qi , Zhao Chenglong , Lv Fengzheng , Qin Xianying , Du Hongda , Kang Feiyu , Li Baohua
Published: April 2018

The development of advanced lithium batteries represents a major technological challenge for the new century. Understanding the fundamental electrode degradation mechanisms is important for battery performance improvements. The complex electrochemical processes inside a working battery are being explored to a limited extent. Various advanced material characterization techniques have been used to monitor dynamic conditions for optimizing battery materials. State‐of‐the‐art atomic force microscopy methods have been applied to energy storage systems, specifically lithium‐ion batteries. Atomic force microscopy is an ideal tool to provide localized morphological, chemical, and physical information at nanoscale for the in‐depth understanding of the electrochemical processes, reaction mechanisms, and degradation of battery materials. Here, we review recent progress in the development and application of atomic force microscopy for high‐performance lithium‐ion batteries. We discuss atomic force microscopy as an analytical tool to help researchers understand graphite, silicon, layered metal oxides, and other representative electrode materials. We summarize the importance of atomic force microscopy technique in studying the next‐generation Li–S and Li–O2 batteries. We also highlight some of the remaining challenges and possible solutions for future development.
Copper(I)‐Catalyzed Four‐Component Coupling Using Renewable Building Blocks of CO2 and Biomass‐Based Aldehydes
Authors: Wu Qiumin , Chen Jinzhu , Guo Xuhong , Xu Yisheng
Published: April 2018

Both carbon dioxide‐ (CO2) and biomass‐based molecules have recently been regarded as renewable, abundant, environmentally benign, and attractive carbon feedstocks for organic synthesis. Therefore, a mild and efficient method for the synthesis of 1,3‐oxazolidin‐2‐ones was developed through a “green” four‐component coupling reaction by using CO2, biomass‐based aldehydes such as furfural and 5‐hydroxymethylfurfural (HMF), terminal aromatic alkynes, and primary aliphatic amines with copper iodide as a catalyst. 24 Furyl‐substituted 1,3‐oxazolidin‐2‐ones were obtained in 29–84 % yield from the four‐component coupling reaction. Moreover, the coupling reaction was applicable to the syntheses of furyl‐containing bisoxazolidinone and polyoxazolidinone under mild conditions.
Petasis/Diels–Alder/Cyclization Cascade Reactions for the Generation of Scaffolds with Multiple Stereogenic Centers and Orthogonal Handles for Library Production
Authors: Flagstad Thomas , Azevedo Carlos M. G. , Min Geanna , Willaume Anthony , Morgentin Rémy , Nielsen Thomas E. , Clausen Mads H.
Published: April 2018

A new effective strategy for the synthesis of sp3‐rich small molecules for library production is presented. The key steps to generate complexity involve a Petasis three‐component reaction followed by an intramolecular Diels–Alder and cyclization to generate a densely enriched tricyclic or tetracyclic scaffolds with 3–4 stereocenters and three handles for decoration. The strategy was used for the production of 143 molecules for the European Lead Factory.
Electrochemical Biosensing in Cancer Diagnostics and Follow‐up
Authors: Freitas Maria , Nouws Henri P. A. , Delerue‐Matos Cristina
Published: April 2018

In cancer, screening and early detection are critical for the success of the patient's treatment and to increase the survival rate. The development of analytical tools for non‐invasive detection, through the analysis of cancer biomarkers, is imperative for disease diagnosis, treatment and follow‐up. Tumour biomarkers refer to substances or processes that, in clinical settings, are indicative of the presence of cancer in the body. These biomarkers can be detected using biosensors, that, because of their fast, accurate and point of care applicability, are prominent alternatives to the traditional methods. Moreover, the constant innovations in the biosensing field improve the determination of normal and/or elevated levels of tumour biomarkers in patients’ biological fluids (such as serum, plasma, whole blood, urine, etc.). Although several biomarkers (DNA, RNA, proteins, cells) are known, the detection of proteins and circulating tumour cells (CTCs) are the most commonly reported due to their approval as tumour biomarkers by the specialized entities and commonly accepted for diagnosis by medical and clinical teams. Therefore, electrochemical immunosensors and cytosensors are vastly described in this review, because of their fast, simple and accurate detection, the low sample volumes required, and the excellent limits of detection obtained. The biosensing strategies reported for the six most commonly diagnosed cancers (lung, breast, colorectal, prostate, liver and stomach) are summarized and the distinct phases of the sensors’ constructions (surface modification, antibody immobilization, immunochemical interactions, detection approach) and applications are discussed.
A methodology for predicting and comparing the full‐scale fire performance of similar materials based on small‐scale testing
Authors: Lannon Chad M. , Stoliarov Stanislav I. , Lord James M. , Leventon Isaac T.
Published: April 2018

Reconstructive fire testing is an important tool used by fire investigators to determine the cause, origin, and progression of a particular fire. Accurate reconstruction of the fire requires the laboratory structure to be outfitted with materials that, in terms of contribution to fire growth, perform similarly to the original materials found at the fire scene. Therefore, a procedure was developed to enable fire investigators to select these replacement materials on the basis of a quantitative assessment of their relative fire performance. This procedure consists of gram‐scale and/or milligram‐scale standard testing accompanied by inverse numerical modeling of these tests, which is used to obtain relevant material properties. A numerical model composed of a detailed pyrolysis submodel and empirical flame heat feedback submodels, which were developed in this study, is subsequently employed to simulate the early stages of the Room Corner Test, which was selected to represent full‐scale material performance. The results of these simulations demonstrate that this procedure can successfully differentiate between fire growth propensities of several commercially available medium density fiberboards.
Geochronology and geochemistry of the Carboniferous felsic rocks in the central Great Xing'an Range, NE China: Implications for the amalgamation history of Xing'an and Songliao–Xilinhot blocks
Authors: Ma Yongfei , Liu Yongjiang , Wang Yan , Tang Zhen , Qian Cheng , Qin Tao , Feng Zhiqiang , Sun Wei , Zang Yanqing
Published: April 2018

The tectonic evolutionary history between the Xing'an Block (XB) and Songliao–Xilinhot Block (SXB) has been hotly debated. Here, we present precise geochronological ages and whole‐rock geochemical data in the central Great Xing'an Range for the Carboniferous felsic rocks to reveal this tectonic history, as the petrogenesis of these rocks were closely related to tectonic activity between the XB and SXB. The age data with detailed geochemical analyses indicate three important stages of magmatism: early Carboniferous, early Late Carboniferous, and middle Late Carboniferous. The early Carboniferous granodiorites formed from the partial melting of metavolcanic rocks at mantle depths and show I‐type features. The early Late Carboniferous monzogranites were generated by the partial melting of metagreywackes at middle to lower crustal depths, and they are S‐type granites. The middle Late Carboniferous rhyolites formed from the partial melting of a thinned lower crust, and they display A‐type characteristics. The data reveal three tectonic evolutionary stages between the XB and SXB during the Carboniferous era: from early Carboniferous subduction to early Late Carboniferous syn‐collision, and to middle Late Carboniferous post‐collisional extension. The accretionary mechanism of each stage featured horizontal accretion above subduction zones, amalgamation of different blocks, and vertical accretion fed by deep mantle materials, respectively.
Nonsteroidal anti‐inflammatory drug use and breast cancer risk in a European prospective cohort study
Authors: Cairat Manon , Fournier Agnès , Murphy Neil , Biessy Carine , Scalbert Augustin , Rinaldi Sabina , Tjønneland Anne , Olsen Anja , Overvad Kim , Arveux Patrick , Boutron‐Ruault Marie‐Christine , Cadeau Claire , Fortner Renée Turzanski , Kaaks Rudolf , Boeing Heiner , Aleksandrova Krasimira , Peeters Petra H.M. , Van Gils Carla H. , Wareham Nicholas J. , Khaw Kay‐Tee , Aune Dagfinn , Riboli Elio , Gunter Marc J. , Dossus Laure
Published: April 2018

Experimental studies have shown a protective effect of nonsteroidal anti‐inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self‐reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard ratios for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow‐up time period of 13 years, 7,379 incident breast cancer cases were diagnosed (816 in situ and 6,563 invasive). There were no statistically significant associations between NSAID use and breast cancer risk, overall and by subtypes. However, a statistically significant interaction was observed for invasive cases between NSAID use and ever use of menopausal hormonal therapy (MHT) among postmenopausal women [MHT users: HRNSAID use = 0.84 (0.73–0.96); non MHT users: HRNSAID use = 1.08 (0.93–1.25); pinteraction = 0.05]. Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in‐depth investigation in studies with accurate data on both NSAID and MHT use.
Identification of a five‐lncRNA signature for predicting the risk of tumor recurrence in patients with breast cancer
Authors: Li Jie , Wang Weida , Xia Peng , Wan Linyun , Zhang Li , Yu Lei , Wang Lily , Chen Xi , Xiao Yun , Xu Chaohan
Published: April 2018

Long non‐coding RNAs (lncRNAs) are a major class of non‐coding RNAs, and the functional deregulations of lncRNAs have been shown to be associated with the development and progression of BC. In this work, we conduct an integrative analysis on five re‐annotated lncRNA expression datasets from the Gene Expression Omnibus (GEO) which included a total of 891 BC samples. We identified a five‐lncRNA signature that was significantly associated with DFS in the training cohort of 327 patients. We found the five‐lncRNA signature could effectively stratify patients in the training dataset into high‐ and low‐risk groups with significantly different DFS (p = 3.29 × 10−5, log‐rank test). The five‐lncRNA signature was effectively validated in four independent cohorts, and prognostic analysis results showed that the five‐lncRNA signature was independent of clinical prognostic factors, such as BC subtypes and adjuvant treatments. Furthermore, GSEA suggested that the five‐lncRNA signature was involved in BC metastasis‐related pathways. Our findings indicate that these five lncRNAs may be implicated in BC pathogenesis, and further, these lncRNAs may potentially serve as novel candidate biomarkers for the identification of BC patients at high risk for tumor recurrence.
In vivo tumor gene delivery using novel peptideticles: pH‐responsive and ligand targeted core–shell nanoassembly
Authors: Alipour Mohsen , Majidi Asia , Molaabasi Fatemeh , Sheikhnejad Reza , Hosseinkhani Saman
Published: April 2018

Modulating cancer causing genes with nucleic acid based‐molecules as cutting‐edge approaches need efficient delivery systems to succeed in clinic. Herein, we report design and fabrication of a novel tissue penetrating peptideticle with charge‐structure switching in tumor microenvironment for an effective gene delivery. The comparative in vitro studies indicate that peptideticles identify and bind to tumor endothelial cells and efficiently penetrate into multicellular tumor spheroid. In addition, negatively charged peptideticle at pH 7.4, prevent unwanted interaction while its sharp charge‐structure switching at pH 6.2–6.9 (e.g. in tumor tissue) facilitates malignant cells penetration. More importantly, upon systemic administration into tumor bearing mice, peptideticles effectively localized in tumor tissue and delivered luciferase gene with a 200‐fold higher efficiency compared to their non‐pH‐responsive counterparts. In conclusion, this study presents a robust nanoassembly of safe materials for high efficient tumor gene delivery.
Effect of cobalt ions on the interaction between macrophages and titanium
Authors: Pettersson Mattias , Pettersson Jean , Molin Thorén Margareta , Johansson Anders
Published: April 2018

Inflammation and bone reduction around dental implants are described as peri‐implantitis and can be caused by an inflammatory response against bacterial products and toxins. Titanium (Ti) forms aggregates with serum proteins, which activate and cause release of the cytokine interleukin (IL‐1β) from human macrophages. It was hypothesized that cobalt (Co) ions can interact in the formation of pro‐inflammatory aggregates, formed by titanium. To test this hypothesis, we differentiated THP‐1 cells into macrophages and exposed them to Ti ions alone or in combination with Co ions to investigate if IL‐1β release and cytotoxicity were affected. We also investigated aggregate formation, cell uptake and human biopsies with inductively coupled plasma atomic emission spectroscopy and electron microscopy. Co at a concentration of 100 µM neutralized the IL‐1β release from human macrophages and affected the aggregate formation. The aggregates formed by Ti could be detected in the cytosol of macrophages. In the presence of Co, the Ti‐induced aggregates were located in the cytosol of the cultured macrophages, but outside the lysosomal structures. It is concluded that Co can neutralize the Ti‐induced activation and release of active IL‐1β from human macrophagesin vitro. Also, serum proteins are needed for the formation of metal‐protein aggregates in cell medium. Furthermore, the structures of the aggregates as well as the localisation after cellular uptake differ if Co is present in a Ti solution. Phagocytized aggregates with a similar appearance seenin vitrowith Ti present, were also visible in a sample from human peri‐implant tissue. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2518–2530, 2018.
TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast‐like cells in a size dependent manner
Authors: Ibrahim Mohamed , Schoelermann Julia , Mustafa Kamal , Cimpan Mihaela R.
Published: April 2018

Human exposure to titanium dioxide nanoparticles (nano‐TiO2) is increasing. An internal source of nano‐TiO2 is represented by titanium‐based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant‐bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano‐TiO2 on SaOS‐2 human osteoblast‐like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano‐TiO2. Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p‐FAKY397) and the expression of vinculin in response to nano‐TiO2 were also assessed. Treatment with nano‐TiO2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS‐2 cells. The phosphorylation of p‐FAKY397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm‐exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS‐2 cells were affected by the selected nano‐TiO2 in a size dependent manner. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2582–2593, 2018.
Evaluation of tacrolimus‐related CYP3A5 genotyping in China: Results from the First External Quality Assessment Exercise
Authors: Lin Guigao , Zhang Xiao , Zhang Kuo , Han Yanxi , Tan Liming , Li Jinming
Published: April 2018

Background

Tacrolimus is the most widely used immunosuppressant in solid organ transplant patients. The cytochrome P450 3A5 (CYP3A5) has been proved to be associated with tacrolimus dose requirement. Molecular detection for CYP3A5 genotyping is demanded for the optimization of treatments of tacrolimus.

Methods

To achieve the consistency and accuracy of the testing results, the Chinese National Center for Clinical Laboratories (NCCL) organized a national external quality assessment(EQA) program to evaluate the performance of laboratories providing CYP3A5 genotyping. Ten validated DNA samples covering the common genetic polymorphisms of CYP3A5 were delivered to 33 voluntary laboratories, and their detecting results and clinical written reports were evaluated.

Results

Thirty‐three datasets were received. The corresponding analytical sensitivity was 95.9% (285/297 challenges; 95% confidence interval: 93.0%‐97.9%), and the analytical specificity was 95.3% (346/363; 95% confidence interval: 92.6%‐97.2%). Thirty of the participating laboratories correctly identified the CYP3A5 allele status for all EQA samples. Three laboratories made genotyping errors, and 2 of them failed to detect any of the homozygotes such as *1/*1 and *3/*3. Twenty‐eight CYP3A5*3 tests reports were submitted, but many reports showed a shortage of essential information. No reports fulfilled all the consensus recommendations for pharmacogenetic test result reporting.

Conclusion

The EQA program highlighted the necessity for an improvement in the accuracy of genotyping for some of the laboratories and a greater education on the reporting of CYP3A5 genotyping results.
Preventative and restorative safety behaviors: Effects on exposure treatment outcomes and risk for future anxious symptoms
Authors: Goodson Jason T. , Haeffel Gerald J.
Published: April 2018

Objectives

Two studies investigated the differential effect of preventative and restorative safety behaviors on the treatment and development of anxiety and depression.

Method

Study 1 investigated the impact of preventative and restorative safety behaviors in prolonged exposure therapy among US veterans with PTSD (N = 95). Study 2 was a 3‐month prospective study investigating preventative and restorative safety behaviors as risk factors for anxious and depressive symptoms in a non‐clinical sample (N = 84).

Results

The results of Study 1 showed that both preventative and restorative safety behaviors were associated with worse treatment outcomes (both PTSD symptoms and depressive symptoms). The results of Study 2 found that preventative, but not restorative, safety behaviors predicted increases in future anxious symptoms. Neither preventative nor restorative safety behaviors conferred risk for increases in future depression symptoms (anhedonia).

Conclusions

Preventative and restorative safety behaviors impact PTSD treatment outcomes, while only preventative safety behaviors predict future anxiety.
A highly sensitive and colorimetric biosensor based on magnetic nano‐DNAzyme for detection of lead (II) ion in real water samples
Authors: Rong Mingge , Li Jun , Hu Jiahui , Chen Aolong , Wu Wenhe , Lyu Jianxin
Published: April 2018

BACKGROUND

Colorimetric biosensors based on DNAzyme provide convenient and selective means for the detection of lead ion (Pb2+), which are critically important to prevent lead exposure and poisoning. However, they still remain challenging because of their limitation of sensitivity (only nmol L‐1 level) and practical application. Herein, we design a highly sensitive, selective, simple, and quantitative platform for direct Pb2+ detection based on the magnetic nano‐DNAzyme in real water samples.

RESULTS

Magnetic beads were modified with enzyme strand of DNAzyme to work as solid phase carriers and hybridized with DNAzyme's substrate strand/horseradish peroxidase molecules double‐codified gold nanoparticles to form a stable magnetic nano‐DNAzyme complex. Under the optimized reaction conditions, the magnetic nano‐DNAzyme had a quantitative detection range from 102 to 108 pmol L‐1, a limit of detection of 32 pmol L‐1 and high selectivity for Pb2+ over other metal ions with an assay time less than 1 h. In addition, this method showed enhanced pH stability and long service life, and had a potential to detect other metal ions only by changing corresponding DNAzyme specific to them. Finally, the magnetic nano‐DNAzyme platform was demonstrated to work well in direct Pb2+ detection in real water samples.

CONCLUSION

The magnetic nano‐DNAzyme system for colorimetric detection of Pb2+ showed high sensitivity and selectivity, simple, enhanced pH stability with long service life in practical application. © 2018 Society of Chemical Industry
Children with kawasaki disease present elevated stiffness of great arteries: Phase‐contrast MRI study
Authors: Schäfer Michal , Truong Uyen , Ivy D. Dunbar , Fonseca Brian , Malone Ladonna , DiMaria Michael , Barker Alex J. , Vargas Daniel , Hunter Kendall S. , Jone Pei‐Ni , Browne Lorna P.
Published: April 2018

Background

Patients with diagnosed Kawasaki disease (KD) are known to develop extracardiac vascular lesions and are prone to accelerated stiffening of medium‐size arteries.

Purpose

To noninvasively evaluate great vessel (central aorta and main pulmonary artery (MPA)) stiffness using phase‐contrast MRI (PC‐MRI).

Study type

Retrospective review.

Subjects

Thirty‐three patients with previously diagnosed KD and 15 control subjects underwent PC‐MRI evaluation.

Field Strength/Sequence

A free‐breathing PC‐MRI sequence was applied with Cartesian encoding and retrospective sorting using a 1.5 or 3.0T system.

Assessment

We evaluated regionally specific vessel stiffness using pulse‐wave velocity (PWV) and relative area change (RAC) at the ascending aorta, descending aorta, and MPA.

Statistical Tests

Hemodynamics among patients with KD and controls were compared using Student's t‐test, Wilcoxon Rank‐sum, and χ2. Additional group‐specific comparisons were performed using Kruskal–Wallis or one‐way analysis of variance (ANOVA).

Results

Patients with KD showed elevated PWV in both ascending (5.0 ± 1.2 vs. 2.4 ± 0.5, P < 0.001) and descending aorta (4.4 ± 2.1 vs. 2.8 ± 0.8, P < 0.001). RAC was correspondingly reduced in both segments (both P < 0.01). PWV measured in MPA was increased in KD patients (2.2 ± 0.5 vs. 1.5 ± 0.6, P = 0.045) while the RAC was reduced (34 ± 6 vs. 47 ± 3, P = 0.045). There were no associations between considered vessel stiffness indices and respective ventricular size and function, functional indices, and no correlations were observed with KD severity markers.

Data Conclusion

Patients with KD have elevated great vessel stiffness measured at the chronic stage of the disease. Accelerated stiffness process does not appear to affect biventricular function in youth

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:1228–1236.
Assessment of a high‐SNR chemical‐shift‐encoded MRI with complex reconstruction for proton density fat fraction (PDFF) estimation overall and in the low‐fat range
Authors: Park Charlie C. , Hooker Catherine , Hooker Jonathan C. , Bass Emily , Haufe William , Schlein Alexandra , Covarrubias Yesenia , Heba Elhamy , Bydder Mark , Wolfson Tanya , Gamst Anthony , Loomba Rohit , Schwimmer Jeffrey , Hernando Diego , Reeder Scott B. , Middleton Michael , Sirlin Claude B. , Hamilton Gavin
Published: April 2018

Background

Improving the signal‐to‐noise ratio (SNR) of chemical‐shift‐encoded MRI acquisition with complex reconstruction (MRI‐C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis.

Purpose

To assess the accuracy of high SNR (Hi‐SNR) MRI‐C versus standard MRI‐C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard.

Study Type

Prospective.

Population/Subjects

In all, 231 adult and pediatric patients with known or suspected NAFLD.

Field Strength/Sequence

PDFF estimated at 3T by three MR techniques: standard MRI‐C; a Hi‐SNR MRI‐C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard).

Assessment

MRI‐PDFF was measured by image analysts using a region of interest coregistered with the MRS‐PDFF voxel.

Statistical Tests

Linear regression analyses were used to assess accuracy and precision of MRI‐estimated PDFF for MRS‐PDFF as a function of MRI‐PDFF using the standard and Hi‐SNR MRI‐C for all patients and for patients with MRS‐PDFF <10%.

Results

In all, 271 exams from 231 patients were included (mean MRS‐PDFF: 12.6% [SD: 10.4]; range: 0.9–41.9). High agreement between MRI‐PDFF and MRS‐PDFF was demonstrated across the overall range of PDFF, with a regression slope of 1.035 for the standard MRI‐C and 1.008 for Hi‐SNR MRI‐C. Hi‐SNR MRI‐C, compared to standard MRI‐C, provided small but statistically significant improvements in the slope (respectively, 1.008 vs. 1.035, P = 0.004) and mean bias (0.412 vs. 0.673, P < 0.0001) overall. In the low‐fat patients only, Hi‐SNR MRI‐C provided improvements in the slope (1.058 vs. 1.190, P = 0.002), mean bias (0.168 vs. 0.368, P = 0.007), intercept (−0.153 vs. −0.796, P < 0.0001), and borderline improvement in the R2 (0.888 vs. 0.813, P = 0.01).

Data Conclusion

Compared to standard MRI‐C, Hi‐SNR MRI‐C provides slightly higher MRI‐PDFF estimation accuracy across the overall range of PDFF and improves both accuracy and precision in the low PDFF range.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:229–238.
Trichilemmal Cyst: Clinical and Sonographic Features
Authors: He Ping , Cui Li‐Gang , Wang Jin‐Rui , Zhao Bo , Chen Wen , Xu Yan
Published: April 2018

Objectives

In this study, we retrospectively reviewed the clinical and sonographic features of patients with trichilemmal cysts.

Methods

Sonographic findings of 54 cases of trichilemmal cysts were retrospectively analyzed from 50 patients, including 4 cases of proliferating trichilemmal cysts. Associated factors of internal calcification–positive cases were also evaluated.

Results

The mean age of the 50 patients was 43.4 years (range, 15−80 years) and the female‐to‐male ratio was 1.3. Overall, 68% of the trichilemmal cysts in the 54 lesions were located in the scalp, and 15% were located in the extremities. All 54 lesions were preoperatively examined by sonography and showed well‐defined, oval‐shaped structures located in subcutaneous soft tissues close to the dermis. Of the 54 lesions, 72% were hypoechoic masses, 89% were heterogeneous, and 65% had internal calcification. Among the internal calcification–positive cases, the mean age of the patients was 43.4 years, and the female‐to‐male ratio was 0.6. Of these lesions, 83% were located in the scalp. We did not find any significant association between calcification, age, or sex (P = .993 and P = .99); however, lesions present in the scalp were significantly associated with internal calcification (P = .005). 81% of the 54 lesions displayed posterior enhancement. but the color Doppler sonography of all lesions revealed no vascularization.

Conclusions

Trichilemmal cysts should be considered to diagnose of well‐defined, hypoechoic lesions with internal calcification and posterior sound enhancement in the subcutaneous soft tissues of the scalp or extremities upon sonography.
Antitumor effect of sorafenib and mammalian target of rapamycin inhibitor in liver transplantation recipients with hepatocellular carcinoma recurrence
Authors: Jung Dong‐Hwan , Tak Eunyoung , Hwang Shin , Song Gi‐Won , Ahn Chul‐Soo , Kim Ki‐Hun , Moon Deok‐Bog , Ha Tae‐Yong , Park Gil‐Chun , Ryoo Baek‐Yeol , Lee Kyung Jin , Kim Nayoung , Kwon Jae‐Hyeon , Jwa Eun‐Kyoung , Lee Sung‐Gyu
Published: April 2018

Both sorafenib and mammalian target of rapamycin inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit in a clinical LT setting. In the laboratory study, the HepG2.2.15 liver tumor cell line and 5 patient‐derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy. An in vivo mouse study also demonstrated similar cytotoxic outcomes. In the clinical study including 232 LT recipients with HCC recurrence, the 3‐month medication drop‐out rate was 35.6% for sorafenib administration and 23.5% for mTORi administration. Postrecurrence survival rates were not different according to sorafenib administration (P = 0.17) but were significantly improved following mTORi administration (P < 0.001). In mTORi subgroups with and without sorafenib, there was no difference in the overall postrecurrence patient survival period (P = 0.26), indicating an absence of synergistic or additional antitumor effect from sorafenib. The median progression‐free and overall survival period was 6.4 and 11.8 months, respectively, after sorafenib administration. Time of tumor recurrence and use of mTORi were independent risk factors. In conclusion, our laboratory study demonstrated synergistic antitumor effects of sorafenib and mTORi, but this was not reproduced in our clinical LT study. Our clinical result of mTORi administration showed improved postrecurrence survival, thus administering mTORi in LT recipients with HCC recurrence appears worthwhile. However, the antitumor effect of sorafenib on posttransplant recurrence was not determined in this retrospective study, thus requiring further studies with early start of sorafenib administration. Liver Transplantation 24 932–945 2018. © 2018 AASLD.
Accelerated Thermal Depolymerization of Cyclic Polyphthalaldehyde with a Polymeric Thermoacid Generator
Authors: Lopez Hernandez Hector , Lee Olivia P. , Possanza Casey Catherine M. , Kaitz Joshua A. , Park Chan Woo , Plantz Christopher L. , Moore Jeffrey S. , White Scott R.
Published: April 2018

Thermally triggerable polymer films that degrade at modest temperatures (≈85 °C) are created from a blend of cyclic polyphthalaldehyde (cPPA) and a polymeric thermoacid generator, poly(vinyl tert‐butyl carbonate sulfone) (PVtBCS). PVtBCS depolymerizes when heated, generating acid which initiates the depolymerization of cPPA into volatile byproducts. The mass loss onset for 2 wt% PVtBCS/cPPA is 22 °C lower than the onset for neat cPPA alone in dynamic thermogravimetric analysis experiments. Increased concentrations of PVtBCS increase the rate of depolymerization of cPPA. Raman spectroscopy reveals that the monomer, o‐phthalaldehyde, is the main depolymerization product of the acid‐catalyzed depolymerization of cPPA. The PVtBCS/cPPA blend is a promising material for the design and manufacture of transient electronic packaging and polymers.
Microstructural correlates of 3D steady‐state inhomogeneous magnetization transfer (ihMT) in the human brain white matter assessed by myelin water imaging and diffusion tensor imaging
Authors: Ercan Ece , Varma Gopal , Mädler Burkhard , Dimitrov Ivan E. , Pinho Marco C. , Xi Yin , Wagner Benjamin C. , Davenport Elizabeth M. , Maldjian Joseph A. , Alsop David C. , Lenkinski Robert E. , Vinogradov Elena
Published: April 2018

Purpose

To compare the recently introduced inhomogeneous magnetization transfer (ihMT) technique with more established MRI techniques including myelin water imaging (MWI) and diffusion tensor imaging (DTI), and to evaluate the microstructural attributes correlating with this new contrast method in the human brain white matter.

Methods

Eight adult healthy volunteers underwent T1‐weighted, ihMT, MWI, and DTI imaging on a 3T human scanner. The ihMT ratio (ihMTR), myelin water fraction (MWF), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) values were calculated from different white matter tracts. The angle () between the directions of the principal eigenvector, as measured by DTI, and the main magnetic field was calculated for all voxels from various fiber tracts. The ihMTR was correlated with MWF and DTI metrics.

Results

A strong correlation was found between ihMTR and MWF (ρ = 0.77, P < 0.0001). This was followed by moderate to weak correlations between ihMTR and DTI metrics: RD (ρ = −0.30, P < 0.0001), FA (ρ = 0.20, P < 0.0001), MD (ρ = −0.19, P < 0.0001), AD (ρ = 0.02, P < 0.0001). A strong correlation was found between ihMTR and (ρ = −0.541, P < 0.0001).

Conclusion

The strong correlation with myelin water imaging and its low coefficient of variation suggest that ihMT has the potential to become a new structural imaging marker of myelin. The substantial orientational dependence of ihMT should be taken into account when evaluating and quantitatively interpreting ihMT results.