bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergency Physician Training on Mild Traumatic Brain Injury: A Systematic Review
Authors: Patrick Sean P. , Gaudet Lindsay A. , Krebs Lynette D. , Chambers Thane , Rowe Brian H.
Published: July 2017

Objectives

Mild traumatic brain injury (mTBI) is the most common emergency department (ED) brain injury presentation worldwide. Despite its frequency, practice variation and care gaps exist among emergency physicians (EPs) in diagnosing and appropriately managing mTBI in the ED. The objective of this review was to identify mTBI‐specific training undertaken to improve the detection and management of mTBIs by EPs and its impact on practice.

Methods

A comprehensive search strategy utilized four bibliographic databases, the gray literature and the keywords concussion, mild traumatic brain injury, medical education, and continuing medical education (CME). To be included, studies were required to report on mTBI training received by practicing EPs at any point during their medical education or career. Studies examining clinical practice guidelines or use of diagnostic tools without active implementation or formal training were not included. Two reviewers screened unique citations for relevance and reviewed the full texts of relevant articles. Two independent researchers extracted data and assessed methodologic quality. At all stages, a third independent reviewer adjudicated discrepancies.

Results

Overall, five studies were included from 409 unique results. None of the included studies were of high quality. Identified training on mTBI consisted of three training toolkits, conference presentations and academic journal articles, and pediatric fellowship training. Training primarily occurred as CME and focused on awareness of and management of mTBI; three studies reported physician practice changes, including increases in the use of evidence‐based return‐to‐school and return‐to‐activity recommendations.

Conclusions

The few studies identified addressing mTBI training targeting EPs demonstrate the limited attention given to this issue. The current evidence‐to‐practice gap in mTBI management places patients at risk for suboptimal care in the ED, and existing mTBI knowledge translation, including education, requires optimization to effectively address the current gap in evidence‐based practice for mTBI diagnosis and management in the ED.
Steady microfluidic measurements of mutual diffusion coefficients of liquid binary mixtures
Authors: Bouchaudy Anne , Loussert Charles , Salmon Jean‐Baptiste
Published: July 2017

We present a microfluidic method leading to accurate measurements of the mutual diffusion coefficient of a liquid binary mixture over the whole solute concentration range in a single experiment. This method fully exploits solvent pervaporation through a poly(dimethylsiloxane) (PDMS) membrane to obtain a steady concentration gradient within a microfluidic channel. Our method is applicable for solutes which cannot permeate through PDMS, and requires the activity and the density over the full concentration range as input parameters. We demonstrate the accuracy of our methodology by measuring the mutual diffusion coefficient of the water (1) + glycerol (2) mixture, from measurements of the concentration gradient using Raman confocal spectroscopy and the pervaporation‐induced flow using particle tracking velocimetry. © 2017 American Institute of Chemical Engineers AIChE J, 63: 358–366, 2018
An Efficient and Environmentally Benign Bentonite–Gold Nanohybrid‐Catalyzed Oxidative Cross‐Coupling of Ketones with Benzylic Primary Alcohols
Authors: Maya R. J. , Varma R. Luxmi
Published: July 2017

An efficient, green and sustainable method for the oxidative C−C coupling of ketones and primary alcohols was developed using an environmentally benign bentonite–gold nanohybrid catalyst. This heterogeneous catalyst affords diverse α,β‐unsaturated ketones in excellent yields under ambient reaction conditions in the presence of Cs2CO3 as weak base. The catalyst is selective, recyclable and only water is produced as the side product. This catalytic system is readily applicable for the gram‐scale synthesis of α,β‐unsaturated ketones.
Cu(TFA)2‐Catalyzed Picolinamido‐Directed C(sp2)−H Cyanation of Naphthalenes by Using Benzoyl Cyanide as a Cyano Source
Authors: Song He , Liu Xiaochong , Wang Chenglong , Qiao Jingyi , Chu Wenyi , Sun Zhizhong
Published: July 2017

A protocol for the Cu(TFA)2‐catalyzed (TFA=trifluoroacetic acid) picolinamido‐directed C8−H cyanation of naphthalene derivatives with benzoyl cyanide as the cyano source has been developed. A series of 8‐cyano‐1‐(picolinamido)naphthalene derivatives were efficiently obtained in moderate to good yields by using this method. We prepared a total of 22 products, 10 of which have not previously been reported. Benzoyl cyanide was originally employed for the C(sp2)−H cyanation of arenes. The picolinamide moiety served a critical role as the directing group in this cyanation reaction of naphthalenes.
Evaluation of wall slip effects on the flow characteristics of petroleum coke–water slurry flow along pipelines
Authors: Zhang Xiaobin , Liu Meng , Bikane Kagiso , Li Yanrong
Published: July 2017

Flow characteristics of petroleum coke–water slurry (PCWS) were investigated in a slurry transportation facility. True rheological properties, drag reduction, and flow resistances of PCWS under the influence of wall slip were studied using the Tikhonov regularization method. Results show that the shear viscosity is insensitive to changes in the shear rate when the solid loading of PCWS is 59.8 wt%. However, the PCWS of 61.1 wt% exhibits typical dilatant fluid properties. As the shear rate increases, the PCWS of 63.4 wt% initially exhibits shear thinning, and then, the viscosity increases sharply when the shear rate exceeds 250 s−1. In addition, the slurry also displays shear thinning at the shear rates exceeding 600 s−1. Modified friction factor‐generalized Reynolds number correlation is established to describe the resistance properties of a laminar flow of PCWS. When increasing the velocity, the drag reduction produced by the wall slip behavior reduces for the 59.8 wt% PCWS but increases for the 61.1 wt% PCWS. The drag reduction decreases at the outset followed by an increase for the 63.4 wt% PCWS. A decrease in the inner diameter of pipeline could enhance the effect of drag reduction of PCWS flowing in a pipeline. © 2017 Curtin University and John Wiley & Sons, Ltd.
Properties and applications of nanoclay reinforced open‐porous polymer composites
Authors: Yüce Elif , Mert E. Hilal , Şen Sinan , Saygı Semih , San Nevim
Published: July 2017

Open‐porous nanoclay reinforced polymer composites were prepared via high internal phase emulsion templating using 1,3‐butanediol dimethacrylate and surface modified montmorillonite (SM‐MMT). Organophilic clay was obtained by using a reactive intercalant—quaternary cocoamine salt having a styryl group—for surface modification of MMT. The clay modification resulted in not only intercalated silicate layers but also nanoclay particles compatible with the continuous phase of the emulsions. It was found that increasing clay amount leads to formation of hierarchical porous structure accompanied with larger cavities and interconnected pores. In this respect, cavity size of the resulting composites was found to be altered between 6.78 and 8.82 μm. On the other hand, as compared to bare composites, addition of clay particles increased compressive modulus of the resulting materials from 26.4 to 72.5 MPa. The adsorption capacities of the porous composites for methyl violet 2B were investigated by batch experiments and discussed as a function of their SM‐MMT loading. It was determined that, the dye adsorption of the composites increased with increasing nanoclay amount in the polymer matrix. Thus, the adsorption percentage of the composite loaded with 7 wt % nanoclay was found to be as high as 88%. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45522.
Agglomerate size evolution in modular twin‐screw extruder: Modeling and validation with CaCO3/LLDPE compounding experiments
Authors: Chen Tao , Lin Hua , Zhao Haili , Chen Xin , Wu Tong , Li Guo , Ji Huajian , Sha Jin , Ma Yulu , Xie Linsheng
Published: July 2017

The screw combination of twin‐screw extruder affects the filler size in inorganic filler‐reinforced polymeric compounds. This article tried to conveniently and precisely model the agglomerate size evolution in modular co‐rotating twin‐screw extruder. The break‐up process of agglomerate was analyzed to obtain the relationship between average deagglomerating energy (M) and agglomerate size, the result presented a mathematic relationship between M and agglomerate size. Numerical simulation study was conducted to consider the effect of kneading blocks (KB) or flight elements (FE) number on dispersion capacity of screw combination. The average deagglomerating energy, calculated based on POLYFLOW simulation, was introduced as major parameter to evaluate the dispersion capacity, which presented a proportional relationship to the KB or FE number. The model was developed by combining the agglomerate break‐up process and simulation results. In validation, CaCO3/linear low‐density polyethylene (LLDPE) compounds were prepared by modular co‐rotating twin‐screw extruder with different screw combinations. The optical image analysis showed that CaCO3 agglomerate size decreased with the KB or FE number rising, while it achieved minimum when the KB number was 4. The model was in accordance with the experimental results, and proved to be valid for KB and FE combinations in preparing CaCO3/LLDPE compounds. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45535.
Copy Number Changes Identified Using Whole Exome Sequencing in Nonsyndromic Cleft Lip and Palate in a Honduran Population
Authors: Cai Yi , Patterson Karynne E. , Reinier Frederic , Keesecker Sarah E. , Blue Elizabeth , Bamshad Michael , Haddad Joseph
Published: July 2017

Background

The majority of cleft lip with or without cleft palate cases appear as an isolated, nonsyndromic entity (NSCLP). With the advent of next generation sequencing, whole exome sequencing (WES) has been used to identify single nucleotide variants and insertion/deletions which cause or increase the risk of NSCLP. However, to our knowledge, there are no published studies using WES in NSCLP to investigate copy number changes (CNCs), which are a major component of human genetic variation. Our study aimed to identify CNCs associated with NSCLP in a Honduran population using WES.

Methods

WES was performed on two to four members of 27 multiplex Honduran families. CNCs were identified using two algorithms, CoNIFER and XHMM. Priority was given to CNCs that were identified in more than one patient and had variant frequencies of less than 5% in reference data sets.

Results

WES completion was defined as >90% of the WES target at >8 × coverage and >80% of the WES target at >20 × coverage. Twenty‐four CNCs that met our inclusion criteria were identified by both CoNIFER and XHMM. These CNCs were confirmed using quantitative PCR. Pedigree analysis produced three CNCs corresponding to ADH7, AHR, and CRYZ segregating with NSCLP. Two of the three CNCs implicate genes, AHR and ADH7, whose known biological functions could plausibly play a role in NSCLP.

Conclusion

WES can be used to detect candidate CNCs that may be involved in the pathophysiology of NSCLP. Birth Defects Research 109:1257–1267, 2017. © 2017 Wiley Periodicals, Inc.
Arranging eukaryotic nuclear DNA polymerases for replication
Authors: Kunkel Thomas A. , Burgers Peter M. J.
Published: July 2017

Biochemical and cryo‐electron microscopy studies have just been published revealing interactions among proteins of the yeast replisome that are important for highly coordinated synthesis of the two DNA strands of the nuclear genome. These studies reveal key interactions important for arranging DNA polymerases α, δ, and ϵ for leading and lagging strand replication. The CMG (Mcm2‐7, Cdc45, GINS) helicase is central to this interaction network. These are but the latest examples of elegant studies performed in the recent past that lead to a much better understanding of how the eukaryotic replication fork achieves efficient DNA replication that is accurate enough to prevent diseases yet allows evolution.
A rare case of Epstein–Barr virus‐related plasmacytoma involving maxillary sinus mucosa
Authors: Gibbs Julie D. , Leon Marino E. , Liu Kenia , Nguyen Johnny , Zhang Ling
Published: July 2017

Key Clinical Message

Extramedullary plasmacytomas, Epstein–Bar virus (EBV) associated, are rarely encountered and usually have a fairly good clinical outcome. EBV+ plasmacytoma may cause a diagnostic dilemma as it phenotypically resembles an aggressive plasmablastic lymphoma (PBL). Herein, we report a unique case with maxillary EBV+ plasmacytoma from a 76‐year‐old immunocompetent individual.
Metallic Bi Nanocrystal‐Modified Defective BiVO4 Photoanodes with Exposed (040) Facets for Photoelectrochemical Water Splitting
Authors: Li Junqi , Guo Liu , Lei Nan , Song Qianqian , Liang Zheng
Published: July 2017

Metallic Bi nanocrystal‐modified defective BiVO4 photoanodes with exposed (040) facets were synthesized though the NaBH4 solution reduction method. B−O bonding at the surface of BiVO4 photoanodes is destroyed, which results in the removal of O atoms and forms oxygen vacancies at the beginning stage of the reduction process, and then Bi3+ ions are reduced to nanometer‐scale metallic Bi that is dispersed uniformly over the surface. BiVO4 photoanodes with this special structure exhibits a high performance for photoelectrochemical water splitting, owing to the synergistic effect of oxygen vacancies and metallic Bi. The presence of oxygen vacancies could significantly increase the capture ability of photogenerated electrons and improve the adsorption properties of H2O molecules in the process of photoelectrochemistry. Metallic Bi nanocrystals on the surface of BiVO4 photoanodes are beneficial for the photo‐response range as well as the separation and consumption of photogenerated carriers, owing to the surface plasmon resonance effect of Bi. In addition, the formation and function mechanism of metallic Bi and oxygen vacancies is discussed in detail.
Estimation of a Competitive Market Price for New Products via the Manufacturing Costs
Authors: Rähse Wilfried
Published: July 2017

Die prognostizierten Marktchancen entscheiden über die Umsetzung eines innovativen Produktes in die Produktion. Die Aussichten verbessern sich bei attraktiven Herstellkosten. Der errechnete Marktpreis ergibt sich aus den Herstell‐ sowie den Einzel‐ und Gemeinkosten des Unternehmens unter Addition einer Gewinnmarge. Eine ergänzende Methode zur Ermittlung des Marktpreises stellt das Zielkostenmanagement dar. Es beruht auf Angebot und Nachfrage und nutzt den Preismeter der Marktforschung. Der festzulegende Marktpreis berücksichtigt zusätzlich die Neuheit und Produktqualität, die Markenstärke und den Wettbewerb.
Removal Performance of Tetracycline and Oxytetracycline From Aqueous Solution Via Natural Zeolites: An Equilibrium and Kinetic Study
Authors: Lye Jimmy Wei Ping , Saman Norasikin , Sharuddin Siti Shilatul Najwa , Othman Nurul Sakinah , Mohtar Safia Syazana , Md Noor Ahmad Mujahid , Buhari Junaidah , Cheu Siew Chin , Kong Helen , Mat Hanapi
Published: July 2017

The persistence of antibiotics in sewage wastewater treatment plants in recent years has emerged as a serious issue. This study therefore evaluated three types of natural zeolites (i.e., NZ01, NZ02, and NZ03) for the removal of selected antibiotics namely tetracycline (TC) and oxytetracycline (OTC) from aqueous solution. The physical and chemical properties of the natural zeolites were characterized using various analytical techniques and the antibiotic removal studies were carried out in a batch adsorption experiment evaluated at various experimental conditions. The highest adsorption capacity was 62.5 and 76.3 μmol/g for TC and OTC, respectively, observed for NZ02 at pH values between 7 and 8. The adsorption of TC and OTC followed the Langmuir and Temkin isotherm models, respectively, whereas the adsorption kinetic data obeyed the Elovich kinetic model. The regeneration study on NZ02 indicated that it can still remove TC and OTC after five adsorption/desorption cycles. The removal efficiency of TC and OTC also improved from approximately 5–39 and 28%, respectively, by addition of NZ02 during the coagulation/flocculation process. These results thus demonstrated the applicability of the natural zeolites, especially NZ02, for the removal of TC and OTC from aqueous solution; hence the potential for the application in sewage treatment process for removal of antibiotics through either conventional adsorption/desorption or adsorptive coagulation/flocculation (ACF) process.
Design, Synthesis, Pharmacological Evaluation and Docking Studies of GluN2B‐Selective NMDA Receptor Antagonists with a Benzo[7]annulen‐7‐amine Scaffold
Authors: Gawaskar Sandeep , Temme Louisa , Schreiber Julian A. , Schepmann Dirk , Bonifazi Alessandro , Robaa Dina , Sippl Wolfgang , Strutz‐Seebohm Nathalie , Seebohm Guiscard , Wünsch Bernhard
Published: July 2017

Antagonists that selectively target GluN2B‐subunit‐containing N‐methyl‐d‐aspartate (NMDA) receptors are of major interest for the treatment of various neurological disorders. In this study, relationships between variously substituted benzo[7]annulen‐7‐amines and their GluN2B affinity were investigated. 2‐Nitro‐5,6,8,9‐tetrahydrobenzo[7]annulen‐7‐one (8) represents the central building block for the introduction of various substituents at the 2‐position and various 7‐amino moieties. N‐(3‐Phenylpropyl)‐6,7,8,9‐tetrahydro‐5H‐benzo[7]annulen‐7‐amines with a 2‐NO2 (7 c), 2‐Cl (15 c), or 2‐OBn group (22 c) show very high GluN2B affinity (Ki=1.6–3.6 nm). Docking studies revealed the same binding poses for benzo[7]annulen‐7‐amines and ifenprodil at the interface of GluN1b and GluN2B subunits. The large 2‐OBn moiety of 22 c occupies a previously unrecognized subpocket, which explains its high GluN2B affinity (Ki=3.6 nm). In two‐electrode voltage clamp experiments and cytoprotection assays, the high‐affinity GluN2B ligands 7 c, 15 c, and 22 c could not inhibit the glutamate‐/glycine‐evoked current and cytotoxic effects. However, the analogous phenols 16 c ((3‐phenylpropyl)amino moiety) and 16 d ((4‐phenylbutyl)amino moiety) with 10‐fold lower GluN2B affinity (Ki=28 and 21 nm, respectively) showed promising inhibition of glutamate‐/glycine‐evoked effects in both assays. The presence of a phenolic hydroxy group seems to be essential for inducing conformational changes of the receptor protein, which finally results in closure of the ion conduction pathway.
Rhodium‐on‐Palladium Nanocatalysts for Selective Methanation of Carbon Dioxide
Authors: Pan Yung‐Tin , Yang Hong
Published: July 2017

Nanocatalysts with a Rh shell and Pd core (Rh‐on‐Pd) were synthesized. These Rh‐on‐Pd catalysts showed the highest selectivity for methane in the methanation of carbon dioxide by hydrogen among Rh, Pd and Rh‐on‐Pd bimetallic core–shell structures tested when the Rh shell became about two atom‐layers thick. In situ environmental transmission electron microscopy (ETEM) study was used to investigate the dynamic structural change of these Rh‐on‐Pd core–shell nanoparticles under hydrogen atmosphere at variable temperatures, showing the feasibility of controlling the surface compositions. Thickening of the Rh shell was observed by nano beam diffraction (NBD) at elevated temperatures during the sintering, resulting in the change of selectivity in methane formation over Rh‐on‐Pd catalysts. This selectivity became similar to that of Rh catalyst at high temperatures due to the disappearance of ligand effects for thick Rh shells. Density functional theory (DFT) calculations suggest CO dissociation on the (111) surface of monolayers or double layers of Rh on Pd structure is energetically favored over either Rh or Pd, showing the potential for producing hydrocarbons through hydrogenation of carbon dioxide.
Dual role of monocyte‐derived dendritic cells in Trypanosoma cruzi infection
Authors: Poncini Carolina V. , González‐Cappa Stella M.
Published: July 2017

Pathogens can cause inflammation when inoculated into the skin. The vector‐transmitted protozoan parasite Trypanosoma cruzi induces poor cellular‐infiltration and disseminates, causing high mortality in the experimental model. Here, we characterized the inflammatory foci at the parasite inoculation site and secondary lymphoid organs using a murine model. While no macrophages and few neutrophils and monocytes (Mo) were recruited into the skin, T. cruzi infection elicited the mobilization of Ly6C+ Mo to draining lymph nodes and spleen. Over time, this population became enriched in CD11b+Ly6C+CD11c+MHCII+CD86+ cells resembling inflammatory dendritic cells (DCs). Adoptive transfer of Ly6C+ Mo purified from the bone marrow of CD11c‐GFP transgenic mice confirmed the monocytic origin of Ly6C+ DCs found in the spleen of infected animals. Isolated Mo‐derived cells not only produced TNF‐α and nitric oxide, but also IL‐10 and displayed a poor capacity to induce lymphoproliferation. Ablation of Mo‐derived cells by 5‐fluorouracil confirmed their dual role during infection, limiting the parasite load by inducible nitric oxide synthase‐related mechanisms and negatively affecting the development of anti‐parasite T‐cell response. This study demonstrated that consistent with their antagonistic properties, these cells not only control the parasite spreading but also its persistence in the host.
Hydrogenation of the Liquid Organic Hydrogen Carrier Compound Monobenzyl Toluene: Reaction Pathway and Kinetic Effects
Authors: Leinweber Anatol , Müller Karsten
Published: July 2017

Liquid organic hydrogen carriers (LOHCs) are an interesting option for storing hydrogen through a reversible chemical reaction. The catalytic hydrogenation reaction was studied for the carrier material monobenzyl toluene. GC analysis was used to quantify the components occurring in a complex reaction mixture. It was shown that the hydrogenation reaction proceeds predominantly by stepwise hydrogenation of the aromatic ring. As the molecular structure of monobenzyl toluene is formally the combination of a xylene and a toluene ring, two possible reaction pathways have been evaluated: hydrogenation of the mono‐substituted side ring (toluene) and di‐substituted main ring (xylene). Intermediates for both pathways were detected during the reaction. Concerning the isomeric structure of benzyl toluene, the fastest hydrogenation was observed for the para species. Isomeric mixtures were hydrogenated the slowest.
On Legalizing Physician‐Assisted Death for Dementia
Authors: Dresser Rebecca
Published: July 2017

Last November, soon after Colorado became the latest state to authorize physician‐assisted suicide, National Public Radio's The Diane Rehm Show devoted a segment to legalization of “physician assistance in dying,” a label that refers to both physician‐assisted suicide and voluntary active euthanasia. Although the segment initially focused on PAD in the context of terminal illness in general, it wasn't long before PAD's potential application to dementia patients came up. A caller said that her mother had Alzheimer's disease and was being cared for at great expense. Suspecting that she will suffer the same fate, the caller reported that she had included in her will “my specific request that if I should be diagnosed, and it is legal to do so, I would like to opt out of a life and many years of suffering.” A few countries, such as the Netherlands and Belgium, already allow PAD for dementia in certain circumstances. It wouldn't be surprising to see a U.S. legalization effort in the coming years.
Decision‐Making for an Incapacitated Pregnant Patient
Authors: Mabel Hilary , Rose Susannah L. , Kodish Eric
Published: July 2017

Decisions about continuing or terminating a pregnancy touch on profound, individualized questions about bodily integrity, reproductive autonomy, deeply held values regarding one's capacity for parenthood, and, in the case of a high‐risk pregnancy, the risks one is willing to take to have a baby. So far as possible, reproductive decisions are made between a patient, in some cases her partner, and her medical provider. However, this standard framework cannot be applied if the patient lacks decision‐making capacity. In this essay, we discuss one such case that came before our clinical ethics team. We describe the challenges of respecting a patient's reproductive preferences when the patient cannot share what those preferences are, and we argue that decisions regarding reproductive health care should not be treated with exceptionalism. Rather, they should proceed under the normal processes of surrogate decision‐making, including the application of substituted judgment. This approach enables us to take the patient's values into account when considering the questions implicated in reproductive health care, just as we do for other kinds of health care decisions in which a patient's deeply held values are salient.
Recombinant covalently closed circular DNA of hepatitis B virus induces long‐term viral persistence with chronic hepatitis in a mouse model
Authors: Li Gaiyun , Zhu Yuanfei , Shao Dianhui , Chang Hao , Zhang Xiaoming , Zhou Dongming , Gao Yueqiu , Lan Ke , Deng Qiang
Published: July 2017

Covalently closed circular DNA of hepatitis B virus (HBV) is critical for viral persistence in vivo. We recently reported a technique involving recombinant covalently closed circular DNA (rcccDNA) of HBV by site‐specific DNA recombination. Using hydrodynamic injection, rcccDNA induces a temporarily prolonged HBV antigenemia in immunocompetent mice, similar to acute resolving HBV infection. In this study, we simulated the pathophysiological impact of chronic hepatitis to reproduce rcccDNA persistence in mouse models. We showed that rcccDNA achieved long‐lasting persistence in the presence of a compromised immune response or when transcriptional activity was repressed. To closely mimic chronic hepatitis, we used a replication‐defective recombinant adenoviral vector to deliver rcccDNA to the liver, which led to prominent HBV persistence throughout the experiment duration (>62 weeks) in transgenic mice expressing Cre recombinase under the albumin promoter. A sustained necroinflammatory response and fibrosis were identified in mouse livers, with dysplastic lesions commonly seen during the late stage of viral persistence, analogous to the progressive pathology of clinical chronic hepatitis. Conclusion: rcccDNA was intrinsically stable in vivo, enabling long‐term persistence in the context of chronic hepatitis, and viral persistence, in turn, may promote progression of chronic liver disease; our study also presented a surrogate model of HBV cccDNA persistence in mice that could advance our understanding of the pathogenesis of chronic hepatitis B. (Hepatology 2018;67:56‐70).
Hepatocyte‐derived exosomes promote T follicular regulatory cell expansion during hepatitis C virus infection
Authors: Cobb Dustin A. , Kim Ok‐Kyung , Golden‐Mason Lucy , Rosen Hugo R. , Hahn Young S.
Published: July 2017

Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease, such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T‐cell responses, yet CD4+ T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody‐producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion. Our analysis revealed a substantial population of Tfr cells in livers of chronic HCV patients that is absent in liver tissues from nonviral hepatitis or healthy subjects. Coculture of PBMCs from healthy subjects with HCV‐infected hepatoma cells resulted in preferential expansion of circulating Tfr cells, leading to suppression of Tfh cells. Additionally, coculture of tonsillar cells with infected hepatoma cells lead to an expansion of germinal center Tfr. Notably, expansion was mediated by transforming growth factor beta (TGF‐β)‐containing exosomes released from HCV‐infected hepatocytes given that blockade of exosome‐associated TGF‐β or inhibition of exosome release abrogated Tfr expansion. Conclusion: These results show that liver‐derived exosomes play a pivotal role in the accumulation of Tfr cells, likely leading to suppression of Tfh responses in HCV‐infected patients. Our study identifies a novel pathway in which HCV infection in hepatocytes exacerbates Tfr cell responses to subvert antiviral immunity. (Hepatology 2018;67:71‐85)
Iron Catalyzed Dehydrocoupling of Amine‐ and Phosphine‐Boranes
Authors: Coles Nathan T. , Webster Ruth L.
Published: July 2017

Catalytic dehydrocoupling methodologies, whereby dihydrogen is released from a substrate (or intermolecularly from two substrates) is a mild and efficient method to construct main group element‐main group element bonds, the products of which can be used in advanced materials, and also for the development of hydrogen storage materials. With growing interest in the potential of compounds such as ammonia‐borane to act as hydrogen storage materials which contain a high weight% of H2, along with the current heightened interest in base metal catalyzed processes, this review covers recent developments in amine and phosphine dehydrocoupling catalyzed by iron complexes. The complexes employed, products formed and mechanistic proposals will be discussed.
A novel humanized anti‐tumor necrosis factor‐related apoptosis‐inducing ligand‐R2 monoclonal antibody induces apoptotic and autophagic cell death
Authors: Chen Longfei , Qiu Yuhe , Hao Zhenliang , Cai Jiong , Zhang Shuyong , Liu Yanxin , Zheng Dexian
Published: July 2017

It is well known that the tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no expression in most normal tissues and cells. While TRAIL engages with its native death receptors, TRAIL receptor 1 (TRAIL‐R1) or 2 (TRAIL‐R2), usually elicits the tumor cell death by apoptosis. In this study, we report that a novel humanized monoclonal antibody against TRAIL‐R2 (named as zaptuzumab) well remain the biological activity of the parental mouse antibody AD5‐10 inducing cell death in various cancer cells, but little effect on normal cells. Zaptuzumab also markedly inhibited the tumor growth in the mouse xenograft of NCI‐H460 without toxicity to the liver and kidney, and the efficacy of tumor suppression was increased significantly while it combined with cis‐dichlorodiamineplatinum. Especially, 131I‐labeled zaptuzumab injected into mouse tail vein specifically targeted to the xenograft of the lung cancer cells. Confocal analysis showed that zaptuzumab bound with TRAIL‐R2 on cell surface could be quickly internalized and transferred into the lysosome. Furthermore, zaptuzumab possessed a high level of antibody‐dependent cytotoxicity as well as complement‐dependent cytotoxicity. Study on the mechanisms of cell death induced by zaptuzumab showed that it efficiently induced both caspase‐dependent apoptosis and autophagic cell death. These data suggest that the humanized anti‐TRAIL‐R2 monoclonal antibody or the second generation of the antibody may have an important clinical usage for cancer immunotherapy. © 2017 IUBMB Life, 69(9):735–744, 2017
Ti6Al4V laser surface preparation and functionalization using hydroxyapatite for biomedical applications
Authors: Faria D. , Abreu C. S. , Buciumeanu M. , Dourado N. , Carvalho O. , Silva F. S. , Miranda G.
Published: July 2017

This work presents a novel texture design for implants surface functionalization, through the creation of line‐shaped textures on Ti6Al4V surfaces and subsequent sintering of hydroxyapatite (HAp) powder into the designated locations. HAp‐rich locations were designed to avoid HAp detachment during insertion, thus guaranteeing an effective osseointegration. This process starts by creating textured lines using a Nd:YAG laser, filling these lines with HAp powder and sintering HAp using a CO2 laser. The adhesion of HAp is known to be influenced by HAp sintering parameters, especially laser power and scanning speed and also by the textured lines manufacturing. Different laser parameters combinations were used to assess the sintering and adhesion of HAp to the textured lines. HAp adhesion was assessed by performing high energy ultrasonic cavitation tests and sliding tests mimicking an implant insertion, with Ti6Al4V/HAp specimens sliding against animal bone. The HAp content retained after these tests was measured and results showed that an excellent HAp sintering and adhesion was achieved when using a scan speed of 1 mm/s and laser power between 9 and 9.6 W. It is important to emphasize that results indicated that the HAp bioactivity was maintained when using these conditions, validating this functionalization process for the production of hip prosthesis with improved bioactivity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1534–1545, 2018.
Single‐Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment
Authors: Dudkowski Caroline , Karim Aziz , Zhao Zhen , Alonso Alberto B. , Garg Dyal , Preston Richard A.
Published: July 2017

Azilsartan medoxomil (AZL‐M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose‐dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M‐II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single‐center, open‐label, phase 1 parallel‐group study that examined the single‐dose (day 1) and multiple‐dose (days 4–8) — 40 mg — pharmacokinetics of AZL and M‐II in 16 subjects with mild and moderate hepatic impairment by Child‐Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M‐II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M‐II. Single and multiple doses of AZL‐M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL‐M is required for subjects with mild and moderate hepatic impairment.
Developing better practices at the institutional level leads to better outcomes after pancreaticoduodenectomy in 3,378 patients: domestic audit of the Japanese Society of Pancreatic Surgery
Authors: Satoi Sohei , Yamamoto Tomohisa , Yoshitomi Hideyuki , Motoi Fuyuhiko , Kawai Manabu , Fujii Tsutomu , Wada Keita , Arimitsu Hidehito , Sho Masayuki , Matsumoto Ippei , Hirano Satoshi , Yanagimoto Hiroaki , Ohtsuka Masayuki , Unno Michiaki , Yamaue Hiroki , Kon Masanori
Published: July 2017

Background

The aim of the present study was to assess recent trends in pancreaticoduodenectomy (PD) and the role of institutional standardization on the development of postoperative complications in 3,378 patients who underwent PD in Japan.

Methods

Data were collected from 3,378 patients who underwent PD in 2006, 2010 and 2014 at 53 institutions. A standardized institution (SI) was defined as one that implements ≥7 of 13 quality initiatives according to departmental policy. There were 1,223 patients in the SI group and 2,155 in the non‐SI group. Clinical parameters were compared over time, and between groups. Risk factors for morbidity and mortality were assessed by logistic regression analysis with a mixed‐effects model.

Results

The number of patients who underwent PD in SIs increased from 16.5% in 2006 to 46.4% in 2014. The SI group experienced an improved process of care and a lower frequency of severe complications vs. the non‐SI group (P < 0.001). Multivariate analysis revealed that the SI group was associated with a lower incidence of delayed gastric emptying (odds ratio −0.499, P = 0.008) and incisional surgical site infection (odds ratio −0.999, P < 0.001).

Conclusion

Standardization of care in PD may be important in reducing post‐PD complications, and is a critical element for improving clinical outcomes.
Miniprobe Endoscopic Sonography for Gastrointestinal Tract Assessment: A Case Series of 1451 Procedures
Authors: Varas Lorenzo Modesto J. , Abad Belando Ramón , Sánchez‐Vizcaíno Mengual Elena
Published: July 2017

Conventional endoscopic sonography has allowed precise diagnostics without disturbances, and miniprobes can be easily introduced through the biopsy channel of the endoscope. Miniprobe endoscopic sonography has many benefits compared with conventional endoscopic sonography. Although there are well‐known indications for miniprobe endoscopic sonography in endoscopic digestive tract assessment, there is still a need for this method to be widely spread among physicians and commonly used by most endoscopists. The aim of this series was to describe a multicenter retrospective experience with 1451 procedures using miniprobes, presenting examples and the applicability and usefulness of this technology in the daily activities of an endoscopy department.
A 2‐Year‐Old Girl with Functional Dystonia Manifesting as Forceful Finger Flexion Producing Fixed Posture of Clenched Hands
Authors: Ghosh Debabrata
Published: July 2017

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Performance evaluation of a collapsed cone dose calculation algorithm forHDRIr‐192 ofAPBItreatments
Authors: Terribilini Dario , Vitzthum Veronika , Volken Werner , Frei Daniel , Loessl Kristina , van Veelen Bob , Manser Peter , Fix Michael K.
Published: July 2017

Purpose

Most dose calculations forHDRbrachytherapy treatments are based on theAAPM‐TG43 formalism. Because patient's anatomy, heterogeneities, and applicator shielding are not considered, the dose calculation based on this formalism is inaccurate in some cases. Alternatively, collapsed cone (CC) methods as well as Monte Carlo (MC) algorithms belong to the model‐based dose calculation algorithms, which are expected to improve the accuracy of calculated dose distributions. In this work, the performance of aCCalgorithm,ACEin Oncentra Brachy 4.5 (ACE4.5), has been investigated by comparing the calculated dose distributions to theAAPM‐TG43 andMCcalculations for 10HDRbrachytherapy accelerated partial breast irradiation treatments (APBI). Comparisons were also performed with a corrected version ofACE4.5 (ACE4.5/corr).

Methods

The brachytherapy source microSelectronmHDR‐v2 (Elekta Brachytherapy) has been implemented in aMCenvironment and validated by comparingMCdose distributions simulated in a water phantom of 80 cm in diameter with dose distributions calculated with theAAPM‐TG43 algorithm. Dose distributions calculated withACE4.5,ACE4.5/corr,AAPM‐TG43 formalism, andMCfor 10APBIpatients plans have then been computed and compared usingHUscaled densities. In addition, individual dose components have been computed usingACE4.5,ACE4.5/corr, andMC, and compared individually.

Results

Local differences betweenMCandAAPM‐TG43 calculated dose distributions in a large water phantom are < 1%. When usingHUs scaled densities for the breast cancer patients, both accuracy levels ofACE4.5 overestimate theMCcalculated dose distributions for all analyzed dosimetric parameters. In the planning target volume (PTV),ACE4.5 (ACE4.5/corr) overestimates on average V100%,PTVby 3% ± 1% (1% ± 1%) and D50,PTVby 3% ± 1% (1% ± 1%) and in the organs at risk D1cc, skinby 4% ± 2% (1% ± 1%), D0.5cc, ribsby 4% ± 2% (0% ± 1%), and D1cc, heartby 8% ± 2% (3% ± 1%) compared toMC. Comparisons of the individual dose components reveals an agreement for the primary component of < 2% local differences for bothACE4.5 andACE4.5/corr. Local differences of about 40% (20%) for the first and residual scatter components where observed when usingACE4.5 (ACE4.5/corr). Using uniform densities for one case shows a better agreement betweenACE4.5 andMCfor all dosimetric parameters considered in this work.

Conclusions

In general, on the 10APBIpatients theACE4.5/corr algorithm results in similar dose distributions as the commonly usedAAPM‐TG43 within thePTV. However, the accuracy of theACE4.5/corr calculated dose distribution is closer toMCthan toAAPM‐TG43. The differences between commercial versionACE4.5 andMCdose distributions are mainly located in the first and residual scatter components. InACE4.5/corr, the changes done in the algorithm for the scatter components substantially reduce these differences.
Visualization of macrophage recruitment in head and neck carcinoma model using fluorine‐19 magnetic resonance imaging
Authors: Khurana Aman , Chapelin Fanny , Xu Hongyan , Acevedo Joseph R. , Molinolo Alfred , Nguyen Quyen , Ahrens Eric T.
Published: July 2017

Purpose

To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine‐19 (19F) MRI technology.

Methods

Tumor cell lines single‐hit/SCC4 or double‐hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density–weighted 19F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue.

Results

The average number of 19F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9 × 1019 and 2.0 × 1019 19F/tumor, respectively; P = 0.0034) two days after contrast injection, signifying increased tumor‐associated macrophages in double‐hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon‐labeled macrophages in double‐hit tumors and to a lesser extent in single‐hit tumors.

Conclusions

This study helps to establish 19F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single‐hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post‐treatment surveillance. Magn Reson Med 79:1972–1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Reliable assessment of the incidence of childhood autoimmune hemolytic anemia
Authors: Aladjidi Nathalie , Jutand Marthe‐Aline , Beaubois Cyrielle , Fernandes Helder , Jeanpetit Julien , Coureau Gaelle , Gilleron Véronique , Kostrzewa Aude , Lauroua Pierre , Jeanne Michel , Thiébaut Rodolphe , Leblanc Thierry , Leverger Guy , Perel Yves
Published: July 2017

Background

Childhood autoimmune hemolytic anemia (AIHA) is a rare and severe disease characterized by hemolysis and positive direct antiglobulin test (DAT). Few epidemiologic indicators are available for the pediatric population. The objective of our study was to reliably estimate the number of AIHA cases in the French Aquitaine region and the incidence of AIHA in patients under 18 years old.

Procedure

In this retrospective study, the capture–recapture method and log‐linear model were used for the period 2000–2008 in the Aquitaine region from the following three data sources for the diagnosis of AIHA: the OBS'CEREVANCE database cohort, positive DAT collected from the regional blood bank database, and the French medico‐economic information system.

Results

A list of 281 different patients was obtained after cross‐matching the three databases; 44 AIHA cases were identified in the period 2000–2008; and the total number of cases was estimated to be 48 (95% confidence interval [CI]: 45–55). The calculated incidence of the disease was 0.81/100,000 children under 18 years old per year (95% CI 0.76–0.92).

Conclusion

Accurate methods are required for estimating the incidence of AIHA in children. Capture–recapture analysis corrects underreporting and provides optimal completeness. This study highlights a possible under diagnosis of this potentially severe disease in various pediatric settings. AIHA incidence may now be compared with the incidences of other hematological diseases and used for clinical or research purposes.
Management of chemotherapy‐induced febrile neutropenia in pediatric oncology patients: A North American survey of pediatric hematology/oncology and pediatric infectious disease physicians
Authors: Maxwell Rochelle R. , Egan‐Sherry Dana , Gill Jonathan B. , Roth Michael E.
Published: July 2017

Background

Chemotherapy‐induced febrile neutropenia (FN) is traditionally managed with hospital admission for parenteral antibiotics until neutropenia resolves. Recent studies have explored risk stratification and the safety of managing “low‐risk” patients as outpatients. Few studies have directly assessed pediatric provider preferences for managing FN.

Procedure

We conducted a survey of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric infectious disease (PID) physicians to assess their FN management preferences using case scenarios with varying risk profiles.

Results

Twenty‐one percent (n = 186) of PHO and 32% (n = 123) of PID physicians completed the survey. Overall, both groups of providers agreed regarding which patients with FN could be managed outpatient. For a child with acute lymphoblastic leukemia receiving maintenance chemotherapy with an absolute neutrophil count (ANC) of 400 cells/μl, 35% (n = 66) of PHO and 49% (n = 60) of PID physicians would consider outpatient management (P = 0.02). Of those physicians selecting inpatient management, 41% (n = 49) of PHO and 52% (n = 33) of PID physicians would be willing to discharge the patient without an increase in ANC, if afebrile with a negative blood culture (P = 0.16). For a similar patient with an ANC of 100 cells/μl, only 23% (n = 35) of PHO and 42% (n = 39) of PID physicians would consider discharge without an increase in ANC (P = 0.002).

Conclusions

Despite the lack of established guidelines for low‐risk pediatric FN, a significant proportion of North American physicians report willingness to modify traditional management. This reinforces the need for evidence‐based low‐risk criteria and outpatient management guidelines to optimize consistency of care for these patients.