bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios
Authors: Willeford Bridget V. , Shapiro‐Dunlap Trudy , Willeford Kenneth O.
Published: June 2017

Preclinical Research

Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high‐risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony‐forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty‐four hours post‐administration, the treated murine population expressed a rapid temporal increase in serum IL‐6 (26‐fold) and INF‐γ (77‐fold) concentrations. IL‐6 can act as a critical signal regulating action against bacterial pathogens. A comparative double‐blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF‐γ, a cytokine associated with promoting antiviral activity. Drug Dev Res 78 : 189–195, 2017. © 2017 Wiley Periodicals, Inc.
A Trizirconium(IV)‐Substituted Sandwiched Polyoxometalate with Mixed Trilacunary Keggin‐/Dawson‐Type Polyoxotungstate Units
Authors: Zhang Zhong , Zhao Jun‐Wei , Yang Guo‐Yu
Published: June 2017

A trizirconium(IV)‐substituted sandwich‐type polyoxotungstate, K7.5H6.5[Zr3(µ2‐OH)2(µ2‐O)(A‐α‐GeW9O34)(1,4,9‐α‐P2W15O56)]·16.5H2O (1), was hydrothermally synthesized and characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis, powder X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, and single‐crystal X‐ray diffraction. The structural unit of 1 consists of trilacunary Dawson‐type phosphotungstate and trilacunary Keggin‐type germanotungstate units that are linked by a trizirconium(IV) cluster.
Photosubstitution of Monodentate Ligands from RuII–Dicarboxybipyridine Complexes
Authors: Caraballo Rolando M. , Rosi Pablo , Hodak José H. , Baraldo Luis M.
Published: June 2017

We report the photophysical and photochemical properties of RuII–polypyridine complexes [Ru(bpy)(dcbpy)py2]2+ (1)2+ and [Ru(dcbpy)2py2]2+ (2)2+ (bpy = 2,2′‐bipyridine, dcbpy = 4,4′‐dicarboxy‐2,2′‐bipyridine, py = pyridine). These complexes combine a monodentate ligand with a chelate bipyridine substituted with carboxylate groups. At low pH, both complexes present metal‐to‐ligand charge transfer absorption bands in the visible region and room‐temperature photoluminescence with long excited‐state lifetimes (τ > 200 ns). At physiological pH, their absorption and emission maxima are displaced to higher energies, with a significant reduction of their emission lifetime. These species show photosubstitution of the monodentate pyridine upon irradiation at 450 nm. At low pH, the quantum yield for this process is very low, but at physiological pH, they are very active, with a φPS,450 value of 0.14 for (1)2+ and of 0.17 for (2)2+. The products of photosubstitution were identified as monoaquo complexes. Both the reactants and the products of the photosubstitution show photoluminescence, but with very different lifetimes, making it possible to monitor the reaction by the time constant of their decay. The ability of complexes (1)2+ and (2)2+ to photorelease monodentate ligands at physiological pH makes them attractive candidates for the delivery of biomolecules linked to more complex structures through the carboxylate functional group.
Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N‐6 adenine‐specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population
Authors: de la Rosa Rosemarie , Steinmaus Craig , Akers Nicholas K. , Conde Lucia , Ferreccio Catterina , Kalman David , Zhang Kevin R. , Skibola Christine F. , Smith Allan H. , Zhang Luoping , Smith Martyn T.
Published: June 2017

Inter‐individual differences in arsenic metabolism have been linked to arsenic‐related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N‐6 adenine‐specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs‐related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic‐cancer case‐control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation‐dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = −1.9%, 95% CI: −3.3, −0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1–0.6) and lung cancer (OR = 0.6; 95% CI: 0.2–1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic‐related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic‐related disease. Environ. Mol. Mutagen. 58:411–422, 2017. © 2017 Wiley Periodicals, Inc.
An improved SPH model for multiphase flows with large density ratios
Authors: Zhu G.X. , Zou L. , Chen Z. , Wang A.M. , Liu M.B.
Published: June 2017

This paper presents a new smoothed particle hydrodynamics (SPH) model for simulating multiphase fluid flows with large density ratios. The new SPH model consists of an improved discretization scheme, an enhanced multiphase interface treatment algorithm, and a coupled dynamic boundary treatment technique. The presented SPH discretization scheme is developed from Taylor series analysis with kernel normalization and kernel gradient correction and is then used to discretize the Navier‐Stokes equation to obtain improved SPH equations of motion for multiphase fluid flows. The multiphase interface treatment algorithm involves treating neighboring particles from different phases as virtual particles with specially updated density to maintain pressure consistency and a repulsive interface force between neighboring interface particles into the pressure gradient to keep sharp interface. The coupled dynamic boundary treatment technique includes a soft repulsive force between approaching fluid and solid particles while the information of virtual particles are approximated using the improved SPH discretization scheme. The presented SPH model is applied to 3 typical multiphase flow problems including dam breaking, Rayleigh‐Taylor instability, and air bubble rising in water. It is demonstrated that inherent multiphase flow physics can be well captured while the dynamic evolution of the complex multiphase interfaces is sharp with consistent pressure across the interfaces.
Plasma cytokine IL‐6 levels and subjective cognitive decline: preliminary findings
Authors: Keegan Andrew P. , Paris Daniel , Luis Cheryl A. , Abdullah Laila , Ait‐Ghezala Ghania , Beaulieu‐Abdelahad David , Pryor Makenzie , Chaykin Jillian , Crynen Gogce , Crawford Fiona , Mullan Michael
Published: June 2017

Objective

Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood‐based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL‐6).

Methods

Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL‐6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern.

Results

Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education.

Conclusions

It will be important to assess how these baseline IL‐6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd.
Provision and perceived quality of mental health services for older care home residents in England: a national survey
Authors: Stewart Karen , Hargreaves Claire , Jasper Rowan , Challis David , Tucker Sue , Wilberforce Mark
Published: June 2017

Objective

This study examined the nature, extent and perceived quality of the support provided by community mental health teams for older people (CMHTsOP) to care home residents.

Methods

A postal survey was sent to all CMHTsOP in England. Information was collected about teams' staffing and their involvement in case finding, assessment, medication reviews, care planning and training as well as team managers' rating of the perceived quality of the service they provided for care home residents. Data were analysed using chi‐squared tests of association and ordinal regression.

Results

Responses were received from 225 (54%) CMHTsOP. Only 18 per cent of these teams contained staff with allocated time for care home work. Services for care home residents varied considerably between teams. Two‐fifths of teams provided formal training to care home staff. Team managers were more likely to perceive the quality of their service to care homes as good if they had a systematic process in place for reviewing antipsychotic drugs or routine mental health reviews, including contact with a GP.

Conclusion

The findings suggested that more evidence is needed on the best approach for supporting care home residents with mental health needs. Areas to consider are the potential benefits of training to care home staff and regular mental health reviews, utilising links between GPs and CMHTsOP. Copyright © 2017 John Wiley & Sons, Ltd.
Persistently low lymphocyte counts after FCR therapy for chronic lymphocytic leukemia are associated with longer overall survival
Authors: Joffe Erel , Ariela Arad N. , Bairey Osnat , Fineman Riva , Ruchlemer Rosa , Rahimi‐Levene Naomi , Shvidel Lev , Greenbaum Uri , Aviv Ariel , Tadmor Tamar , Braester Andrei , Goldschmidt Neta , Polliack Aaron , Herishanu Yair
Published: June 2017

Decreased absolute lymphocyte counts (ALCs) following frontline therapy for chronic lymphocytic leukemia may be associated with disease control, even in patients without evidence of minimal residual disease. We studied the prognostic significance of ALCs during the first year following treatment with fludarabine, cyclophosphamide, and rituximab (FCR).

We evaluated 99 patients who achieved a partial response without lymphocytosis (<4.0 × 103cells/μL) or better after FCR. Absolute lymphocyte counts were recorded at 3‐, 6‐, 9‐, and 12‐month posttreatment and correlated with overall survival (OS) and event‐free survival (EFS). For each time point, analyses were limited to patients without lymphocytosis, so as to avoid possible biases from undocumented disease progressions.

Lymphopenia (ALC < 1.0 × 103cells/μL) at 3 m after FCR (69% of patients n = 68), was associated with a longer OS (5y OS 91% vs 64%, P = .001), as were ALC ≤ 2 × 103 cells/μL at 6 m (5y OS 85% vs 48%, P = .004) and ALC ≤ 1.8 × 103 cells/μL at 9 m (5y OS 93% vs 54%, P = .009). A normal‐range ALC (≤4 × 103 cells/μL) at 12 m was also associated with a 91% 5y OS. Higher ALCs (but without lymphocytosis) were associated with shorter EFS (median EFS 27 months for ALC > 1.8 vs not reached for ALC ≤ 0.7 at 9 months, P < .0001).

In conclusion, lower ALC levels in the first few months following frontline FCR therapy were associated with longer OS and EFS. Possible explanations may be that lower ALCs reflect deeper clonal suppression or protracted Treg depletion. Absolute lymphocyte count levels may be a cheap and widely available prognostic marker, though the added value for clinical practice is the minimal residual disease era needs to be explored.
Changes in chronic disease management among community health centers (CHCs) in China: Has health reform improved CHC ability?
Authors: Wang Zhaoxin , Shi Jianwei , Wu Zhigui , Xie Huiling , Yu Yifan , Li Ping , Liu Rui , Jing Limei
Published: June 2017

Since the 1980s, China has been criticized for its mode of chronic disease management (CDM) that passively provides treatment in secondary and tertiary hospitals but lacks active prevention in community health centers (CHCs). Since there are few systematic evaluations of the CHCs' methods for CDM, this study aimed to analyze their abilities. On the macroperspective, we searched the literature in China's largest and most authoritative databases and the official websites of health departments. Literature was used to analyze the government's efforts in improving CHCs' abilities to perform CDM. At the microlevel, we examined the CHCs' longitudinal data after the New Health Reform in 2009, including financial investment, facilities, professional capacities, and the conducted CDM activities. A policy analysis showed that there was an increasing tendency towards government efforts in developing CDM, and the peak appeared in 2009. By evaluating the reform at CHCs, we found that there was an obvious increase in fiscal and public health subsidies, large‐scale equipment, general practitioners, and public health physicians. The benefited vulnerable population in this area also rose significantly. However, rural centers were inferior in their CDM abilities compared with urban ones, and the referral system is still not effective in China. This study showed that CHCs are increasingly valued in managing chronic diseases, especially after the New Health Reform in 2009. However, we still need to improve collaborative management for chronic diseases in the community and strengthen the abilities of CHCs, especially in rural areas.
Headwater stream length dynamics across four physiographic provinces of theAppalachianHighlands
Authors: Jensen Carrie K. , McGuire Kevin J. , Prince Philip S.
Published: June 2017

Understanding patterns of expansion, contraction, and disconnection of headwater stream length in diverse settings is invaluable for the effective management of water resources as well as for informing research in the hydrology, ecology, and biogeochemistry of temporary streams. More accurate mapping of the stream network and quantitative measures of flow duration in the vast headwater regions facilitate implementation of water quality regulation and other policies to protect waterways. We determined the length and connectivity of the wet stream and geomorphic channel network in 3 forested catchments (<75 ha) in each of 4 physiographic provinces of the Appalachian Highlands: the New England, Appalachian Plateau, Valley and Ridge, and Blue Ridge. We mapped wet stream length 7 times at each catchment to characterize flow conditions between exceedance probabilities of <5% and >90% of the mean daily discharge. Stream network dynamics reflected geologic controls at both regional and local scales. Wet stream length was most variable at two Valley and Ridge catchments on a shale scarp slope and changed the least in the Blue Ridge. The density and source area of flow origins differed between the crystalline and sedimentary physiographic provinces, as the Appalachian Plateau and Valley and Ridge had fewer origins with much larger contributing areas than New England and the Blue Ridge. However, the length and surface connectivity of the wet stream depended on local lithology, geologic structure, and the distribution of surficial deposits such as boulders, glacially derived material, and colluival debris or sediment valley fills. Several proxies indicate the magnitude of stream length dynamics, including bankfull channel width, network connectivity, the base flow index, and the ratio of geomorphic channel to wet stream length. Consideration of geologic characteristics at multiple spatial scales is imperative for future investigations of flow intermittency in headwaters.
TNF‐α‐Induced NOD2 and RIP2 Contribute to the Up‐Regulation of Cytokines Induced by MDP in Monocytic THP‐1 Cells
Authors: Chen Xiaobin , Xiao Zhilin , Xie Xiumei , Liu Xueting , Jiang Manli , Yuan Chuang , Yang Li , Hu Jinyue
Published: June 2017

Nucleotide‐binding oligomerization domain containing 2 (NOD2)‐induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro‐inflammatory TNF‐α on NOD2‐induced inflammation is not fully understood. In this study, we found unexpectedly that TNF‐α up‐regulated NOD2 ligand MDP‐induced production of the CXC chemokines, including CXCL1, 2, and 8, and the pro‐inflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, in a dose‐dependent manner at both mRNA and protein levels in monocytic THP‐1 cells. Though TNF‐α induced the up‐regulation of ubiquitin‐editing enzyme A20, an important negative regulator for Toll‐like receptor‐ and NOD2‐induced inflammatory responses, the over‐expression of A20 by gene transfer did not reversed MDP‐induced production of cytokines, suggested that A20 did not regulate the functions of NOD2 in THP‐1 cells. Meanwhile, we found that TNF‐α up‐regulated NOD2 and its down‐stream adaptor protein RIP2 at both mRNA and protein levels. MDP induced the activation of ERK, JNK, p38 and NF‐κB, and TNF‐α pre‐treatment augmented this activation. The results from pharmacological inhibition assay showed that cytokine production was dependent on MAPK signaling. In addition, we found that the pre‐treatment of THP‐1 cells with MDP down‐regulated the mRNA levels of cytokine induced by MDP re‐treatment. MDP pre‐treatment up‐regulated NOD2, but down‐regulated RIP2, and down‐regulated NOD2 signal transduction induced by MDP re‐stimulation. Taking together, these results suggested that TNF‐α is a positive regulator for NOD2 functions via up‐regulation of NOD2 and its signal adaptor RIP2, and TNF‐α‐induced A20 does not regulate MDP‐induced inflammatory responses in THP‐1 cells. J. Cell. Biochem. 119: 5072–5081, 2018. © 2017 Wiley Periodicals, Inc.
Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells
Authors: Wilkinson Emma L. , Sidaway James E. , Cross Michael J.
Published: June 2017

The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co‐A reductase inhibitor drugs. We utilized human cardiac microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability. Statin treatment of HCMECs stimulated activation of ERK5 and translocation to the plasma membrane resulting in co‐localization with the tight junction protein ZO‐1 and a concomitant reduction in endothelial cell permeability. Statin mediated activation of ERK5 was a consequence of reduced isoprenoid synthesis following HMG Co‐A reductase inhibition. Statin pretreatment could overcome the effect of doxorubicin in reducing endothelial tight junction formation and prevent increased permeability. Our data provide the first evidence for the role of ERK5 in regulating endothelial tight junction formation and endothelial cell permeability. Statin mediated ERK5 activation and the resulting decrease in cardiac endothelial cell permeability may contribute to the cardioprotective effects of statins in reducing doxorubicin‐induced cardiotoxicity.
Changes in the biomechanical properties of a single cell induced by nonthermal atmospheric pressure micro‐dielectric barrier discharge plasma
Authors: Choi Hyeongwon , Choi Eun Ha , Kim Kyung Sook
Published: June 2017

Mechanical properties of a single cell are closely related to the fate and functions of the cell. Changes in mechanical properties may cause diseases or cell apoptosis. Selective cytotoxic effects of nonthermal atmospheric pressure micro‐dielectric barrier discharge (DBD) plasma have been demonstrated on cancer cells. In this work, changes in the mechanical properties of a single cell induced by nonthermal atmospheric pressure micro‐DBD plasma were investigated using atomic force microscopy (AFM). Two cervical cancer cell lines (HeLa and SiHa) and normal human fibroblast cells (HFBs) were exposed to micro‐DBD plasma for various exposure times. The elasticity of a single cell was determined by force–distance curve measurement using AFM. Young's modulus was decreased by plasma treatment for all cells. The Young's modulus of plasma‐treated HeLa cells was decreased by 75% compared to nontreated HeLa cells. In SiHa cells and HFBs, elasticity was decreased slightly. Chemical changes induced by the plasma treatment, which were observed by Raman spectroscopy, were also significant in HeLa cells compared to SiHa cells and HFBs. These results suggested that the molecular changes induced by micro‐DBD plasma were related to cell mechanical changes.
Odd 4‐edge‐colorability of graphs
Authors: Petruševski Mirko
Published: June 2017

An odd k‐edge‐coloring of a graph G is a (not necessarily proper) edge‐coloring with at most k colors such that each nonempty color class induces a graph in which every vertex is of odd degree. Pyber (1991) showed that every simple graph is odd 4‐edge‐colorable, and Lužar et al. (2015) showed that connected loopless graphs are odd 5‐edge‐colorable, with one particular exception that is odd 6‐edge‐colorable. In this article, we prove that connected loopless graphs are odd 4‐edge‐colorable, with two particular exceptions that are respectively odd 5‐ and odd 6‐edge‐colorable. Moreover, a color class can be reduced to a size at most 2.
Development and characterization of a 99mTc‐tricarbonyl–labelled estradiol derivative obtained by “Click Chemistry” with potential application in estrogen receptors imaging
Authors: Tejería María Emilia , Giglio Javier , Dematteis Silvia , Rey Ana
Published: June 2017

Assessment of the presence of estrogen receptors in breast cancer is crucial for treatment planning. With the objective to develop a potential agent for estrogen receptors imaging, we present the development and characterization of a 99mTc‐tricarbonyl–labelled estradiol derivative. Using ethinylestradiol as starting material, an estradiol derivative bearing a 1,4‐disubstituted 1,2,3‐triazole–containing tridentate ligand system was synthesized by “Click Chemistry” and fully characterized. Labelling with high yield and radiochemical purity was achieved through the formation of a 99mTc‐tricarbonyl complex. The radiolabelled compound was stable, exhibited moderate binding to plasma protein (approximately 33%) and lipophilicity in the adequate range (logP 1.3 ± 0.1 at pH 7.4). Studies in MCF7 showed promising uptake values (approximately 2%). However, more than 50% of the activity is quickly released from the cell. Biodistribution experiments in normal rats confirmed the expected “in vivo” stability of the radiotracer but showed very high gastrointestinal and liver activity, which is inconvenient for in vivo applications. Taking into consideration the well‐documented influence of the chelating system in the physicochemical and biological behaviour of technetium‐labelled small biomolecules, research will be continued using the same pharmacophore but different complexation modalities of technetium.
Magnetic resonance spin–spin relaxation time estimation in a rat model of fatty liver disease
Authors: Alghamdi Sami , Sinclair Benjamin , Cowin Gary , Brereton Ian , Tesiram Yasvir A.
Published: June 2017

Purpose

To compare mono‐ and bi‐exponential relaxation model equations to discriminate between normal and fatty liver disease.

Materials and Methods

Six rats on a choline deficient amino acid modified (CDAA) diet and six on normal chow were studied. Multiple spin echo images with increasing echo times (TEs) were collected at 9.4T. Pixel‐wise T2 maps were generated using mono‐exponential decay function to calculate T2M, and a bi‐exponential to calculate, short T2 component (T2S), long T2 component (T2L), and fractions of these components (ρS, ρL), respectively. Statistical F‐tests and Akaike's information criterion (AIC) were used to assess the relative performance of the two models.

Results

F‐test and AIC showed that in the CDAA group, T2 bi‐exponential model described the signal of T2 weighted imaging of the liver better than the mono‐exponential model. Controls were best described by the mono‐exponential model. Mean values for T2M, T2L, T2S, ρS, ρL were 31.2 ± 0.7 ms, 72.8 ± 3.3 ms, 8.2 ± 0.6 ms,71.2 ± 2.1%, 30.4 ± 1.3%, respectively, in CDAA rats, compared with 18.8 ± 0.5 ms, 32.3 ± 0.7 ms, 9.2 ± 1.8 ms, 79 ± 2%, 21.0 ± 1.1% in controls.

Conclusion

In the fatty liver of CDAA rats we have shown that T2 weighted images fit the bi‐exponential model better than mono‐exponential decays thus providing a better description of the data.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:468–476.
Whole‐lesion histogram analysis of the apparent diffusion coefficient: Evaluation of the correlation with subtypes of mucinous breast carcinoma
Authors: Guo Yuan , Kong Qing‐cong , Zhu Ye‐qing , Liu Zhen‐zhen , Peng Ling‐rong , Tang Wen‐Jie , Yang Rui‐meng , Xie Jia‐jun , Liu Chun‐ling
Published: June 2017

Purpose

To evaluate the utility of the whole‐lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC.

Materials and Methods

This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC‐A (20 cases) and PMBC‐B (17 cases) groups. All patients underwent preoperative diffusion‐weighted imaging (DWI) at 1.5T and the whole‐lesion ADC assessments were generated. Histogram‐derived ADC parameters were compared between PMBC vs. MMBC and PMBC‐A vs. PMBC‐B, and receiver operating characteristic (ROC) curve analysis was used to determine optimal histogram parameters for differentiating these groups.

Results

The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25th (P = 0.004), 50th (P = 0.004), 75th (P = 0.006), and 90th percentiles (P = 0.013) and skewness (P = 0.021) than did the MMBC group. The 25th percentile of ADC values achieved the highest area under the curve (AUC) (0.792), with a cutoff value of 1.345 × 10−3mm2/s, in distinguishing PMBC and MMBC. The PMBC‐A group showed significantly higher ADC values for the mean (P = 0.049), 25th (P = 0.015), and 50th (P = 0.026) percentiles and skewness (P = 0.004) than did the PMBC‐B group. The 25th percentile of the ADC cutoff value (1.476 × 10−3mm2/s) demonstrated the best AUC (0.837) among the ADC values for distinguishing PMBC‐A and PMBC‐B.

Conclusion

Whole‐lesion ADC histogram analysis enables comprehensive evaluation of an MBC in its entirety and differentiating subtypes of MBC. Thus, it may be a helpful and supportive tool for conventional MRI.

Level of Evidence: 4

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:391–400.
Cloning and characterization of iron‐superoxide dismutase in Antarctic yeast strain Rhodotorula mucilaginosa AN5
Authors: Kan Guangfeng , Wen Hua , Wang Xiaofei , Zhou Ting , Shi Cuijuan
Published: June 2017

A novel superoxide dismutase gene from Antarctic yeast Rhodotorula mucilaginosa AN5 was cloned, sequenced, and then expressed in Escherichia coli. The R. mucilaginosa AN5 SOD (RmFeSOD) gene was 639 bp open reading frame in length, which encoded a protein of 212 amino acids with a deduced molecular mass of 23.5 kDa and a pI of 7.89. RmFeSOD was identified as iron SOD type with a natural status of homodimer. The recombinant RmFeSOD showed good pH stability in the pH 1.0–9.0 after 1 h incubation. Meanwhile, it was found to behave relatively high thermostability, and maintained more than 80% activity at 50 °C for 1 h. By addition of 1 mM metal ions, the enzyme activity increased by Zn2+, Cu2+, Mn2+, and Fe3+, and inhibited only by Mg2+. RmFeSOD showed relatively low tolerance to some compounds, such as PMSF, SDS, Tween‐80, Triton X‐100, DMSO, β‐ME, and urea. However, DTT showed no inhibition to enzyme activity. Using copper stress experiment, the RmFeSOD recombinant E. coli exhibited better growth than non‐recombinant bacteria, which revealed that RmFeSOD might play an important role in the adaptability of heavy metals.
Trace determination of five triazole fungicide residues in traditional Chinese medicine samples by dispersive solid‐phase extraction combined with ultrasound‐assisted dispersive liquid–liquid microextraction and UHPLC–MS/MS
Authors: Ma Shuping , Yuan Xucan , Zhao Pengfei , Sun Hong , Ye Xiu , Liang Ning , Zhao Longshan
Published: June 2017

A novel and reliable method for determination of five triazole fungicide residues (triadimenol, tebuconazole, diniconazole, flutriafol, and hexaconazol) in traditional Chinese medicine samples was developed using dispersive solid‐phase extraction combined with ultrasound‐assisted dispersive liquid–liquid microextraction before ultra‐high performance liquid chromatography with tandem mass spectrometry. The clean up of the extract was conducted using dispersive solid‐phase extraction by directly adding sorbents into the extraction solution, followed by shaking and centrifugation. After that, a mixture of 400 μL trichloromethane (extraction solvent) and 0.5 mL of the above supernatant was injected rapidly into water for the dispersive liquid–liquid microextraction procedure. The factors affecting the extraction efficiency were optimized. Under the optimum conditions, the calibration curves showed good linearity in the range of 2.0–400 (tebuconazole, diniconazole, and hexaconazole) and 4.0–800 ng/g (triadimenol and flutriafol) with the regression coefficients higher than 0.9958. The limit of detection and limit of quantification for the present method were 0.5–1.1 and 1.8–4.0 ng/g, respectively. The recoveries of the target analytes ranged from 80.2 to 103.2%. The proposed method has been successfully applied to the analysis of five triazole fungicides in traditional Chinese medicine samples, and satisfactory results were obtained.
Evaluation of a novel metal–organic framework as an adsorbent for the extraction of multiclass pesticides from coconut palm (Cocos nucifera L.): An analytical approach using matrix solid‐phase dispersion and liquid chromatography
Authors: de Jesus Jemmyson Romário , Wanderley Kaline Amaral , Alves Júnior Severino , Navickiene Sandro
Published: June 2017

We report the synthesis, characterization, and application of [Zn(1,4‐benzenedicarboxylate)(H2O)2]n, Zn(1,4‐benzenedicarboxylate)0.99(NH2‐1,4‐benzenedicarboxylate)0.01(H2O)2]n, [Zn(1,4‐benzenedicarboxylate)0.95(NH2‐1,4‐benzenedicarboxylate)0.05(H2O)2]n, and [Zn(1,4‐benzenedicarboxylate)0.9(NH2‐1,4‐benzenedicarboxylate)0.1(H2O)2]n as sorbents for the extraction of multiclass pesticides from coconut palm. Liquid chromatography with ultraviolet diode array detection was used as the analysis technique, and the experiments were performed at one fortification level (0.1 μg/g). The recoveries were 47–67, 51–70, 58–72, and 64–76% for [Zn(1,4‐benzenedicarboxylate)(H2O)2]n, Zn(1,4‐benzenedicarboxylate)0.99(NH2‐1,4‐benzenedicarboxylate)0.01(H2O)2]n, [Zn(1,4‐benzenedicarboxylate)0.95(NH2‐1,4‐benzenedicarboxylate)0.05(H2O)2]n, and [Zn(1,4‐benzenelate)0.95(NH2‐1,4‐benzenedicarboxylate)0.05(H2O)2]n, and [Zn(1,4‐benzenedicarboxylate)0.9(NH2‐1,4‐benzenedicarboxylate)0.1(H2O)2]n, respectively, with relative standard deviation ranging from 1 to 7% (n = 3). Detection and quantification limits were 0.01–0.05 and 0.05–0.2 μg/g, respectively, for the different pesticides studied. The method developed was linear over the range tested (0.01–10.0 μg/g) with r2 > 0.9991. A direct comparison of [Zn(1,4‐benzenedicarboxylate)0.9(NH2‐1,4‐benzenedicarboxylate)0.1(H2O)2]n with the commercially available neutral alumina showed that [Zn(1,4‐benzenedicarboxylate)0.9(NH2‐1,4‐benzenedicarboxylate)0.1(H2O)2]n was a similar extracting phase for the pesticides investigated.
Insurance status as a predictor of mortality in patients undergoing head and neck cancer surgery
Authors: Rohlfing Matthew L. , Mays Ashley C. , Isom Scott , Waltonen Joshua D.
Published: June 2017

Objective

Explore relationship between insurance status and survival, determine outcomes that vary based on insurance status, and identify potential areas of intervention.

Study Design

Retrospective cohort analysis of patients who underwent resection of an upper aerodigestive tract malignancy at a single tertiary care hospital during a 5‐year period.

Methods

Patients were categorized into four groups by insurance status: Medicaid or uninsured, Medicare and under 65 years of age, Medicare and 65 years or older, and private insurance. Data were collected from the medical record and analyzed with respect to survival and other outcomes.

Results

The final cohort consisted of 860 patients. Survival analysis demonstrated a hazard ratio of 2.1 (95% confidence interval [CI], 1.5–3.0) for the Medicaid/uninsured group when compared to the private insurance group. When adjusted for other variables, mortality was still different across insurance groups (P = 0.002). The following also were different across insurance groups: tumor stage (P < 0.001), American Society of Anesthesiologists score (P < 0.001), length of stay (P < 0.001), and complications (P = 0.021). The Medicaid/uninsured group was most likely to have a complication (odds ratio [OR] = 2.10, 95% CI 1.24–3.56, P = 0.006).

Conclusion

Medicaid/uninsured patients present with more advanced tumors and have poorer survival than privately insured patients. Insurance status is predictive of tumor stage, comorbidity burden, length of stay, and complications. Specifically, the Medicaid/uninsured group had high rates of tobacco use and alcohol abuse, advanced stage tumors, and postoperative complications. Because alcohol abuse and advanced stage also were predictors of poor survival, they may contribute to the survival disparity for socially disadvantaged patients.

Level of Evidence

4. Laryngoscope, 127:2784–2789, 2017
Frequency‐dependent inhibition of bladder function by saphenous nerve stimulation in anesthetized rats
Authors: Moazzam Zainab , Yoo Paul B.
Published: June 2017

Aims

Percutaneous tibial nerve stimulation (PTNS) is an effective neuromodulation therapy for treating overactive bladder (OAB). The therapeutic effects are achieved by repeatedly applying electrical stimulation through a percutaneous needle electrode that is used to target the tibial nerve (TN). Anatomical studies indicate there can be multiple saphenous nerve (SAFN) branches located near the site of electrical stimulation, and therefore we investigated the possibility of evoking a bladder‐inhibitory reflex by electrically activating the SAFN.

Materials and Methods

Acute experiments were conducted in 26 urethane‐anesthetized rats. Changes in bladder contraction rate (BCR) and bladder capacity were measured in response to 10‐min SAFN stimulation trials. Electrical pulses were applied at 25 µA and at stimulation frequencies between 2 Hz and 50 Hz.

Results

We report that SAFN stimulation at 20 Hz was most effective at reflexively decreasing the BCR (53.8 ± 5.4% from baseline) and also increasing the bladder capacity (145.8 ± 43.5% from baseline). In contrast, SAFN stimulation at other frequencies yielded inconsistent changes in bladder function. Carry‐over effects were minimized by randomizing the sequence of SAFN stimulation trials and also by allowing the bladder to return to the baseline conditions.

Conclusions

With notable changes in both the BCR and bladder capacity, our findings provide evidence of a novel bladder‐inhibitory reflex in anesthetized rats that is mediated by the SAFN. Further work is needed to determine the clinical relevance of this neural pathway.
Coupled finite particle method with a modified particle shifting technology
Authors: Huang C. , Zhang D. H. , Shi Y. X. , Si Y. L. , Huang B.
Published: June 2017

The conventional SPH method has been frustrated with the low accuracy originated from the particle inconsistency. The finite particle method (FPM) is an improved SPH method with a higher‐order accuracy. However, the numerical accuracy and stability of FPM depend on the uniformity of particles. Facing the disorder particles, the conventional FPM may suffer from an ill‐conditioned corrective matrix and is difficult to conduct longtime simulations. A popular and robust particle regularization scheme is the so‐called particle shifting technology (PST), which can effectively enhance the accuracy and stability of particle methods. In the context of FPM, PST is analyzed and discussed, and a modified PST (MPST) is proposed. Modified PST saves great amount of computational cost with respect to the conventional PST and acquires better features of accuracy and stability. Finally, the coupled FPM method by combining MPST and δ‐SPH is developed to simulate a series of viscous flows. The numerical results indicate that MPST is effective in improving accuracy, stability, and efficiency of PST, and the coupled FPM is shown to be robust for simulating viscous flows and has a higher accuracy and stability.
Elastin‐like polypeptide switches: A design strategy to detect multimeric proteins
Authors: Dhandhukia Jugal P. , Brill Dab A. , Kouhi Aida , Pastuszka Martha K. , MacKay J. Andrew
Published: June 2017

Elastin‐Like Polypeptides (ELPs) reversibly phase separate in response to changes in temperature, pressure, concentration, pH, and ionic species. While powerful triggers, biological microenvironments present a multitude of more specific biological cues, such as antibodies, cytokines, and cell‐surface receptors. To develop better biosensors and bioresponsive drug carriers, rational strategies are required to sense and respond to these target proteins. We recently reported that noncovalent association of two ELP fusion proteins to a “chemical inducer of dimerization” small molecule (1.5 kDa) induces phase separation at physiological temperatures. Having detected a small molecule, here we present the first evidence that ELP multimerization can also detect a much larger (60 kDa) protein target. To demonstrate this strategy, ELPs were biotinylated at their amino terminus and mixed with tetrameric streptavidin. At a stoichiometric ratio of [4:1], two to three biotin‐ELPs associate with streptavidin into multimeric complexes with an apparent Kd of 5 nM. The increased ELP density around a streptavidin core strongly promotes isothermal phase separation, which was tuned to occur at physiological temperature. This phase separation reverses upon saturation with excess streptavidin, which only favors [1:1] complexes. Together, these findings suggest that ELP association with multimeric biomolecules is a viable strategy to deliberately engineer ELPs that respond to multimeric protein substrates.
Rigidity of the extracellular part of HER2: Evidence from engineering subdomain interfaces and shared‐helix DARPin‐DARPin fusions
Authors: Jost Christian , Stüber Jakob C. , Honegger Annemarie , Wu Yufan , Batyuk Alexander , Plückthun Andreas
Published: June 2017

The second member of the human ErbB family of receptor tyrosine kinases, HER2/hErbB2, is regarded as an exceptional case: The four extracellular subdomains could so far only be found in one fixed overall conformation, designated “open” and resembling the ligand‐bound form of the other ErbB receptors. It thus appears to be different from the extracellular domains of the other family members that show inter‐subdomain flexibility and exist in a “tethered” form in the absence of ligand. For HER2, there was so far no direct evidence for such a tethered conformation on the cell surface. Nonetheless, alternative conformations of HER2 in vivo could so far not be excluded. We now demonstrate the rigidity of HER2 on the surface of tumor cells by employing two orthogonal approaches of protein engineering: To directly test the potential of the extracellular domain of HER2 to adopt a pseudo‐tethered conformation on the cell surface, we first designed HER2 variants with a destabilized interface between extracellular subdomains I and III that would favor deviation from the “open” conformation. Secondly, we used differently shaped versions of a Designed Ankyrin Repeat Protein (DARPin) fusion, recognizing subdomain I of HER2, devised to work as probes for a putative pseudo‐tethered extracellular domain of HER2. Combining our approaches, we exclude, on live cells and in vitro, that significant proportions of HER2 deviate from the “open” conformation.
Distributed event‐triggered consensus control with fully continuous communication free for general linear multi‐agent systems under directed graph
Authors: Liu Xiangdong , Du Changkun , Liu Haikuo , Lu Pingli
Published: June 2017

This paper considers the distributed event‐triggered consensus problem for multi‐agent systems with general linear dynamics under a directed graph. We propose a novel distributed event‐triggered consensus controller with state‐dependent threshold for each agent to achieve consensus. In this strategy, continuous communication in both controller update and triggering condition monitoring is not required, which means the proposed strategy is fully continuous communication free. Each agent only needs to monitor its own state continuously to determine if the event is triggered. Additionally, the approach shown here provides consensus with guaranteed positive inter‐event time intervals. Therefore, there is no Zeno behavior under the proposed consensus control algorithm. Finally, numerical simulations are given to illustrate the theoretical results.
Resilience dimensions and mental health outcomes in bipolar disorder in a follow‐up study
Authors: Echezarraga A. , Calvete E. , González‐Pinto A.M. , Las Hayas C.
Published: June 2017

The individual process of resilience has been related to positive outcomes in mental disorders. We aimed (a) to identify the resilience domains from the Resilience Questionnaire for Bipolar Disorder that are associated cross sectionally and longitudinally with mental health outcomes in bipolar disorder (BD) and (b) to explore cross‐lagged associations among resilience factors. A clinical adult sample of 125 patients diagnosed with BD (62.10% female, mean age = 46.13, SD = 10.89) gave their informed consent and completed a battery of disease‐specific tools on resilience, personal recovery, symptomatology, psychosocial functioning, and quality of life, at baseline and at follow‐up (n = 63, 58.10% female, mean age = 45.13, SD = 11.06, participation rate = 50.40%). Resilience domains of self‐management of BD, turning point, self‐care, and self‐confidence were significantly associated with mental health indicators at baseline. In addition, self‐confidence at baseline directly predicted an increase in personal recovery at follow‐up, and self‐confidence improvement mediated the relationship between interpersonal support and self‐care at baseline and personal recovery at follow‐up. These findings highlight that resilience domains are significantly associated with positive mental health outcomes in BD and that some predict personal recovery at follow‐up. Moreover, some resilience factors improve other resilience factors over time.
Defective Tungsten Oxide Hydrate Nanosheets for Boosting Aerobic Coupling of Amines: Synergistic Catalysis by Oxygen Vacancies and Brønsted Acid Sites
Authors: Zhang Ning , Li Xiyu , Liu Yifei , Long Ran , Li Mengqiao , Chen Shuangming , Qi Zeming , Wang Chengming , Song Li , Jiang Jun , Xiong Yujie
Published: June 2017

Adsorption and activation of molecules on a surface holds the key to heterogeneous catalysis toward aerobic oxidative reactions. To achieve high catalytic activities, a catalyst surface should be rationally tailored to interact with both organic substrates and oxygen molecules. Here, a facile bottom‐up approach to defective tungsten oxide hydrate (WO3·H2O) nanosheets that contain both surface defects and lattice water is reported. The defective WO3·H2O nanosheets exhibit excellent catalytic activity for aerobic coupling of amines to imines. The investigation indicates that the oxygen vacancies derived from surface defects supply coordinatively unsaturated sites to adsorb and activate oxygen molecules, producing superoxide radicals. More importantly, the Brønsted acid sites from lattice water can contribute to enhancing the adsorption and activation of alkaline amine molecules. The synergistic effect of oxygen vacancies and Brønsted acid sites eventually boosts the catalytic activity, which achieves a kinetic rate constant of 0.455 h−1 and a turnover frequency of 0.85 h−1 at 2 h, with the activation energy reduced to ≈35 kJ mol−1. This work provides a different angle for metal oxide catalyst design by maneuvering subtle structural features, and highlights the importance of synergistic effects to heterogeneous catalysts.