bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of sediment mutagenicity in areas under the influence of a contaminated site undergoing a remediation process
Authors: Gameiro Paula Hauber , Pereira Naiara Costa , Rocha Jocelita Aparecida Vaz , Leal Karen Alam , Vargas Vera Maria Ferrão
Published: April 2018

Soil contamination enters aquatic ecosystems affecting sediment quality. The region studied is the Taquari River, Brazil, close to a site contaminated by wood preservatives, with a runoff route into the river. The first stage of the remediation process (In this article, the terms intervention and remediation have been used with slightly different meanings. We consider intervention to be the first phase of the remediation process, which aims to remove active sources) was an intervention to remove the main active sources. The Salmonella/microsome assay and polycyclic aromatic hydrocarbons (PAHs) were used to assess sediment quality in organic extracts during different intervention phases. The strains used were TA98, TA97a, and TA100 with and without S9mix (±S9). The results indicated the presence of pro‐mutagens at site Ta010 (closest to the contaminated site) in all samplings, and the highest result occurred before intervention for TA100 + S9 (1,672 ± 215.9 rev/g). These values decreased during (83 ± 23.6 rev/g) and after this process (403 ± 105.9 rev/g), although the PAHs concentrations increased. Samples from this site presented PAHs with a carcinogenic potential during the assessed periods. After intervention, Ta006 (4 km downstream from Ta010) showed the most significant mutagenesis for TA100 + S9 (764 ± 230.2 rev/g) and, although the total PAHs values were lower, the species considered carcinogenic had higher concentrations. Mutagenesis predicted values of PAHs confirmed that carcinogenic species were predominantly detected by TA100, and the other PAHs by TA97a strains. Marked contaminant release to the river was observed, mainly in Ta010 at different periods. Mutagenicity and PAHs values in an internal stream, upstream from Ta010, showed a dispersion route of these agents. Thus, contamination in Ta010 and possible contribution to Ta006, after intervention, provides a warning regarding environmental quality in the region. Environ. Mol. Mutagen. 59:625–638, 2018. © 2018 Wiley Periodicals, Inc.
A circular nonhomogeneous hidden Markov field for the spatial segmentation of wildfire occurrences
Authors: Ameijeiras‐Alonso Jose , Lagona Francesco , Ranalli Monia , Crujeiras Rosa M.
Published: April 2018

Motivated by studies of wildfire seasonality, we propose a nonhomogeneous hidden Markov random field to model the spatial distribution of georeferenced fire occurrences during the year, by representing occurrence times as circular data. The model is based on a mixture of Kato–Jones circular densities, whose parameters vary across space according to a latent nonhomogeneous Potts model, modulated by georeferenced covariates. It allows us to segment fire occurrences according to a finite number of latent classes that represent the conditional distributions of the data under specific periods of the year, simultaneously accounting for unobserved heterogeneity and spatial autocorrelation. Further, it parsimoniously accommodates specific features of wildfire occurrence data such as multimodality, skewness, and kurtosis. Due to the numerical intractability of the likelihood function, estimation of the parameters is based on composite likelihood methods. It reduces to a computationally efficient expectation–maximization algorithm that iteratively alternates the maximization of a weighted composite likelihood function with weights updating. The proposal is illustrated in a study of wildfire occurrences in the Iberian Peninsula during a decade.
Development and validation of a new cognitive screening test: The Hong Kong Brief Cognitive Test (HKBC)
Authors: Chiu Helen F.K. , Zhong Bao‐Liang , Leung Tony , Li S.W. , Chow Paulina , Tsoh Joshua , Yan Connie , Xiang Yu‐Tao , Wong Mike
Published: April 2018

Objectives

To develop and examine the validity of a new brief cognitive test with less educational bias for screening cognitive impairment.

Methods

A new cognitive test, Hong Kong Brief Cognitive Test (HKBC), was developed based on review of the literature, as well as the views of an expert panel. Three groups of subjects aged 65 or above were recruited after written consent: normal older people recruited in elderly centres, people with mild NCD (neurocognitive disorder), and people with major NCD. The brief cognitive test, Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA), were administered to the subjects. The performance of HKBC in differentiating subjects with major NCD, mild NCD, and normal older people were compared with the clinical diagnosis, as well as the MMSE and MoCA scores.

Results

In total, 359 subjects were recruited, with 99 normal controls, 132 subjects with major NCD, and 128 with mild NCD. The mean MMSE, MoCA, and HKBC scores showed significant differences among the 3 groups of subjects. In the receiving operating characteristic curve analysis of the HKBC in differentiating normal subjects from those with cognitive impairment (mild NCD + major NCD), the area under the curve was 0.955 with an optimal cut‐off score of 21/22. The performances of MMSE and MoCA in differentiating normal from cognitively impaired subjects are slightly inferior to the HKBC.

Conclusions

The HKBC is a brief instrument useful for screening cognitive impairment in older adults and is also useful in populations with low educational level.
Influence of Progenitor‐Derived Regeneration Markers on Hepatitis C Virus–Related Cirrhosis Outcome (ANRS CO12 CirVir Cohort)
Authors: Wendum Dominique , Layese Richard , Ganne‐Carrié Nathalie , Bourcier Valérie , Merabtene Fatiha , Cagnot Carole , Sauce Emmanuel , Barget Nathalie , Bedossa Pierre , Terris Benoit , Selves Janick , Bioulac‐Sage Paulette , Sturm Nathalie , Sattonnet Christophe , Nahon Pierre , Roudot‐Thoraval Françoise , Ziol Marianne ,   for the ANRS CO12 CirVir Group
Published: April 2018

Progenitor‐derived regeneration gives rise to the aberrant expression of biliary markers such as cytokeratin 7 (K7) and epithelial cell adhesion molecule (EpCAM) in hepatocytes. We aimed to describe the expression of these molecules in patients with compensated hepatitis C virus (HCV)–related cirrhosis and to investigate its potential influence on cirrhosis complications. Among patients with Child‐Pugh A uncomplicated HCV‐related cirrhosis enrolled in the prospective ANRS CO12 CirVir cohort, we selected individuals with a liver biopsy collected within 2 years before inclusion in the study. K7 and EpCAM immunostaining identified intermediate hepatobiliary cells. The influence of biliary marker expres‐sion in hepatocytes on decompensation events and the occurrence of hepatocellular carcinoma (HCC) was studied using a multivariate Cox proportional hazards regression model. Among the 337 patients eligible for the study (men, 67%; median age, 52 years), 198 (58.8%) had biopsies with K7‐positive hepatocytes including extensive staining in 40 (11.9%) and 203 had EpCAM‐positive hepatocytes (60.6%). During follow‐up (median, 54.2 months), 47 patients (14%) experienced a decompensation event, and HCC was diagnosed in 37 patients (11%). Extensive K7 staining was independently associated with the occurrence of a decompensation event (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.30‐6.89; P = 0.010). EpCAM expression was independently associated with HCC occurrence (HR, 2.37; 95% CI, 1.07‐5.23; P =0.033) along with age and a low prothrombin ratio. Conclusion: Progenitor‐derived regeneration depicted by K7 and EpCAM immunostaining of hepatocytes in liver biopsies of patients with compensated HCV‐related cirrhosis marks a cirrhosis stage more prone to develop complications. (HEPATOLOGY 2018; 68:1534‐1548).
Care pathways in the transition of patients between district psychiatric hospital centres (DPCs) and community mental health services
Authors: Sather Eva W. , Svindseth Marit F. , Crawford Paul , Iversen Valentina C.
Published: April 2018

Rationale, aims, and objectives

Patients with mental health problems experience numerous transitions into and out of hospital. Primary care providers have mixed success in identifying and managing patients' needs. This study explores health personnel's experience of care pathways in patient transition between inpatient and community mental health services.

Methods

A descriptive qualitative design was chosen. Four focus group interviews with 12 informants from 7 different communities were conducted. Interviews were analyzed thematically.

Results

Two main themes were identified: integrated care and patient activation. The participants shared their experiences on topics that can affect smooth care pathways in mental health. Six promoting factors were identified for successful patient transition: opportunities for information sharing, implementation of systematic plans, use of e‐messages, around‐the‐clock care, designating one responsible health person in each system for each patient, and the involvement of patients and their families. The following barriers were all found to impede the patients' transition between levels of care: the lack of a single responsible person at each health care level, insufficient meetings, the absence of systematic plans, difficulties in identifying the right staff at different levels, delays in information sharing, and the complexity of welfare systems negatively affecting patient dignity.

Conclusions

Systems and procedures should be developed to ensure clear responsibilities and transparency at each stage of the pathways of care. A single person should take charge of ensuring sufficient connection and communication between inpatient and community mental health services. Finally, both patient and staff in community services should be linked through a direct telephone number with around‐the‐clock availability.
Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse
Authors: Lee Jeansun , Dieckmann Nele M.G. , Edgar James R. , Griffiths Gillian M. , Siegel Richard M.
Published: April 2018

Introduction

T cell and NK cell cytotoxicity can be mediated via the perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a type II transmembrane protein that binds its cognate receptor Fas (CD95). Membrane‐bound FasL is expressed on the plasma membrane of activated lymphocytes and is the main form of FasL with cytotoxic activity, but whether FasL is delivered to the immune synapse along with granzyme and perforin‐containing granules is unclear.

Methods

We stably expressed FasL‐fluorescent fusion proteins into human NK cells and examined the localization of FasL relative to other intracellular markers by confocal and immunoelectron microscopy, and examined the trafficking of FasL during formation of immune synapses with HLA‐deficient B cells.

Results

FasL co‐localized with CD63 more strongly than perforin or Lamp1+ in cytolytic granules. Electron microscopy revealed that FasL is enriched on intraluminal vesicles (ILVs) adjacent to the dense‐core within cytolytic granules. In NK cells forming immune synapses with HLA‐deficient B cells, a portion of FasL‐containing granules re‐localize toward the immune synapse, while a distinct pool of FasL remains at the distal pole of the cell.

Conclusions

Localization of FasL to intra‐luminal vesicles within cytolytic granules facilitates FasL trafficking to immune synapses and cytotoxic function in NK cells.
Umbilical cord arterial base deficit and arterial pH as predictors of adverse outcomes among term neonates
Authors: Knutzen Liv , Anderson‐Knight Hannah , Svirko Elena , Impey Lawrence
Published: April 2018

Objective

To determine the importance of arterial pH and arterial base deficit (ABD) for predicting adverse outcomes among all term neonates, regardless of acidemic status.

Methods

The present observational cohort study included consecutive term, non‐anomalous singleton neonates with validated paired cord gas data at a single UK teaching hospital between June 23, 2005, and December 31, 2009. Outcomes included encephalopathy (Sarnat grade 2–3) and/or death; 5‐minute Apgar score below 7; a composite neurologic adverse outcome; and systemic involvement. Comparison of areas under the curve and hierarchical logistical regressions were used to examine the importance of arterial pH and arterial base deficit (ABD) in predicting adverse outcomes.

Results

There were 8759 neonates included. In all, 111 (1.3%) neonates had high ABD (≥12 mmol/L). Encephalopathy and/or death was recorded in 17 (0.2%) neonates in the whole cohort and 6 (5.4%) from the high ABD group. The mean arterial pH values for these two groups were 7.23 and 7.03, respectively. Comparison of the area under the receiver operating characteristic curves showed that adding ABD to arterial pH did not improve the prediction. Further, hierarchical logistic regression analysis demonstrated that ABD was not an independent predictor of adverse outcomes when adjusted for arterial pH.

Conclusions

ABD demonstrated no predictive value for adverse neonatal outcomes beyond using arterial pH alone.
Endometrial cancer after endometrial ablation or resection for menorrhagia
Authors: Kalampokas Emmanouil , McRobbie Sarah , Payne Fiona , Parkin David E.
Published: April 2018

Objective

To assess the incidence of endometrial cancer after endometrial ablation or resection (EA/R) for menorrhagia.

Method

The present retrospective observational cohort study included women who underwent EA/R for menorrhagia at Aberdeen Royal Infirmary between February 1, 1990 and December 31, 1997. Follow‐up data until 2015 were examined. To assess risk of endometrial cancer, each woman was matched by age to the annual observed incidence of endometrial cancer in northeast Scotland for each year from the date of EA/R until 2015.

Results

During the 7‐year study period, 901 eligible women (mean age 42.3 ± 5.7 years; range 26–50 years) underwent EA/R. Of these patients, 204 (22.6%) subsequently had a hysterectomy for reasons other than endometrial cancer, and 695 (77.1%) did not. The overall incidence of endometrial cancer was 0.2% (2/901); the risk of developing endometrial cancer after EA/R was calculated as 11.1 per 100 000 women years. The mean expected incidence for all women and the subgroup with no hysterectomy was estimated to be 26.5 and 35.6 occurrences per 100 000 women years, respectively. The observed incidence was significantly lower versus the mean expected risk for both groups (P<0.001).

Conclusion

The findings indicate that the risk of endometrial cancer could be significantly reduced but not eliminated by EA/R.
SPECIFYING A SYSTEM USING ERA INFORMATION MODELS
Authors: Baker Loyd J. , Long James E.
Published: April 2018

Stating the requirements for systems or business processes as a hierarchical collection of English text that can only be analyzed/ verified by human inspection has proven time and again to be labor intensive and generally, inadequate. Projects employing a traditional document‐centered system engineering approach have experienced significant numbers of mis‐interpretations of the customer's requirements, or late‐detected design errors results in increased costs, schedule slips, reduced capability, or canceled programs. We have historically fixed requirements problems, that should have been understood and resolved early, during integration and test where it is more costly to identify and fix. Now that computerized system engineering support tools are available on the engineer's desktop, the leading edge aerospace/commercial corporations are transitioning from a document‐centered to a model‐driven system engineering approach to developing, analyzing, and managing explicit system/process specifications. Information and operational models (of varying levels of detail) not only aid in the understanding and communication of intentions such that incorrect assumptions can be eliminated early, they directly support the development of system verification plans.
Ocular implant containing bevacizumab‐loaded chitosan nanoparticles intended for choroidal neovascularization treatment
Authors: Badiee Parisa , Varshochian Reyhaneh , Rafiee‐Tehrani Morteza , Abedin Dorkoosh Farid , Khoshayand Mohammad Reza , Dinarvand Rassoul
Published: April 2018

Choroidal neovascularization (CNV) is among the leading causes of blindness worldwide. Bevacizumab has demonstrated promising effects on CNV treatment; however, frequent intravitreal injection is its major drawback. Current study aimed to address this issue by developing a sustained release formulation through nanoparticles of bevacizumab imbedded in an ocular implant. Bevacizumab‐loaded chitosan nanoparticles were prepared by ionic gelation method and inserted in the matrix of hyaluronic acid and zinc sulfate. Despite the common approaches in using ultraviolet (UV)‐spectrophotometry, microprotein‐Bradford, and bicinchoninic acid (BCA), assay for protein assessment, our results revealed a remarkable UV–Vis absorption overlap of protein and chitosan during these analysis and thus enzyme‐linked immunosorbent assay was employed for the antibody concentration assay. The size of optimized nanoparticles obtained through statistical analysis based on design of experiments was 78.5 ± 1.9 nm with polydispersity index of 0.13 ± 0.05 and the entrapment‐efficiency and loading‐efficiency were 67.6 ± 6.7 and 15.7 ± 5.7%, respectively. The scanning electron microscopy and confocal microscopy images revealed a homogenous distribution of nanoparticles in the implant matrix and the release test results indicated an appropriate extended release of bevacizumab from the carrier over two months. In conclusion, the prepared system provided a sustained release bevacizumab delivery formulation which can introduce a promising ocular drug delivery system intended for posterior segment disease. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2261–2271, 2018.
Fabrication and evaluation of a nerve guidance conduit capable of Ca2+ ion release to accelerate axon extension in peripheral nerve regeneration
Authors: Zargar Kharazi Anousheh , Dini Ghasem , Naser Reza
Published: April 2018

In this study, biodegradable nanocomposites consisting of poly (glycerol sebacate) (PGS) elastomeric matrix and the reinforcing phase of calcium titanate (CaTiO3) nanoparticles were fabricated as a nerve guidance conduit (NGC) for peripheral nerve regeneration. CaTiO3 nanoparticles were synthesized via the sol‐gel method and calcined at 800°C for 60 min. PGS elastomer was synthesized via the polycondensation reaction of glycerol and sebacate (1:1) and 2.5 and 5 wt. percentages of the synthesized CaTiO3 nanoparticles were added to the PGS prepolymer solution. The composites obtained were heated in order to make crosslinks in the pre‐polymer. CaTiO3 nanoparticles, PGS elastomer, and the composites fabricated were characterized in terms of their structural, chemical, physical, mechanical, and cell response properties to evaluate the feasibility of using the nanocomposite for NGC applications. The results indicated that CaTiO3 nanoparticles were 50 nm in size. When the nanoparticles were added to the PGS, the elastic modulus and tensile strength of the nanocomposite reached values of about 1 and 0.5 MPa, respectively that are near those of natural nerves. The degradation behavior and swelling of the nanocomposites, as compared with those of the PGS elastomer, were controlled by introducing CaTiO3 into the PGS, which swelling limitation could prevent nerve compression. It was observed that Ca2+ ions established chemical bonds with PGS, which led to high crosslink densities that, in turn, contribute to improved mechanical properties of the composite. The Ca2+ ions released from the nanocomposite samples were in the nontoxic range. The PC12 cell line on the surface of the nanocomposite specimens showed good cell adhesion and proliferation with improved axon outgrowth and extension. Based on the results obtained the fabricated PGS/CaTiO3 nanocomposite may be recommended as a suitable NGC with desirable effects on peripheral nerve regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2181‐2189, 2018.
Soluble laminin polymers enhance axon growth of primary neurons in vitro
Authors: Haggerty Agnes E. , Al‐Ali Hassan , Oudega Martin
Published: April 2018

A substrate of laminin polymers formed at pH 4 (acidic pH‐induced laminin; aLam) promotes neurite growth of embryonic rat cortical neurons better than a substrate of similar but structurally different laminin polymers formed at neutral pH (neutral pH‐induced laminin; nLam). We investigated the effects of these laminin polymers, used as soluble supplements, on neurite growth of cultured adult rat primary dorsal root ganglion neurons. When added to the culture medium, aLam was found to promote neurite growth about twofold better than nLam. Immunoblocking experiments revealed that aLam elicited neurite growth to a similar extent through the α1 or α3 integrin subunit, while nLam required the availability of the α1 integrin subunit to elicit neurite growth. With aLam, but not nLam, immunoblocking of the α1 or α3 subunit resulted in an increase in the protein level of the alternative subunit. The presence of a mature focal adhesion complex, which is associated with neurite growth, was elevated in neurons in the presence of aLam relative to nLam or culture medium. Our data indicated that the two types of laminin polymers promote neurite growth of adult rat primary sensory neurons to a different degree, likely through different ligand–receptor interactions. These findings support the potential of soluble laminin polymers as injectable therapeutics for eliciting axon growth after nervous system injury. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2372–2381, 2018.
A ternary nanofibrous scaffold potential for central nerve system tissue engineering
Authors: Saadatkish Niloufar , Nouri Khorasani Saied , Morshed Mohammad , Allafchian Ali‐Reza , Beigi Mohammad‐Hossein , Masoudi Rad Maryam , Esmaeely Neisiany Rasoul , Nasr‐Esfahani Mohammad‐Hossein
Published: April 2018

In the present research, a ternary polycaprolactone (PCL)/gelatin/fibrinogen nanofibrous scaffold for tissue engineering application was developed. Through this combination, PCL improved the scaffold mechanical properties; meanwhile, gelatin and fibrinogen provided more hydrophilicity and cell proliferation. Three types of nanofibrous scaffolds containing different fibrinogen contents were prepared and characterized. Morphological study of the nanofibers showed that the prepared nanofibers were smooth, uniform without any formation of beads with a significant reduction in nanofiber diameter after incorporation of fibrinogen. The chemical characterization of the scaffolds confirmed that no chemical reaction occurred between the scaffold components. The tensile test results of the scaffolds showed that increasing in fibrinogen content led to a decrease in mechanical properties. Furthermore, adipose‐derived stem cells were employed to evaluate cell–scaffold interaction. Cell culture results indicated that higher cell proliferation occurred for the higher amount of fibrinogen. Statistical analysis was also carried out to evaluate the significant difference for the obtained results of water droplet contact angle and cell culture. Therefore, the results confirmed that PCL/gel/fibrinogen scaffold has a good potential for tissue engineering applications including central nerve system tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2394–2401, 2018.
How Can We Improve Osteoporosis Care? A Systematic Review and Meta-Analysis of the Efficacy of Quality Improvement Strategies for Osteoporosis
Authors: Nayak Smita , Greenspan Susan L
Published: April 2018

Although osteoporosis affects 10 million people in the United States, screening and treatment rates remain low. We performed a systematic review and meta-analysis of the efficacy of quality improvement strategies to improve osteoporosis screening (bone mineral density [BMD]/dual-energy X-ray absorptiometry [DXA] testing) and/or treatment (pharmacotherapy) initiation rates. We developed broad literature search strategies for PubMed, Embase, and Cochrane Library databases, and applied inclusion/exclusion criteria to select relevant studies. Random-effects meta-analyses were performed for outcomes of BMD/DXA testing and/or osteoporosis treatment. Forty-three randomized clinical studies met inclusion criteria. For increasing BMD/DXA testing in patients with recent or prior fracture, meta-analyses demonstrated several efficacious strategies, including orthopedic surgeon or fracture clinic initiation of osteoporosis evaluation or management (risk difference 44%, 95% confidence interval [CI] 26%–63%), fracture liaison service/case management (risk difference 43%, 95% CI 23%–64%), multifaceted interventions targeting providers and patients (risk difference 24%, 95% CI 15%–32%), and patient education and/or activation (risk difference 16%, 95% CI 6%–26%). For increasing osteoporosis treatment in patients with recent or prior fracture, meta-analyses demonstrated significant efficacy for interventions of fracture liaison service/case management (risk difference 20%, 95% CI 1%–40%) and multifaceted interventions targeting providers and patients (risk difference 12%, 95% CI 6%–17%). The only quality improvement strategy for which meta-analysis findings demonstrated significant improvement of osteoporosis care for patient populations including individuals without prior fracture was patient self-scheduling of DXA plus education, for increasing the outcome of BMD testing (risk difference 13%, 95% CI 7%–18%). The meta-analyses findings were limited by small number of studies in each analysis; high between-study heterogeneity; sensitivity to removal of individual studies; and unclear risk of bias of included studies. Despite the limitations of the current body of evidence, our findings indicate there are several strategies that appear worthwhile to enact to try to improve osteoporosis screening and/or treatment rates. © 2018 American Society for Bone and Mineral Research.
Genomewide Association Study Identifies Cxcl Family Members as Partial Mediators of LPS-Induced Periodontitis
Authors: Hiyari Sarah , Green Elissa , Pan Calvin , Lari Soma , Davar Mina , Davis Richard , Camargo Paulo M , Tetradis Sotirios , Lusis Aldons J , Pirih Flavia Q
Published: April 2018

Periodontitis (PD) is characterized by bacterial infection and inflammation of tooth-supporting structures and can lead to tooth loss. PD affects ∼47% of the US population over age 30 years and has a heritability of about 50%. Although the host immunoinflammatory response and genetic background play a role, little is known of the underlying genetic factors. We examined natural genetic variation in lipopolysaccharide (LPS)-induced PD across a panel of inbred mouse strains, the hybrid mouse diversity panel (HMDP). We observed a strain-dependent sixfold difference in LPS-induced bone loss across the HMDP with a heritability of 53%. We performed a genomewide association study (GWAS) using FAST-LMM, which corrects for population structure, and identified loci significantly associated with PD. We examined candidate genes at a locus on chromosome 5, which suggested a relationship between LPS-induced bone loss and, together with expression data, identified Cxcl family members as associated with PD. We observed an increase in Cxcl10 protein, as well as immune cells and pro-inflammatory cytokines in C57BL/6J (high bone loss strain) but not in A/J (low bone loss strain) after LPS injections. Genetic deletion of CXCR3 (Cxcl9 and10 receptor) demonstrated a ∼50% reduction in bone loss and reduced osteoclasts after LPS injections. Furthermore, WT mice treated with AMG-487 (a CXCR3 antagonist) showed a ∼45% reduction in bone loss and decreased osteoclasts after LPS injections. We conclude that CXCR3 is a strong candidate for modulating the host response in individuals susceptible to PD. © 2018 American Society for Bone and Mineral Research.
One‐pot solvent‐free synthesis of novel functionalized ethyl 2‐(alkylimino)‐4‐methyl‐3‐(alkanoyl)‐2,3‐dihydrothiazole‐5‐carboxylates
Authors: Iravani Nasir , Keshavarz Mosadegh , Hosseini Fatemeh
Published: April 2018

A green and efficient one‐pot two‐step synthesis of ethyl 2‐(alkylimino)‐4‐methyl‐3‐(alkanoyl)‐2,3‐dihydrothiazole‐5‐carboxylates from the reaction between acyl chlorides, ammonium thiocyanate, primary alkylamines, and ethyl 2‐chloroacetoacetae under mild, solvent‐ and catalyst‐free conditions at room temperature is presented. This efficient and straightforward technique gave the expected products in good to high yields in 2–4 hr without the creation of any by‐product in all reactions.
χ‐bounded families of oriented graphs
Authors: Aboulker P. , Bang‐Jensen J. , Bousquet N. , Charbit P. , Havet F. , Maffray F. , Zamora J.
Published: April 2018

A famous conjecture of Gyárfás and Sumner states for any tree T and integer k, if the chromatic number of a graph is large enough, either the graph contains a clique of size k or it contains T as an induced subgraph. We discuss some results and open problems about extensions of this conjecture to oriented graphs. We conjecture that for every oriented star S and integer k, if the chromatic number of a digraph is large enough, either the digraph contains a clique of size k or it contains S as an induced subgraph. As an evidence, we prove that for any oriented star S, every oriented graph with sufficiently large chromatic number contains either a transitive tournament of order 3 or S as an induced subdigraph. We then study for which sets of orientations of P4 (the path on four vertices) similar statements hold. We establish some positive and negative results.
Knowledge exchange partnership leads to digital transformation at Hydro‐X Water Treatment, Ltd.
Authors: Heinze Aleksej , Griffiths Marie , Fenton Alex , Fletcher Gordon
Published: April 2018

To attract a generation of workers and consumers who have never known a world without Wi‐Fi, smartphones, or social media, organizations increasingly have no choice but to incorporate digital technology into every aspect of their operations and processes. The leaders of Hydro‐X, a privately owned British enterprise, met the challenge of digital transformation by forming a knowledge exchange partnership with a local university and applying two business models to assess the current state of digital maturity at the firm and map out a strategy to improve it. Their experiences reflect the HINGE project planning methodology: Horizon scanning to evaluate the competition, Internal auditing, New model creation, Gap analysis, and Evaluation of options to determine next steps. As a result of their efforts, Hydro‐X fostered an intrapreneurial spirit among its staff and refined its e‐commerce platform to digitally target key audiences in order to tap into a new source of revenue.
Hybrid self‐assessment drives quality improvement at auto parts manufacturer
Authors: Ahidar Ikram , Sarsri Driss , Sefiani Naoufal
Published: April 2018

Organizations that strive for excellence must continually assess their processes, products, and services in order to improve them. By conducting such a self‐assessment, business leaders can identify potential areas for improvement. But which assessment tool is best? The answer for one Moroccan tier‐2 automotive parts supplier was to create a custom evaluation instrument, based on quality management standards developed by the International Automotive Task Force for the automotive sector and the European Foundation for Quality Management's model of excellence.
Fertilization with nitrogen and/or phosphorus lowers soil organic carbon sequestration in alpine meadows
Authors: Li Jin Hua , Hou Yi Lin , Zhang Sen Xi , Li Wen Jin , Xu Dang Hui , Knops Johannes M. H. , Shi Xiao Ming
Published: April 2018

Nutrient additions can increase carbon (C) inputs to soil, but there is no consensus about the response of soil organic C (SOC) storage and C sequestration. For the Tibetan alpine meadows, little is known about the effects and mechanisms of nitrogen (N) and phosphorus (P) addition on SOC stocks. In this study, we applied N and/or P fertilization for 7 years and analyzed soil changes in bulk density, pH, SOC, soil inorganic C (SIC), δ13C, and microbial biomass C (MBC), as well as stocks of SOC, SIC, and MBC for soil to a depth of 40 cm. We found that C:N decreased in 0–20 cm, and pH decreased at both 0–20 cm and 20–40 cm after fertilization. Fertilization with N and/or P decreased SOC stocks in 0–20 cm by 5–12% and SOC stocks from 0 to 40 cm by 3–5%. This SOC stock decline was associated with changes in SOC concentration but not with changes in bulk density. The SIC stock was 18% of total soil C, and was not influenced by either N or P fertilization. Soil δ13C in the 0–20 cm layer was depleted by fertilization with N or N + P, whereas P enriched soil δ13C. Soil MBC was positively correlated with SOC concentration, whereas soil δ13C was negatively correlated with SOC concentration. Soil δ13C, as a proxy of decomposition rate, indicated potentially higher SOC decomposition under N fertilization. These findings suggest that fertilization with N and/or P lowered SOC sequestration in Tibetan alpine meadows.
ATG12 expression quantitative trait loci associated with head and neck squamous cell carcinoma risk in a Chinese Han population
Authors: Song Xueyao , Yuan Zhiyao , Yuan Hua , Wang Lihua , Ji Pei , Jin Guangfu , Dai Juncheng , Ma Hongxia
Published: April 2018

Autophagy is an essential process to maintain cellular homeostasis and functions, which has been demonstrated to play an important role in the different stages of tumorigenesis. To evaluate whether the genetic variants in autophagy‐related genes influence the head and neck squamous cell carcinoma (HNSCC) risk, we conducted a case‐control study to analyze 11 tagging single nucleotide polymorphisms (SNPs) of three core autophagosome formation genes (ATG5, ATG12, and ATG16L1) with 576 HNSCC cases and 1552 healthy controls among Chinese population. Finally, we identified that rs26537 of ATG12 (additive model: adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.03‐1.37, P = 0.017) and rs4663402 in ATG16L1 (additive model: adjusted OR = 1.39, 95%CI = 1.08‐1.80, P = 0.010) were significantly associated with the increased risk of HNSCC. However, no association was detected between other SNPs and HNSCC risk. The results of expression quantitative trait loci (eQTL) analysis based on Genotype‐Tissue Expression (GTEx) accessible data, showed that the risk allele of rs26537 was significantly associated with up‐regulated expression of ATG12 (P = 0.0021). Further luciferase activity assay indicated that rs26537 T > C in ATG12 intron one region significantly enhanced transcription activity. These results suggested that ATG12 eQTL SNP rs26537 might contribute to an allele‐specific effect on the expression of host gene ATG12 and explain a fraction of HNSCC genetic susceptibility.
Global Patterns in the Motivations and Behaviors of Tournament Anglers Targeting Bedding Bass
Authors: Hargrove John S. , Allen Micheal S. , Weyl Olaf L. F. , Crandall Chelsey A. C. , Austin James D.
Published: April 2018

Angling for adult black bass Micropterus spp. as they defend nests containing eggs or fry (i.e., bed-fishing) has drawn concerns from fishery managers and anglers due to negative impacts on reproductive success. Research efforts, however, have failed to consider bed-fishing scenarios other than male-directed targeting, which may inaccurately reflect angler behaviors. To gain insights into the behaviors, motivations, and attitudes associated with bed-fishing across a large extent of the global distribution of black bass, we surveyed tournament anglers from the southeastern United States and South Africa (where black bass were introduced in 1928). Responses from 440 black bass tournament anglers indicated that during the reproductive season nearly half of all anglers spent 50% or more of their time bed-fishing and that larger, female fish were preferential targets. Overall, the responses from U.S. and South African anglers were very similar, but significant attitudinal differences were associated with the perceived impacts of bed-fishing on adult reproduction and juvenile production. Our results suggest that there are commonalities among the preferences and behavior of anglers from disparate geographic regions, and we highlight the need for future research on the impacts of size- and sex-selective bed-fishing of basses.
Hyperpolarized ketone body metabolism in the rat heart
Authors: Miller Jack J. , Ball Daniel R. , Lau Angus Z. , Tyler Damian J.
Published: April 2018

The aim of this work was to investigate the use of 13C‐labelled acetoacetate and β‐hydroxybutyrate as novel hyperpolarized substrates in the study of cardiac metabolism. [1‐13C]Acetoacetate was synthesized by catalysed hydrolysis, and both it and [1‐13C]β‐hydroxybutyrate were hyperpolarized by dissolution dynamic nuclear polarization (DNP). Their metabolism was studied in isolated, perfused rat hearts. Hyperpolarized [1‐13C]acetoacetate metabolism was also studied in the in vivo rat heart in the fed and fasted states. Hyperpolarization of [1‐13C]acetoacetate and [1‐13C]β‐hydroxybutyrate provided liquid state polarizations of 8 ± 2% and 3 ± 1%, respectively. The hyperpolarized T1 values for the two substrates were 28 ± 3 s (acetoacetate) and 20 ± 1 s (β‐hydroxybutyrate). Multiple downstream metabolites were observed within the perfused heart, including acetylcarnitine, citrate and glutamate. In the in vivo heart, an increase in acetylcarnitine production from acetoacetate was observed in the fed state, as well as a potential reduction in glutamate. In this work, methods for the generation of hyperpolarized [1‐13C]acetoacetate and [1‐13C]β‐hydroxybutyrate were investigated, and their metabolism was assessed in both isolated, perfused rat hearts and in the in vivo rat heart. These preliminary investigations show that DNP can be used as an effective in vivo probe of ketone body metabolism in the heart.
Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Behavioral Domain
Authors: Lytle Leslie A. , Nicastro Holly L. , Roberts Susan B. , Evans Mary , Jakicic John M. , Laposky Aaron D. , Loria Catherine M.
Published: April 2018

Background

The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments.

Objectives

The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity‐related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high‐priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self‐monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed.

Significance

Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field.
Upcycling of contaminated post‐industrial polypropylene waste: A design from recycling case study
Authors: Ragaert Kim , Hubo Sara , Delva Laurens , Veelaert Lore , Du Bois Els
Published: April 2018

This paper presents a detailed case study on the effective upcycling of a post‐industrial plastic waste stream to a renewed compound, fit for re‐use in a new application. The material investigated was a PET‐contaminated recycled PP, destined for a high‐impact, medium‐stiffness application. After two research trials and one large‐scale industrial trial, an upcycling formulation was determined to bring the recyclate to the required level of the new application, thus closing this specific material loop within the case company. The used methodology adheres to the Design from Recycling principle, in which industrially available (mechanically) recycled polymer materials are matched to potential new products. The design strategy starts from either the properties of an available recycled polymer (and then defines the product) or from the functional boundary conditions of the product (and then selects the material and/or an optional material upcycling step). The Design from Recycling principles can elegantly be combined with those of Design for Recycling, within the framework of a Circular Economy. POLYM. ENG. SCI., 58:528–534, 2018. © 2017 Society of Plastics Engineers
Deciphering RGDechi peptide‐α5β1 integrin interaction mode in isolated cell membranes
Authors: Russo Luigi , Farina Biancamaria , Del Gatto Annarita , Comegna Daniela , Di Gaetano Sonia , Capasso Domenica , Liguoro Annamaria , Malgieri Gaetano , Saviano Michele , Fattorusso Roberto , Zaccaro Laura
Published: April 2018

Integrins are a large family of heterodimeric receptors critically engaged in pathological processes such as tumor progression and metastasis. Although they are validated therapeutic targets, the molecular determinants governing integrin‐ligand interactions are not yet fully understood, leading to a scarcity of integrin sub‐type exclusive antagonists. In the past decade, we have investigated the biological behavior of the RGDechi, a chimeric peptide able to specifically bind αvβ3 integrin without cross reacting with αvβ5 and αIIbβ3 integrins. Here we have investigated the capability of the peptide to bind α5β1 integrin and characterized the molecular determinants governing this interaction through a combined experimental and computational approach. The detailed comparison of RGDechi‐α5β1 structural model with that previously determined of RGDechi in complex with αvβ3 shows how the bifunctional nature of the peptide renders the molecule an important tool to recognize integrins with different recognition modalities, providing novel insight on the structural requirements needed to their specific recognition.
Biophysical characterization and molecular simulation of electrostatically driven self‐association of a single‐chain antibody
Authors: O'Brien Christopher J. , Calero‐Rubio Cesar , Razinkov Vladimir I. , Robinson Anne S. , Roberts Christopher J.
Published: April 2018

Colloidal protein–protein interactions (PPI) are often expected to impact key behaviors of proteins in solution, such as aggregation rates and mechanisms, aggregate structure, protein solubility, and solution viscosity. PPI of an anti‐fluorescein single chain antibody variable fragment (scFv) were characterized experimentally at low to intermediate ionic strength using a combination of static light scattering and sedimentation equilibrium ultracentrifugation. Surprisingly, the results indicated that interactions were strongly net‐attractive and electrostatics promoted self‐association. Only repulsive interactions were expected based on prior work and calculations based a homology model of a related scFv crystal structure. However, the crystal structure lacks the charged, net‐neutral linker sequence. PyRosetta was used to generate a set of scFv structures with different linker conformations, and coarse‐grained Monte Carlo simulations were used to evaluate the effect of different linker configurations via second osmotic virial coefficient (B22) simulations. The results show that the configuration of the linker has a significant effect on the calculated B22 values, and can result in strong electrostatic attractions between oppositely charged residues on the protein surface. This is particularly relevant for development of non‐natural antibody products, where charged linkers and other loop regions may be prevalent. The results also provide a preliminary computational framework to evaluate the effect of unstructured linkers on experimental protein–protein interaction parameters such as B22.
Quantitative Systems Pharmacology Model of hUGT1A1‐modRNA Encoding for the UGT1A1 Enzyme to Treat Crigler‐Najjar Syndrome Type 1
Authors: Apgar Joshua F. , Tang Jian‐Ping , Singh Pratap , Balasubramanian Nanda , Burke John , Hodges Michael R. , Lasaro Melissa A. , Lin Lin , Miliard Bjorn L. , Moore Kristi , Jun Lucy S. , Sobolov Susan , Wilkins Anna Katharina , Gao Xiang
Published: April 2018

Crigler‐Najjar syndrome type 1 (CN1) is an autosomal recessive disease caused by a marked decrease in uridine‐diphosphate‐glucuronosyltransferase (UGT1A1) enzyme activity. Delivery of hUGT1A1‐modRNA (a modified messenger RNA encoding for UGT1A1) as a lipid nanoparticle is anticipated to restore hepatic expression of UGT1A1, allowing normal glucuronidation and clearance of bilirubin in patients. To support translation from preclinical to clinical studies, and first‐in‐human studies, a quantitative systems pharmacology (QSP) model was developed. The QSP model was calibrated to plasma and liver mRNA, and total serum bilirubin in Gunn rats, an animal model of CN1. This QSP model adequately captured the observed plasma and liver biomarker behavior across a range of doses and dose regimens in Gunn rats. First‐in‐human dose projections made using the translated model indicated that 0.5 mg/kg Q4W dose should provide a clinically meaningful and sustained reduction of >5 mg/dL in total bilirubin levels.
Synthesis and Fluorescence Property of a New Dendritic Perylenediimide‐Naphthalimide Derivative
Authors: Cheng Huan‐Ren , Lu Xiao‐Ju , Zhang Yong , Deng Xiang‐Yi
Published: April 2018

In this paper, a new perylenediimide‐naphthalimide compound has been constructed. The dendritic compound was charactarized by high resolution mass spectrometry (HRMS), it presented a rapid fluorescence response to Fe3+ ions and three times of enhanced core emission (at 600 nm) with energy transfer efficiency of 55% and the two photon fluorescence experiment indicate that the dendritic compound showed a good two photon fluorescence property. Meanwhile, the relations between the molecular structure and its fluorescence property have been discussed. Furthermore, the compound was successfully applied to the imaging of Fe3+ ions in Hela cells.
Sulfur Hosts against the Shuttle Effect
Authors: Wang Yazhou , Huang Xiaoxiao , Zhang Shanqing , Hou Yanglong
Published: April 2018

Lithium–sulfur (Li–S) batteries are considered as a substitute for conventional batteries as they are the most promising next‐generation energy‐storage system due to their high energy densities. However, their short cycling life, limited sulfur loading, severe polysulfide shuttling, and low sulfur utilization critically impede grid‐level‐storage energy techniques in Li–S batteries. The lithium shuttle effect results in rapid capacity fading and battery failure. The design and fabrication of sulfur hosts are key points to eliminate the aforementioned issues, especially the shuttle effect. In the past decade, spatial encapsulation and chemical interaction have improved the adsorption capacity of lithium polysulfides for the sulfur hosts and thus prolonged the lifetime of Li–S batteries. In an attempt to promote future research on the sulfur cathode and foster breakthroughs in Li–S batteries, recent achievements are highlighted, mechanical insights are discussed, and the remaining challenges and future research directions in the innovation of sulfur cathodes are identified.