bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased risk of second malignant neoplasms in adolescents and young adults with cancer
Authors: Lee Jean S. , DuBois Steven G. , Coccia Peter F. , Bleyer Archie , Olin Rebecca L. , Goldsby Robert E.
Published: October 2015

BACKGROUND

The authors describe the incidence and characteristics of secondary malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors compared with those in younger and older cancer survivors.

METHODS

Children aged ≤14 years, AYAs aged 15 to 39, and older adults aged ≥40 years at the time of primary diagnosis who were reported as cancer survivors in the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2011 were compared in this population‐based analysis. The primary analysis was the risk that an SMN would occur ≥5 years after the original diagnosis for patients who had the more common AYA cancers (leukemia, lymphoma, testicular malignancy, ovarian malignancy, melanoma, and cancers of the thyroid, breast, soft tissue, or bone). The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence of SMN for the selected cancers were assessed. The risk of SMN for the entire cohort also was analyzed.

RESULTS

Of the 148,558 AYA survivors who were diagnosed with a selected cancer, 7384 developed an SMN 5 years after their original diagnosis. The SIRs (95% confidence intervals [CIs]) were 1.58 (95% CI, 1.55‐1.62) for AYAs, 4.26 (95% CI, 3.77‐4.80) for children, and 1.10 (95% CI, 1.09‐1.11) for older adults, and the AERs were 22.9, 16.6, and 14.7, respectively. The cumulative incidence of SMN at 30 years was 13.9% for the AYA group. The most common SMNs in AYAs were breast cancer, gastrointestinal cancer, genital cancers, and melanoma. AYAs who had received radiation therapy had a higher cumulative incidence of SMN.

CONCLUSIONS

AYAs who survive cancer for more than 5 years have a higher relative risk of SMN compared with the general population and have a higher absolute risk of SMN compared with younger or older cancer survivors. Cancer 2016;122:116–123. © 2015 American Cancer Society.
BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer
Authors: Sakamoto Ikuko , Hirotsu Yosuke , Nakagomi Hiroshi , Ouchi Hidetaka , Ikegami Atsushi , Teramoto Katsuhiro , Amemiya Kenji , Mochizuki Hitoshi , Omata Masao
Published: October 2015

BACKGROUND

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer.

METHODS

Ninety‐five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next‐generation sequencing.

RESULTS

Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high‐grade serous adenocarcinomas).

CONCLUSIONS

In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. Cancer 2016;122:84–90. © 2015 American Cancer Society.
Patient‐reported physical functioning predicts the success of hematopoietic cell transplantation (BMT CTN 0902)
Authors: Wood William A. , Le‐Rademacher Jennifer , Syrjala Karen L. , Jim Heather , Jacobsen Paul B. , Knight Jennifer M. , Abidi Muneer H. , Wingard John R. , Majhail Navneet S. , Geller Nancy L. , Rizzo J. Douglas , Fei Mingwei , Wu Juan , Horowitz Mary M. , Lee Stephanie J.
Published: October 2015

BACKGROUND

In hematopoietic cell transplantation (HCT), current risk adjustment strategies are based on clinical and disease‐related variables. Although patient‐reported outcomes (PROs) predict mortality in multiple cancers, they have been less well studied within HCT. Improvements in risk adjustment strategies in HCT would inform patient selection, patient counseling, and quality reporting. The objective of the current study was to determine whether pre‐HCT PROs, in particular physical health, predict survival among patients undergoing autologous or allogeneic transplantation.

METHODS

In this secondary analysis, the authors studied pre‐HCT PROs that were reported by 336 allogeneic and 310 autologous HCT recipients enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902 protocol, a study with broad representation of patients who underwent transplantation in the United States.

RESULTS

Among allogeneic HCT recipients, the pre‐HCT Medical Outcomes Study Short Form‐36 Health Survey (SF‐36) physical component summary (PCS) scale independently predicted overall mortality (hazards ratio, 1.40 per 10‐point decrease;P<.001) and performed at least as well as currently used, non‐PRO risk indices. Survival probability estimates at 1 year for the first, second, third, and fourth quartiles of the baseline PCS were 50%, 65%, 75%, and 83%, respectively. Early post‐HCT decreases in PCS were associated with higher overall and treatment‐related mortality. When adjusted for patient variables included in the US Stem Cell Therapeutic Outcomes Database model for transplant center‐specific reporting, the SF‐36 PCS retained independent prognostic value.

CONCLUSIONS

PROs have the potential to improve prognostication in HCT. The authors recommend the routine collection of PROs before HCT, and consideration of the incorporation of PROs into risk adjustment for quality reporting.Cancer2016;122:91–98.©2015 American Cancer Society.
Progress in Synthesis of Highly Active and Stable Nickel‐Based Catalysts for Carbon Dioxide Reforming of Methane
Authors: Kawi Sibudjing , Kathiraser Yasotha , Ni Jun , Oemar Usman , Li Ziwei , Saw Eng Toon
Published: October 2015

In recent decades, rising anthropogenic greenhouse gas emissions (mainly CO2 and CH4) have increased alarm due to escalating effects of global warming. The dry carbon dioxide reforming of methane (DRM) reaction is a sustainable way to utilize these notorious greenhouse gases. This paper presents a review of recent progress in the development of nickel‐based catalysts for the DRM reaction. The enviable low cost and wide availability of nickel compared with noble metals is the main reason for persistent research efforts in optimizing the synthesis of nickel‐based catalysts. Important catalyst features for the rational design of a coke‐resistant nickel‐based nanocatalyst for the DRM reaction are also discussed. In addition, several innovative developments based on salient features for the stabilization of nickel nanocatalysts through various means (which include functionalization with precursors, synthesis by plasma treatment, stabilization/confinement on mesoporous/microporous/carbon supports, and the formation of metal oxides) are highlighted. The final part of this review covers major issues and proposed improvement strategies pertaining to the rational design of nickel‐based catalysts with high activity and stability for the DRM reaction.
Molecular Catalyst Immobilized Photocathodes for Water/Proton and Carbon Dioxide Reduction
Authors: Tian Haining
Published: October 2015

As one of the components in a tandem photoelectrochemical cell for solar‐fuel production, the photocathode carries out the reduction reaction to convert solar light and the corresponding substrate (e.g., proton and CO2) into target fuels. Immobilizing molecular catalysts onto the photocathode is a promising strategy to enhance the interfacial electron/hole‐transfer process and to improve the stability of the catalysts. Furthermore, the molecular catalysts are beneficial in improving the selectivity of the reduction reaction, particularly for CO2 reduction. On the photocathode, the binding mode of the catalysts and the arrangement between the photosensitizer and the catalyst also play crucial roles in the performance and stability of the final device. How to firmly and effectively immobilize the catalyst on the photoelectrode is now becoming a scientific question. Recent publications on molecular catalyst immobilized photocathodes are therefore surveyed.
Competitive SWIFT cluster templates enhance detection of aging changes
Authors: Rebhahn Jonathan A. , Roumanes David R. , Qi Yilin , Khan Atif , Thakar Juilee , Rosenberg Alex , Lee F. Eun‐Hyung , Quataert Sally A. , Sharma Gaurav , Mosmann Tim R.
Published: October 2015

Clustering‐based algorithms for automated analysis of flow cytometry datasets have achieved more efficient and objective analysis than manual processing. Clustering organizes flow cytometry data into subpopulations with substantially homogenous characteristics but does not directly address the important problem of identifying the salient differences in subpopulations between subjects and groups. Here, we address this problem by augmenting SWIFT—a mixture model based clustering algorithm reported previously. First, we show that SWIFT clustering using a “template” mixture model, in which all subpopulations are represented, identifies small differences in cell numbers per subpopulation between samples. Second, we demonstrate that resolution of inter‐sample differences is increased by “competition” wherein a joint model is formed by combining the mixture model templates obtained from different groups. In the joint model, clusters from individual groups compete for the assignment of cells, sharpening differences between samples, particularly differences representing subpopulation shifts that are masked under clustering with a single template model. The benefit of competition was demonstrated first with a semisynthetic dataset obtained by deliberately shifting a known subpopulation within an actual flow cytometry sample. Single templates correctly identified changes in the number of cells in the subpopulation, but only the competition method detected small changes in median fluorescence. In further validation studies, competition identified a larger number of significantly altered subpopulations between young and elderly subjects. This enrichment was specific, because competition between templates from consensus male and female samples did not improve the detection of age‐related differences. Several changes between the young and elderly identified by SWIFT template competition were consistent with known alterations in the elderly, and additional altered subpopulations were also identified. Alternative algorithms detected far fewer significantly altered clusters. Thus SWIFT template competition is a powerful approach to sharpen comparisons between selected groups in flow cytometry datasets. © 2015 The Authors. Published Wiley Periodicals Inc.
Detection of early stage changes associated with adipogenesis using Raman spectroscopy under aseptic conditions
Authors: Mitchell Adam , Ashton Lorna , Yang Xuebin B. , Goodacre Royston , Smith Alistair , Kirkham Jennifer
Published: October 2015

There is growing interest in the development of methods capable of non‐invasive characterization of stem cells prior to their use in cell‐based therapies. Raman spectroscopy has previously been used to detect biochemical changes commensurate with the osteogenic, cardiogenic, and neurogenic differentiation of stem cells. The aim of this study was to characterize the adipogenic differentiation of live adipose derived stem cells (ASCs) under aseptic conditions. ASCs were cultured in adipogenic or basal culture medium for 14 days in customized culture flasks containing quartz windows. Raman spectra were acquired every 3 days. Principal component analysis (PCA) was used to identify spectral changes in the cultures over time. Adipogenic differentiation was confirmed using quantitative reverse transcription polymerase chain reaction for the marker genes PPARγ and ADIPOQ and Oil red O staining performed. PCA demonstrated that lipid associated spectral features varied throughout ASC differentiation with the earliest detection of the lipid associated peak at 1,438 cm−1 after 3 days of induction. After 7 days of culture there were clear differences between the spectra acquired from ASCs in adipogenic or basal culture medium. No changes were observed in the spectra acquired from undifferentiated ASCs. Significant up‐regulation in the expression of both PPARγ and ADIPOQ genes (P < 0.001) was observed after 14 days of differentiation as was prominent Oil red O staining. However, the Raman sampling process resulted in weaker gene expression compared with ASCs that had not undergone Raman analysis. This study demonstrated that Raman spectroscopy can be used to detect biochemical changes associated with adipogenic differentiation in a non‐invasive and aseptic manner and that this can be achieved as early as three days into the differentiation process. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of the International Society for Advancement of Cytometry.
Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish
Authors: Montgomery Jacob E. , Wiggin Timothy D. , Rivera‐Perez Luis M. , Lillesaar Christina , Masino Mark A.
Published: October 2015

Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5‐HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5‐HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5‐HT antibody labeling and transgenic markers of tph2‐expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer‐Agduhr double‐prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2‐expressing ISNs. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 673–687, 2016
Synthesis of the Single‐Crystalline Form and First‐Principles Calculations of Photomagnetic Copper(II) Octacyanidomolybdate(IV)
Authors: Umeta Yoshikazu , Chorazy Szymon , Nakabayashi Koji , Ohkoshi Shin‐ichi
Published: October 2015

A gel crystallization technique was successfully applied in the pioneering preparation of a single‐crystalline form of the three‐dimensional copper(II) octacyanidomolybdate(IV) network, which is a photomagnetic material. This assembly crystallizes with the formula {[CuII(H2O)]2[MoIV(CN)8]}·2H2O in the tetragonal crystal system and reveals a three‐dimensional cyanido‐bridged framework constructed of five‐coordinate square‐pyramidal [CuII(H2O)(NC)4]2– complexes and [MoIV(CN)8]4– ions of square‐antiprismatic geometry. First‐principles calculations by the GGA + U method indicate that the visible‐light absorption band, crucial for the observation of a photomagnetic effect, is interpreted in terms of MoIV to CuII charge transfer, which is enabled owing to the accompanying pz → spx transition of the nitrogen atoms of the bridging cyanido ligands. The optical transitions in the visible range are anisotropic, and the most efficient light absorption along the [111] direction corresponds to the alignment of the cyanide bridges.
Hydride Abstraction and Deprotonation – an Efficient Route to Low Coordinate Phosphorus and Arsenic Species
Authors: Taylor Laurence J. , Bühl Michael , Wawrzyniak Piotr , Chalmers Brian A. , Woollins J. Derek , Slawin Alexandra M. Z. , Fuller Amy L. , Kilian Petr
Published: October 2015

Treatment of Acenap(PiPr2)(EH2) (Acenap = acenaphthene‐5,6‐diyl; 1a, E = As; 1b, E = P) with Ph3C·BF4 resulted in hydride abstraction to give [Acenap(PiPr2)(EH)][BF4] (2a, E = As; 2b, E = P). These represent the first structurally characterised phosphino/arsino‐phosphonium salts with secondary arsine/phosphine groups, as well as the first example of a Lewis base stabilised primary arsenium cation. Compounds 2a and 2b were deprotonated with NaH to afford low coordinate species Acenap(PiPr2)(E) (3a, E = As; 3b, E = P). This provides an alternative and practical synthetic pathway to the phosphanylidene‐σ4‐phosphorane 3b and provides mechanistic insight into the formation of arsanylidene‐σ4‐phosphorane 3a, indirectly supporting the hypothesis that the previously reported dehydrogenation of 1a occurs via an ionic mechanism.
Ferrocene‐Based N‐Heterocyclic Carbenes with Functionalised Benzyl Substituents
Authors: Thie Charlotte , Bruhn Clemens , Siemeling Ulrich
Published: October 2015

We describe herein N‐heterocyclic carbenes (NHCs) with a 1,1′‐ferrocenylene backbone that contain substituents at the nitrogen atoms relevant for applications in the area of metallopharmaceuticals, namely benzyl units functionalised with dimethylamino and methoxy groups at the para position. These carbenes are too unstable for isolation. They were generated from the corresponding formamidinium tetrafluoroborates by deprotonation and efficiently trapped in situ. Trapping with elemental selenium afforded the corresponding selenourea derivatives, the 77Se NMR chemical shifts of which are in accord with the comparatively high electrophilicity typical of expanded‐ring NHCs. Coordinative trapping with [{Rh(μ‐Cl)(cod)}2] (cod = cycloocta‐1,5‐diene) furnished air‐stable complexes of the type [RhCl(cod)(NHC)], the benzyl CH2 groups of which are engaged in pronounced anagostic C–H···Rh interactions, both in solution and in the solid state.
Surface Termination Effect of Boron‐Doped Diamond on the Electrochemical Oxidation of Adenosine Phosphate
Authors: Asai Kai , Ivandini Tribidasari A. , Falah Muhammad M. , Einaga Yasuaki
Published: October 2015

Electrochemical oxidation of adenosine phosphates, including adenosine 5′‐monophosphate (AMP), adenosine 5′‐diphosphate (ADP), and adenosine 5′‐triphosphate (ATP), have been studied using boron‐doped diamond (BDD) electrodes. Cyclic voltammograms in phosphate buffer solution pH 7.4 showed a typical oxidation peak at the potential of around +1.3 V (vs. Ag/AgCl) attributable to the oxidation of adenine base moiety. This peak appears at both cathodically and anodically treated BDD. However, investigation at low pH showed, whereas the oxidation peak could be well observed for the oxidation of each AMP, ADP, and ATP at cathodically treated BDD, it was only found for the oxidation of AMP at anodically‐treted BDD electrodes. Linear calibration curve can be achieved in the concentration range of 20 to 200 μM with an average detection limit of 2 μM (S/N=3). Furthermore, cathodic treatment has demonstrated its ability to maintain the electrode surface from biofouling, resulting in the excellent stability of current responses.
Electrochemical Determination of Bisphenol A Using a Molecularly Imprinted Chitosan‐acetylene Black Composite Film Modified Glassy Carbon Electrode
Authors: Tan Yuanbin , Jin Jing , Zhang Shenghui , Shi Zhen , Wang Jinshou , Zhang Jingdong , Pu Wenhong , Yang Changzhu
Published: October 2015

In this study, a simple electrochemical sensor based on glassy carbon electrode (GCE) modified with molecularly imprinted chitosan film doping with acetylene black (AB) has been developed for the determination of bisphenol A (BPA). Several important parameters controlling the performance of the sensor are investigated and optimised. Two good linear relationships between the oxidation peak current and BPA concentration are obtained in the ranges from 0.005 to 0.20 μM and 0.50 to 10.00 μM with a detection limit of 2 nM (S/N=3). Meanwhile, the fabricated sensor shows good selectivity and high sensitivity. The construction of this sensor is relatively simple and provided a rapid and economical electrochemical method for the determination of BPA. The sensor is successfully employed to detect BPA in drinking water samples.
Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain‐injured patients
Authors: Drijkoningen David , Leunissen Inge , Caeyenberghs Karen , Hoogkamer Wouter , Sunaert Stefan , Duysens Jacques , Swinnen Stephan P
Published: October 2015

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum‐optimized voxel‐based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I–IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. Hum Brain Mapp 36:4897–4909, 2015. © 2015 Wiley Periodicals, Inc.
Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment
Authors: Denier Niklaus , Schmidt André , Gerber Hana , Vogel Marc , Huber Christian G. , Lang Undine E. , Riecher‐Rossler Anita , Wiesbeck Gerhard A. , Radue Ernst‐Wilhelm , Walter Marc , Borgwardt Stefan
Published: October 2015

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross‐over, double‐blind, vehicle‐controlled study, 29 heroin‐maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting‐state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed‐based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin‐associated increase in fALFF was mainly dominated by slow‐4 (0.027–0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. Hum Brain Mapp 36:5287–5300, 2015. © 2015 Wiley Periodicals, Inc.
Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach
Authors: Burden Natalie , Benstead Rachel , Clook Mark , Doyle Ian , Edwards Peter , Maynard Samuel K , Ryder Kathryn , Sheahan Dave , Whale Graham , van Egmond Roger , Wheeler James R , Hutchinson Thomas H
Published: October 2015

The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals—the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417–421. © 2015 SETAC

Key Points

There is much scope to advance the application of the 3Rs (replacement, refinement, and reduction in the use of animals) in regulatory ecotoxicity testing. A working group of experts in this field across academia, government organizations, and industry have identified the key drivers in which there are high demands on vertebrate testing, and have explored opportunities to address them. The group proposes a pragmatic strategy whereby key short-, medium-, and long-term goals could be achieved to enable realistic progress in advancing the application of the 3Rs in this area. This evaluation will help to inform the development of high-impact projects that facilitate the uptake of novel 3Rs approaches relevant to regulatory ecotoxicology.
Biodistribution and toxicity of spherical aluminum oxide nanoparticles
Authors: Park Eun‐Jung , Lee Gwang‐Hee , Yoon Cheolho , Jeong Uiseok , Kim Younghun , Cho Myung‐Haing , Kim Dong‐Wan
Published: October 2015

With the rapid development of the nano‐industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ‐aluminum oxide hydroxide nanoparticles (γ‐AlOHNPs), γ‐ and α‐AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ‐AlONPs, followed by the α‐AlONPs and γ‐AlOHNPs. In mice, γ‐AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)‐8 were observed in the blood of mice dosed with γ‐AlOHNPs (10 mg kg−1). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS‐2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK‐293 (kidney). The results showed γ‐AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ‐AlOHNPs, but not γ‐AlONPs or α‐AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ‐AlOHNPs compared with γ‐AlONPs and α‐AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs. Copyright © 2015 John Wiley & Sons, Ltd.
Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children ≤2 Years of Age: A Comparison of the Predictive Performance of 4 Allometric Models
Authors: Mahmood Iftekhar
Published: October 2015

The objective of this study was to evaluate the predictive performance of 4 allometric models to predict clearance in pediatric ages ranging from premature neonates to children ≤2 years of age. Four allometric models were used to predict clearances of 28 drugs in children from preterm neonates to 2 years of age (n = 564). The 4 models are (1) basal metabolic rate–dependent model; (2) age‐dependent exponent model; (3) an allometric model based on kidney and liver weights as well as kidney and liver blood flow; and (4) an allometric model based on a fixed exponent of 0.75. The predictive performance of these models was evaluated by comparing the predicted clearance of the studied drugs with the observed clearance in an individual child. The results of the study indicated that the 3 new proposed models predicted the mean clearance of the drugs with reasonable accuracy (≤50% prediction error). On the other hand, the exponent of 0.75 produced substantial prediction error. Predicted individual clearance values were ≥50% in approximately 30% of the children by the proposed 3 methods and 73% by exponent 0.75. The 3 new proposed allometric models can predict mean clearances of drugs in children from premature neonates to ≤2 years of age with reasonable accuracy and are of practical value during pediatric drug development.
Perceived social impact, social worth, and job performance: Mediation by motivation
Authors: Castanheira Filipa
Published: October 2015

This study was designed to test the relationship between perceived social impact, social worth, supervisor‐rated job performance (1 month later), and mediating effects by commitment to customers and work engagement. The hypotheses were tested with structural equation modeling analysis in a field study with 370 customer‐service employees from bank, retail, and sales positions. Results confirm that perceived social impact is associated with better job performance and that this relationship is mediated by work engagement. Furthermore, results support a second mediating mechanism in which perceived social impact and social worth are associated with engagement through affective commitment to customers. Finally, it was found that engaged employees are rated as better performers by supervisors 1 month later. This study supports the motivational approach to performance and highlights the role that interactions with customers may play in motivating service employees. Practical implications are discussed by highlighting the need to consider the social dynamics in service contexts. Copyright © 2015 John Wiley & Sons, Ltd.
In vitro screening of natural feed additives from crustaceans, diatoms, seaweeds and plant extracts to manipulate rumen fermentation
Authors: Belanche Alejandro , Ramos‐Morales Eva , Newbold C Jamie
Published: October 2015

BACKGROUND

Eight natural products from animal, unicellular algae, brown seaweed and plant origins were chosen according to their theoretical antimicrobial activity: Diatomaceous earths (DE), insoluble chitosan (ICHI), soluble chitosan (CHI), seaweed meal (SWM), Ascophyllum nodosum (ASC), Laminaria digitata (LAM), neem oil (NOIL) and an ivy fruit extract rich in saponins (IVY). Dose–response incubations were conducted to determine their effect on rumen fermentation pattern and gas production, while their anti‐protozoal activity was tested using 14C‐labelled bacteria.

RESULTS

DE, SWM, NOIL and ICHI had very small effects on rumen function when used at inclusion rate up to 2 g L−1. ASC had anti‐protozoal effects (up to −23%) promoting a decrease in gas production and methanogenesis (−15%). LAM increased VFA production (+7%) and shifted from butyrate to acetate. CHI also shifted fermentation towards propionate production and lower methane (−23%) and protozoal activity (−56%). IVY decreased protozoal activity (−39%) and ammonia concentration (−56%), as well as increased feed fermentation (+11% VFA concentration) and shifted from acetate to propionate production.

CONCLUSIONS

ASC, LAM, CHI and IVY showed promising potential in vitro as feed additives to improve rumen function, thus more research is needed to investigate their mode of action in the rumen microbial ecosystem. © 2015 Society of Chemical Industry
Long‐term intake of white tea prevents oxidative damage caused by adriamycin in kidney of rats
Authors: Espinosa Cristóbal , López‐Jiménez José A , Pérez‐Llamas Francisca , Guardiola Francisco A , Esteban Maria A , Arnao Marino B , Zamora Salvador
Published: October 2015

BACKGROUND

White tea infusion (Camelia sinensis) has antioxidants properties. The infusion contains polyphenols that have been proposed to induce antioxidant response element (ARE) response via nuclear factor E2‐related factor 2 (NRF2). Adriamycin (ADR) has antitumour properties and oxidative effects. Oxidative stress is related to a variety of kidney diseases. Prevention of the oxidative stress through long‐term intake of white tea and the study of the molecular mechanisms involved in protection could be of great interest. Rats were given distilled water, 0.015 or 0.045 g of solid white tea extract kg−1 body weight for 12 months. Animals received an injection of ADR. In kidney, oxidative stress parameters were measured, the expressions of nuclear factor E2‐related factor 2 gene (Nrf2), and detoxifying and antioxidants genes were analysed, and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured.

RESULTS

ADR administration increased oxidative parameters and decreased the antioxidant activity; significantly increased the expression of analysed genes and the activity of CAT and SOD and decreased GR activity. The highest white tea dose protected redox status and inhibited ARE response.

CONCLUSION

Long‐term intake of white tea protected kidney against the oxidative stress. ADR activated the ARE response but in animals treated with the highest dose of white tea, this response was inhibited, probably for antioxidant protection. © 2015 Society of Chemical Industry
Mapping the potential beverage quality of coffee produced in the Zona da Mata, Minas Gerais, Brazil
Authors: Silva Samuel de Assis , de Queiroz Daniel Marçal , Ferreira Williams Pinto Marques , Corrêa Paulo Cesar , Rufino José Luis dos Santos
Published: October 2015

BACKGROUND

Detailed knowledge of coffee production systems enables optimization of crop management, harvesting and post‐harvest techniques. In this study, coffee quality is mapped as a function of coffee variety, altitude and terrain aspect attributes. The work was performed in the Zona da Mata, Minas Gerais, Brazil.

RESULTS

A large range of coffee quality grades was observed for the Red Catuai variety. For the Yellow Catuai variety, no quality grades lower than 70 were observed. Regarding the terrain aspect, samples from the southeast‐facing slope (SEFS) and the northwest‐facing slope (NWFS) exhibited distinct behaviors. The SEFS samples had a greater range of quality grades than did the NWFS samples. The highest grade was obtained from an NWFS point. The lowest quality values and the largest range of grades were observed at lower altitudes. The extracts from the highest‐altitude samples did not produce any low‐quality coffee.

CONCLUSIONS

The production site's position and altitude are the primary variables that influenced the coffee quality. The study area has micro‐regions with grades ranging from 80 to 94. These areas have the potential for producing specialty coffees. © 2015 Society of Chemical Industry
Biliary strictures and recurrence after liver transplantation for primary sclerosing cholangitis: A retrospective multicenter analysis
Authors: Hildebrand Tatiana , Pannicke Nadine , Dechene Alexander , Gotthardt Daniel N. , Kirchner Gabriele , Reiter Florian P. , Sterneck Martina , Herzer Kerstin , Lenzen Henrike , Rupp Christian , Barg‐Hock Hannelore , de Leuw Philipp , Teufel Andreas , Zimmer Vincent , Lammert Frank , Sarrazin Christoph , Spengler Ulrich , Rust Christian , Manns Michael P. , Strassburg Christian P. , Schramm Christoph , Weismüller Tobias J. ,   for the German PSC Study Group
Published: October 2015

Liver transplantation (LT) is the only definitive treatment for patients with end‐stage liver disease due to primary sclerosing cholangitis (PSC), but a high rate of biliary strictures (BSs) and of recurrent primary sclerosing cholangitis (recPSC) has been reported. In this multicenter study, we analyzed a large patient cohort with a long follow‐up in order to evaluate the incidence of BS and recPSC, to assess the impact on survival after LT, and to identify risk factors. We collected clinical, surgical, and laboratory data and records on inflammatory bowel disease (IBD), immunosuppression, recipient and graft outcome, and biliary complications (based on cholangiography and histology) of all patients who underwent LT for PSC in 10 German transplant centers between January 1990 and December 2006; 335 patients (68.4% men; mean age, 38.9 years; 73.5% with IBD) underwent transplantation 8.8 years after PSC diagnosis with follow‐up for 98.8 months. The 1‐, 5‐, and 10‐year recipient and graft survival was 90.7%, 84.8%, 79.4% and 79.1%, 69.0%, 62.4%, respectively. BS was diagnosed in 36.1% after a mean time of 3.9 years, and recPSC was diagnosed in 20.3% after 4.6 years. Both entities had a significant impact on longterm graft and recipient survival. Independent risk factors for BS were donor age, ulcerative colitis, chronic ductopenic rejection, bilirubin, and international normalized ratio (INR) at LT. Independent risk factors for recPSC were donor age, IBD, and INR at LT. These variables were able to categorize patients into risk groups for BS and recPSC. In conclusion, BS and recPSC affect longterm graft and patient survival after LT for PSC. Donor age, IBD, and INR at LT are independent risk factors for BS and recPSC and allow for risk estimation depending on the recipient‐donor constellation. Liver Transpl 22:42‐52, 2016. © 2015 AASLD.
Production of Immunoabsorbent Nanoparticles by Displaying Single‐Domain Protein A on Potato Virus X
Authors: Uhde‐Holzem Kerstin , McBurney Michael , Tiu Brylee David B. , Advincula Rigoberto C. , Fischer Rainer , Commandeur Ulrich , Steinmetz Nicole F.
Published: October 2015

The combination of antibodies with nanoparticles provides wide‐ranging applications in biosensing. While several covalent presentation strategies have been established, there is need for alternative, non‐covalent methods to provide a routine for scalable nanomanufacturing. We report the multivalent presentation of the B domain of Staphylococcus aureus protein A (SpAB) on potato virus X (PVX) nanoparticles. Three different synthetic strategies were used to obtain chimeric PVXSpAB filaments. The protein A fragments displayed on the surface of all three PVX chimeras remained fully functional as an immunoabsorbent for antibody capture enabling biosensing. The new biomaterials presented could find applications as diagnostic tools for biomedical or environmental monitoring.
High Strength Self‐Healing Magnetic Elastomers With Shape Memory Effect
Authors: Feng Xian Qi , Zhang Gong Zheng , Bai Quan Ming , Jiang Hao Yang , Xu Bo , Li Huan Jun
Published: October 2015

Development of self‐healing and shape memory elastomers is important for artificial smart materials. Here, a novel shape memory magnetic elastomer with high mechanical strength consisting of conventional polymer and Fe3O4 nanoparticles is reported. The elastomer exhibit superparamagnetism, and superior self‐healing performance at elevated temperature. The tensile strength of the healed elastomer can be up to 12.0 MPa, and almost equal to that of virginal sample. These materials are capable of remote controlling in shape memory process and actuating behavior, and can be used in many applications, ranging from wireless‐controller to actuator or biomedical devices, and other remote shape memory systems.
Nondestructive Quantification of Local Plasticizer Concentration in PVC by 1H NMR Relaxometry
Authors: Adams Alina , Kwamen Rance , Woldt Benjamin , Graß Michael
Published: October 2015

The properties of plasticized poly(vinyl chloride) (PVC) , one of the most important polymers today, are strongly dictated by the concentration of plasticizer. Yet, it has been impossible to quantify this concentration at different positions inside a PVC product without its destruction because of a lack of suitable analytical methods. Thus, this paper introduces a simple, fast, and efficient way to determine truly nondestructively the concentration of plasticizer in PVC by single‐sided nuclear magnetic resonance (NMR). With the help of correlation curves between the concentration of plasticizer inside nonaged PVC samples and the corresponding volume‐averaged NMR parameters, single‐sided NMR allows the quantification of the local concentration of plasticizer in aged PVC plates at different depths by spatially resolved relaxation measurements. The presented approach represents a fundamental step toward in situ characterization of plasticized PVC.

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Poly(ADP‐ribosyl)ation is involved in pro‐survival autophagy in porcine blastocysts
Authors: Lee Hye Ran , Gupta Mukesh Kumar , Kim Duk Hyeon , Hwang Jeong Ho , Kwon Bumsup , Lee Hoon Taek
Published: October 2015

Poly(ADP‐ribosyl)ation (PARylation) prevents apoptosis through its involvement in pro‐survival autophagy in cultured cells; whether or not the same is true for pre‐implantation embryos has not yet been documented. In this study, we investigated the participation of PARylation and autophagy in in vitro porcine pre‐implantation embryo development. The transcript levels of autophagy‐related genes and poly(ADP‐ribose) polymerase 1 (PARP1), an enzyme required for PARylation, were transiently up‐regulated by fertilization, decreased at the late 1‐cell stage, and maintained until the blastocyst stage. LC3, a marker of autophagosomes, and poly(ADP‐ribose) (PAR) polymer were present in all stages of pre‐implantation development. Exposure of embryos to 3‐methyladenine, an autophagy inhibitor, or 3‐aminobenzamide, a PARP inhibitor, suppressed the development of blastocysts. Pharmacological inhibition of PARylation further suppressed pro‐survival autophagy by decreasing the expression of autophagy‐related genes (ATG5, BECLIN1, and LC3) and decreasing LC3 protein abundance while increasing the rate of apoptosis in blastocysts. Deficiency in autophagy also induced abnormal accumulation of SQSTM1/p62 aggregates in porcine blastocysts. Collectively, these data suggest that PARylation is involved in selective autophagic degradation of ubiquitinated proteins, functioning in a pro‐survival role, in porcine in vitro‐produced embryos. These pro‐survival regulatory mechanisms may be important for the control of embryo quality. Mol. Reprod. Dev. 83: 37–49, 2016. © 2015 Wiley Periodicals, Inc.
Endoneurial edema in sural nerve may indicate recent onset inflammatory neuropathy
Authors: Üçeyler Nurcan , Necula Gina , Wagemann Esther , Toyka Klaus V. , Sommer Claudia
Published: October 2015

Introduction: Sural nerve biopsy is an important means of establishing the diagnosis of inflammatory neuropathies. We investigated the diagnostic value of endoneurial edema. Methods: Diagnostic sural nerve biopsies from 42 patients with inflammatory and 28 patients with noninflammatory neuropathies were re‐evaluated for the presence of endoneurial edema. Edema was assessed on hematoxylin‐eosin stained paraffin and frozen sections and on azure II‐methylene blue stained semithin sections. We determined the area of endoneurial edema on digitized images in relation to the entire endoneurial area of each fascicle. Results: Edema was more extensive in neuropathies with short disease duration (≤12 months) as compared to long duration (>12 months; P < 0.01). Edema in inflammatory neuropathies of ≤12 months duration covered a larger area than in noninflammatory neuropathies (P < 0.01), and the extent of edema correlated negatively with disease duration (P < 0.05). Conclusions: Endoneurial edema may be a useful additional disease marker in inflammatory neuropathies of recent onset. Muscle Nerve 53: 705–710, 2016
Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks
Authors: Kannurpatti Sridhar S. , Sanganahalli Basavaraju G. , Herman Peter , Hyder Fahmeed
Published: October 2015

Mitochondrial Ca2+ uptake influences both brain energy metabolism and neural signaling. Given that brain mitochondrial organelles are distributed in relation to vascular density, which varies considerably across brain regions, we hypothesized different physiological impacts of mitochondrial Ca2+ uptake across brain regions. We tested the hypothesis by monitoring brain “intrinsic activity” derived from the resting state functional MRI (fMRI) blood oxygen level dependent (BOLD) fluctuations in different functional networks spanning the somatosensory cortex, caudate putamen, hippocampus and thalamus, in normal and perturbed mitochondrial Ca2+ uptake states. In anesthetized rats at 11.7 T, mitochondrial Ca2+ uptake was inhibited or enhanced respectively by treatments with Ru360 or kaempferol. Surprisingly, mitochondrial Ca2+ uptake inhibition by Ru360 and enhancement by kaempferol led to similar dose‐dependent decreases in brain‐wide intrinsic activities in both the frequency domain (spectral amplitude) and temporal domain (resting state functional connectivity; RSFC). The fact that there were similar dose‐dependent decreases in the frequency and temporal domains of the resting state fMRI‐BOLD fluctuations during mitochondrial Ca2+ uptake inhibition or enhancement indicated that mitochondrial Ca2+ uptake and its homeostasis may strongly influence the brain's functional organization at rest. Interestingly, the resting state fMRI‐derived intrinsic activities in the caudate putamen and thalamic regions saturated much faster with increasing dosage of either drug treatment than the drug‐induced trends observed in cortical and hippocampal regions. Regional differences in how the spectral amplitude and RSFC changed with treatment indicate distinct mitochondrion‐mediated spontaneous neuronal activity coupling within the various RSFC networks determined by resting state fMRI. Copyright © 2015 John Wiley & Sons, Ltd.