bluuebunny/crossref_metadata_2025 huggingface dataset:
EphA4‐deleted microenvironment regulates cancer development and leukemoid reaction of the isografted 4T1 murine breast cancer via reduction of an IGF1 signal
Authors: Jing Xuefeng , Sonoki Takashi , Miyajima Masayasu , Sawada Takahiro , Terada Nanako , Takemura Shigeki , Sakaguchi Kazushige
Published: February 2016

EphA4 belongs to the largest family of receptor tyrosine kinases (RTKs). Although EphA4 is highly expressed in the central nervous system, EphA4 has also been implicated in cancer progression. Most of the studies focus on the expression and function in tumor cells. It is unknown whether EphA4‐deleted microenvironment affects tumor progression. Some of cancers in animals and humans, such as 4T1 cancer cells, are known to produce a large amount of granulocyte colony‐stimulating factors (G‐CSF/Csf3) which can stimulate myeloproliferation, such as myeloid‐derived suppressor cells (MDSCs) leading to a poor recipient prognosis. We isografted 4T1 breast cancer cells into both EphA4‐knockout and control wild‐type female littermate mice. The results showed that the EphA4‐deleted host could inhibit primary tumor growth and tumor metastasis mainly by decreasing the amount of IGF1 synthesis in the circulation and locally tissues. The EphA4‐deleted microenvironment and delayed tumor development reduced the production of G‐CSF resulting in the decrease of splenomegaly and leukemoid reaction including MDSCs, which in turn inhibit the tumor progression. This inhibition can be reversed by supplying the mice with IGF1. However, an excess of IGF1 supply over demand to the control mice could not further accelerate the tumor growth and metastasis. A better understanding and re‐evaluation of the main role of IGF1 in regulating tumor progression could further enhance our cognition of the tumor development niche. Our findings demonstrated that EphA4‐deleted microenvironment impairs tumor‐supporting conditions. Conclusion: Host EphA4 expression regulates cancer development mainly via EphA4‐mediated IGF1 synthesis signal. Thus, targeting this signaling pathway may provide a potential therapeutic option for cancer treatment.
The prognostic significance of monoclonal immunoglobulin gene rearrangement in conjunction with histologic B‐cell aggregates in the bone marrow of patients with diffuse large B‐cell lymphoma
Authors: Cho Yoon Ah , Yang Woo Ick , Song Jae‐Woo , Min Yoo Hong , Yoon Sun Och
Published: February 2016

Bone marrow involvement (BMI) is a well‐known poor prognostic factor in patients with diffuse large B‐cell lymphoma (DLBCL). This study robustly investigated the significance of monoclonal immunoglobulin gene rearrangement combined with histologic B‐cell aggregates in bone marrow (BM) in the detection of a poor prognostic group. Pretreatment BM samples of 394 DLBCL patients were analyzed via the immunoglobulin gene rearrangement study and the microscopic examination. Monoclonal immunoglobulin gene rearrangement was detected in 25.4% of cases. Histologic B‐cell aggregates with the features of large B‐cell lymphoma aggregates, small cell B‐cell lymphoma aggregates, or B‐cell aggregates of unknown biological potential were observed in 12% of cases (6.9%, 1.3%, and 3.8%, respectively). Histologic B‐cell aggregates were more associated with monoclonality than polyclonality. Cases with both monoclonality and histologic B‐cell aggregates demonstrated close association with poor prognostic factors such as a higher International Prognostic Index score and showed an inferior overall survival rate when compared to cases with only monoclonality or only histologic B‐cell aggregates. From the findings, a combination of monoclonality and histologic B‐cell aggregates within the bone marrow was highly associated with poor prognosis and could be used to determine high‐risk DLBLC patients with greater sensitivity and specificity than conventional microscopic examination or immunoglobulin gene rearrangement study alone.
Long‐term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers
Authors: Søgaard Kirstine K. , Farkas Dóra K , Pedersen Lars , Lund Jennifer L. , Thomsen Reimar W. , Sørensen Henrik T.
Published: February 2016

Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994–2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori‐related) and gastric ulcers (dominantly lifestyle‐related) compared with the general population. We started follow‐up 1‐year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1–5‐year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31–1.44) and 1.30 (95% CI: 1.23–1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking‐ and alcohol‐related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized.
Mixed‐methods Evaluation of the Good Behaviour Game in English Primary Schools
Authors: Coombes Lindsey , Chan Gail , Allen Debby , Foxcroft DAVID R.
Published: February 2016

Inclusivity of all children in education and within educational settings is an important value and goal. Yet, where settings and practices are not oriented for inclusivity and engagement, some children can struggle with academic tasks and are often marginalised and exhibit disruptive behaviours. The study reported here addresses the social nature of school as a community for learning through a mixed‐methods concurrent triangulation evaluation of the implementation of the Good Behaviour Game (GBG) in six primary (elementary) schools with 10 classes and 222 children in Oxfordshire, England. The Teacher Observation of Classroom Adaptations ‐ Revised (TOCA‐R) was administered in individual interviews with class teachers. Additionally, individual semi‐structured interviews were conducted with teachers, coaches and head teachers (n = 22). In a pre–post design, improvements in child adaptation were observed on all TOCA‐R subscales. In an integrative analysis that brought together quantitative and qualitative findings, pupil improvement was identified in three major areas: inclusion and social participation, behaviour, and concentration. Interview results also highlighted the substantial practical challenges associated with implementing and using the GBG in schools in the UK. Overall, the results of this study support the idea that social relationships within the school community, between pupils and between pupils and teachers, provide an important context for learning and social development. Copyright © 2016 John Wiley & Sons, Ltd.
Dehalogenation Activity of Selected Fungi Toward δ‐Iodo‐γ‐Lactone Derived from trans,trans‐Farnesol
Authors: Gliszczyńska Anna , Gładkowski Witold , Świtalska Marta , Wietrzyk Joanna , Szumny Antoni , Gębarowska Elżbieta , Wawrzeńczyk Czesław
Published: February 2016

Time‐course of biotransformation of racemic trans‐4‐((E)‐4′,8′‐dimethylnona‐3′,7′‐dien‐1‐yl)‐5‐iodomethyl‐4‐methyldihydrofuran‐2‐one (1) in fungal and yeast cultures was investigated. In these conditions, the substrate 1 was enantioselectively dehalogenated yielding 4‐((E)‐4′,8′‐dimethylnona‐3′,7′‐dien‐1‐yl)‐4‐methyl‐5‐methylenedihydrofuran‐2‐one (2) and its structure was established based on the spectroscopic data. The most effective biocatalyst used was Didymosphaeria igniaria, which catalyzed the process with highest rate and enantioselectivity (ee of product = 76%). The antiproliferative activity of δ‐iodo‐γ‐lactone 1, product of its biotransformation 2, and starting substrate (farnesol) were evaluated toward two cancer cell lines: A549 (human lung adenocarcinoma) and HL‐60 (human promyelocytic leukemia).
Supramolecular Photoinduced Electron Transfer between a Redox‐Active Hexanuclear Metal–Organic Cylinder and an Encapsulated Ruthenium(II) Complex
Authors: Yang Lu , He Cheng , Liu Xin , Zhang Jing , Sun Hui , Guo Huimin
Published: February 2016

By using redox‐active nickel(II) ions as the connect nodes, a hexanuclear metal–organic cylinder (Ni‐YL) was achieved through self‐assembly with a large cavity and an opening windows capable to accommodate guest molecules. The suitable cavity of Ni‐YL provides an opportunity to encapsulate the anionic ruthenium bipyridine derivative [Ru(dcbpy)3] (dcbpy=2,2′‐bipyridine‐4,4′‐dicarboxylic acid) as the photosensitizer for light‐driven reactions. The host–guest behavior between Ni‐YL and [Ru(dcbpy)3] was investigated by mass spectrometry, NMR spectroscopy, and computational studies, revealing an effective binding of the guest [Ru(dcbpy)3] within the cavity of Ni‐YL. Optical experiments suggested a pseudo‐intramolecular photoinduced electron transfer (PET) process between the [Ru(dcbpy)3] and the host Ni‐YL, leading to an efficient light‐driven hydrogen production based on this system. Control experiments with a mononuclear Ni complex as a reference photocatalyst and the inactive [Fe(dcbpy)3] as an inhibitor for comparison were also performed to confirm such a supramolecular photocatalysis process.
Diastereoselective Radical Hydroacylation of Alkylidenemalonates with Aliphatic Aldehydes Initiated by Photolysis of Hypervalent Iodine(III) Reagents
Authors: Selvakumar Sermadurai , Sakamoto Ryu , Maruoka Keiji
Published: February 2016

Diastereoselective radical hydroacylation of chiral alkylidenemalonates with aliphatic aldehydes is realized by the combination of a hypervalent iodine(III) reagent and UV‐light irradiation. The reaction is initiated by the photolysis of hypervalent iodine(III) reagents under mild, metal‐free conditions, and is the first example of diastereoselective addition of acyl radicals to olefins to afford chiral ketones in a highly stereoselective fashion. The obtained optically active ketones are useful chiral synthons, as exemplified by the short formal synthesis of (−)‐methyleneolactocin.
Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives
Authors: Łukowska‐Chojnacka Edyta , Staniszewska Monika , Bondaryk Małgorzata , Maurin Jan K. , Bretner Maria
Published: February 2016

A series of new N‐substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase‐catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347–354, 2016. © 2016 Wiley Periodicals, Inc.
Boron Nitride Nanotubes and Layer‐By‐Layer Polyelectrolyte Coating for Yeast Cell Surface Engineering
Authors: Emanet Melis , Fakhrullin Rawil , Çulha Mustafa
Published: February 2016

The application of living microbial cells as molecular engines for a variety of biotechnological applications including cell‐based biosensing is an ongoing research effort. However, there are significant difficulties to overcome such as the fragile structures of microbial cells and the weak efficiency of developed systems for detecting toxic agents in the environment. In this Communication, we demonstrate the interfacing of hydroxylated boron nitride nanotubes (BNNT‐OHs) with live yeast cell surfaces. BNNT‐OHs were incorporated with polyelectrolytes (PEs) using layer‐by‐layer deposition onto live Saccharomyces cerevisiae cells. The PE‐ and BNNT‐OH‐coated yeast was characterized using spectroscopic and imaging techniques (dynamic light scattering, FTIR, and SEM). Importantly, BNNT‐OH‐coated yeast cells were viable after the surface modification with nanotubes. We believe that BNNT‐OHs‐functionalized yeast will find numerous applications in biotechnology.
Stabilization over frequency‐selective channels subject to transmission delay and signal‐to‐noise ratio limitations
Authors: Barforooshan Mohsen , Mahboobi Esfanjani Reza
Published: February 2016

The stabilizability problem of an unstable non‐minimum phase (NMP) plant, controlled over a signal‐to‐noise ratio (SNR) constrained channel with transmission delay, is investigated in this article. A dynamical output feedback controller is used to stabilize the single‐input single‐output plant where the control data are exchanged via an NMP bandwidth‐limited communication medium. For the first time, a novel description of SNR is used to solve stabilizability problem when the NMP channel imposes a constant delay on transmitted data. It is demonstrated that the presence of time‐delay in the channel model as well as its NMP zeros increases the value of SNR needed for stabilizability of the closed‐loop system. The main results are illustrated and discussed through numerical examples. © 2016 Wiley Periodicals, Inc. Complexity 21: 557–565, 2016
Bang‐bang cycle‐slip detector improves jitter‐tolerance in SONET PLL/DLL CDR
Authors: Guinea J. A.
Published: February 2016

The phase‐locked loop circuit (PLL) cycle‐slips (CS) phenomenon is a problem in two‐level baseband clock and data recovery (CDR) data‐synchronization. A singular example is that of a CDR synchronizer that uses a PLL in cascaded with delay‐lock‐loop (P/DLL) architecture. The CS issue is most evident when testing jitter‐tolerance to sine‐modulated jitter, particularly for sine‐modulated jitter‐frequencies near the PLL bandwidth. Reuse of a bang‐bang frequency‐detector, already on board of reference‐less CDRs, does CS detection and provides for suppression producing a clean demodulation. In the cascaded‐DLL of Rhee's P/DLL [1], this CS‐suppressed PLL‐clock assures proper DLL operation to broadband the jitter‐tolerance recommendation of the synchronous optical network (SONET). Copyright © 2016 John Wiley & Sons, Ltd.
Ten principles from evolutionary ecology essential for effective marine conservation
Authors: Kindsvater Holly K. , Mangel Marc , Reynolds John D. , Dulvy Nicholas K.
Published: February 2016

Sustainably managing marine species is crucial for the future health of the human population. Yet there are diverse perspectives concerning which species can be exploited sustainably, and how best to do so. Motivated by recent debates in the published literature over marine conservation challenges, we review ten principles connecting life‐history traits, population growth rate, and density‐dependent population regulation. We introduce a framework for categorizing life histories, POSE (Precocial–Opportunistic–Survivor–Episodic), which illustrates how a species’ life‐history traits determine a population's compensatory capacity. We show why considering the evolutionary context that has shaped life histories is crucial to sustainable management. We then review recent work that connects our framework to specific opportunities where the life‐history traits of marine species can be used to improve current conservation practices.
Energy partitioning and its controls over a heterogeneous semi‐arid shrubland ecosystem in the Lake Naivasha Basin, Kenya
Authors: Odongo Vincent Omondi , van der Tol Christiaan , Becht Robert , Hoedjes Joost C. B. , Ghimire Chandra Prasad , Su Zhongbo
Published: February 2016

This paper reports on the energy balance and partitioning analysed from 3‐year micrometeorological flux measurements of energy and water fluxes over a heterogeneous semi‐arid shrubland ecosystem in Lake Naivasha basin. The measurements enabled the characterization of the seasonal and interannual variability of the energy and water fluxes of the ecosystem covering two wet years (2012 and 2013) and one drought year (2014). On an annual scale, more than 60% of net radiation (Rn) was partitioned as latent (LE) and sensible (H) energy flux, with the latter being the larger consumer of Rn (~34%) and dominant for most months. The transition from H to LE dominance occurred from early noon to late afternoon in the wettest months of April and May. The residual energy balance closure term (C) accounted for between 25 and 40% of the Rn with the imbalance tending to be highest during periods of high insolation. Annual evapotranspiration was estimated at 873 mm, 632 mm and 537 mm for year 2012, 2013 and 2014 respectively. This accounted for at least 80% of the annual precipitation received for the respective years. Surface conductance (gs) scaled significantly with leaf expansion and Priestley–Taylor α coefficient, but was limited during periods of drought because of inadequate soil moisture suggesting that, change in LE was paralleled by changes in green leaf area index. Low values of decoupling coefficient (Ω) during these periods indicated that evapotranspiration was strongly controlled by gs and vapour pressure deficit (VPD). However, under non‐limiting moisture conditions evapotranspiration was decoupled from the atmosphere. This suggested that during the dry seasons and periods of prolonged drought, a lack of moisture in combination with high VPD leads to significant decreases in stomatal conductance that eventually limits partitioning of available energy into LE in the semi‐arid ecosystem part of the Lake Naivasha basin. However, during wet season these factors are non‐limiting and radiation is the dominant control of energy partitioning into LE in the ecosystem. The coupling and decoupling pattern provide insights towards formulating models that quantify evapotranspiration for ecosystems that experience seasonal shifts in controlling factors. Copyright © 2016 John Wiley & Sons, Ltd.
Unknown Camphor: Regioselective Rearrangement under Acylation in a CF3SO3H/(CF3CO)2O System
Authors: Kovalev Vladimir , Shokova Elvira , Chertkov Vyacheslav , Tafeenko Victor
Published: February 2016

The utility of camphor in the chemical sciences is vast and well documented, yet the creation of camphor‐derived potentially useful bicyclo[2.2.1]heptane scaffolds still remains one of the great challenges of synthetic organic chemistry. Herein, we show that CF3SO3H/(CF3CO)2O‐mediated acylation of camphor with benzoic acids is accompanied by a cascade of alkyl and hydride shifts and opens access to a new type of polyfunctional isoborneol. In case of salicylic acids, camphor feels the presence of the ortho‐hydroxy group in the aryl moiety, the influence of which provokes cleavage of the bicycloheptane skeleton to lead to monocyclic carvenone.
Prevotella denticola Lipopolysaccharide from a Cystic Fibrosis Isolate Possesses a Unique Chemical Structure
Authors: Di Lorenzo Flaviana , Silipo Alba , Matier Thomas , Hanuszkiewicz Anna , Elborn J. Stuart , Lanzetta Rosa , Sturiale Luisa , Scamporrino Andrea , Garozzo Domenico , Valvano Miguel A. , Tunney Michael M. , Molinaro Antonio
Published: February 2016

We report the first complete structural characterization of the lipopolysaccharide (LPS) from a cystic fibrosis (CF) clinical isolate of Prevotella denticola (B003V1S1X). Chemical, spectroscopic, and spectrometric analyses revealed a unique rough‐type LPS (LOS) structure. The structure has a highly negatively charged heptasaccharide core region containing hexoses, with the first two sugars, 3‐deoxy‐D‐manno‐oct‐2‐ulosonic acid (Kdo) and mannose, highly phosphorylated. Furthermore, the lipid A moiety has the typical structure for the genus Prevotella, and was also highly phosphorylated.
Fe‐Cu metastable material as a mesoporous layer for dye‐sensitized solar cells
Authors: Alami Abdul Hai , Abed Jehad , Almheiri Meera , Alketbi Afra , Aokal Camilia
Published: February 2016

This study investigates the performance of dye‐sensitized solar cells constructed with a Fe‐Cu metastable material as the mesoporous layer on which a natural organic dye is applied. The synthesis of the Fe‐Cu material is done via a high throughput process that produces nanosized particles from elemental metallic powders. Xanthophyll is singled out as the organic natural dye of choice among other dyes that were extracted, as it exhibited wider spectral absorptivity in terms of wavelength range and magnitude. Two compact solar cells were constructed and tested; one is a reference cell with a TiO2 working electrode and the other with a Fe‐Cu working electrode. The results show a better power conversion efficiency for the Fe‐Cu‐based solar cell 0.943% compared to 0.638% for the TiO2, and the number of carriers in the former is found to be orders of magnitude higher than the latter (1019 vs. 1032, respectively). A thorough optical, electrical, and thermal analysis of the Fe‐Cu material is conducted and used to explain the obtained results.
Lethal and sublethal effects of phthalate diesters in Silurana tropicalis larvae
Authors: Mathieu-Denoncourt Justine , Martyniuk Christopher J. , Loughery Jennifer R. , Yargeau Viviane , de Solla Shane R. , Langlois Valerie S.
Published: February 2016

Phthalates are compounds used in polymers to increase their flexibility and are now ubiquitous in the environment as a result of widespread use. Because few studies have focused on the adverse effects of these chemicals in aquatic species, the present study aimed to determine the effects of phthalate diesters in amphibians. Western clawed frog (Silurana tropicalis) tadpoles were acutely exposed to water spiked with monomethyl phthalate (MMP; 1.3–1595.5 mg/L), dimethyl phthalate (DMP; 0.03–924.0 mg/L), or dicyclohexyl phthalate (DCHP; 0.3–99.3 mg/L). Because few studies have addressed the toxicity of these specific phthalates in most organisms, the present study used higher concentrations of these chemicals to determine their toxicity pathways in amphibians and at the same time investigate a suite of genes known to be altered by the well-studied phthalates. Both DMP and DCHP increased larval mortality (9.1–924.0 mg/L DMP and 4.1–99.3 mg/L DCHP), increased frequency of malformations in tadpoles (0.1–34.1 mg/L DMP and 4.1–19.0 mg/L DCHP), and up-regulated cellular stress-related messenger-RNA (mRNA) levels (4.1 mg/L DCHP). To characterize the molecular toxicity pathway of these phthalates in tadpoles, transcriptome analysis was conducted using a custom microarray. Parametric analysis of gene set enrichment revealed important changes in the expression of genes related to drug metabolism and transport, liver metabolism, xenobiotic clearance, and xenobiotic metabolism after DMP and DCHP treatments, although these responses were less pronounced with MMP (the metabolite of DMP). The present study is one of the few studies that demonstrated complementarity between gene expression analysis and organismal effects. Environ Toxicol Chem 2016;35:2511–2522. © 2016 SETAC
Dose metrics assessment for differently shaped and sized metal-based nanoparticles
Authors: Hua Jing , Vijver Martina G. , Chen Guangchao , Richardson Michael K. , Peijnenburg Willie J.G.M.
Published: February 2016

The mean primary diameter (d) of nanoparticles (NPs) is commonly used as the best basis to assess the dose metric for expressing the toxicity of spherical NPs. However, d bears no relevance for nonspherical NPs. In the present study, the mean surface area to volume ratio, applicable to both spherical and nonspherical NPs, was used to replace d given the aim of obtaining the best dose metric (volume, surface area, or number) of differently shaped metallic NPs in vivo (9 organisms) and in vitro (6 mammalian cell lines). The slope of the curves obtained by relating the total particle number of NPs at various effect concentrations to the mean surface area to volume ratio was subsequently used to deduce the best dose metric. For the majority of the organisms studied, it was found that NP volume is the most appropriate dose metric, independent of the composition of the NPs tested. For 3 organisms exposed to Ag NPs, however, surface area was found to be the best dose metric. It is therefore concluded that the optimum dose metric depends on organism and NP properties. Environ Toxicol Chem 2016;35:2466–2473. © 2016 SETAC
Antitumour effects of the essential oil from Mentha x villosa combined with 5‐fluorouracil in mice
Authors: Amaral Ricardo Guimarães , Andrade Luciana Nalone , Dória Grace Anne Azevedo , Barbosa‐Filho José Maria , de Sousa Damião Pergentino , Carvalho Adriana Andrade , Thomazzi Sara Maria
Published: February 2016

In the previous study, we demonstrated that the essential oil from the leaves of Mentha x villosa (EOMV) shows antitumour activities. In the present paper, the effects of the combination of 5‐fluorouracil (5‐FU) with the EOMV were determined in mice transplanted with Sarcoma 180 tumour cells. Hematological and biochemical analyses, as well as morphological analyses of the tumour and the organs (liver, spleen and kidney) were performed in order to evaluate the toxicological aspects. The combination of the EOMV (50 and 100 mg/kg/day) with 5‐FU (10 mg/kg/day) led to a higher tumour growth inhibition rate (58.9% and 65.7%, respectively) when compared with 5‐FU alone at 10 mg/kg/day (30.2%). The combined use of 5‐FU (10 mg/kg/day) with the EOMV (50 and 100 mg/kg/day) showed similar tumour growth inhibition rate to that of 5‐FU alone at the highest dose (25 mg/kg/day) with less severe leukopenia. However, neither the enzymatic activity of transaminases nor the urea and creatinine levels were modified when compared with the 5‐FU groups. These findings indicate that the EOMV may enhance the therapeutic effectiveness of chemotherapeutic drugs. Copyright © 2016 John Wiley & Sons, Ltd.
An Adaptive Multiscale Ensemble Learning Paradigm for Nonstationary and Nonlinear Energy Price Time Series Forecasting
Authors: Zhu Bangzhu , Shi Xuetao , Chevallier Julien , Wang Ping , Wei Yi‐Ming
Published: February 2016

For forecasting nonstationary and nonlinear energy prices time series, a novel adaptive multiscale ensemble learning paradigm incorporating ensemble empirical mode decomposition (EEMD), particle swarm optimization (PSO) and least square support vector machines (LSSVM) with kernel function prototype is developed. Firstly, the extrema symmetry expansion EEMD, which can effectively restrain the mode mixing and end effects, is used to decompose the energy price into simple modes. Secondly, by using the fine‐to‐coarse reconstruction algorithm, the high‐frequency, low‐frequency and trend components are identified. Furthermore, autoregressive integrated moving average is applicable to predicting the high‐frequency components. LSSVM is suitable for forecasting the low‐frequency and trend components. At the same time, a universal kernel function prototype is introduced for making up the drawbacks of single kernel function, which can adaptively select the optimal kernel function type and model parameters according to the specific data using the PSO algorithm. Finally, the prediction results of all the components are aggregated into the forecasting values of energy price time series. The empirical results show that, compared with the popular prediction methods, the proposed method can significantly improve the prediction accuracy of energy prices, with high accuracy both in the level and directional predictions. Copyright © 2016 John Wiley & Sons, Ltd.
Pre‐reconstruction of cervical‐to‐petrous internal carotid artery: An improved technique for treatment of vascular lesions involving internal carotid artery at the lateral skull base
Authors: Li Fang‐Da , Gao Zhi‐Qiang , Ren Hua‐Liang , Liu Chang‐Wei , Song Xiao‐Jun , Li Yan‐Feng , Zheng Yue‐Hong
Published: February 2016

Background

Reconstruction of the internal carotid artery (ICA) is an operative challenge for lesions involving the lateral skull base because of excessive blood loss, intraoperative cranial nerve injury, and difficulties in cerebral protection.

Methods

Between January 2010 and October 2014, 9 patients with vascular lesions at the lateral skull base were treated with a “pre‐reconstruction” technique, which means reconstruction of the ICA in advance of excising the lesions.

Results

All operations were technically successful with no mortality or strokes. The mean blood loss was 921 ± 210 mL. The mean total clamping time was 18 ± 5 minutes. Among the 5 patients without invasion of specific cranial nerves, no long‐term sequelae occurred during the follow‐up period ranging from 11 to 54 months.

Conclusion

With less blood loss, slighter cranial nerve injuries, and shorter clamping time, the “pre‐reconstruction” technique was safe and effective for the treatment of vascular lesions at the lateral skull base. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1562–E1567, 2016
Human intrahepatic regulatory T cells are functional, require IL‐2 from effector cells for survival, and are susceptible to Fas ligand‐mediated apoptosis
Authors: Chen Yung‐Yi , Jeffery Hannah C. , Hunter Stuart , Bhogal Ricky , Birtwistle Jane , Braitch Manjit Kaur , Roberts Sheree , Ming Mikaela , Hannah Jack , Thomas Clare , Adali Gupse , Hübscher Stefan G. , Syn Wing‐Kin , Afford Simon , Lalor Patricia F. , Adams David H. , Oo Ye H.
Published: February 2016

Regulatory T cells (Treg) suppress T effector cell proliferation and maintain immune homeostasis. Autoimmune liver diseases persist despite high frequencies of Treg in the liver, suggesting that the local hepatic microenvironment might affect Treg stability, survival, and function. We hypothesized that interactions between Treg and endothelial cells during recruitment and then with epithelial cells within the liver affect Treg stability, survival, and function. To model this, we explored the function of Treg after migration through human hepatic sinusoidal‐endothelium (postendothelial migrated Treg [PEM Treg]) and the effect of subsequent interactions with cholangiocytes and local proinflammatory cytokines on survival and stability of Treg. Our findings suggest that the intrahepatic microenvironment is highly enriched with proinflammatory cytokines but deficient in the Treg survival cytokine interleukin (IL)‐2. Migration through endothelium into a model mimicking the inflamed liver microenvironment did not affect Treg stability; however, functional capacity was reduced. Furthermore, the addition of exogenous IL‐2 enhanced PEM Treg phosphorylated STAT5 signaling compared with PEMCD8. CD4 and CD8 T cells are the main source of IL‐2 in the inflamed liver. Liver‐infiltrating Treg reside close to bile ducts and coculture with cholangiocytes or their supernatants induced preferential apoptosis of Treg compared with CD8 effector cells. Treg from diseased livers expressed high levels of CD95, and their apoptosis was inhibited by IL‐2 or blockade of CD95. Conclusion: Recruitment through endothelium does not impair Treg stability, but a proinflammatory microenvironment deficient in IL‐2 leads to impaired function and increased susceptibility of Treg to epithelial cell‐induced Fas‐mediated apoptosis. These results provide a mechanism to explain Treg dysfunction in inflamed tissues and suggest that IL‐2 supplementation, particularly if used in conjunction with Treg therapy, could restore immune homeostasis in inflammatory and autoimmune liver disease. (Hepatology 2016;64:138–150)
Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice
Authors: Gong Qi , Hu Zhimin , Zhang Feifei , Cui Aoyuan , Chen Xin , Jiang Haoyang , Gao Jing , Chen Xuqing , Han Yamei , Liang Qingning , Ye Dewei , Shi Lei , Chin Y. Eugene , Wang Yu , Xiao Hui , Guo Feifan , Liu Yong , Zang Mengwei , Xu Aimin , Li Yu
Published: February 2016

Among the 22 fibroblast growth factors (FGFs), FGF21 has now emerged as a key metabolic regulator. However, the mechanism whereby FGF21 mediates its metabolic actions per se remains largely unknown. Here, we show that FGF21 represses mammalian target of rapamycin complex 1 (mTORC1) and improves insulin sensitivity and glycogen storage in a hepatocyte‐autonomous manner. Administration of FGF21 in mice inhibits mTORC1 in the liver, whereas FGF21‐deficient mice display pronounced insulin‐stimulated mTORC1 activation and exacerbated hepatic insulin resistance (IR). FGF21 inhibits insulin‐ or nutrient‐stimulated activation of mTORC1 to enhance phosphorylation of Akt in HepG2 cells at both normal and IR condition. TSC1 deficiency abrogates FGF21‐mediated inhibition of mTORC1 and augmentation of insulin signaling and glycogen synthesis. Strikingly, hepatic βKlotho knockdown or hepatic hyperactivation of mTORC1/ribosomal protein S6 kinase 1 abrogates hepatic insulin‐sensitizing and glycemic‐control effects of FGF21 in diet‐induced insulin‐resistant mice. Moreover, FGF21 improves methionine‐ and choline‐deficient diet‐induced steatohepatitis. Conclusions: FGF21 acts as an inhibitor of mTORC1 to control hepatic insulin action and maintain glucose homeostasis, and mTORC1 inhibition by FGF21 has the therapeutic potential for treating IR and type 2 diabetes. (Hepatology 2016;64:425‐438)
Proton Transfer Influence on Geometry and Electron Density in Benzoic Acid–Pyridine Complexes
Authors: Majerz Irena
Published: February 2016

The influence of the proton transfer on the geometry of donor and acceptor molecule in benzoic acid–pyridine complexes is investigated by theoretical calculations at the B3LYP/6‐311++G** level of theory. Systematic shifts of the H‐atom in the H‐bond are reflected in the geometry of the COOH group and the lengths of aromatic ring bond lengths of the proton acceptor. Changes in electron densities have been studied by atoms in molecules analysis. A systematic natural bond orbital analysis has been performed to study the proton transfer mechanism. Two donor orbitals are engaged in the proton transfer process which is accompanied by a change in orbital delocalization of H‐atom that can switch between two donor orbitals so the path of proton transfer in intermolecular H‐bond is not determined by the orbital shape. Theoretical results have been confirmed by experimental results published previously.
Leaf‐Critical and Leaf‐Stable Graphs
Authors: Wiener Gábor
Published: February 2016

The minimum leaf number ml(G) of a connected graph G is defined as the minimum number of leaves of the spanning trees of G if G is not hamiltonian and 1 if G is hamiltonian. We study nonhamiltonian graphs with the property for each or for each . These graphs will be called ‐leaf‐critical and l‐leaf‐stable, respectively. It is far from obvious whether such graphs exist; for example, the existence of 3‐leaf‐critical graphs (that turn out to be the so‐called hypotraceable graphs) was an open problem until 1975. We show that l‐leaf‐stable and l‐leaf‐critical graphs exist for every integer , moreover for n sufficiently large, planar l‐leaf‐stable and l‐leaf‐critical graphs exist on n vertices. We also characterize 2‐fragments of leaf‐critical graphs generalizing a lemma of Thomassen. As an application of some of the leaf‐critical graphs constructed, we settle an open problem of Gargano et al. concerning spanning spiders. We also explore connections with a family of graphs introduced by Grünbaum in correspondence with the problem of finding graphs without concurrent longest paths.
How often are hospitalized patients and providers on the same page with regard to the patient's primary recovery goal for hospitalization?
Authors: Figueroa Jose F. , Schnipper Jeffrey L. , McNally Kelly , Stade Diana , Lipsitz Stuart R. , Dalal Anuj K.
Published: February 2016

BACKGROUND

To deliver high‐quality, patient‐centered care during hospitalization, healthcare providers must correctly identify the patient's primary recovery goal.

OBJECTIVE

To determine the degree of concordance between patients and key hospital providers.

DESIGN

A validated questionnaire administered to a random sample of hospitalized patients alongside their nurse and physician provider. Goals included: “be cured,” “live longer,” “improve/maintain health,” “be comfortable,” “accomplish a particular life goal,” or “other.”

SETTING

Major academic hospital in Boston, Massachusetts.

PARTICIPANTS

Adult patients admitted for more than 48 hours from November 2013 to May 2014 were eligible. When a patient was incapacitated, a legal proxy was interviewed. The nurse and physician provider were then interviewed within 24 hours.

MEASUREMENTS

Frequencies of responses for each recovery goal and the rate of concordance among the patient, nurse, and physician provider were measured. The frequency of responses across groups were compared using adjusted χ2 analyses. Inter‐rater agreement was measured using 2‐way Kappa tests.

RESULTS

All 3 participants were interviewed in 109 of the 181 (60.2%) patients approached (or with proxy available). Significant differences in selected goals were observed across respondent groups (P < 0.001). Patients frequently chose “be cured” (46.8%). Nurses and physician providers frequently selected “improve or maintain health” (38.5% and 46.8%, respectively). All 3 participants selected the same goal in 22 cases (20.2%). Inter‐rater agreement was poor to slight for all pairs (kappa 0.09 [−0.03‐0.19], 0.19 [0.08‐0.30], and 0.20 [0.08‐0.32] for patient‐physician, patient‐nurse, and nurse‐physician, respectively).

CONCLUSIONS

We observed poor to slight concordance among hospitalized patients and key medical team members with regard to the patient's primary recovery goal. Journal of Hospital Medicine 2016;11:615–619. © 2016 Society of Hospital Medicine
Usefulness of MR elastography for detecting clinical progression of cirrhosis from child‐pugh class A to B in patients with type C viral hepatitis
Authors: Takamura Tomohiro , Motosugi Utaroh , Ichikawa Shintaro , Sano Katsuhiro , Morisaka Hiroyuki , Ichikawa Tomoaki , Enomoto Nobuyuki , Onishi Hiroshi
Published: February 2016

Purpose

To evaluate the usefulness of magnetic resonance elastography (MRE) in detecting the clinical progression of cirrhosis from Child‐Pugh class A to B in patients with hepatitis C.

Materials and Methods

We reviewed the data of 101 consecutive patients with type C viral hepatitis and clinically suspected cirrhosis who fulfilled the all following criteria: available MRE at 1.5 Tesla (T) or 3.0T and laboratory tests within a month, Child‐Pugh class A, platelet count less than 155 × 103/μL, no clinical history of hepatocellular carcinoma, and ≥6 months of follow‐up after MRE. We longitudinally analyzed the incidence of cirrhosis progression as defined by the clinical progression from Child‐Pugh class A to B at two subsequent follow‐up points. Risk of cirrhosis progression was assessed by Cox analyses and Kaplan‐Meyer methods.

Results

Cirrhosis progression was noted in 25 patients during the follow‐up period. Liver stiffness (hazard ratio [HR] by 1 kPa increase = 1.397; P = 0.0074), Child‐Pugh score of 6 versus score 5 (HR of 3.085; P = 0.0276), and treatment responses to anti‐viral therapy versus nonresponse (HR of <0.001, P = 0.0006) were independent risk factors of cirrhosis progression. The 1‐year risk (0.7%; 95% confidence interval, 0.1–4.2%) of cirrhosis progression was negligible in patients with liver stiffness of <3.3 kPa or response to anti‐viral treatment.

Conclusion

MRE is useful to stratify the risk of cirrhosis progression in patients with hepatitis C. J. Magn. Reson. Imaging 2016;44:715–722.
Rapid breath‐hold assessment of myocardial velocities using spiral UNFOLD‐ed SENSE tissue phase mapping
Authors: Kowalik Grzegorz T. , Muthurangu Vivek , Khushnood Abbas , Steeden Jennifer A.
Published: February 2016

Purpose

To develop and validate a rapid breath‐hold tissue phase mapping (TPM) sequence.

Materials and Methods

The sequence was based on an efficient uniform density spiral acquisition, combined with data acceleration. A novel acquisition and reconstruction strategy enabled combination of UNFOLD (2×) and SENSE (3×): UNFOLD‐ed SENSE. The sequence was retrospectively cardiac‐gated, and a graphics processing unit (GPU) was used for rapid “online” reconstruction. The optimal UNFOLD parameters for the data were calculated using an in silico model. The technique was validated on a 1.5T MR scanner in 15 patients with known aortic valve disease, against a respiratory self‐navigated free‐breathing TPM technique. Quantitative image quality measures (velocity‐to‐noise and edge sharpness) were made as well as calculation of longitudinal, radial, and tangential myocardial velocities in the left ventricle.

Results

The proposed breath‐hold TPM data took eight heartbeats to acquire. The breath‐hold TPM images had significantly higher edge sharpness (P = 0.0014) than the self‐navigated TPM images, but with significantly lower velocity‐to‐noise ratio (P < 0.0001). There was excellent agreement (r > 0.94) in the longitudinal, radial, and tangential velocities between the self‐navigated data and the proposed breath‐hold TPM sequence.

Conclusion

We demonstrate the feasibility of using spiral UNFOLD‐ed SENSE to measure myocardial velocities using a rapid breath‐hold spiral TPM sequence. This novel technique might enable accurate measurement of myocardial velocities, in a short scan time, which is especially important in a busy clinical workflow. J. MAGN. RESON. IMAGING 2016;44:1003–1009.
Status of microbial diversity in agroforestry systems in Tamil Nadu, India
Authors: Radhakrishnan Srinivasan , Varadharajan Mohan
Published: February 2016

Soil is a complex and dynamic biological system. Agroforestry systems are considered to be an alternative land use option to help and prevent soil degradation, improve soil fertility, microbial diversity, and organic matter status. An increasing interest has emerged with respect to the importance of microbial diversity in soil habitats. The present study deals with the status of microbial diversity in agroforestry systems in Tamil Nadu. Eight soil samples were collected from different fields in agroforestry systems in Cuddalore, Villupuram, Tiruvanamalai, and Erode districts, Tamil Nadu. The number of microorganisms and physico‐chemical parameters of soils were quantified. Among different microbial population, the bacterial population was recorded maximum (64%), followed by actinomycetes (23%) and fungi (13%) in different samples screened. It is interesting to note that the microbial population was positively correlated with the physico‐chemical properties of different soil samples screened. Total bacterial count had positive correlation with soil organic carbon (C), moisture content, pH, nitrogen (N), and micronutrients such as Iron (Fe), copper (Cu), and zinc (Zn). Similarly, the total actinomycete count also showed positive correlations with bulk density, moisture content, pH, C, N, phosphorus (P), potassium (K), calcium (Ca), copper (Cu), magnesium (Mg), manganese (Mn), and zinc (Zn). It was also noticed that the soil organic matter, vegetation, and soil nutrients altered the microbial community under agroforestry systems.
Analysis of a large choroideremia dataset does not suggest a preference for inclusion of certain genotypes in future trials of gene therapy
Authors: Freund Paul R. , Sergeev Yuri V. , MacDonald Ian M.
Published: February 2016

Background

Choroideremia (CHM) is an X‐linked degeneration of the retinal pigment epithelium, photoreceptors, and choroid, which causes nyctalopia and progressive constriction of visual fields leading to blindness. The CHM gene encodes Rab escort protein 1 (REP‐1). In this work, we reviewed the phenotypes and genotypes of affected males with the purpose of understanding the functional effects of CHM mutations and their relationship with the phenotypes.

Methods

A retrospective review of 128 affected males was performed analyzing the onset of symptoms, visual acuity, and visual fields with respect to their mutations in the CHM gene.

Results

In rank order, reflecting data from this report, the most common mutations found in the CHM gene were nonsense mutations (41%), exon deletions (37%), and splice sites (14%) associated with a loss of functional protein. In the pool of 106 CHM mutations, we discovered four novel missense mutations (c.238C>T; p.L80F, c.819G>T; p.Q273H, c.1327A>G; p.M443V, and c.1370C>T; p.L457P) predicted to be severe changes affecting protein stability and folding with the effect similar to that of other types of mutations. No significant genotype–phenotype correlation was found with respect to the onset of nyctalopia, the onset of other visual symptoms, visual acuity, or width of visual fields.

Conclusion

There is no evidence to support exclusion of CHM patients from clinical trials based on their genotypes or any potential genotype–phenotype correlations.
Erythrocyte linoleic acid, but not oleic acid, is associated with improvements in body composition in men and women
Authors: Belury Martha A. , Cole Rachel M. , Bailey Brittney E. , Ke Jia‐Yu , Andridge Rebecca R. , Kiecolt‐Glaser Janice K.
Published: February 2016

Scope

Supplementation with linoleic acid (LA; 18:2Ω6)‐rich oils increases lean mass and decreases trunk adipose mass in people. Erythrocyte fatty acids reflect the dietary pattern of fatty acid intake and endogenous metabolism of fatty acids. The aim of this study is to determine the relationship of erythrocyte LA, with aspects of body composition, insulin resistance, and inflammation. Additionally, we tested for relationships of oleic acid (OA) and the sum of long chain omega‐three fatty acids (LC‐Ω3‐SUM), on the same outcomes.

Methods and results

Men and women (N = 139) were evaluated for body composition, insulin resistance, and serum inflammatory markers, IL‐6, and c‐reactive protein (CRP) and erythrocyte fatty acid composition after an overnight fast. LA was positively related to appendicular lean mass/body mass index and inversely related to trunk adipose mass. Additionally, LA was inversely related to insulin resistance and IL‐6. While there was an inverse relationship between OA or LC‐Ω3‐SUM with markers of inflammation, there were no relationships between OA or LC‐Ω3‐SUM with body composition or HOMA‐IR.

Conclusion

Higher erythrocyte LA was associated with improved body composition, insulin resistance, and inflammation. Erythrocyte OA or LC‐Ω3‐SUM was unrelated to body composition and insulin resistance. There is much controversy about whether all unsaturated fats have the same benefits for metabolic syndrome and weight gain. We sought to test the strength of the relationships between three unsaturated fatty acid in erythrocytes with measurements of body composition, metabolism, and inflammation in healthy adults. Linoleic acid, but not oleic acid or the sum of long‐chain omega 3 fatty acids (w3), was associated with increased appendicular lean mass and decreased trunk adipose mass and insulin resistance.